How does the HIV genome differ from ours?
It contains +ssRNA and needs a reverse transcriptase to make DNA that gets incorporated into the host genome.
What type of virus is HIV? What are its special characteristics?
+ssRNA, enveloped virus w/glycoproteins on the envelope (gp120 binds cell surface receptor on target cell, gp41 burrows into host cell membrane and initiates fusion and release of genome + capsid into target cell), capsize (p24), 2 ssRNAs, reverse transcriptase, protease and integrase enzymes.
Most prevalent type of HIV worldwide?
HIV-1. HIV-2 is restricted to west Africa and is less pathogenic.
Origins of HIV?
HIV-1 from chimps. Note that cutting primate meat was likely the mode of transmission.
How can gp120 specificity for different cell surface receptors change to rate of progression of HIV?
In initial infection HIV codes specifically for cells expressing CCR5 and CD4 surface receptors. These receptors are not located on all cells, mainly on CD4 T cells, macrophages and dendritic calls that have already been exposed to antigen. When the gp120 on HIV can cross react with CXCR4, that receptor is on many other cells and HIV disease progression is dramatically accelerated.
How does initial HIV infection occur?
The virus can pass through vaginal epithelial breaks or be taken up by Langerhans cell sampling. The Langerhans cells and regional CD4+ cells are infected by the virus and migrate to regional lymph nodes. This is where viral explosion really occurs because there are so many cells expressing CCR5 and CD4 that can be infected.
What cells are responsible for the initial burst of viremia with HIV infection? What is the other pathway these cells may take?
Memory and activated CD4 T-cells, they produce a lot of virus. They may also become latently infected for long periods of time.
How do the plasma viral load and CD4 T-cell counts change over the course of HIV infection?
Yellow = viral load. Dark blue = CD4 T cell count. Light blue = anti-HIV-1 Ab. Initially the viral load spikes and then drops. CD4 count slowly drops over time and years later the viral load will rise again.
What are the AIDS-defining illnesses (CD4 < 200)
CMV retinits, Kaposi sarcoma, toxoplasmosis, hairy leukoplakia, pneumocystis pneumonia and thrush.
Where in the female genital tract is HIV most likely to transmit?
Cervix (single layer of squamous epithelium overlying mucosa w/lots of active CD4+ cells susceptible to infection) and vagina (only when superimposed STD or mucosal injury is present).
Why are MSM at high risk for HIV infection?
The GI tract is lined by a single layer of epithelium, has high levels of bacteria and consequently high levels of active CD4+ T-cells that are very susceptible to transmission.
Why does circumcision reduce HIV infection?
The foreskin harbors bacteria and active CD4+ T-cells that are susceptible to HIV infection.
What are people with HIV at higher risk to transmit disease to partners?
When viral loads are higher, they are at high risk for transmission. Note that early on people don’t even know they are infected because all they have are flu-like symptoms.
Why does the simple fact that you have an STD increase your risk for HIV?
Infection = inflammation = activation of CD4 T-cells and overexpression of CD4 and CCR5, which allow HIV binding and infection. Transcription factors are also increased in these cells which propagates virion production and release. Ulcers also increase risk for direct exposure. Note that risk of infection increases by 60%.
When does perinatal transmission happen?
Women are at particularly high risk if the viral load is high at the time of birth/don’t know they are infected. Note that it is probably not a good idea to do invasive prenatal diagnosis in infected women.
A patient presents with a fever, soar throat, skin rash, body aches, lymphadenopathy, nausea and vomiting. He reports having sex with other men. What is the most important indicator in his history that makes you want to further investigate HIV infection? How do you make a definitive diagnosis?
Lymphadenopathy. ELISA test can screen. Western blot followed by PCR is done for confirmatory diagnosis. Note that an individual is only positive if they are positive for all antibodies against all HIV proteins. If all antibodies are not positive it is an indeterminate test and you need to test later or test for HIV-2.
Stages following early HIV infection?
Eclipse: no proteins, RNA or Ab present; I: RNA + II: p24 antigen + III: ELISA + IV-VI: Western blot - then +
4 types of HIV drugs
1) Entry inhibitors (CCR5) 2) Reverse transcriptase inhibitors 3) Integrase inhibitors 4) Protease inhibitors. Note that all of these drugs are non-virocidal, they are all virostatic.
Post-natal care for mothers with HIV
Anti-retroviral drugs for mother and baby