Human Immunodeficiency Virus (HIV) and AIDS: Virology, Pathogenesis, Clinical Stages, and Diagnostics

Flashcard study set covering the biology, replication, transmission, immunology, clinical progression, diagnostic algorithms, and pediatric criteria for Human Immunodeficiency Virus (HIV) and AIDS.

When was AIDS first identified as a global outbreak, and what is its typical progression timeframe?

AIDS was first identified as a global outbreak in 1981; progression to this advanced stage of HIV infection typically takes 1 to 15 years and presents as a cluster of diseases associated with progressive immune system dysfunction.

To which viral family does HIV belong, and how does it differ from many other members regarding oncogenesis?

HIV belongs to the retrovirus family, but unlike many members linked to oncogenesis, HIV is a non-oncogenic retrovirus.

What are the primary epidemiological and clinical differences between HIV-1 and HIV-2?

HIV-1 is prevalent worldwide, whereas HIV-2 is concentrated in West Africa and is associated with slower disease progression and intrinsic resistance to certain antiretrovirals.

What are the roles of envelope glycoproteins gp120 and gp41, and which viral gene encodes them?

Both are encoded by the env viral gene; gp120 serves as the viral attachment protein for host cell adsorption, while transmembrane gp41 mediates fusion between viral and host cellular membranes.

How does the humoral immune response target the HIV envelope glycoprotein gp120?

Blocking antibodies directed against gp120 bind to it and block adsorption of the virus to new target cells.

Which viral gene encodes the capsid protein p24, and what makes it a valuable early diagnostic marker?

Capsid protein p24 is encoded by the gag viral gene; it has high genetic stability with no mutations, making it an early diagnostic marker before seroconversion (though it disappears once circulating antibodies rise and clear free virions).

What key viral replication enzymes are encoded by the HIV pol gene?

The pol gene encodes reverse transcriptase, integrase, and protease.

What primary receptor and coreceptors are required for HIV cellular attachment and entry?

Envelope glycoprotein gp120 binds to the primary host CD4 receptor (on T lymphocytes, monocytes, macrophages, and dendritic cells), followed by interaction with chemokine coreceptors CCR5 (on macrophages) or CXCR4 (on T lymphocytes) to initiate membrane fusion.

What processes do reverse transcriptase and integrase carry out during HIV proviral formation?

Reverse transcriptase synthesizes a linear double-stranded DNA copy (provirus) from the viral RNA genome, which is then transported to the nucleus where integrase integrates it into host cell chromosomes.

How is the HIV virion released from host cells, and how does it mature?

The assembled capsid is released by budding through the host cell cytoplasmic membrane without cell lysis, acquiring its lipid envelope with viral glycoproteins; maturation takes place outside the host cell via viral protease cleavage.

Which body fluids are known to transmit HIV, and which fluids have never been shown to cause transmission?

HIV is transmitted via blood, semen, rectal secretions, breast milk, and donated organs; contact with sweat, tears, or saliva has never been shown to result in transmission.

What is the estimated transmission rate of HIV from contaminated needle-stick accidents compared to transfusion of contaminated blood products?

Needle-stick injuries or fluid splashes in healthcare workers have a transmission rate of $0.3\%$, whereas transfusion of blood and blood products from an HIV-infected donor carries a $100\%$ transmission rate.

What are the primary cellular and tissue reservoirs of HIV in the human body?

Cellular reservoirs include CD4+ T cells, macrophages, brain microglia, and astrocytes; the largest tissue reservoir is gut-associated lymphoid tissue (GALT), which contains the body's largest pool of CD4+ T cells.

What role do HIV-infected monocytes play in systemic and neurological dissemination?

Infected monocytes act as vehicles crossing the blood-brain barrier to infect cells within the central nervous system (contributing to HIV-associated neurocognitive disease) and can bind and replicate HIV in CD4-negative epithelial tissues such as the kidneys.

What four mechanisms allow HIV to evade immune clearance and persist long-term?

High rates of genomic and antigenic variation (mutations), proviral integration into host chromosomes, persistence within macrophages, and sequestration in lymphoid tissues.

What is the primary mechanism of CD4+ T cell loss during progressive HIV infection?

CD4+ T cells are depleted quantitatively due to markedly diminished cell survival rather than direct cell lysis, alongside qualitative functional impairment.

What CD4+ cell count thresholds define immune dysfunction versus frank immunosuppression (AIDS)?

Progressive immune dysfunction occurs when CD4+ T cells drop below $500\,\text{cells/mm}^3$, and frank immunosuppression (AIDS) is established when levels fall below $200\,\text{cells/mm}^3$.

What are the clinical and serological characteristics of primary (acute) HIV infection?

Viremia becomes detectable in 4 to 11 days, presenting with flu-like symptoms (fever, fatigue) and transient non-tender lymphadenopathy; the patient is highly infectious and seronegative until an immune response emerges within 3 months, dropping plasma viremia.

Why is the asymptomatic stage (clinical latency) lasting 1 to 10 years not considered a true virological latency?

It is not true latency because active viral replication continues inside lymphoid organs, even though the patient exhibits few or no symptoms and circulating plasma viremia remains low.

What causes Persistent Generalized Lymphadenopathy (PGL), and why is the disappearance of enlarged nodes an unfavorable sign?

PGL is caused by reactive follicular hyperplasia from virus trapping in lymph nodes; the disappearance of enlarged nodes signifies advanced disease progression with lymphoid architecture burnout and loss of virus-trapping capacity.

What constitutional symptoms and secondary infections characterize AIDS-Related Complex (ARC)?

ARC precedes clinical AIDS and is characterized by chronic diarrhea, unexplained fever, fatigue, weight loss, night sweats, oral thrush (candidiasis), herpes zoster, and tuberculosis.

What opportunistic infections and malignancies serve as CDC AIDS-defining conditions?

Malignancies include Kaposi's sarcoma (vascular endothelium); opportunistic infections include Pneumocystis jirovecii pneumonia, CMV retinitis and pneumonitis, Cryptococcal meningitis, pulmonary Mycobacteria infections, and progressive multifocal leukoencephalopathy (JC virus).

What is the eclipse phase in HIV Nucleic Acid Testing (NAT)?

The eclipse phase (or NAT window) is the initial 1 to 2 weeks post-infection during which HIV RNA assays yield negative results before viral RNA levels rise to detectable thresholds.

Why does p24 antigen testing typically become negative around day 50 post-infection?

Circulating p24 antigen disappears due to clearance by rising host anti-p24 antibodies that neutralize and clear free virions.

How long after exposure do anti-HIV antibodies become detectable, and what do 3rd to 5th generation immunoassays detect?

Specific anti-HIV antibodies appear within 30 to 90 days (IgM followed by lifelong IgG); 3rd through 5th generation immunoassays detect both IgM and IgG antibodies.

How is the CD4+ T lymphocyte count measured, and how is it clinically utilized?

CD4+ T cells are measured using flow cytometry; it is used to assess immune dysfunction, monitor disease progression, and stage AIDS ($< 200\,\text{cells/mm}^3$), but it is not used for initial HIV diagnosis.

What is the difference between genotypic and phenotypic HIV resistance testing?

Genotypic testing detects known drug-resistance mutations using sequencing or PCR, whereas phenotypic testing measures the viral ability to replicate in cell culture across varying concentrations of antiretroviral drugs.

Why is HIV diagnosis in infants under 18 months performed with NAT rather than standard antibody tests?

Maternal IgG antibodies passively cross the placenta and circulate in the infant for months, creating false-positive antibody results; diagnosis must be established using 2 positive NAT results on 2 separate non-cord blood samples.

What criteria definitively exclude HIV infection in non-breastfed exposed infants?

Definitive exclusion requires 2 negative NAT tests (one at age $> 1\text{ month}$ and one at age $> 4\text{ months}$) OR 2 negative antibody tests from separate specimens at age $> 6\text{ months}$.

What is the recommended NAT monitoring protocol for breastfed infants born to HIV-positive mothers?

Breastfed infants should be tested every 3 months by NAT; if the mother has a detectable viral load, NAT is recommended at a monthly rate.