HIV Infection and AIDS

Epidemiology

Worldwide

• At the end of 2018, there were approximately 37 million infected people.
• Sub-Saharan Africa:
  • The most affected area in the world
  • Approximately > 10% of adults aged 15–49 years are affected.
  • Accounts for > 50% of total global human immunodeficiency Immunodeficiency Chédiak-Higashi Syndrome virus Virus Viruses are infectious, obligate intracellular parasites composed of a nucleic acid core surrounded by a protein capsid. Viruses can be either naked (non-enveloped) or enveloped. The classification of viruses is complex and based on many factors, including type and structure of the nucleoid and capsid, the presence of an envelope, the replication cycle, and the host range. Virology ( HIV HIV Anti-HIV Drugs) infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease

United States

• Approximately 38,700 new cases diagnosed each year
• Approximately 1.1 million individuals currently living with HIV HIV Anti-HIV Drugs
• HIV HIV Anti-HIV Drugs infection highest among Hispanics and African Americans (likely due to socioeconomic factors)
• Gay and bisexual males account for most newly diagnosed cases.
• Children usually acquire infection from their mother in utero or via subsequent breastfeeding Breastfeeding Breastfeeding is often the primary source of nutrition for the newborn. During pregnancy, hormonal stimulation causes the number and size of mammary glands in the breast to significantly increase. After delivery, prolactin stimulates milk production, while oxytocin stimulates milk expulsion through the lactiferous ducts, where it is sucked out through the nipple by the infant. Breastfeeding.

Etiology and Transmission

HIV HIV Anti-HIV Drugs

• Genus, Lentivirus Lentivirus A genus of the family retroviridae consisting of non-oncogenic retroviruses that produce multi-organ diseases characterized by long incubation periods and persistent infection. Lentiviruses are unique in that they contain open reading frames (orfs) between the pol and env genes and in the 3′ env region. Five serogroups are recognized, reflecting the mammalian hosts with which they are associated. HIV-1 is the type species. Human Immunodeficiency Virus (HIV); family, Retroviridae Retroviridae The human immunodeficiency virus (HIV) is a species of Lentivirus, a genus of the family Retroviridae, which causes HIV infections and acquired immunodeficiency syndrome (AIDS). The virus has high genetic variability and is divided into 2 major types, HIV type 1 (HIV-1) and HIV type 2 (HIV-2). The human immunodeficiency virus is a single-stranded, positive-sense, enveloped RNA virus, which targets and destroys WBCs, leading to frequent opportunistic infections and, eventually, death. Human Immunodeficiency Virus (HIV)
• Structure:
  • Virion envelope Envelope Bilayer lipid membrane acquired by viral particles during viral morphogenesis. Although the lipids of the viral envelope are host derived, various virus-encoded integral membrane proteins, i.e. Viral envelope proteins are incorporated there. Virology contains 2 membrane glycoproteins Glycoproteins Conjugated protein-carbohydrate compounds including mucins, mucoid, and amyloid glycoproteins. Basics of Carbohydrates:
    • Gp41 (transmembrane)
    • Gp120 (surface/docking protein)
  • Matrix protein Matrix protein Proteins associated with the inner surface of the lipid bilayer of the viral envelope. These proteins have been implicated in control of viral transcription and may possibly serve as the ‘glue’ that binds the nucleocapsid to the appropriate membrane site during viral budding from the host cell. Parainfluenza Virus p17: surrounds the virus Virus Viruses are infectious, obligate intracellular parasites composed of a nucleic acid core surrounded by a protein capsid. Viruses can be either naked (non-enveloped) or enveloped. The classification of viruses is complex and based on many factors, including type and structure of the nucleoid and capsid, the presence of an envelope, the replication cycle, and the host range. Virology core
  • Virus Virus Viruses are infectious, obligate intracellular parasites composed of a nucleic acid core surrounded by a protein capsid. Viruses can be either naked (non-enveloped) or enveloped. The classification of viruses is complex and based on many factors, including type and structure of the nucleoid and capsid, the presence of an envelope, the replication cycle, and the host range. Virology core:
    • Capsid Capsid The outer protein protective shell of a virus, which protects the viral nucleic acid. Capsids are composed of repeating units (capsomers or capsomeres) of capsid proteins which when assembled together form either an icosahedral or helical shape. Virology protein p24
    • 2 single-stranded, enveloped positive-sense ribonucleic acid Ribonucleic acid A polynucleotide consisting essentially of chains with a repeating backbone of phosphate and ribose units to which nitrogenous bases are attached. RNA is unique among biological macromolecules in that it can encode genetic information, serve as an abundant structural component of cells, and also possesses catalytic activity. RNA Types and Structure ( RNA RNA A polynucleotide consisting essentially of chains with a repeating backbone of phosphate and ribose units to which nitrogenous bases are attached. RNA is unique among biological macromolecules in that it can encode genetic information, serve as an abundant structural component of cells, and also possesses catalytic activity. RNA Types and Structure) molecules coated with nucleocapsid protein
    • Enzymes Enzymes Enzymes are complex protein biocatalysts that accelerate chemical reactions without being consumed by them. Due to the body’s constant metabolic needs, the absence of enzymes would make life unsustainable, as reactions would occur too slowly without these molecules. Basics of Enzymes (reverse transcriptase, integrase, protease)
• Subtypes of HIV HIV Anti-HIV Drugs:
  • HIV-1:
    • Most common species worldwide
    • Similar to the simian immunodeficiency Immunodeficiency Chédiak-Higashi Syndrome virus Virus Viruses are infectious, obligate intracellular parasites composed of a nucleic acid core surrounded by a protein capsid. Viruses can be either naked (non-enveloped) or enveloped. The classification of viruses is complex and based on many factors, including type and structure of the nucleoid and capsid, the presence of an envelope, the replication cycle, and the host range. Virology in chimpanzees
    • 4 distinct subgroups (M, N, O, and P)
    • Subgroup M: 90% of HIV HIV Anti-HIV Drugs/AIDS (acquired immunodeficiency Immunodeficiency Chédiak-Higashi Syndrome syndrome) worldwide
  • HIV-2:
    • Lower infectivity, less virulent, largely confined to West Africa 
    • Similar to simian immunodeficiency Immunodeficiency Chédiak-Higashi Syndrome virus Virus Viruses are infectious, obligate intracellular parasites composed of a nucleic acid core surrounded by a protein capsid. Viruses can be either naked (non-enveloped) or enveloped. The classification of viruses is complex and based on many factors, including type and structure of the nucleoid and capsid, the presence of an envelope, the replication cycle, and the host range. Virology from sooty mangabey monkeys
    • 8 known subgroups (A to H)
• Transmission through bodily fluids (i.e., blood, semen, vaginal secretions, and breast milk)

Modes of HIV HIV Anti-HIV Drugs transmission

Sexual:

• Unprotected sex Sex The totality of characteristics of reproductive structure, functions, phenotype, and genotype, differentiating the male from the female organism. Gender Dysphoria:
  • Responsible for 80% of infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease
  • Unprotected receptive anal intercourse Anal intercourse Hemorrhoids (URAI) in men and women > unprotected receptive vaginal intercourse
• In anal intercourse Anal intercourse Hemorrhoids, infection occurs:
  • With direct inoculation into the blood in the presence of traumatic tears
  • With easy access to target cells beneath the fragile rectal mucosal membrane
• In the United States, risk noted:
  • In men who have sex Sex The totality of characteristics of reproductive structure, functions, phenotype, and genotype, differentiating the male from the female organism. Gender Dysphoria with men (highest)
  • Heterosexual individuals
• In Africa, reported infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease are predominantly via heterosexual transmission (limited data on homosexual transmission rates).

Parenteral:

• Intravenous (IV) drug use and sharing needles 
• Accidental needle punctures in medical professionals

Vertical:

• Mother to child during pregnancy Pregnancy The status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth. Pregnancy: Diagnosis, Physiology, and Care, delivery, or breastfeeding Breastfeeding Breastfeeding is often the primary source of nutrition for the newborn. During pregnancy, hormonal stimulation causes the number and size of mammary glands in the breast to significantly increase. After delivery, prolactin stimulates milk production, while oxytocin stimulates milk expulsion through the lactiferous ducts, where it is sucked out through the nipple by the infant. Breastfeeding
• Most cases occur during delivery.
• Risk factors for vertical transmission Vertical transmission The transmission of infectious disease or pathogens from one generation to another. It includes transmission in utero or intrapartum by exposure to blood and secretions, and postpartum exposure via breastfeeding. Congenital TORCH Infections:
  • No antiretroviral therapy Antiretroviral therapy Antiretroviral therapy (ART) targets the replication cycle of the human immunodeficiency virus (HIV) and is classified based on the viral enzyme or mechanism that is inhibited. The goal of therapy is to suppress viral replication to reach the outcome of undetected viral load. Anti-HIV Drugs or prophylaxis Prophylaxis Cephalosporins
  • Elevated maternal viral load
  • Rupture of membranes > 4 hours

Factors affecting transmission

• Viral load:
  • Quantity of HIV HIV Anti-HIV Drugs is the primary factor determining transmission.
  • Transmission unlikely if with suppressed viral load (defined as having a viral load of < 400 HIV HIV Anti-HIV Drugs RNA RNA A polynucleotide consisting essentially of chains with a repeating backbone of phosphate and ribose units to which nitrogenous bases are attached. RNA is unique among biological macromolecules in that it can encode genetic information, serve as an abundant structural component of cells, and also possesses catalytic activity. RNA Types and Structure copies/mL)
• Type of sexual contact:
  • Receptive anal sex Sex The totality of characteristics of reproductive structure, functions, phenotype, and genotype, differentiating the male from the female organism. Gender Dysphoria is the most high risk.
  • Circumcision reduces the risk of transmission.
• Mucosal damage: Inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body’s defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation, tears, sexually transmitted infection Sexually Transmitted Infection Sexually transmitted infections (STIs) are infections that spread either by vaginal intercourse, anal sex, or oral sex. Symptoms and signs may include vaginal discharge, penile discharge, dysuria, skin lesions (e.g., warts, ulcers) on or around the genitals, and pelvic pain. Some infections can lead to infertility and chronic debilitating disease. Sexually Transmitted Infections (STIs), and irritation of the genital mucous membranes increase transmission risk.
• Recent HIV HIV Anti-HIV Drugs infection: elevated risk of transmission due to high viral load

Pathophysiology

HIV replication HIV replication Human Immunodeficiency Virus (HIV) cycle

• Target cells: CD4+ T cells T cells Lymphocytes responsible for cell-mediated immunity. Two types have been identified – cytotoxic (t-lymphocytes, cytotoxic) and helper T-lymphocytes (t-lymphocytes, helper-inducer). They are formed when lymphocytes circulate through the thymus gland and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen. T cells: Types and Functions, macrophages Macrophages The relatively long-lived phagocytic cell of mammalian tissues that are derived from blood monocytes. Main types are peritoneal macrophages; alveolar macrophages; histiocytes; kupffer cells of the liver; and osteoclasts. They may further differentiate within chronic inflammatory lesions to epithelioid cells or may fuse to form foreign body giant cells or langhans giant cells. Innate Immunity: Phagocytes and Antigen Presentation, and dendritic cells Dendritic cells Specialized cells of the hematopoietic system that have branch-like extensions. They are found throughout the lymphatic system, and in non-lymphoid tissues such as skin and the epithelia of the intestinal, respiratory, and reproductive tracts. They trap and process antigens, and present them to T-cells, thereby stimulating cell-mediated immunity. They are different from the non-hematopoietic follicular dendritic cells, which have a similar morphology and immune system function, but with respect to humoral immunity (antibody production). Skin: Structure and Functions
• HIV cell entry HIV cell entry Human Immunodeficiency Virus (HIV):
  • The virion first enters via a break in a mucous membrane Mucous membrane An epithelium with mucus-secreting cells, such as goblet cells. It forms the lining of many body cavities, such as the digestive tract, the respiratory tract, and the reproductive tract. Mucosa, rich in blood and lymph vessels, comprises an inner epithelium, a middle layer (lamina propria) of loose connective tissue, and an outer layer (muscularis mucosae) of smooth muscle cells that separates the mucosa from submucosa. Barrett Esophagus. 
  • The virion then crosses the mucosal barrier and seeks target cells.
• HIV replication:
  1. Membrane fusion and binding of receptors Receptors Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors (entry): the virion (carrying viral RNA RNA A polynucleotide consisting essentially of chains with a repeating backbone of phosphate and ribose units to which nitrogenous bases are attached. RNA is unique among biological macromolecules in that it can encode genetic information, serve as an abundant structural component of cells, and also possesses catalytic activity. RNA Types and Structure, reverse transcriptase, integrase, and other proteins Proteins Linear polypeptides that are synthesized on ribosomes and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of amino acids determines the shape the polypeptide will take, during protein folding, and the function of the protein. Energy Homeostasis) initiates entry into the host cell.
     • Virion binds the CD4 receptor Receptor Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors and a chemokine receptor Receptor Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors (CCR5 on macrophages Macrophages The relatively long-lived phagocytic cell of mammalian tissues that are derived from blood monocytes. Main types are peritoneal macrophages; alveolar macrophages; histiocytes; kupffer cells of the liver; and osteoclasts. They may further differentiate within chronic inflammatory lesions to epithelioid cells or may fuse to form foreign body giant cells or langhans giant cells. Innate Immunity: Phagocytes and Antigen Presentation, CXCR4 on T cells T cells Lymphocytes responsible for cell-mediated immunity. Two types have been identified – cytotoxic (t-lymphocytes, cytotoxic) and helper T-lymphocytes (t-lymphocytes, helper-inducer). They are formed when lymphocytes circulate through the thymus gland and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen. T cells: Types and Functions).
       • Macrophage-tropic viruses Viruses Minute infectious agents whose genomes are composed of DNA or RNA, but not both. They are characterized by a lack of independent metabolism and the inability to replicate outside living host cells. Virology: R5 strains
       • T cell-tropic viruses Viruses Minute infectious agents whose genomes are composed of DNA or RNA, but not both. They are characterized by a lack of independent metabolism and the inability to replicate outside living host cells. Virology: X4 strains
     • Binding of gp120 with CD4 and the chemokine receptors Receptors Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors leads to a conformational change, exposing the fusion domain at gp41.
     • This process pulls the viral and cellular membranes together, fusing them. 
  2. The capsid Capsid The outer protein protective shell of a virus, which protects the viral nucleic acid. Capsids are composed of repeating units (capsomers or capsomeres) of capsid proteins which when assembled together form either an icosahedral or helical shape. Virology protein shell (surrounding the viral RNA RNA A polynucleotide consisting essentially of chains with a repeating backbone of phosphate and ribose units to which nitrogenous bases are attached. RNA is unique among biological macromolecules in that it can encode genetic information, serve as an abundant structural component of cells, and also possesses catalytic activity. RNA Types and Structure and proteins Proteins Linear polypeptides that are synthesized on ribosomes and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of amino acids determines the shape the polypeptide will take, during protein folding, and the function of the protein. Energy Homeostasis) is uncoated as the virion traverses the cytoplasm.
  3. Reverse transcription Transcription Transcription of genetic information is the first step in gene expression. Transcription is the process by which DNA is used as a template to make mRNA. This process is divided into 3 stages: initiation, elongation, and termination. Stages of Transcription: Reverse transcriptase-mediated synthesis Synthesis Polymerase Chain Reaction (PCR) of proviral deoxyribonucleic acid Deoxyribonucleic acid A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). DNA Types and Structure ( DNA DNA A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). DNA Types and Structure) (from the viral RNA RNA A polynucleotide consisting essentially of chains with a repeating backbone of phosphate and ribose units to which nitrogenous bases are attached. RNA is unique among biological macromolecules in that it can encode genetic information, serve as an abundant structural component of cells, and also possesses catalytic activity. RNA Types and Structure) occurs.
  4. Integration: Viral DNA DNA A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). DNA Types and Structure is transported across the nucleus Nucleus Within a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (cell nucleolus). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the endoplasmic reticulum. A cell may contain more than one nucleus. The Cell: Organelles and integrated into the host DNA DNA A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). DNA Types and Structure, facilitated by integrase. 
  5. Replication: Viral DNA DNA A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). DNA Types and Structure is transcribed, and multiple copies of new HIV HIV Anti-HIV Drugs RNA RNA A polynucleotide consisting essentially of chains with a repeating backbone of phosphate and ribose units to which nitrogenous bases are attached. RNA is unique among biological macromolecules in that it can encode genetic information, serve as an abundant structural component of cells, and also possesses catalytic activity. RNA Types and Structure form and are transported to the cytoplasm.
     • New HIV HIV Anti-HIV Drugs RNA RNA A polynucleotide consisting essentially of chains with a repeating backbone of phosphate and ribose units to which nitrogenous bases are attached. RNA is unique among biological macromolecules in that it can encode genetic information, serve as an abundant structural component of cells, and also possesses catalytic activity. RNA Types and Structure becomes the genome Genome The complete genetic complement contained in the DNA of a set of chromosomes in a human. The length of the human genome is about 3 billion base pairs. Basic Terms of Genetics of a new virus Virus Viruses are infectious, obligate intracellular parasites composed of a nucleic acid core surrounded by a protein capsid. Viruses can be either naked (non-enveloped) or enveloped. The classification of viruses is complex and based on many factors, including type and structure of the nucleoid and capsid, the presence of an envelope, the replication cycle, and the host range. Virology. 
     • Other copies of the RNA RNA A polynucleotide consisting essentially of chains with a repeating backbone of phosphate and ribose units to which nitrogenous bases are attached. RNA is unique among biological macromolecules in that it can encode genetic information, serve as an abundant structural component of cells, and also possesses catalytic activity. RNA Types and Structure are used to make new HIV HIV Anti-HIV Drugs proteins Proteins Linear polypeptides that are synthesized on ribosomes and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of amino acids determines the shape the polypeptide will take, during protein folding, and the function of the protein. Energy Homeostasis.
  6. Assembly: New viral RNA RNA A polynucleotide consisting essentially of chains with a repeating backbone of phosphate and ribose units to which nitrogenous bases are attached. RNA is unique among biological macromolecules in that it can encode genetic information, serve as an abundant structural component of cells, and also possesses catalytic activity. RNA Types and Structure + proteins Proteins Linear polypeptides that are synthesized on ribosomes and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of amino acids determines the shape the polypeptide will take, during protein folding, and the function of the protein. Energy Homeostasis + enzymes Enzymes Enzymes are complex protein biocatalysts that accelerate chemical reactions without being consumed by them. Due to the body’s constant metabolic needs, the absence of enzymes would make life unsustainable, as reactions would occur too slowly without these molecules. Basics of Enzymes move to the cell surface and form a noninfectious particle.
  7. Budding Budding Mycology and maturation:
     • Particle (viral RNA RNA A polynucleotide consisting essentially of chains with a repeating backbone of phosphate and ribose units to which nitrogenous bases are attached. RNA is unique among biological macromolecules in that it can encode genetic information, serve as an abundant structural component of cells, and also possesses catalytic activity. RNA Types and Structure + proteins Proteins Linear polypeptides that are synthesized on ribosomes and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of amino acids determines the shape the polypeptide will take, during protein folding, and the function of the protein. Energy Homeostasis) eventually buds out of the host cell with the immature HIV HIV Anti-HIV Drugs.
     • Viral protein protease then cleaves newly synthesized polyproteins, producing a mature HIV HIV Anti-HIV Drugs.

Natural history

Acute phase Acute phase Short Bowel Syndrome (infection, dissemination, retroviral syndrome):

• HIV HIV Anti-HIV Drugs infects and destroys CD4+ T cells T cells Lymphocytes responsible for cell-mediated immunity. Two types have been identified – cytotoxic (t-lymphocytes, cytotoxic) and helper T-lymphocytes (t-lymphocytes, helper-inducer). They are formed when lymphocytes circulate through the thymus gland and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen. T cells: Types and Functions, macrophages Macrophages The relatively long-lived phagocytic cell of mammalian tissues that are derived from blood monocytes. Main types are peritoneal macrophages; alveolar macrophages; histiocytes; kupffer cells of the liver; and osteoclasts. They may further differentiate within chronic inflammatory lesions to epithelioid cells or may fuse to form foreign body giant cells or langhans giant cells. Innate Immunity: Phagocytes and Antigen Presentation, and dendritic cells Dendritic cells Specialized cells of the hematopoietic system that have branch-like extensions. They are found throughout the lymphatic system, and in non-lymphoid tissues such as skin and the epithelia of the intestinal, respiratory, and reproductive tracts. They trap and process antigens, and present them to T-cells, thereby stimulating cell-mediated immunity. They are different from the non-hematopoietic follicular dendritic cells, which have a similar morphology and immune system function, but with respect to humoral immunity (antibody production). Skin: Structure and Functions in mucosal tissues.
• Dissemination and replication in lymph nodes Lymph Nodes They are oval or bean shaped bodies (1 – 30 mm in diameter) located along the lymphatic system. Lymphatic Drainage System: Anatomy occur, then proceed to other lymphoid compartments (more CD4+ target cells) → viremia Viremia The presence of viruses in the blood. Erythema Infectiosum. 
• Further spread to the plasma Plasma The residual portion of blood that is left after removal of blood cells by centrifugation without prior blood coagulation. Transfusion Products and other organs follows. 
• Antiviral Antiviral Antivirals for Hepatitis B immune response leads to seroconversion (about 3–7 weeks).
• CD8+ cytolytic T lymphocytes T lymphocytes Lymphocytes responsible for cell-mediated immunity. Two types have been identified – cytotoxic (t-lymphocytes, cytotoxic) and helper T-lymphocytes (t-lymphocytes, helper-inducer). They are formed when lymphocytes circulate through the thymus gland and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen. T cells: Types and Functions (CTLs) are activated, and this immune response produces a partial control of viral replication.
• Acute retroviral syndrome:
  • Clinical presentation of self-limited acute viral illness
  • Associated with millions of copies of HIV HIV Anti-HIV Drugs RNA RNA A polynucleotide consisting essentially of chains with a repeating backbone of phosphate and ribose units to which nitrogenous bases are attached. RNA is unique among biological macromolecules in that it can encode genetic information, serve as an abundant structural component of cells, and also possesses catalytic activity. RNA Types and Structure/mL of plasma Plasma The residual portion of blood that is left after removal of blood cells by centrifugation without prior blood coagulation. Transfusion Products
  • High likelihood of transmission during this period

Chronic phase/clinical latency:

• Low-level replication of virus Virus Viruses are infectious, obligate intracellular parasites composed of a nucleic acid core surrounded by a protein capsid. Viruses can be either naked (non-enveloped) or enveloped. The classification of viruses is complex and based on many factors, including type and structure of the nucleoid and capsid, the presence of an envelope, the replication cycle, and the host range. Virology in lymphoid tissues and slow progressive T cell depletion
• Sustained replication generates mutation Mutation Genetic mutations are errors in DNA that can cause protein misfolding and dysfunction. There are various types of mutations, including chromosomal, point, frameshift, and expansion mutations. Types of Mutations, contributing to viral escape Escape With constant immune mechanisms holding unstable tumor cells in equilibrium, tumor-cell variants may emerge. These cancer cells may express fewer antigens on their surfaces or lose their MHC class I expression.Variants may also protect themselves from T-cell attack via expression of IC molecules on their surfaces, like normal cells.Creation of an immunosuppressive state in the microenvironment is another way to grow without immunologic interference. Cancer Immunotherapy from the control of CD8+ CTLs.
• Virus Virus Viruses are infectious, obligate intracellular parasites composed of a nucleic acid core surrounded by a protein capsid. Viruses can be either naked (non-enveloped) or enveloped. The classification of viruses is complex and based on many factors, including type and structure of the nucleoid and capsid, the presence of an envelope, the replication cycle, and the host range. Virology may evolve and undergo coreceptor switch (instead of 1 coreceptor, virus Virus Viruses are infectious, obligate intracellular parasites composed of a nucleic acid core surrounded by a protein capsid. Viruses can be either naked (non-enveloped) or enveloped. The classification of viruses is complex and based on many factors, including type and structure of the nucleoid and capsid, the presence of an envelope, the replication cycle, and the host range. Virology can rely on either CCR5 or CXCR4).

AIDS:

• Ongoing activation of T cells T cells Lymphocytes responsible for cell-mediated immunity. Two types have been identified – cytotoxic (t-lymphocytes, cytotoxic) and helper T-lymphocytes (t-lymphocytes, helper-inducer). They are formed when lymphocytes circulate through the thymus gland and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen. T cells: Types and Functions results in extensive death of CD4+ T cells T cells Lymphocytes responsible for cell-mediated immunity. Two types have been identified – cytotoxic (t-lymphocytes, cytotoxic) and helper T-lymphocytes (t-lymphocytes, helper-inducer). They are formed when lymphocytes circulate through the thymus gland and differentiate to thymocytes. When exposed to an antigen, they divide rapidly and produce large numbers of new T cells sensitized to that antigen. T cells: Types and Functions.
• Profound immunodeficiency Immunodeficiency Chédiak-Higashi Syndrome leads to opportunistic infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease (usual cause of death).

Clinical Presentation

Categories of HIV HIV Anti-HIV Drugs infection

The Centers for Disease Control and Prevention (CDC) classification notes that CD4+ T lymphocyte count Lymphocyte count The number of lymphocytes per unit volume of blood. Lymphocytosis is: 

• A reliable indicator Indicator Methods for assessing flow through a system by injection of a known quantity of an indicator, such as a dye, radionuclide, or chilled liquid, into the system and monitoring its concentration over time at a specific point in the system. Body Fluid Compartments of disease progression
• A guide to the clinical and therapeutic management of HIV HIV Anti-HIV Drugs infection

Clinical course and symptoms

Acute retroviral syndrome ( acute phase Acute phase Short Bowel Syndrome):

• 3–6 weeks after infection
• Infectious mononucleosis-like presentation:
  • Fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever, fatigue Fatigue The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. Fibromyalgia, myalgias Myalgias Painful sensation in the muscles. Tick-borne Encephalitis Virus (most common)
  • Retro-orbital headache Headache The symptom of pain in the cranial region. It may be an isolated benign occurrence or manifestation of a wide variety of headache disorders. Brain Abscess (may have aseptic meningitis Meningitis Meningitis is inflammation of the meninges, the protective membranes of the brain, and spinal cord. The causes of meningitis are varied, with the most common being bacterial or viral infection. The classic presentation of meningitis is a triad of fever, altered mental status, and nuchal rigidity. Meningitis), joint pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways, and rash Rash Rocky Mountain Spotted Fever
  • Sore throat Sore throat Pharyngitis is an inflammation of the back of the throat (pharynx). Pharyngitis is usually caused by an upper respiratory tract infection, which is viral in most cases. It typically results in a sore throat and fever. Other symptoms may include a runny nose, cough, headache, and hoarseness. Pharyngitis and painful mouth sores (aphthous ulcers)
  • Hepatosplenomegaly Hepatosplenomegaly Cytomegalovirus
  • Swollen lymph nodes Lymph Nodes They are oval or bean shaped bodies (1 – 30 mm in diameter) located along the lymphatic system. Lymphatic Drainage System: Anatomy (mainly cervical, axillary, and occipital Occipital Part of the back and base of the cranium that encloses the foramen magnum. Skull: Anatomy)
  • Nausea Nausea An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. Antiemetics, vomiting Vomiting The forcible expulsion of the contents of the stomach through the mouth. Hypokalemia, diarrhea Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. Diarrhea, and weight loss Weight loss Decrease in existing body weight. Bariatric Surgery

Chronic infection (clinical latency):

• Few or no clinical manifestations of infection
• Minor opportunistic infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease:
  • Thrush
  • Vaginal candidiasis Candidiasis Candida is a genus of dimorphic, opportunistic fungi. Candida albicans is part of the normal human flora and is the most common cause of candidiasis. The clinical presentation varies and can include localized mucocutaneous infections (e.g., oropharyngeal, esophageal, intertriginous, and vulvovaginal candidiasis) and invasive disease (e.g., candidemia, intraabdominal abscess, pericarditis, and meningitis). Candida/Candidiasis
  • Herpes zoster Herpes Zoster Varicella-zoster virus (VZV) is a linear, double-stranded DNA virus in the Herpesviridae family. Shingles (also known as herpes zoster) is more common in adults and occurs due to the reactivation of VZV. Varicella-Zoster Virus/Chickenpox
  • Tuberculosis Tuberculosis Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis complex bacteria. The bacteria usually attack the lungs but can also damage other parts of the body. Approximately 30% of people around the world are infected with this pathogen, with the majority harboring a latent infection. Tuberculosis spreads through the air when a person with active pulmonary infection coughs or sneezes. Tuberculosis

AIDS:

• Without treatment, progression to AIDS takes place after a chronic phase of 7–10 years.
• AIDS-defining diseases and malignancies
• Opportunistic infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease
• Wasting syndrome Wasting syndrome Involuntary weight loss of greater than 10 percent associated with intermittent or constant fever and chronic diarrhea or fatigue for more than 30 days in the absence of a defined cause other than HIV infection. A constant feature is major muscle wasting with scattered myofiber degeneration. A variety of etiologies, which vary among patients, contributes to this syndrome. AIDS-defining Conditions 
• Encephalopathy Encephalopathy Hyper-IgM Syndrome associated with HIV HIV Anti-HIV Drugs

AIDS

• Defined as:
  •  CD4+ T cell count of < 200 cells/μL or a CD4+ T cell percentage of total lymphocytes Lymphocytes Lymphocytes are heterogeneous WBCs involved in immune response. Lymphocytes develop from the bone marrow, starting from hematopoietic stem cells (HSCs) and progressing to common lymphoid progenitors (CLPs). B and T lymphocytes and natural killer (NK) cells arise from the lineage. Lymphocytes: Histology of < 14%
  • And/or at least 1 AIDS-defining condition (opportunistic infection(s) or illnesses associated with immunosuppression)
• AIDS-defining conditions AIDS-defining conditions Chronic HIV infection and depletion of CD4 cells eventually results in acquired immunodeficiency syndrome (AIDS), which can be diagnosed by the presence of certain opportunistic diseases called AIDS-defining conditions. These conditions include a wide spectrum of bacterial, viral, fungal, and parasitic infections as well as several malignancies and generalized conditions. AIDS-defining Conditions:
  • Fungal and parasitic infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease:
    • Candidiasis Candidiasis Candida is a genus of dimorphic, opportunistic fungi. Candida albicans is part of the normal human flora and is the most common cause of candidiasis. The clinical presentation varies and can include localized mucocutaneous infections (e.g., oropharyngeal, esophageal, intertriginous, and vulvovaginal candidiasis) and invasive disease (e.g., candidemia, intraabdominal abscess, pericarditis, and meningitis). Candida/Candidiasis 
    • Cryptococcal meningitis Cryptococcal meningitis Meningeal inflammation produced by cryptococcus neoformans, an encapsulated yeast that tends to infect individuals with acquired immunodeficiency syndrome and other immunocompromised states. The organism enters the body through the respiratory tract, but symptomatic infections are usually limited to the lungs and nervous system. The organism may also produce parenchymal brain lesions (torulomas). Clinically, the course is subacute and may feature headache; nausea; photophobia; focal neurologic deficits; seizures; cranial neuropathies; and hydrocephalus. Cryptococcus/Cryptococcosis
    • Cryptosporidium Cryptosporidium A genus of coccidian parasites of the family cryptosporidiidae, found in the intestinal epithelium of many vertebrates including humans. Hyper-IgM Syndrome or Cystoisospora Cystoisospora Cystoisospora is a genus within the Coccidia subclass of protozoans. They are single-celled, obligate intracellular parasites that cause intestinal infections in humans. Humans are the only host for these species, and they are both transmitted through the fecal-oral route. The symptoms of cystoisosporiasis are watery diarrhea, abdominal pain, and fever. Cystoisospora/Cystoisosporiasis and Cyclospora/Cyclosporiasis ( enteritis Enteritis Inflammation of any segment of the small intestine. Lactose Intolerance/ diarrhea Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. Diarrhea)
    • Coccidioidomycosis Coccidioidomycosis Coccidioidomycosis, commonly known as San Joaquin Valley fever, is a fungal disease caused by Coccidioides immitis or Coccidioides posadasii. When Coccidioides spores are inhaled, they transform into spherules that result in infection. Coccidioidomycosis is also a common cause of community-acquired pneumonia and can cause severe disease in the immunocompromised. Coccidioides/Coccidioidomycosis
    • Pneumocystis jirovecii pneumonia Pneumonia Pneumonia or pulmonary inflammation is an acute or chronic inflammation of lung tissue. Causes include infection with bacteria, viruses, or fungi. In more rare cases, pneumonia can also be caused through toxic triggers through inhalation of toxic substances, immunological processes, or in the course of radiotherapy. Pneumonia
    • Cerebral toxoplasmosis Toxoplasmosis Toxoplasmosis is an infectious disease caused by Toxoplasma gondii, an obligate intracellular protozoan parasite. Felines are the definitive host, but transmission to humans can occur through contact with cat feces or the consumption of contaminated foods. The clinical presentation and complications depend on the host’s immune status. Toxoplasma/Toxoplasmosis 
    • Histoplasmosis Histoplasmosis Histoplasmosis is an infection caused by Histoplasma capsulatum, a dimorphic fungus. Transmission is through inhalation, and exposure to soils containing bird or bat droppings increases the risk of infection. Most infections are asymptomatic; however, immunocompromised individuals generally develop acute pulmonary infection, chronic infection, or even disseminated disease. Histoplasma/Histoplasmosis
  • Bacterial infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease:
    • Mycobacterium Mycobacterium Mycobacterium is a genus of the family Mycobacteriaceae in the phylum Actinobacteria. Mycobacteria comprise more than 150 species of facultative intracellular bacilli that are mostly obligate aerobes. Mycobacteria are responsible for multiple human infections including serious diseases, such as tuberculosis (M. tuberculosis), leprosy (M. leprae), and M. avium complex infections. Mycobacterium avium-intracellulare
    • M. tuberculosis Tuberculosis Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis complex bacteria. The bacteria usually attack the lungs but can also damage other parts of the body. Approximately 30% of people around the world are infected with this pathogen, with the majority harboring a latent infection. Tuberculosis spreads through the air when a person with active pulmonary infection coughs or sneezes. Tuberculosis
    • Salmonella Salmonella Salmonellae are gram-negative bacilli of the family Enterobacteriaceae. Salmonellae are flagellated, non-lactose-fermenting, and hydrogen sulfide-producing microbes. Salmonella enterica, the most common disease-causing species in humans, is further classified based on serotype as typhoidal (S. typhi and paratyphi) and nontyphoidal (S. enteritidis and typhimurium). Salmonella septicemia
    • Nocardia Nocardia Nocardia is a branching, filamentous, gram-positive bacilli. It is partially acid fast due to the presence of mycolic acids in the cell wall. Nocardia is a ubiquitous soil organism that most commonly affects immunocompromised patients. Nocardia is transmitted via inhalation of aerosolized bacteria or less commonly, via direct contact with wounds. Nocardia/Nocardiosis
  • Viral infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease:
    • Herpes zoster Herpes Zoster Varicella-zoster virus (VZV) is a linear, double-stranded DNA virus in the Herpesviridae family. Shingles (also known as herpes zoster) is more common in adults and occurs due to the reactivation of VZV. Varicella-Zoster Virus/Chickenpox
    • Cytomegalovirus Cytomegalovirus CMV is a ubiquitous double-stranded DNA virus belonging to the Herpesviridae family. CMV infections can be transmitted in bodily fluids, such as blood, saliva, urine, semen, and breast milk. The initial infection is usually asymptomatic in the immunocompetent host, or it can present with symptoms of mononucleosis. Cytomegalovirus (CMV) infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease
    • Herpes simplex Herpes Simplex A group of acute infections caused by herpes simplex virus type 1 or type 2 that is characterized by the development of one or more small fluid-filled vesicles with a raised erythematous base on the skin or mucous membrane. It occurs as a primary infection or recurs due to a reactivation of a latent infection. Congenital TORCH Infections virus Virus Viruses are infectious, obligate intracellular parasites composed of a nucleic acid core surrounded by a protein capsid. Viruses can be either naked (non-enveloped) or enveloped. The classification of viruses is complex and based on many factors, including type and structure of the nucleoid and capsid, the presence of an envelope, the replication cycle, and the host range. Virology ( HSV HSV Herpes simplex virus (HSV) is a double-stranded DNA virus belonging to the family Herpesviridae. Herpes simplex virus commonly causes recurrent infections involving the skin and mucosal surfaces, including the mouth, lips, eyes, and genitals. Herpes Simplex Virus 1 and 2) encephalitis Encephalitis Encephalitis is inflammation of the brain parenchyma caused by an infection, usually viral. Encephalitis may present with mild symptoms such as headache, fever, fatigue, and muscle and joint pain or with severe symptoms such as seizures, altered consciousness, and paralysis. Encephalitis
    • Progressive multifocal Multifocal Retinoblastoma leukoencephalopathy 
  • Malignancies:
    • Lymphoma Lymphoma A general term for various neoplastic diseases of the lymphoid tissue. Imaging of the Mediastinum (Burkitt’s, immunoblastic)
    • Kaposi Kaposi A multicentric, malignant neoplastic vascular proliferation characterized by the development of bluish-red cutaneous nodules, usually on the lower extremities, most often on the toes or feet, and slowly increasing in size and number and spreading to more proximal areas. The tumors have endothelium-lined channels and vascular spaces admixed with variably sized aggregates of spindle-shaped cells, and often remain confined to the skin and subcutaneous tissue, but widespread visceral involvement may occur. Hhv-8 is the suspected cause. There is also a high incidence in AIDS patients. AIDS-defining Conditions‘s sarcoma
    • Invasive cervical and anal carcinomas
  • Miscellaneous:
    • Wasting syndrome Wasting syndrome Involuntary weight loss of greater than 10 percent associated with intermittent or constant fever and chronic diarrhea or fatigue for more than 30 days in the absence of a defined cause other than HIV infection. A constant feature is major muscle wasting with scattered myofiber degeneration. A variety of etiologies, which vary among patients, contributes to this syndrome. AIDS-defining Conditions attributed to HIV HIV Anti-HIV Drugs
    • HIV-associated encephalopathy Encephalopathy Hyper-IgM Syndrome

Selected infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease and conditions

• P. jiroveci pneumonia Pneumonia Pneumonia or pulmonary inflammation is an acute or chronic inflammation of lung tissue. Causes include infection with bacteria, viruses, or fungi. In more rare cases, pneumonia can also be caused through toxic triggers through inhalation of toxic substances, immunological processes, or in the course of radiotherapy. Pneumonia:
  • Risk factors:
    • CD4 count < 200/µL
    • Thrush
    • Previous Pneumocystis pneumonia Pneumonia Pneumonia or pulmonary inflammation is an acute or chronic inflammation of lung tissue. Causes include infection with bacteria, viruses, or fungi. In more rare cases, pneumonia can also be caused through toxic triggers through inhalation of toxic substances, immunological processes, or in the course of radiotherapy. Pneumonia
    • Weight loss Weight loss Decrease in existing body weight. Bariatric Surgery
  • Symptoms include dyspnea Dyspnea Dyspnea is the subjective sensation of breathing discomfort. Dyspnea is a normal manifestation of heavy physical or psychological exertion, but also may be caused by underlying conditions (both pulmonary and extrapulmonary). Dyspnea, fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever, and a non-productive cough.
  • Physical exam findings:
    • Tachypnea Tachypnea Increased respiratory rate. Pulmonary Examination
    • Tachycardia Tachycardia Abnormally rapid heartbeat, usually with a heart rate above 100 beats per minute for adults. Tachycardia accompanied by disturbance in the cardiac depolarization (cardiac arrhythmia) is called tachyarrhythmia. Sepsis in Children
    • Crackles and rhonchi Rhonchi Asthma; normal auscultation in 50% of cases
  • Chest X-ray X-ray Penetrating electromagnetic radiation emitted when the inner orbital electrons of an atom are excited and release radiant energy. X-ray wavelengths range from 1 pm to 10 nm. Hard x-rays are the higher energy, shorter wavelength x-rays. Soft x-rays or grenz rays are less energetic and longer in wavelength. The short wavelength end of the x-ray spectrum overlaps the gamma rays wavelength range. The distinction between gamma rays and x-rays is based on their radiation source. Pulmonary Function Tests shows bilateral interstitial infiltrates.
  • Diagnosis: special silver staining of respiratory secretions showing classic cysts Cysts Any fluid-filled closed cavity or sac that is lined by an epithelium. Cysts can be of normal, abnormal, non-neoplastic, or neoplastic tissues. Fibrocystic Change
  • Treatment:
    • Trimethoprim-sulfamethoxazole
    • Alternative: clindamycin Clindamycin An antibacterial agent that is a semisynthetic analog of lincomycin. Lincosamides + primaquine Primaquine An aminoquinoline that is given by mouth to produce a radical cure and prevent relapse of vivax and ovale malarias following treatment with a blood schizontocide. It has also been used to prevent transmission of falciparum malaria by those returning to areas where there is a potential for re-introduction of malaria. Adverse effects include anemias and GI disturbances. Antimalarial Drugs
    • Moderate or severe hypoxemia Hypoxemia Neonatal Respiratory Distress Syndrome: tapering doses of prednisone Prednisone A synthetic anti-inflammatory glucocorticoid derived from cortisone. It is biologically inert and converted to prednisolone in the liver. Immunosuppressants added
• Cryptococcal meningitis Cryptococcal meningitis Meningeal inflammation produced by cryptococcus neoformans, an encapsulated yeast that tends to infect individuals with acquired immunodeficiency syndrome and other immunocompromised states. The organism enters the body through the respiratory tract, but symptomatic infections are usually limited to the lungs and nervous system. The organism may also produce parenchymal brain lesions (torulomas). Clinically, the course is subacute and may feature headache; nausea; photophobia; focal neurologic deficits; seizures; cranial neuropathies; and hydrocephalus. Cryptococcus/Cryptococcosis: 
  • Greatest risk if CD4 count < 100/µL
  • Symptoms include headache Headache The symptom of pain in the cranial region. It may be an isolated benign occurrence or manifestation of a wide variety of headache disorders. Brain Abscess, fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever, altered mental status Altered Mental Status Sepsis in Children, and neurologic deficits Neurologic Deficits High-Risk Headaches.
  • Exam shows meningismus Meningismus Subarachnoid Hemorrhage in < 40% of patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship.
  • Diagnosis:
    • Lumbar puncture Lumbar Puncture Febrile Infant including measurement of opening pressure
    • Cerebrospinal fluid Cerebrospinal Fluid A watery fluid that is continuously produced in the choroid plexus and circulates around the surface of the brain; spinal cord; and in the cerebral ventricles. Ventricular System: Anatomy (CSF): ↓ white blood cell count, ↑ protein, ↓ or normal glucose Glucose A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. Lactose Intolerance 
    • CSF India ink India ink Cryptococcus/Cryptococcosis staining ( encapsulated Encapsulated Klebsiella yeast Yeast A general term for single-celled rounded fungi that reproduce by budding. Brewers’ and bakers’ yeasts are saccharomyces cerevisiae; therapeutic dried yeast is yeast, dried. Mycology organisms), culture
    • CSF cryptococcal antigen Antigen Substances that are recognized by the immune system and induce an immune reaction. Vaccination testing
    • Serum cryptococcal antigen Serum cryptococcal antigen Cryptococcus/Cryptococcosis testing
  • Treatment:
    • Amphotericin B Amphotericin B Macrolide antifungal antibiotic produced by streptomyces nodosus obtained from soil of the orinoco river region of venezuela. Polyenes and flucytosine Flucytosine Flucytosine is a pyrimidine analog that disrupts fungal DNA and RNA synthesis. Flucytosine is always used in combination with other antifungal agents and is primarily used to treat cryptococcal meningitis. Flucytosine, Griseofulvin, and Terbinafine for 2 weeks
    • Then oral fluconazole Fluconazole Triazole antifungal agent that is used to treat oropharyngeal candidiasis and cryptococcal meningitis in aids. Azoles for 8 weeks or until the patient is culture negative
• Toxoplasma Toxoplasma Toxoplasmosis is an infectious disease caused by Toxoplasma gondii, an obligate intracellular protozoan parasite. Felines are the definitive host, but transmission to humans can occur through contact with cat feces or the consumption of contaminated foods. The clinical presentation and complications depend on the host’s immune status. Toxoplasma/Toxoplasmosis encephalitis Encephalitis Encephalitis is inflammation of the brain parenchyma caused by an infection, usually viral. Encephalitis may present with mild symptoms such as headache, fever, fatigue, and muscle and joint pain or with severe symptoms such as seizures, altered consciousness, and paralysis. Encephalitis:
  • Greatest risk if CD4 count < 100/uL
  • Symptoms include headache Headache The symptom of pain in the cranial region. It may be an isolated benign occurrence or manifestation of a wide variety of headache disorders. Brain Abscess, confusion, fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever, seizures Seizures A seizure is abnormal electrical activity of the neurons in the cerebral cortex that can manifest in numerous ways depending on the region of the brain affected. Seizures consist of a sudden imbalance that occurs between the excitatory and inhibitory signals in cortical neurons, creating a net excitation. The 2 major classes of seizures are focal and generalized. Seizures, and lethargy Lethargy A general state of sluggishness, listless, or uninterested, with being tired, and having difficulty concentrating and doing simple tasks. It may be related to depression or drug addiction. Hyponatremia.
  • Exam shows ataxia Ataxia Impairment of the ability to perform smoothly coordinated voluntary movements. This condition may affect the limbs, trunk, eyes, pharynx, larynx, and other structures. Ataxia may result from impaired sensory or motor function. Sensory ataxia may result from posterior column injury or peripheral nerve diseases. Motor ataxia may be associated with cerebellar diseases; cerebral cortex diseases; thalamic diseases; basal ganglia diseases; injury to the red nucleus; and other conditions. Ataxia-telangiectasia, focal neurologic, and sensory Sensory Neurons which conduct nerve impulses to the central nervous system. Nervous System: Histology deficits.
  • Diagnosis:
    • Brain Brain The part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem. Nervous System: Anatomy, Structure, and Classification imaging: multiple ring-enhancing lesions
    • + Toxoplasma Toxoplasma Toxoplasmosis is an infectious disease caused by Toxoplasma gondii, an obligate intracellular protozoan parasite. Felines are the definitive host, but transmission to humans can occur through contact with cat feces or the consumption of contaminated foods. The clinical presentation and complications depend on the host’s immune status. Toxoplasma/Toxoplasmosis gondii IgG IgG The major immunoglobulin isotype class in normal human serum. There are several isotype subclasses of igg, for example, igg1, igg2a, and igg2b. Hypersensitivity Pneumonitis antibody
    • Typical clinical syndrome
  • Treatment: pyrimethamine Pyrimethamine One of the folic acid antagonists that is used as an antimalarial or with a sulfonamide to treat toxoplasmosis. Antimalarial Drugs, sulfadiazine Sulfadiazine One of the short-acting sulfonamides used in combination with pyrimethamine to treat toxoplasmosis in patients with acquired immunodeficiency syndrome and in newborns with congenital infections. Sulfonamides and Trimethoprim, and folinic acid for 6 weeks
• Disseminated M. avium complex (MAC) infection: 
  • Greatest risk if CD4 count < 50/µL
  • Symptoms include fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever, weight loss Weight loss Decrease in existing body weight. Bariatric Surgery, night sweats Night sweats Tuberculosis, abdominal pain Abdominal Pain Acute Abdomen, and diarrhea Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. Diarrhea.
  • Exam shows lymphadenopathy Lymphadenopathy Lymphadenopathy is lymph node enlargement (> 1 cm) and is benign and self-limited in most patients. Etiologies include malignancy, infection, and autoimmune disorders, as well as iatrogenic causes such as the use of certain medications. Generalized lymphadenopathy often indicates underlying systemic disease. Lymphadenopathy and hepatosplenomegaly Hepatosplenomegaly Cytomegalovirus.
  • Laboratory studies: severe anemia Anemia Anemia is a condition in which individuals have low Hb levels, which can arise from various causes. Anemia is accompanied by a reduced number of RBCs and may manifest with fatigue, shortness of breath, pallor, and weakness. Subtypes are classified by the size of RBCs, chronicity, and etiology. Anemia: Overview and Types (due to bone marrow Bone marrow The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. Bone Marrow: Composition and Hematopoiesis involvement), ↑ alkaline phosphatase Alkaline Phosphatase An enzyme that catalyzes the conversion of an orthophosphoric monoester and water to an alcohol and orthophosphate. Osteosarcoma, ↑ lactate dehydrogenase Lactate Dehydrogenase Osteosarcoma
  • Diagnosis: blood cultures
  • Treatment:
    • Macrolide (e.g., clarithromycin Clarithromycin A semisynthetic macrolide antibiotic derived from erythromycin that is active against a variety of microorganisms. It can inhibit protein synthesis in bacteria by reversibly binding to the 50s ribosomal subunits. This inhibits the translocation of aminoacyl transfer-RNA and prevents peptide chain elongation. Macrolides and Ketolides, azithromycin Azithromycin A semi-synthetic macrolide antibiotic structurally related to erythromycin. It has been used in the treatment of Mycobacterium avium intracellulare infections, toxoplasmosis, and cryptosporidiosis. Macrolides and Ketolides) + ethambutol Ethambutol An antitubercular agent that inhibits the transfer of mycolic acids into the cell wall of the tubercle Bacillus. It may also inhibit the synthesis of spermidine in mycobacteria. The action is usually bactericidal, and the drug can penetrate human cell membranes to exert its lethal effect. Antimycobacterial Drugs 
    • +/- Rifabutin Rifabutin A broad-spectrum antibiotic that is being used as prophylaxis against disseminated Mycobacterium avium complex infection in HIV-positive patients. Diseases of the Uvea (if with ↑ mycobacterial burden)
• Nervous system Nervous system The nervous system is a small and complex system that consists of an intricate network of neural cells (or neurons) and even more glial cells (for support and insulation). It is divided according to its anatomical components as well as its functional characteristics. The brain and spinal cord are referred to as the central nervous system, and the branches of nerves from these structures are referred to as the peripheral nervous system. Nervous System: Anatomy, Structure, and Classification manifestations of AIDS:
  • 90% of patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship exhibit neurologic involvement on autopsy.
  • Some findings:
    • Vacuolar myelopathy: microscopically resembles subacute combined degeneration Subacute combined degeneration A neuropathy due to vitamin B12 deficiency or to excessive nitrous oxide inhalation. It is associated with overproduction of the myelinolytic tumor necrosis factor-alpha. Posterior Cord Syndrome (vitamin B₁₂ deficiency)
    • AIDS-associated peripheral neuropathies Neuropathies Chédiak-Higashi Syndrome (most common: distal sensory Sensory Neurons which conduct nerve impulses to the central nervous system. Nervous System: Histology polyneuropathy Polyneuropathy Polyneuropathy is any disease process affecting the function of or causing damage to multiple nerves of the peripheral nervous system. There are numerous etiologies of polyneuropathy, most of which are systemic and the most common of which is diabetic neuropathy. Polyneuropathy)
    • HIV HIV Anti-HIV Drugs meningoencephalitis Meningoencephalitis Encephalitis: dementia Dementia Major neurocognitive disorders (NCD), also known as dementia, are a group of diseases characterized by decline in a person’s memory and executive function. These disorders are progressive and persistent diseases that are the leading cause of disability among elderly people worldwide. Major Neurocognitive Disorders, ataxia Ataxia Impairment of the ability to perform smoothly coordinated voluntary movements. This condition may affect the limbs, trunk, eyes, pharynx, larynx, and other structures. Ataxia may result from impaired sensory or motor function. Sensory ataxia may result from posterior column injury or peripheral nerve diseases. Motor ataxia may be associated with cerebellar diseases; cerebral cortex diseases; thalamic diseases; basal ganglia diseases; injury to the red nucleus; and other conditions. Ataxia-telangiectasia, bowel and bladder Bladder A musculomembranous sac along the urinary tract. Urine flows from the kidneys into the bladder via the ureters, and is held there until urination. Pyelonephritis and Perinephric Abscess incontinence
    • AIDS dementia Dementia Major neurocognitive disorders (NCD), also known as dementia, are a group of diseases characterized by decline in a person’s memory and executive function. These disorders are progressive and persistent diseases that are the leading cause of disability among elderly people worldwide. Major Neurocognitive Disorders complex or HIV HIV Anti-HIV Drugs encephalopathy Encephalopathy Hyper-IgM Syndrome

Diagnosis

Diagnostic approach

• Pre-test counseling:
  • Discuss the indication for HIV HIV Anti-HIV Drugs testing.
  • Risk assessment Risk assessment The qualitative or quantitative estimation of the likelihood of adverse effects that may result from exposure to specified health hazards or from the absence of beneficial influences. Preoperative Care (patient risk behaviors)
  • Implications of positive test results
  • Discuss confidentiality Confidentiality Confidentiality is a set of rules that dictates the protection of health information shared by a patient with a physician. In general, this information should only be used to dictate medical decision-making steps and can only be disclosed to a 3rd party with the patient’s express consent. Patient-Doctor Confidentiality and follow-up.
• Indications for testing:
  • Screening Screening Preoperative Care: Test all adolescents and adults at increased risk for HIV HIV Anti-HIV Drugs infection, and all pregnant women.
  • Any patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with features of acute or chronic HIV HIV Anti-HIV Drugs infection
• Laboratory testing:
  • 4th-generation enzyme immunoassay (EIA) for HIV-1 and -2
    • Detects antibodies Antibodies Immunoglobulins (Igs), also known as antibodies, are glycoprotein molecules produced by plasma cells that act in immune responses by recognizing and binding particular antigens. The various Ig classes are IgG (the most abundant), IgM, IgE, IgD, and IgA, which differ in their biologic features, structure, target specificity, and distribution. Immunoglobulins: Types and Functions (generally appear 3–12 weeks following infection) and p24 antigen Antigen Substances that are recognized by the immune system and induce an immune reaction. Vaccination of HIV HIV Anti-HIV Drugs
    • Negative result: no need for further testing
    • Positive result: Test HIV-1 and -2 antibody differentiation immunoassay.
    • Indeterminate result: Test with FDA-approved HIV-1 nucleic acid test. 
  • Other tests for HIV HIV Anti-HIV Drugs:
    • Western blot: separation of viral proteins Proteins Linear polypeptides that are synthesized on ribosomes and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of amino acids determines the shape the polypeptide will take, during protein folding, and the function of the protein. Energy Homeostasis by molecular weight on polyacrylamide gel (2 bands present = positive)
    • Reverse transcriptase-polymerase chain reaction Reverse transcriptase-polymerase chain reaction A variation of the pcr technique in which cDNA is made from RNA via reverse transcription. The resultant cDNA is then amplified using standard pcr protocols. Polymerase Chain Reaction (PCR) ( RT-PCR RT-PCR A variation of the pcr technique in which cDNA is made from RNA via reverse transcription. The resultant cDNA is then amplified using standard pcr protocols. Polymerase Chain Reaction (PCR)) testing: virus Virus Viruses are infectious, obligate intracellular parasites composed of a nucleic acid core surrounded by a protein capsid. Viruses can be either naked (non-enveloped) or enveloped. The classification of viruses is complex and based on many factors, including type and structure of the nucleoid and capsid, the presence of an envelope, the replication cycle, and the host range. Virology quantification or HIV HIV Anti-HIV Drugs RNA RNA A polynucleotide consisting essentially of chains with a repeating backbone of phosphate and ribose units to which nitrogenous bases are attached. RNA is unique among biological macromolecules in that it can encode genetic information, serve as an abundant structural component of cells, and also possesses catalytic activity. RNA Types and Structure for monitoring

Additional tests and monitoring

• HIV-related:
  • CD4+ T cell count (assess immune function)
  • Viral RNA RNA A polynucleotide consisting essentially of chains with a repeating backbone of phosphate and ribose units to which nitrogenous bases are attached. RNA is unique among biological macromolecules in that it can encode genetic information, serve as an abundant structural component of cells, and also possesses catalytic activity. RNA Types and Structure load (assess viremia Viremia The presence of viruses in the blood. Erythema Infectiosum)
  • HIV HIV Anti-HIV Drugs resistance Resistance Physiologically, the opposition to flow of air caused by the forces of friction. As a part of pulmonary function testing, it is the ratio of driving pressure to the rate of air flow. Ventilation: Mechanics of Breathing testing or genotyping Genotyping Methods used to determine individuals’ specific alleles or snps (single nucleotide polymorphisms). Polymerase Chain Reaction (PCR) (rate of HIV HIV Anti-HIV Drugs resistance Resistance Physiologically, the opposition to flow of air caused by the forces of friction. As a part of pulmonary function testing, it is the ratio of driving pressure to the rate of air flow. Ventilation: Mechanics of Breathing to current therapy: 4%–10%)
  • HLA-B HLA-B Class I human histocompatibility (HLA) surface antigens encoded by more than 30 detectable alleles on locus B of the HLA complex, the most polymorphic of all the HLA specificities. Several of these antigens (e.g., hla-b27, -b7, -b8) are strongly associated with predisposition to rheumatoid and other autoimmune disorders. Like other class I HLA determinants, they are involved in the cellular immune reactivity of cytolytic T lymphocytes. Organ Transplantation*5701:
    • Obtain before starting patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship on an abacavir Abacavir Anti-HIV Drugs (ABC)-containing regimen 
    • If positive, patient should not get ABC due to hypersensitivity reaction
• HBV HBV Hepatitis B virus (HBV) is a partially double-stranded DNA virus, which belongs to the Orthohepadnavirus genus and the Hepadnaviridae family. Hepatitis B virus is transmitted by exposure to infectious blood or body fluids. Examples of types of exposure include sexual intercourse, IV drug use, and childbirth. Hepatitis B Virus and HCV HCV Hepatitis C is an infection of the liver caused by the hepatitis C virus (HCV). Hepatitis C virus is an RNA virus and a member of the genus Hepacivirus and the family Flaviviridae. The infection can be transmitted through infectious blood or body fluids and may be transmitted during childbirth or through IV drug use or sexual intercourse. Hepatitis C Virus serology Serology The study of serum, especially of antigen-antibody reactions in vitro. Yellow Fever Virus (viral hepatitis status affects choice of therapy) 
• Other sexually transmitted diseases
• Other tests needed for monitoring and determination of co-morbidities:
  • Basic metabolic panel Basic Metabolic Panel Primary vs Secondary Headaches
  • Liver function tests Liver function tests Liver function tests, also known as hepatic function panels, are one of the most commonly performed screening blood tests. Such tests are also used to detect, evaluate, and monitor acute and chronic liver diseases. Liver Function Tests (some of the antiretrovirals cause alterations in liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy function)
  • Complete blood count (CBC) with differential count
  • Fasting lipid profile Lipid profile Lipid Disorders (some antiretrovirals cause lipid problems)
  • Fasting glucose Glucose A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. Lactose Intolerance or hemoglobin A1c Hemoglobin A1c Products of non-enzymatic reactions between glucose and hemoglobin a, occurring as a minor fraction of the hemoglobin components of human erythrocytes. Hemoglobin a1c is hemoglobin a with glucose covalently bound to the terminal valine of the beta chain. Glycated hemoglobin a is used as an index of the average blood sugar level over a lifetime of erythrocytes. Diabetes Mellitus (antiretrovirals cause issues with glucose Glucose A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. Lactose Intolerance tolerance Tolerance Pharmacokinetics and Pharmacodynamics)
  • Urinalysis Urinalysis Examination of urine by chemical, physical, or microscopic means. Routine urinalysis usually includes performing chemical screening tests, determining specific gravity, observing any unusual color or odor, screening for bacteriuria, and examining the sediment microscopically. Urinary Tract Infections (UTIs) in Children (due to the prevalence Prevalence The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. Measures of Disease Frequency of HIV HIV Anti-HIV Drugs nephropathy)
  • Pregnancy Pregnancy The status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth. Pregnancy: Diagnosis, Physiology, and Care test (treatment needed in pregnant women)
• Monitoring:
  • Viral RNA RNA A polynucleotide consisting essentially of chains with a repeating backbone of phosphate and ribose units to which nitrogenous bases are attached. RNA is unique among biological macromolecules in that it can encode genetic information, serve as an abundant structural component of cells, and also possesses catalytic activity. RNA Types and Structure load ( indicator Indicator Methods for assessing flow through a system by injection of a known quantity of an indicator, such as a dye, radionuclide, or chilled liquid, into the system and monitoring its concentration over time at a specific point in the system. Body Fluid Compartments of antiretroviral therapy Antiretroviral therapy Antiretroviral therapy (ART) targets the replication cycle of the human immunodeficiency virus (HIV) and is classified based on the viral enzyme or mechanism that is inhibited. The goal of therapy is to suppress viral replication to reach the outcome of undetected viral load. Anti-HIV Drugs response):
    • ↓ Viral loads indicate effective treatment
    • A prognostic marker in long-term treatment
  • CD4+ T cell count: increases with antiretroviral therapy Antiretroviral therapy Antiretroviral therapy (ART) targets the replication cycle of the human immunodeficiency virus (HIV) and is classified based on the viral enzyme or mechanism that is inhibited. The goal of therapy is to suppress viral replication to reach the outcome of undetected viral load. Anti-HIV Drugs (ART)

Management

Antiretroviral drugs

• Reverse transcriptase inhibitors Reverse Transcriptase Inhibitors Inhibitors of reverse transcriptase (rna-directed DNA polymerase), an enzyme that synthesizes DNA on an RNA template. Anti-HIV Drugs interfere with the translation Translation Translation is the process of synthesizing a protein from a messenger RNA (mRNA) transcript. This process is divided into three primary stages: initiation, elongation, and termination. Translation is catalyzed by structures known as ribosomes, which are large complexes of proteins and ribosomal RNA (rRNA). Stages and Regulation of Translation of viral RNA RNA A polynucleotide consisting essentially of chains with a repeating backbone of phosphate and ribose units to which nitrogenous bases are attached. RNA is unique among biological macromolecules in that it can encode genetic information, serve as an abundant structural component of cells, and also possesses catalytic activity. RNA Types and Structure into DNA DNA A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). DNA Types and Structure:
  • Nucleoside reverse transcriptase inhibitors Nucleoside Reverse Transcriptase Inhibitors Anti-HIV Drugs (NRTIs) (e.g., zidovudine Zidovudine A dideoxynucleoside compound in which the 3′-hydroxy group on the sugar moiety has been replaced by an azido group. This modification prevents the formation of phosphodiester linkages which are needed for the completion of nucleic acid chains. The compound is a potent inhibitor of HIV replication, acting as a chain-terminator of viral DNA during reverse transcription. It improves immunologic function, partially reverses the HIV-induced neurological dysfunction, and improves certain other clinical abnormalities associated with aids. Its principal toxic effect is dose-dependent suppression of bone marrow, resulting in anemia and leukopenia. Anti-HIV Drugs, emtricitabine Emtricitabine A deoxycytidine analog and reverse transcriptase inhibitor with antiviral activity against HIV-1 and hepatitis B viruses. It is used to treat HIV infections. Anti-HIV Drugs, tenofovir Tenofovir An adenine analog reverse transcriptase inhibitor with antiviral activity against HIV-1 and hepatitis b. It is used to treat HIV infections and chronic hepatitis b, in combination with other antiviral agents, due to the emergence of antiviral drug resistance when it is used alone. Anti-HIV Drugs)
  • Non-nucleoside reverse transcriptase inhibitors Non-Nucleoside Reverse Transcriptase Inhibitors Anti-HIV Drugs (NNRTIs) (e.g., efavirenz Efavirenz Anti-HIV Drugs, doravirine Doravirine Anti-HIV Drugs, etravirine Etravirine Anti-HIV Drugs)
• Protease inhibitors Protease Inhibitors Compounds which inhibit or antagonize biosynthesis or actions of proteases (endopeptidases). Anti-HIV Drugs (PIs):
  • Block the cleavage of protein precursors necessary for the production of infectious viral particles 
  • Examples: atazanavir Atazanavir Anti-HIV Drugs, darunavir, lopinavir Lopinavir An HIV protease inhibitor used in a fixed-dose combination with ritonavir. It is also an inhibitor of cytochrome p-450 cyp3a. Anti-HIV Drugs
• Integrase strand transfer inhibitors Integrase Strand Transfer Inhibitors Anti-HIV Drugs
  • Prevent the insertion of the viral genome Viral genome The complete genetic complement contained in a DNA or RNA molecule in a virus. Virology into the host DNA DNA A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). DNA Types and Structure 
  • Examples: dolutegravir Dolutegravir Anti-HIV Drugs, elvitegravir Elvitegravir Anti-HIV Drugs
• Entry inhibitors Entry Inhibitors Anti-HIV Drugs:
  • CCR5 antagonist:
    • Inhibits the attachment of the virus Virus Viruses are infectious, obligate intracellular parasites composed of a nucleic acid core surrounded by a protein capsid. Viruses can be either naked (non-enveloped) or enveloped. The classification of viruses is complex and based on many factors, including type and structure of the nucleoid and capsid, the presence of an envelope, the replication cycle, and the host range. Virology to the CD4 cell by blocking binding of gp120 
    • Maraviroc Maraviroc A cyclohexane and triazole derivative that acts as an antagonist of the ccr5 receptor. It prevents infection by HIV-1 virus strains which use ccr5 as a co-receptor for membrane fusion and cellular entry. Anti-HIV Drugs
  • Fusion inhibitor:
    • Interferes with fusion of the cell membranes of HIV HIV Anti-HIV Drugs and the CD4 cell 
    • Enfuvirtide Enfuvirtide A synthetic 36-amino acid peptide that corresponds to the heptad repeat sequence of HIV-1 gp41. It blocks HIV cell fusion and viral entry and is used with other anti-retrovirals for combination therapy of HIV infections and aids. Anti-HIV Drugs
  • Attachment inhibitor:
    • Binds gp120, preventing viral attachment 
    • Fostemsavir Fostemsavir Anti-HIV Drugs
  • Post-attachment inhibitor Post-Attachment Inhibitor Anti-HIV Drugs:
    • Blocks CD4 molecule, thus inhibiting virion entry
    • Ibalizumab Ibalizumab Anti-HIV Drugs

Treatment approach

• Initiate antiretroviral therapy Antiretroviral therapy Antiretroviral therapy (ART) targets the replication cycle of the human immunodeficiency virus (HIV) and is classified based on the viral enzyme or mechanism that is inhibited. The goal of therapy is to suppress viral replication to reach the outcome of undetected viral load. Anti-HIV Drugs (ART) promptly!
• Goals:
  • Suppress plasma Plasma The residual portion of blood that is left after removal of blood cells by centrifugation without prior blood coagulation. Transfusion Products HIV HIV Anti-HIV Drugs RNA RNA A polynucleotide consisting essentially of chains with a repeating backbone of phosphate and ribose units to which nitrogenous bases are attached. RNA is unique among biological macromolecules in that it can encode genetic information, serve as an abundant structural component of cells, and also possesses catalytic activity. RNA Types and Structure.
  • Improve immunologic function.
  • Reduce HIV-associated complications and prolong survival.
  • Prevent HIV HIV Anti-HIV Drugs transmission.
• Avoiding resistance Resistance Physiologically, the opposition to flow of air caused by the forces of friction. As a part of pulmonary function testing, it is the ratio of driving pressure to the rate of air flow. Ventilation: Mechanics of Breathing: Triple-drug therapy given HIV HIV Anti-HIV Drugs resistance Resistance Physiologically, the opposition to flow of air caused by the forces of friction. As a part of pulmonary function testing, it is the ratio of driving pressure to the rate of air flow. Ventilation: Mechanics of Breathing develops quickly to 1- or 2-drug regimens.
• Combination ART for treatment-naive patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship (IAS-USA, 2022):
  • Bictegravir Bictegravir Anti-HIV Drugs + tenofovir alafenamide Tenofovir Alafenamide Anti-HIV Drugs + emtricitabine Emtricitabine A deoxycytidine analog and reverse transcriptase inhibitor with antiviral activity against HIV-1 and hepatitis B viruses. It is used to treat HIV infections. Anti-HIV Drugs 
  • Dolutegravir Dolutegravir Anti-HIV Drugs + tenofovir alafenamide Tenofovir Alafenamide Anti-HIV Drugs/disoproxil fumarate Fumarate Citric Acid Cycle + emtricitabine Emtricitabine A deoxycytidine analog and reverse transcriptase inhibitor with antiviral activity against HIV-1 and hepatitis B viruses. It is used to treat HIV infections. Anti-HIV Drugs or lamivudine Lamivudine A reverse transcriptase inhibitor and zalcitabine analog in which a sulfur atom replaces the 3′ carbon of the pentose ring. It is used to treat HIV disease. Anti-HIV Drugs 
  • Dolutegravir Dolutegravir Anti-HIV Drugs + abacavir Abacavir Anti-HIV Drugs + lamivudine Lamivudine A reverse transcriptase inhibitor and zalcitabine analog in which a sulfur atom replaces the 3′ carbon of the pentose ring. It is used to treat HIV disease. Anti-HIV Drugs: only for individuals who are HLA-B HLA-B Class I human histocompatibility (HLA) surface antigens encoded by more than 30 detectable alleles on locus B of the HLA complex, the most polymorphic of all the HLA specificities. Several of these antigens (e.g., hla-b27, -b7, -b8) are strongly associated with predisposition to rheumatoid and other autoimmune disorders. Like other class I HLA determinants, they are involved in the cellular immune reactivity of cytolytic T lymphocytes. Organ Transplantation*5701 negative and without chronic HBV HBV Hepatitis B virus (HBV) is a partially double-stranded DNA virus, which belongs to the Orthohepadnavirus genus and the Hepadnaviridae family. Hepatitis B virus is transmitted by exposure to infectious blood or body fluids. Examples of types of exposure include sexual intercourse, IV drug use, and childbirth. Hepatitis B Virus 
  • Dolutegravir Dolutegravir Anti-HIV Drugs + lamivudine Lamivudine A reverse transcriptase inhibitor and zalcitabine analog in which a sulfur atom replaces the 3′ carbon of the pentose ring. It is used to treat HIV disease. Anti-HIV Drugs, except for:
    • Individuals with HIV HIV Anti-HIV Drugs RNA RNA A polynucleotide consisting essentially of chains with a repeating backbone of phosphate and ribose units to which nitrogenous bases are attached. RNA is unique among biological macromolecules in that it can encode genetic information, serve as an abundant structural component of cells, and also possesses catalytic activity. RNA Types and Structure > 500,000 copies/mL
    • Individuals with HBV HBV Hepatitis B virus (HBV) is a partially double-stranded DNA virus, which belongs to the Orthohepadnavirus genus and the Hepadnaviridae family. Hepatitis B virus is transmitted by exposure to infectious blood or body fluids. Examples of types of exposure include sexual intercourse, IV drug use, and childbirth. Hepatitis B Virus co-infection
    • Individuals needing to initiate ART before the results of HIV HIV Anti-HIV Drugs genotypic resistance Resistance Physiologically, the opposition to flow of air caused by the forces of friction. As a part of pulmonary function testing, it is the ratio of driving pressure to the rate of air flow. Ventilation: Mechanics of Breathing testing for reverse transcriptase or HBV HBV Hepatitis B virus (HBV) is a partially double-stranded DNA virus, which belongs to the Orthohepadnavirus genus and the Hepadnaviridae family. Hepatitis B virus is transmitted by exposure to infectious blood or body fluids. Examples of types of exposure include sexual intercourse, IV drug use, and childbirth. Hepatitis B Virus testing are available
• Once initiated, treatment is indefinite.

Immune reconstitution inflammatory syndrome (IRIS)

• Worsening of preexisting or untreated opportunistic infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease when combination antiretroviral therapy Antiretroviral therapy Antiretroviral therapy (ART) targets the replication cycle of the human immunodeficiency virus (HIV) and is classified based on the viral enzyme or mechanism that is inhibited. The goal of therapy is to suppress viral replication to reach the outcome of undetected viral load. Anti-HIV Drugs (cART) is initiated:
  • Paradoxical IRIS: worsening of known or pre-existing condition
  • Unmasking IRIS: symptoms associated with previously undiagnosed condition
• Frequently seen in tuberculosis Tuberculosis Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis complex bacteria. The bacteria usually attack the lungs but can also damage other parts of the body. Approximately 30% of people around the world are infected with this pathogen, with the majority harboring a latent infection. Tuberculosis spreads through the air when a person with active pulmonary infection coughs or sneezes. Tuberculosis
• Onset: 1 week to a few months of cART initiation
• Pathogenesis: inflammatory response similar to type IV hypersensitivity reaction Type IV hypersensitivity reaction Type IV hypersensitivity reaction, or delayed-type hypersensitivity, is a cell-mediated response to antigen exposure. The reaction involves T cells, not antibodies, and develops over several days. Presensitized T cells initiate the immune defense, leading to tissue damage. Type IV Hypersensitivity Reaction
• Treatment:
  • Treat opportunistic infection.
  • May delay antiretroviral therapy Antiretroviral therapy Antiretroviral therapy (ART) targets the replication cycle of the human immunodeficiency virus (HIV) and is classified based on the viral enzyme or mechanism that is inhibited. The goal of therapy is to suppress viral replication to reach the outcome of undetected viral load. Anti-HIV Drugs (e.g., cryptococcal and tuberculous meningitis Meningitis Meningitis is inflammation of the meninges, the protective membranes of the brain, and spinal cord. The causes of meningitis are varied, with the most common being bacterial or viral infection. The classic presentation of meningitis is a triad of fever, altered mental status, and nuchal rigidity. Meningitis)
  • Glucocorticoids Glucocorticoids Glucocorticoids are a class within the corticosteroid family. Glucocorticoids are chemically and functionally similar to endogenous cortisol. There are a wide array of indications, which primarily benefit from the antiinflammatory and immunosuppressive effects of this class of drugs. Glucocorticoids as needed with a subsequent taper

Prevention and Prophylaxis

General prevention

• Safe-sex practices (use of condoms Condoms A sheath that is worn over the penis during sexual behavior in order to prevent pregnancy or spread of sexually transmitted disease. Nonhormonal Contraception)
• Treatment of sexually transmitted diseases 
• Male circumcision
• Use of sterile Sterile Basic Procedures instruments 
• Proper personal protective equipment Personal protective equipment Specialized clothing or equipment worn for protection against health hazards. Personal protective equipment may include masks; respiratory protective devices; head protective devices; eye protective devices; ear protective devices; protective clothing; and protective footwear. Leptospira/Leptospirosis for medical professionals
• Opioid Opioid Compounds with activity like opiate alkaloids, acting at opioid receptors. Properties include induction of analgesia or narcosis. Constipation substitution therapy (↓ illicit drug and injection use)
• Adequate pre- and perinatal care (to reduce transmission to infants)
• Pre- and post-exposure prophylaxis Prophylaxis Cephalosporins 
• Adequate ART for infected individuals

Prophylaxis Prophylaxis Cephalosporins

• Post-exposure prophylaxis Prophylaxis Cephalosporins:
  • Within 72 hours of exposure after contact with mucous membranes or parenteral contact with HIV-infected materials
  • Taken for 28 days
  • Combination of 3 antiretroviral drugs 
  • Options:
    • Raltegravir Raltegravir Anti-HIV Drugs + tenofovir-emtricitabine 
    • Dolutegravir Dolutegravir Anti-HIV Drugs + tenofovir-emtricitabine
• Pre-exposure prophylaxis Prophylaxis Cephalosporins (PrEP):
  • Reduce the risk in uninfected high-risk individuals:
    • Sexual partners of HIV-infected patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship
    • Men/ transgender Transgender Persons having a sense of persistent identification with, and expression of, gender-coded behaviors not typically associated with one’s anatomical sex at birth, with or without a desire to undergo sex reassignment procedures. Gender Dysphoria women who have sex Sex The totality of characteristics of reproductive structure, functions, phenotype, and genotype, differentiating the male from the female organism. Gender Dysphoria with men
    • Men (who do not use condoms Condoms A sheath that is worn over the penis during sexual behavior in order to prevent pregnancy or spread of sexually transmitted disease. Nonhormonal Contraception) in high-prevalence areas
  • Combination of emtricitabine Emtricitabine A deoxycytidine analog and reverse transcriptase inhibitor with antiviral activity against HIV-1 and hepatitis B viruses. It is used to treat HIV infections. Anti-HIV Drugs and tenofovir Tenofovir An adenine analog reverse transcriptase inhibitor with antiviral activity against HIV-1 and hepatitis b. It is used to treat HIV infections and chronic hepatitis b, in combination with other antiviral agents, due to the emergence of antiviral drug resistance when it is used alone. Anti-HIV Drugs
• Perinatal prophylaxis Prophylaxis Cephalosporins:
  • Highest risk of HIV HIV Anti-HIV Drugs transmission is during delivery.
  • Goal is to block transmission (from mother to baby):
    • Treat HIV-positive patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship immediately and do not wait for genotyping Genotyping Methods used to determine individuals’ specific alleles or snps (single nucleotide polymorphisms). Polymerase Chain Reaction (PCR).
    • Regimen can be changed later.
  • Zidovudine Zidovudine A dideoxynucleoside compound in which the 3′-hydroxy group on the sugar moiety has been replaced by an azido group. This modification prevents the formation of phosphodiester linkages which are needed for the completion of nucleic acid chains. The compound is a potent inhibitor of HIV replication, acting as a chain-terminator of viral DNA during reverse transcription. It improves immunologic function, partially reverses the HIV-induced neurological dysfunction, and improves certain other clinical abnormalities associated with aids. Its principal toxic effect is dose-dependent suppression of bone marrow, resulting in anemia and leukopenia. Anti-HIV Drugs or 3-drug regimen (depending on maternal viral load/risk of transmission) given to infant as prophylaxis Prophylaxis Cephalosporins

HIV in Special Populations

Pregnancy Pregnancy The status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth. Pregnancy: Diagnosis, Physiology, and Care

• Testing:
  • HIV HIV Anti-HIV Drugs testing as part of prenatal care Prenatal care Prenatal care is a systematic and periodic assessment of pregnant women during gestation to assure the best health outcome for the mother and her fetus. Prenatal care prevents and identifies maternal and fetal problems that adversely affect the pregnancy outcome. Prenatal Care
  • Repeat test in 3rd trimester in patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship at high risk for HIV HIV Anti-HIV Drugs infection
  • Repeat test in patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with sexually transmitted disease Sexually Transmitted Disease Sexually transmitted diseases (STDs) are infections that spread either by vaginal intercourse, anal sex, or oral sex. Symptoms and signs may include vaginal discharge, penile discharge, dysuria, skin lesions (e.g., warts, ulcers) on or around the genitals, and pelvic pain. Some infections can lead to infertility and chronic debilitating disease. Sexually Transmitted Infections (STIs)
• Transmission:
  • During pregnancy Pregnancy The status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth. Pregnancy: Diagnosis, Physiology, and Care
  • Delivery (highest risk)
  • Breastfeeding Breastfeeding Breastfeeding is often the primary source of nutrition for the newborn. During pregnancy, hormonal stimulation causes the number and size of mammary glands in the breast to significantly increase. After delivery, prolactin stimulates milk production, while oxytocin stimulates milk expulsion through the lactiferous ducts, where it is sucked out through the nipple by the infant. Breastfeeding
• Risk depends on maternal viral load.
• Maternal management:
  • Reducing transmission:
    • cART throughout pregnancy Pregnancy The status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth. Pregnancy: Diagnosis, Physiology, and Care
    • Breastfeeding Breastfeeding Breastfeeding is often the primary source of nutrition for the newborn. During pregnancy, hormonal stimulation causes the number and size of mammary glands in the breast to significantly increase. After delivery, prolactin stimulates milk production, while oxytocin stimulates milk expulsion through the lactiferous ducts, where it is sucked out through the nipple by the infant. Breastfeeding should be avoided in the United States (alternative infant nutrition easily available) but not in developing nations.
  • Delivery method for mothers who did not receive ART (high risk of transmission): cesarean delivery Cesarean Delivery Cesarean delivery (CD) is the operative delivery of ≥ 1 infants through a surgical incision in the maternal abdomen and uterus. Cesarean deliveries may be indicated for a number of either maternal or fetal reasons, most commonly including fetal intolerance to labor, arrest of labor, a history of prior uterine surgery, fetal malpresentation, and placental abnormalities. Cesarean Delivery, if possible (based on obstetric indications)
  • Delivery methods for mothers on ART:
    • Maternal viral load > 1,000 copies/mL (high risk of transmission): cesarean delivery Cesarean Delivery Cesarean delivery (CD) is the operative delivery of ≥ 1 infants through a surgical incision in the maternal abdomen and uterus. Cesarean deliveries may be indicated for a number of either maternal or fetal reasons, most commonly including fetal intolerance to labor, arrest of labor, a history of prior uterine surgery, fetal malpresentation, and placental abnormalities. Cesarean Delivery at 38 weeks (before labor and rupture of membranes)
    • Maternal viral load ≤ 1,000 copies/mL but > 50 copies/mL: vaginal delivery possible (decide by obstetric indications)
    • Maternal viral load < 50 copies/mL: vaginal delivery possible (decide by obstetric indications)
  • Postpartum: Treatment should be continued by the mother.

Newborns

• HIV HIV Anti-HIV Drugs diagnostic testing for all infants with perinatal HIV HIV Anti-HIV Drugs exposure:
  • Use PCR PCR Polymerase chain reaction (PCR) is a technique that amplifies DNA fragments exponentially for analysis. The process is highly specific, allowing for the targeting of specific genomic sequences, even with minuscule sample amounts. The PCR cycles multiple times through 3 phases: denaturation of the template DNA, annealing of a specific primer to the individual DNA strands, and synthesis/elongation of new DNA molecules. Polymerase Chain Reaction (PCR) ( HIV HIV Anti-HIV Drugs RNA RNA A polynucleotide consisting essentially of chains with a repeating backbone of phosphate and ribose units to which nitrogenous bases are attached. RNA is unique among biological macromolecules in that it can encode genetic information, serve as an abundant structural component of cells, and also possesses catalytic activity. RNA Types and Structure or HIV HIV Anti-HIV Drugs DNA DNA A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). DNA Types and Structure nucleic acid tests):
    • Not HIV HIV Anti-HIV Drugs antibody immunoassay
    • False positives in antibody tests in children < 18 months of age (circulating maternal antibodies Antibodies Immunoglobulins (Igs), also known as antibodies, are glycoprotein molecules produced by plasma cells that act in immune responses by recognizing and binding particular antigens. The various Ig classes are IgG (the most abundant), IgM, IgE, IgD, and IgA, which differ in their biologic features, structure, target specificity, and distribution. Immunoglobulins: Types and Functions still present)
  • Timing:
    • 14–21 days
    • 1–2 months
    • 4–6 months
• Low risk of perinatal HIV HIV Anti-HIV Drugs transmission:
  • Considered in:
    • Mothers on ART during pregnancy Pregnancy The status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth. Pregnancy: Diagnosis, Physiology, and Care with compliance Compliance Distensibility measure of a chamber such as the lungs (lung compliance) or bladder. Compliance is expressed as a change in volume per unit change in pressure. Veins: Histology
    • Confirmed HIV HIV Anti-HIV Drugs RNA RNA A polynucleotide consisting essentially of chains with a repeating backbone of phosphate and ribose units to which nitrogenous bases are attached. RNA is unique among biological macromolecules in that it can encode genetic information, serve as an abundant structural component of cells, and also possesses catalytic activity. RNA Types and Structure level of < 50 copies/mL (viral suppression Suppression Defense Mechanisms) near delivery
  • Neonatal medication: zidovudine Zidovudine A dideoxynucleoside compound in which the 3′-hydroxy group on the sugar moiety has been replaced by an azido group. This modification prevents the formation of phosphodiester linkages which are needed for the completion of nucleic acid chains. The compound is a potent inhibitor of HIV replication, acting as a chain-terminator of viral DNA during reverse transcription. It improves immunologic function, partially reverses the HIV-induced neurological dysfunction, and improves certain other clinical abnormalities associated with aids. Its principal toxic effect is dose-dependent suppression of bone marrow, resulting in anemia and leukopenia. Anti-HIV Drugs for 4 weeks
• High risk of perinatal HIV HIV Anti-HIV Drugs transmission:
  • Considered in:
    • Mothers without antepartum/intrapartum ART or only intrapartum ART
    • Mothers without viral suppression Suppression Defense Mechanisms
    • Mothers with acute HIV HIV Anti-HIV Drugs during pregnancy Pregnancy The status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth. Pregnancy: Diagnosis, Physiology, and Care or breastfeeding Breastfeeding Breastfeeding is often the primary source of nutrition for the newborn. During pregnancy, hormonal stimulation causes the number and size of mammary glands in the breast to significantly increase. After delivery, prolactin stimulates milk production, while oxytocin stimulates milk expulsion through the lactiferous ducts, where it is sucked out through the nipple by the infant. Breastfeeding
  • Intrapartum: IV zidovudine Zidovudine A dideoxynucleoside compound in which the 3′-hydroxy group on the sugar moiety has been replaced by an azido group. This modification prevents the formation of phosphodiester linkages which are needed for the completion of nucleic acid chains. The compound is a potent inhibitor of HIV replication, acting as a chain-terminator of viral DNA during reverse transcription. It improves immunologic function, partially reverses the HIV-induced neurological dysfunction, and improves certain other clinical abnormalities associated with aids. Its principal toxic effect is dose-dependent suppression of bone marrow, resulting in anemia and leukopenia. Anti-HIV Drugs in HIV HIV Anti-HIV Drugs RNA RNA A polynucleotide consisting essentially of chains with a repeating backbone of phosphate and ribose units to which nitrogenous bases are attached. RNA is unique among biological macromolecules in that it can encode genetic information, serve as an abundant structural component of cells, and also possesses catalytic activity. RNA Types and Structure >1000 copies/mL
  • Birth to 6 weeks (presumptive HIV HIV Anti-HIV Drugs therapy for neonate Neonate An infant during the first 28 days after birth. Physical Examination of the Newborn):
    • Zidovudine Zidovudine A dideoxynucleoside compound in which the 3′-hydroxy group on the sugar moiety has been replaced by an azido group. This modification prevents the formation of phosphodiester linkages which are needed for the completion of nucleic acid chains. The compound is a potent inhibitor of HIV replication, acting as a chain-terminator of viral DNA during reverse transcription. It improves immunologic function, partially reverses the HIV-induced neurological dysfunction, and improves certain other clinical abnormalities associated with aids. Its principal toxic effect is dose-dependent suppression of bone marrow, resulting in anemia and leukopenia. Anti-HIV Drugs + lamivudine Lamivudine A reverse transcriptase inhibitor and zalcitabine analog in which a sulfur atom replaces the 3′ carbon of the pentose ring. It is used to treat HIV disease. Anti-HIV Drugs + nevirapine Nevirapine A potent, non-nucleoside reverse transcriptase inhibitor used in combination with nucleoside analogues for treatment of HIV infections and aids. Anti-HIV Drugs 
    • Zidovudine Zidovudine A dideoxynucleoside compound in which the 3′-hydroxy group on the sugar moiety has been replaced by an azido group. This modification prevents the formation of phosphodiester linkages which are needed for the completion of nucleic acid chains. The compound is a potent inhibitor of HIV replication, acting as a chain-terminator of viral DNA during reverse transcription. It improves immunologic function, partially reverses the HIV-induced neurological dysfunction, and improves certain other clinical abnormalities associated with aids. Its principal toxic effect is dose-dependent suppression of bone marrow, resulting in anemia and leukopenia. Anti-HIV Drugs + lamivudine Lamivudine A reverse transcriptase inhibitor and zalcitabine analog in which a sulfur atom replaces the 3′ carbon of the pentose ring. It is used to treat HIV disease. Anti-HIV Drugs + raltegravir Raltegravir Anti-HIV Drugs
• Presumed newborn Newborn An infant during the first 28 days after birth. Physical Examination of the Newborn exposure:
  • Considered in:
    • Mothers who have at least 1 positive HIV HIV Anti-HIV Drugs test at delivery or postpartum
    • Mothers whose newborns have a positive HIV HIV Anti-HIV Drugs antibody test
  • Same medications as presumptive HIV HIV Anti-HIV Drugs therapy for neonate Neonate An infant during the first 28 days after birth. Physical Examination of the Newborn
• Newborn Newborn An infant during the first 28 days after birth. Physical Examination of the Newborn with HIV HIV Anti-HIV Drugs (confirmed HIV HIV Anti-HIV Drugs virologic test): Use 3-drug ART (using appropriate doses).

Children

• Transmission:
  • Vertical transmission Vertical transmission The transmission of infectious disease or pathogens from one generation to another. It includes transmission in utero or intrapartum by exposure to blood and secretions, and postpartum exposure via breastfeeding. Congenital TORCH Infections (most common route of transmission) 
  • Others: blood transfusion, sexual abuse Sexual Abuse Sexual abuse and assault are major public health problems that affect many people from all walks of life, including people of all ages and genders, but it is more prevalent in women and girls, with reports of up to 1 in 3 experiencing sexual assault at some time in their life. Sexual Abuse, injection drug use
  • Increased risk of HIV HIV Anti-HIV Drugs infection among those having unprotected sex Sex The totality of characteristics of reproductive structure, functions, phenotype, and genotype, differentiating the male from the female organism. Gender Dysphoria, and teenage boys who have intercourse with partners of same sex Sex The totality of characteristics of reproductive structure, functions, phenotype, and genotype, differentiating the male from the female organism. Gender Dysphoria
• Presentation:
  • Children:
    • Infant rapid progressors: develop severe signs of AIDS early in life that contribute to death (by age 2–4 years)
    • Unique features: short stature, developmental delay, aspiration and swallowing Swallowing The act of taking solids and liquids into the gastrointestinal tract through the mouth and throat. Gastrointestinal Motility problems, recurrent ear infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease, and delayed puberty Delayed Puberty Delayed puberty (DP) is defined as the lack of testicular growth in boys past the age of 14 and the lack of thelarche in girls past the age of 13. Delayed puberty affects up to 5% of healthy boys and girls, and half of all cases are due to constitutional growth delay. Delayed Puberty
  • Adolescents: often asymptomatic until CD4 count falls
  • Other findings:
    • Opportunistic infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease
    • Organ system disease (e.g., nephropathy, encephalopathy Encephalopathy Hyper-IgM Syndrome, hepatitis)
    • Malignancy Malignancy Hemothorax (e.g., non-Hodgkin’s lymphoma Lymphoma A general term for various neoplastic diseases of the lymphoid tissue. Imaging of the Mediastinum)
• Diagnosis:
  • < 18 months: PCR PCR Polymerase chain reaction (PCR) is a technique that amplifies DNA fragments exponentially for analysis. The process is highly specific, allowing for the targeting of specific genomic sequences, even with minuscule sample amounts. The PCR cycles multiple times through 3 phases: denaturation of the template DNA, annealing of a specific primer to the individual DNA strands, and synthesis/elongation of new DNA molecules. Polymerase Chain Reaction (PCR) ( HIV HIV Anti-HIV Drugs RNA RNA A polynucleotide consisting essentially of chains with a repeating backbone of phosphate and ribose units to which nitrogenous bases are attached. RNA is unique among biological macromolecules in that it can encode genetic information, serve as an abundant structural component of cells, and also possesses catalytic activity. RNA Types and Structure or HIV HIV Anti-HIV Drugs DNA DNA A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). DNA Types and Structure nucleic acid tests), not HIV HIV Anti-HIV Drugs antibody immunoassay
  • > 18 months: HIV HIV Anti-HIV Drugs antibody immunoassay
• Management:
  • Combination antiretroviral therapy Antiretroviral therapy Antiretroviral therapy (ART) targets the replication cycle of the human immunodeficiency virus (HIV) and is classified based on the viral enzyme or mechanism that is inhibited. The goal of therapy is to suppress viral replication to reach the outcome of undetected viral load. Anti-HIV Drugs (3-drug regimen)
  • Treat opportunistic infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease
• Prevention:
  • Routine “opt out” testing ( HIV HIV Anti-HIV Drugs test is included in standard preventive tests and patient is given opportunity to decline)
  • Treat pregnant women to reduce viral load (↓ transmission).
  • Infant prophylaxis Prophylaxis Cephalosporins
  • In United States: no breastfeeding Breastfeeding Breastfeeding is often the primary source of nutrition for the newborn. During pregnancy, hormonal stimulation causes the number and size of mammary glands in the breast to significantly increase. After delivery, prolactin stimulates milk production, while oxytocin stimulates milk expulsion through the lactiferous ducts, where it is sucked out through the nipple by the infant. Breastfeeding 
  • Routine screening Screening Preoperative Care offered at least by the age of 16 in high-prevalence areas

• Immunologic categories:
  • Stages of HIV HIV Anti-HIV Drugs in children are dependent on age and CD4 T cell count.
  • If a stage 3 opportunistic infection is detected, the patient has AIDS regardless of level of CD4 T cell count.

Elderly

• In 2018, > 50% of HIV-infected Americans were > 50 years of age.
• Challenges:
  • Age-related liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy/kidney function decline may increase side effects of ART or drug toxicity Toxicity Dosage Calculation.
  • Higher risk of drug-to-drug interactions
  • Age and HIV HIV Anti-HIV Drugs increase the risk of cardiovascular disease, bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Bones: Structure and Types loss, and cancer.

Differential Diagnosis

• Infectious mononucleosis Mononucleosis Infectious mononucleosis (IM), also known as “the kissing disease,” is a highly contagious viral infection caused by the Epstein-Barr virus. Its common name is derived from its main method of transmission: the spread of infected saliva via kissing. Clinical manifestations of IM include fever, tonsillar pharyngitis, and lymphadenopathy. Mononucleosis (IM): a contagious viral infection caused by the Epstein-Barr virus Epstein-Barr Virus Epstein-Barr virus (EBV) is a linear, double-stranded DNA virus belonging to the Herpesviridae family. This highly prevalent virus is mostly transmitted through contact with oropharyngeal secretions from an infected individual. The virus can infect epithelial cells and B lymphocytes, where it can undergo lytic replication or latency. Epstein-Barr Virus. Transmission is via the spread of infected saliva Saliva The clear, viscous fluid secreted by the salivary glands and mucous glands of the mouth. It contains mucins, water, organic salts, and ptyalin. Salivary Glands: Anatomy. Clinical manifestations include fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever, tonsillar pharyngitis Pharyngitis Pharyngitis is an inflammation of the back of the throat (pharynx). Pharyngitis is usually caused by an upper respiratory tract infection, which is viral in most cases. It typically results in a sore throat and fever. Other symptoms may include a runny nose, cough, headache, and hoarseness. Pharyngitis, and lymphadenopathy Lymphadenopathy Lymphadenopathy is lymph node enlargement (> 1 cm) and is benign and self-limited in most patients. Etiologies include malignancy, infection, and autoimmune disorders, as well as iatrogenic causes such as the use of certain medications. Generalized lymphadenopathy often indicates underlying systemic disease. Lymphadenopathy. The infection can be similar to acute retroviral syndrome. Diagnosis is clinical and confirmed through heterophile antibody testing. 
• Toxoplasmosis Toxoplasmosis Toxoplasmosis is an infectious disease caused by Toxoplasma gondii, an obligate intracellular protozoan parasite. Felines are the definitive host, but transmission to humans can occur through contact with cat feces or the consumption of contaminated foods. The clinical presentation and complications depend on the host’s immune status. Toxoplasma/Toxoplasmosis: a disease caused by T. gondii, a parasite that lives in the feline gut (definite host). Transmission is by consumption of raw meat or food contaminated by cat feces. Presentation depends on the host’s immunity. Immunocompetent patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship usually have no or mild viral symptoms. Immunocompromised immunocompromised A human or animal whose immunologic mechanism is deficient because of an immunodeficiency disorder or other disease or as the result of the administration of immunosuppressive drugs or radiation. Gastroenteritis patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship develop cerebral or ocular toxoplasmosis Toxoplasmosis Toxoplasmosis is an infectious disease caused by Toxoplasma gondii, an obligate intracellular protozoan parasite. Felines are the definitive host, but transmission to humans can occur through contact with cat feces or the consumption of contaminated foods. The clinical presentation and complications depend on the host’s immune status. Toxoplasma/Toxoplasmosis.
• Cryptococcosis Cryptococcosis Cryptococcosis is an opportunistic, fungal infection caused by the Cryptococcus species. The principal pathogens in humans are C. neoformans (primary) and C. gattii. The majority of affected patients are immunocompromised. Patients with AIDS, chronic steroid use, and organ transplant are particularly affected. Cryptococcosis is an AIDS-defining illness and typically associated with CD4 count < 100 cells/μL. Cryptococcus/Cryptococcosis: a fungal infection that most often affects immunocompromised immunocompromised A human or animal whose immunologic mechanism is deficient because of an immunodeficiency disorder or other disease or as the result of the administration of immunosuppressive drugs or radiation. Gastroenteritis patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship (e.g., AIDS, malignancy Malignancy Hemothorax, transplant recipients, chronic corticosteroid use). Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship present with headaches and abnormal mental status. Cryptococcal capsular antigen Antigen Substances that are recognized by the immune system and induce an immune reaction. Vaccination in CSF and culture establish the diagnosis.
• Hodgkin’s lymphoma Lymphoma A general term for various neoplastic diseases of the lymphoid tissue. Imaging of the Mediastinum: a malignancy Malignancy Hemothorax of B lymphocytes B lymphocytes Lymphoid cells concerned with humoral immunity. They are short-lived cells resembling bursa-derived lymphocytes of birds in their production of immunoglobulin upon appropriate stimulation. B cells: Types and Functions within the lymph nodes Lymph Nodes They are oval or bean shaped bodies (1 – 30 mm in diameter) located along the lymphatic system. Lymphatic Drainage System: Anatomy. Presentation of the disease is with palpable nontender lymphadenopathy Lymphadenopathy Lymphadenopathy is lymph node enlargement (> 1 cm) and is benign and self-limited in most patients. Etiologies include malignancy, infection, and autoimmune disorders, as well as iatrogenic causes such as the use of certain medications. Generalized lymphadenopathy often indicates underlying systemic disease. Lymphadenopathy, mostly in the neck Neck The part of a human or animal body connecting the head to the rest of the body. Peritonsillar Abscess, supraclavicular area, and axilla Axilla The axilla is a pyramid-shaped space located between the upper thorax and the arm. The axilla has a base, an apex, and 4 walls (anterior, medial, lateral, posterior). The base of the pyramid is made up of the axillary skin. The apex is the axillary inlet, located between the 1st rib, superior border of the scapula, and clavicle. Axilla and Brachial Plexus: Anatomy. Constitutional “B symptoms” ( fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever, night sweats Night sweats Tuberculosis, and weight loss Weight loss Decrease in existing body weight. Bariatric Surgery) are also noted. The pathognomic histological finding is a Reed-Sternberg cell (giant B cells B cells Lymphoid cells concerned with humoral immunity. They are short-lived cells resembling bursa-derived lymphocytes of birds in their production of immunoglobulin upon appropriate stimulation. B cells: Types and Functions with eosinophilic inclusions).