HIV and AIDS

What year is considered the first zoonotic transmission of HIV?

1921, with the identification of patient zero.

How many people are estimated to be living with HIV globally?

Approximately 78 million, with an additional 39 million having died from AIDS-related illnesses.

What significant medical conditions are associated with AIDS?

Clusters of Pneumocystis pneumonia (PCP) and Kaposi's sarcoma.

What was the original name for AIDS before 1982?

GRID (Gay-Related Immune Deficiency).

When was HIV first isolated, and from whom?

In 1983 from the lymph node of a patient with lymphadenopathy.

What blood test was developed in 1984 for HIV detection?

The ELISA blood test.

What type of virus is HIV classified as?

A retrovirus, specifically a lentivirus.

What is the size range of HIV particles?

80-120 nm.

What is the structure of HIV's genetic material?

HIV has two strands of positive-sense RNA, which is linear and non-segmented.

What are the three enzymes encoded by the POL gene in HIV?

Reverse transcriptase, integrase, and protease.

What are the two main types of HIV?

HIV-1 and HIV-2.

What is the primary group of HIV-1 and how is it divided?

The M (major) group, which is divided into 9 clades: A to D, F, G, H, J, and K.

What is the significance of the Vpx protein in HIV-2?

It replaces Vpu and plays a role in the virus's lifecycle.

What is the role of the accessory protein VIF in HIV?

It counteracts the inhibitory effect of the host cell enzyme APOBEC3G, promoting viral replication.

How does HIV enter host cells?

Gp120 binds to CD4 and a chemokine receptor (CCR5 or CXCR4), leading to membrane fusion.

What is the role of reverse transcriptase in HIV's infectious cycle?

It synthesizes DNA from the viral RNA genome.

What is the average mutation rate of HIV due to reverse transcriptase's lack of proofreading?

One mutation occurs every 17,000 bases.

What is the significance of the avidity assay in HIV diagnostics?

It measures the IgM to IgG ratio to differentiate between recent acute and chronic infections.

What is the function of the HIV protein TAT?

It is required for the elongation of viral transcripts.

How does the HIV virus acquire its envelope?

It acquires envelope glycoproteins as it buds off from the host cell membrane.

What is the primary reason for HIV's hypervariability?

The high mutation rate due to reverse transcriptase's lack of proofreading ability and the rapid production of viruses.

What does the POL gene encode?

reverse transcriptase, integrase, protease

What is the role of DNA integrase?

It integrates DNA into the host genome

What is the role of protease?

Protease breaks down proteins into amino acids.

What is the role of chemokines?

Attract other immune cells to sites of inflammation (low to high concentration)

What are the groups of HIV-1?

M (major), N (near), O, P

What clades can the M group be divided into?

A to D, F,G,H,J + K

Which clade is most prominent in the US + Europe?

B

How many with HIV-2 actually develop AIDS?

20-25% - remainder are Long-Term Non Progressors

Which types of HIV-2 are most common?

A + B

Which GAG subunit does HIV-2 have as opposed to 1?

p26 instead of p24 in capsid

How many enzymes in the capsid of HIV?

3 - RT, DNAI + protease

Which gp's are on the receptors of the virion?

120-41 (dimers) + trimers on the envelope

What do long terminal repeats do?

Control transcription of viral genome - integration of DNA into host cell genome + binding site for host transcription factors

What is the role of VIF?

Counteracts inhibitory effect of host cell enzyme (apobec3g) - promotes viral replication

What is the role of Vpu?

Downregulates host cell CD4 expression - enhances release of virus from cells - counteracts IFN

What is the diameter of an HIV virus particle?

Approximately 120 nm

What is the outer layer of the HIV virus called?

The Envelope

What is the lipid envelope of the HIV virus derived from?

It is stolen from the host cell membrane when the virus buds out.

What is the function of gp120 in the HIV virus?

It binds to CD4 receptors on T cells.

What role does gp41 play in the HIV virus structure?

It helps the virus fuse with the host cell.

What are the two main proteins that form the envelope trimers in HIV?

gp120 and gp41

What is the p24 capsid in the HIV virus?

A cone-shaped protein shell that encases the virus's genetic material.

What is the genetic material of the HIV virus?

Two copies of ssRNA (single-stranded RNA)

What is the function of reverse transcriptase (p64) in HIV?

It converts viral RNA into DNA.

What is the role of p10 protease in the HIV virus?

It is an enzyme that cuts viral proteins.

What are MHC proteins in the context of HIV?

Stolen host proteins incorporated into the envelope.

What occurs during Stage 1 of HIV infection?

The virus enters through blood or mucosa, infecting CD4+ T cells and dendritic cells, and travels to lymph nodes to establish infection.

What happens during Stage 2 of HIV infection?

The infection spreads from lymphoid tissues into the bloodstream, leading to viremia, where the virus is present in large numbers, and the patient may experience flu-like symptoms.

What is the body's response during Stage 3 of HIV infection?

The body produces anti-HIV antibodies and HIV-specific CTLs, achieving partial control of viral replication and a temporary decrease in viral load, making the patient feel better.

Describe Stage 4 of HIV infection.

In this clinical latency phase, the virus is trapped in lymphoid tissues, replicating at low levels. It can last for years (average 8-10 years without treatment), and the patient feels mostly normal.

What factors accelerate the progression to AIDS in Stage 5?

Other microbial infections activate the immune system, increasing viral replication, which overwhelms immune control.

What characterizes the final stage of HIV infection, AIDS?

Destruction of lymphoid tissues, depletion of CD4+ T cells (below 200 cells/μL), immune system collapse, and the occurrence of opportunistic infections and cancers.

R5 Tropic virus

CCR5 Coreceptor

Dual-tropic virus

CD4 Receptor

X4-tropic virus

CXCR4 Coreceptor

What is the function of the accessory protein VIF in HIV?

Counteracts the inhibitory effect of the host cell enzyme APOBEC3G and promotes viral replication.

How does the accessory protein VPR contribute to HIV infection?

Increases replication, promotes HIV infection of macrophages, and induces G2 cell cycle arrest.

What role does the accessory protein VPU play in HIV?

Down regulates host cell CD4 expression and enhances the release of the virus from cells by counteracting IFN-stimulated protein tetherin.

What is the function of the accessory protein REV in HIV?

Promotes nuclear export of partially spliced viral RNAs.

What is the role of the accessory protein TAT in HIV?

Required for the elongation of viral transcripts.

How does the accessory protein NEF affect host cells?

Down regulates host cell CD4 expression and MHC I expression.

What indicates that a person is HIV seropositive?

Detection of serum antibodies to the envelope and gag proteins.

How are viral loads monitored in HIV patients?

By quantitating and assessing positive viral loads using qPCR.

What is the significance of CD4+ cell counts in HIV diagnostics?

They are enumerated along with CD8+ T cell counts to determine the CD4/CD8 ratio.

What does an avidity assay measure in HIV diagnostics?

The IgM to IgG ratio to differentiate between recent acute and chronic infections.

Why is sequencing the PR and RT genes important in HIV diagnostics?

To determine the presence of transmitted drug resistance.

What does sequencing the V3 loop help determine in HIV diagnostics?

Viral tropism.

What additional screening is recommended for HIV patients?

Screening for other blood-borne pathogens such as HBV and HCV, which can lead to faster progression to AIDS.

What are the primary routes of HIV transmission?

Sexual route, blood products (transfusion, intravenous drug use), and mother to child (in utero, during labor, or breastfeeding).

What occurs during Stage 1 of HIV infection, known as the Eclipse phase?

It lasts more than 2 weeks, involves HIV infection of first cells, systemic spread via lymph nodes, interferon response, establishment of a viral reservoir, and massive replication of HIV in GALT leading to tissue destruction and enteropathy.

What are the characteristics of Stage 2 of HIV infection?

Known as the Acute phase, it lasts from less than 2 to more than 4 weeks, features high levels of viraemia (up to 10^7 IU/mL), flu-like symptoms, peak viraemia with detectable immune response, and a decline in CD4+ T cells.

What defines Stage 3 of HIV infection?

The chronic phase, where a viral set point is established, progressive CD4+ T cell loss occurs, chronic inflammation and immune cell exhaustion develop, leading to progression towards AIDS.

What is the duration and risk factors associated with Stage 4 AIDS?

It lasts between 1-20 years, where CD4+ T cell counts per microlitre increase the risk of infections; less than 200 cells/microlitre heightens risk for life-threatening AIDS-defining illnesses like PCP or oesophageal candidiasis.

What are the risks associated with CD4+ T cell counts in AIDS?

More than 200 cells/microlitre increases risk of life-threatening illnesses; more than 100 cells/microlitre increases risk of CMV retinitis, PML, and HIV-associated wasting syndrome.

What are the different rates of progression to AIDS?

Typical progression occurs in 80% of HIV-1 infections, rapid progression in 10%, and non-progressors account for 10%.

HAART

A combination of 3 or more drugs from different classes used to treat HIV infection.

Entry Inhibitors

Block HIV from entering cells.

CCR5 Antagonists

Maraviroc.

Fusion Inhibitors

Enfuvirtide.

Attachment Inhibitors

Fostemsavir.

Reverse Transcriptase Inhibitors

Stop HIV from copying its genetic material.

NRTIs

Nucleoside type: Abacavir, Emtricitabine, Lamivudine, Tenofovir (TAF/TDF), and older drugs.

NNRTIs

Non-nucleoside type: Doravirine, Efavirenz, Etravirine, Nevirapine, Rilpivirine.

Integrase Inhibitors

Prevent HIV DNA from integrating into human DNA.

Protease Inhibitors

Stop HIV from maturing.

Assembly Inhibitors

New class - blocks viral assembly.

Boosters

Enhance other drugs' effectiveness.

Viral load

The amount of virus in your blood after initial infection predicts how fast HIV progresses to AIDS.

Initial Infection

Viral load spikes dramatically when first infected.

Early Drop

Immune system fights back, viral load decreases.

Setpoint

Viral load stabilizes at a certain level - this is the critical predictor.

Long-term

Viral load gradually increases as immune system weakens over years.

Progressors

Patient group with the highest viral load; disease advances relatively quickly.

Long-term Nonprogressors

Patient group with medium viral load; disease progresses slowly over many years.

Elite Controllers

Patient group with the lowest/undetectable viral load; can control virus naturally without treatment.

CD4 Count

Shows immune system health declining as viral load increases.

CD4 drops below 350-500

Treatment (HAART) typically begins when CD4 count drops below this range.

AIDS diagnosis

Occurs when CD4 is very low.