What type of lymphadenopathy is significant?
Axillary and lymphadenopathy > 1cm.
What is used to measure viral load? What is used to measure immune function?
Plasma HIV RNA PCR. CD4 count is key in determining when to start prophylaxis for opportunistic infections and ART.
Goal of ART
Maximize viral suppression in blood. Note that suppression will not be comprehensive and replication will still be going on in the lymph nodes.
Clinical criteria for initiation of ART regardless of CD4 count
AIDS defining illness, pregnant, nephropathy, HBV, acute opportunistic infection and > 50 yrs old.
Recommendations for initating ART based on CD4 count
< 200. < 350 + Hx of AIDS-defining illness. 350-500. > 500 data is inconsistent. Also consider if there is a rapid decline in CD4 cells (800 -> 400).
Why would you withhold ART in a patient that qualifies for them?
Non-compliance and other medical conditions that may be exacerbated by the side effects.
5 classes of drugs used for HIV
1) Entry inhibitors (Maraviroc) 2) Fusion inhibitors (Fuzeon) 3) RT inhibitors (AZT) 4) Integrase inhibitors (Raltegravir) 5) Protease inhibitors (Indinavir)
NRTIs I should know
Zidovuidine (AZT) is not really used. Lamivudine (3TC), Emtricitabine (FTC), Abacavir (ABC) and Tenofovir (TNF) all have additional activity against Hep B.
NNRTIs I should know
Efavirenz (backbone drug).
PIs I should know
Keletra (lopinivir + ritonavir), Atazanavir, Darunavir. These are backbone agents.
Backbone agents. What do you combine them with?
Protease inhibitors, NNRTI or integrase inhibitor. These will drop the viral load by 2-2.5 logs. You combine the backbone agents with 2 NRTIs which are weaker inhibitors that only trop viral load by .5-1.5 logs.
What do you have to do before prescribing Abacavir?
Get a genotype looking for HLA-B*5071 because these people have hypersensitivity and anaphylaxis. NEVER RECHALLENGE BECAUSE OF LIFE-THREATENING ANAPHYLAXIS.
Drug associated with Fanconi’s syndrome?
NRTI: Tenofovir. This is in combination with emtricitibine in Truvada.
Backbone of atripla, the most common ART therapy?
NNRTI: Efavirenz. It is combines with emtricitabine and tenofovir NRTIs.
Side effect of efavirenz?
Nightmares, they go away over time.
Toxicities associated with protease inhibitors?
P450 interactions, insulin resistance, hyperglycemia, diabetes, dyslipidemia, fat redistribution and MI.
What is ritonavir typically used for?
To boost other protease inhibitors. It blocks clearance of other PIs.
Common side effect of indinavir?
The actual drug crystalizes to form kidney stones (not calcium oxalate, etc)
Common side effect of atazanavir
Classes of drugs you use for salvage if patients become resistant to normal drugs?
T20 (fusion inhibitor). Note that this is not used often because patients have to inject themselves two times a day. Maraviroc (CCR5 antagonist entry inhibitor). Note that this will only work if HIV is specific for CCR5. Raltegravir and dolutegravir (integrase inhibitors and backbone agents).
Dual mixed tropism in HIV
Tropism for CCR5 and CXCR4
How do you enhance patient compliance?
Prescribe the least number of pills, avoid “d” drugs
Quad pill (stribilid) used to avoid CNS effects that follow atripla use?
Has Elvitegravir (integrase inhibitor), cobicistat (CP3A inhibitor prolongs drug life), tenofovir and emtricitabine.
When do you consider C-section for a pregnant woman with HIV?
Viral load > 1000
When do you start ART in a pregnant woman who has normal CD4 count and low viral load?
When do start a baby on ART who had an HIV+ mother
6-12 hours after birth
How do you monitor ART?
Check for compliance at 4-6 weeks, get CD4 (recovery may take months to years) and viral load to see how meds are working, check glucose/lipids/LFTs/CBC for toxicity. After this initial follow-up, then see at 3 month intervals.
Most common cause of virologic failure?
Non-adherence. This allows for development of resistant viruses and increases in viral load.