Pathogens VIb - HIV Flashcards
HIV: Life and times
What happens during the eclipse phase?
-
Infection up to four weeks late,
> Virus is undergoing all the steps of its life cycle.
> Symptoms do not develop and the virus itself is not even detectable to any of our testing during this time.
HIV: Life and times
What happens during the Symptomatic phase?
-Non-specific “flu-like” infection lasting for a couple of weeks.
- This is accompanied by a fall in CD4+ cell numbers, a huge rise in viral loads and eventual activation of CD8+, cytotoxic T-cells. These kill a lot of the infected cells and form partially effective memory responses.
- 2/3weeks, serum IgM and IgG will rise. This means that by 60-90 days post-infection, viral p24 [CA] protein and IgG are detectable on our tests. (patient’s symptoms will disappear, so they are unlikely to think to get tested now!)
HIV: Life and times
What happens during the Latency phase?
-Recombinant forms not cleared by CD8+ responses or IgG begin to form reservoirs within the body. These flare up repeatedly, constantly depleting CD4+ cells.
- Once CD4+ counts drop below 200 cells/mm3 the patient will be experiencing extremely serious opportunistic problems.
- This is coupled by a huge rise in viral loads (often 105 or greater. Even with treatment at this point the outlook is quite bleak. We need to stop people getting here!
.
In the latency phase some People progress inside 5 years, others seem to go for 10-20 years with no problems and CD4+ counts >350 cells/mm3. We refer to these as…
- “long-term non-progressors” or “elite controllers”.
> Some are possibly due to HIV-2 rather than HIV-1 infections,
What 4 KEY THINGS should HIV testing be?
Confidential
Fast
Cheap
Accessible
Cultural and structural barriers are important to avoid
We now use self testing to reach more people as it has more than 99% sensitivity what is the problem tho?
- Can cause false positives. The tests are reactive and other things can trip them off
- NOT diagnostic for HIV, they simply say that the person should come for a lab-based test.
What 2 tests can we use to diagnose HIV?
1- Point of care testing:
Looks for Anti-Hiv IgG + P24 CA protein
> Can not use until 90 days post infection.
2- 4th gen Sandwich-ELISA testing for IgG/IgM and CA protein
> Serum takes + results generated 24hrs after
> Smallest window for detection at 45days
What is RT-PCR used for?
- Samples form patients that are confirmed to be living with HIV and use this to calculate the viral load.
> aim of therapy is to reduce viral load to undetectable - Genotyping of the virus is essential. The protease, reverse transcriptase and integrase are key drug targets and resistance would be a major block to therapy.
What did the HIV-1 M strain emerge from and how?
- Simian immune deficiency virus (SIV) of chimpanzees (and likely gorillas) some time around 1910-1930.
> Crossed to humans during blood-to-blood contact in hunting
HIV-2 jumped from what animal?
- Sooty mangabeys
First human infection of HIV was when?
- 1950-60 in congo
How do:
- Nucleotide/nucleoside reverse transcriptase inhibitors
- Non-nucleoside RTs
- Intergrase inhibitors
- Proteas inhibitors
Work as antiretrovirals
- Some (e.g. elvitegravir) must be co-administered with drugs like cobicistat, while protease inhibitors are boosted with low-dose ritonavir, both to inhibit CYP450 enzymes
A newly diagnosed patient will start with what medication?
- 2 NRTIs and a third agent, usually an integrase inhibitor, taken daily for life.
NRTIs: Tenofovir (either disoproxil [DX] or alafenamide fumarate [AF]) and Emtricitabine. > Can be given as a single combined pill > called Truvada®
II: Dolutegravir and Bictegravir are popular
Why are integrate inhibitors preferred over Protease inhibitors?
- e.g. Ritonavir > LOT of nausea and side effects
What is available recently for HIV patients?
- Single pill including all 3 necessary components
> Biktarvy
