HIV Flashcards
Important questions/education for patients newly diagnosed w/HIV
- Start with what do they know
- How are they coping?
- sources of support
- offer counseling
- how/when contracted
- HIV is no longer a ‘death sentence’
- Diabetes mellitus can be a useful analogy
- Chronic, incurable disease
- Not immediately fatal
- Eventually requires medications in most cases
- Can usually be controlled with careful adherence, management, and follow-up
- As with the care of persons with diabetes, working in a team and providing continuing education is essential throughout the course of the disease
- Diabetes mellitus can be a useful analogy
- Patients educated about HIV and the potential for resistance have better adherence to therapy
Relationship between HIV and CD4
HIV Infection is characterized by a steady decline in the number of CD4 cells
At what CD4 count do HIV infected patients develop a high risk for opportunistic infections?
How did AIDS mortality changed from 1996 to 2001
show how haart has changed mortality. After 1996 – had PIs, which changed the game. At that time, AIDS was #1 cause of death in youngmen
Can keep from opportunist infections and death
Common responses to how they are coping w/dx of HIV
Common responses (in my experience):
- “I’ve tried not to think about it, ever since I found out”
- “I’ve watched so many friends die, and now I’m next”
- “My friends tell me it’s not that big a deal”
- “I’ve been researching this on the internet and I have a 10-page list of questions for you”
Why is it important to know how/when a patient contracted HIV?
- Risk factor identification can guide counseling and prevention
- Resistance
- Increasing transmission of drug-resistant HIV strains
- Resistance testing indicated for patients infected for ALL newly diagnosed patients, even if antiretroviral therapy is not being considered in the near future
- Primary HIV Infection (PHI)
- Loss of HIV-specific CD4 cells occurs immediately after PHI
- Some evidence that early treatment of PHI may favorably influence subsequent course of disease
CD4 Count, Viral Load, and Clinical Course
Early infection – may have rash, pharyngitis, lad, but pass off as sth else
Some progress quickly, but typically several years until CD4 count
Consideration if HIV+, HCV ab negative, elevated transaminases?
- Up to 19% of HIV+ individuals with chronic hepatitis C have negative HCV Ab titers
- HCV RNA PCR (viral load) testing is indicated if chronic hepatitis C suspected
- # 1 cause of death for aids is End stage liver dz, predominantly 2/2 chronic hep c
Goals of Treatment with ART
- Reduce HIV-related morbidity
- Prolong the duration and quality of survival
- Restore and/or preserve immunologic function
- Maximally and durably suppress HIV viral load
- Prevent HIV transmission
What is ART recommended for and why?
- ALL Persons Living with HIV
- To reduce morbidity and mortality
- To prevention transmission of HIV
- Perinatal
- Heterosexual
- MSM
- PWID
- * Patients starting ART should be willing and able to commit to treatment and understand the importance of adherence.
How have ART initiation guidelines changed over the years?
- Used to be much more conservative - concern regarding SEs (obs studies not sufficient evidence)
- HPTN 052 – major study that was pivotal in looking at reduction in transmission w/HAART vs deferral showing HAART significantly reduced transmission such that the trial was stopped
- TEMPRANO: final big RCT that showed benefit of immediate start >500
HAART vs ART
used to be “highly active” after introduction of Pis which lead to drop in death rates. Now all are highly active, so we just call combo art.
How has ART eligibility changed over time?
Now finally recommend all be treated!
Currently available ARTs
- TAF is new – same as tenofovir but less renal toxicity
- Complera: RPV/TDF/FTC (not for VL >100K or CD4
- Stribild: EVG/COBI/TDF/FTC (COBI inhibits active tubular secretion of creatinine, resulting in increases in serum creatinine and a reduction in estimated creatinine clearance (CrCl) without reducing glomerular function.73 A
- Atripla : EVF/TDF /FTC
- Truvada: TDF/FTC
- Ziagen: ABC/3TC
- Atazanavir/cobicistat?
- Darunavir/ cobisstat?
- Genvoya EVG/COBI/FTC/TAF
- TAF Tenofovir Adlafenamide (TAF) prodrug of TDF
- Triumeq (DTG/ABC/3TC)
- Evotaz (ATZ+ Cobicistat)
- Prezcobix (DRV+ COBI)
- TAF is being evaluated in 3 combinations:
- elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide
- darunavir/cobicistat/emtricitabine/tenofovir alafenamide
- emtricitabine/tenofovir alafenamide
HIV Replication Cycle and Sites of Drug Activity
- Key is trying to attack virus where it replicates. Now say use either a PI combo w/ritonavir, or II. Have removed NNRTIs as primary tx.
- Ritonavir is booster – boosts effectiveness w/o increasing Ses
- Fewer interactions w/IEs as they don’t go through same pathway
- Reverse Transcriptase
- HIV is a retrovirus, uses RT to make RNA into proviral DNA. Humans don’t have RT.
- Protease
- functions to cut the long protein precursors made in the translation process into functional pieces. If not performed properly HIV is not viable.
Necessary steps, tests before starting ART
- HIV Ab Confirmation, HIV VL, CD4, HIV Genotype
- Assess understanding of disease
- Assess Readiness to start
- Current and PMH
- Social History: Travel, Sexual, Substance use
- Alcohol and Drug Use Disorder Screen
- Mental Illness Screen
- Housing status
- Support systems
- Pregnancy/ contraceptive use
- Baseline labs: CBC, Renal Function, LFTs, Hep A, B, C status, TB status
When is HLA-B*5701 screening recommended?
- before starting ABC (abacovir), to reduce risk of hypersensitivity reaction (HSR)
- HLA-B*5701-positive patients should not receive ABC
- Positive status should be recorded as an ABC allergy
- If HLA-B*5701 testing is not available, ABC may be initiated after counseling and with appropriate monitoring for HSR
When is Coreceptor tropism assay recommended?
- Should be performed when a CCR5 antagonist
- is being considered
- Phenotype assays have been used; genotypic test now available but has been studied less thoroughly
- Consider in patients with virologic failure on a CCR5 antagonist (though does not rule out resistance to CCR5 antagonist)
Initial ART regimens: recommended
Main are integrase inhibitor based and one PI based
RAL (Raltegravir) is BID and that is why people don’t use it
DTG/ABC/3TC (only if HLA-B neg) is ONE pill
For which patients are integrase inhibitors approved?
all are approved for naive pts
Pros and Cons to the IE raltegravir
- Pro: the longest clinical trial and post-marketing experience and has been shown to have durable potency.
- Cons: twice daily dosing, II resistance mutations.
(don’t memorize)
Pros and Cons to the IE Elvitegravir
- Pro: within a fixed-dose combination product taken as a single-tablet, once-daily regimen.
- Cons:
- must be given with food.
- Cobi is a potent CYP3A4 inhibitor that may result in drug-drug interaction with other concomitant medications.
- the fixed-dose combination product is only approved for patients with estimated creatinine clearance of ≥70 mL/min.
(don’t memorize)
Pros and Cons to the IE Dolutegravir
- the most recently approved INSTI
- Pro: It can be given once daily with or without food.
- Pro: In randomized trials, DTG was non-inferior to RAL and was superior to both DRV/r and EFV (because of fewer drug discontinuations in those who received DTG).
- Con: DTG has the shortest duration of follow-up and limited post-marketing experience to date.
(don’t memorize)
Recommended ART in CKD (eGFR
- Consider avoiding TDF
- If eGFR
- EVG/c/TDF/FTC
- ATV/c + TDF
- DRV/c + TDF
- Options:
- ABC/3TC if HLA-B*5701 negative (if HIV RNA >100,000, do not use with EFV or ATV/r; if CrCl
- DRV/r + RAL
- LPV/r + 3TC
- Modify TDF dose
Guidelines for Prevention and Treatment of Opportunistic Infections in HIV-Infected Adults and Adolescents. December 2015.
