BHIVA What To Start Flashcards
What are the 4 options recommended as initial treatment for MOST people living with HIV
- Bictegravir/emtricitabine/TAF
- Dolutegravir plus FTC/TAF or FTC/TDF*
3 Dolutegravir/lamivudine**
4 Dolutegravir/ lamivudine/abacavir***
bone/renal caveats
**no BL lamivudine R, VL<500 000, CD4> 200 no active hepatitis B
** HLA B*5701 negative and estimated 10-year risk of CVD less than 10%
What ART is recommended in certain clinical situations (there are 4)
1.Darunavir/r or c plus FTC Plus TAF or TDf
2.Doravirine plus emtricitabine or lamivudine plus TDF or TAF
3. Efavirenz plus FTC or 3TC plus TDF or TAF (1st line in TB or pregnancy)
4.Raltegravir plus emtricitabine plus TDF or TAF (need bl <100 000)
Which clinical trials compare Dolutegravir vs efavirenz
Advance
NAMSAL
Single
Summarise the ADVANCE trial
Open label RCT
Compared Dolutegravir TDF/FTC, Dolutegravir TAF/FTC and TDF/FTC efavirenz
There was non inferiority between the arms at week 48 however a greater proportion of those taking Dolutegravir were virally suppressed 85% vs 79% this was driven by adverse event related discontinuation
Summarise the NAMSAL trial
Large double blind RCT
Abacavir/3Tc/ Dolutegravir and TDF/FTC/efavirenz
VL outcomes favouring Dolutegravir 74% vs 69%
Summarise the SINGLE study
Large double blind RCT
Compared abacavir/3TC and Dolutegravir to TDF/FTC/efavirenz
VL advantage and less adverse events in Dolutegravir arm
Which clinical trials compare Dolutegravir and bictegravir
GS-1490 and GS 1489
What were the conclusions of GS1490 and GS1489
Non inferiority for virological success
No difference in serious adverse events
Which studies looked at the two drug regimen Dolutegravir/lamivudine as first line treatment
GEMINI 1 and 2
Summarise the GEMINI studies
Large double blind RCT
Compared DTG/3TC with TDF/FTC/DTG
Non inferiority
Virological failure was higher in the two drug regimen in patients with CD4 <200 79% vs 92% wk 48
In which individuals is DTG/3TC not recommended as initial treatment
Pre treatment VL >500 000
CD4 <200
Hepatitis B co-infection
Transmitted drug resistance
M184v
HIV associated cognitive impairment
Caution if PHI OI and renal impairment
Studies evaluating the use of Doravirine
DRIVE-ahead and DRIVE-forward
Summarise Drive ahead and Drive forward
Both double blind non-inferiority trials
Drive ahead compared Doravirine/lamivudine/tenofovir with tdf ftc efavirenz
Drive forward compares Doravirine with boosted darunavir both given with either tdf/ftc (87%) or abacavir /3TC (13%)
What was the outcome of Drive ahead and Drive forward
Both demonstrated non- inferiority however less side effects with Doravirine
Currently a lack of evidence in comparison to an INSTI so not a first line drug
Which study compared Raltegravir to Dolutegravir and what were there conclusions?
SPRING-2
Raltegravir has increased risk of virological failure in people with a baseline viral load >100 000 along with a numerically higher risk of resistance development due to low genetic barrier
Which study compared Darunavir/ritonavir to Dolutegravir and what were the findings
FLAMINGO study
Darunavir/r is inferior to Dolutegravir as more people discontinued it due to adverse side effects but there was no resistance and no difference in rates of virological failure.
Which study compared Darunavir/r with Raltegravir and what did they find?
ACTG5257
Higher proportion of people with undetectable VL in Raltegravir arm. But people were more likely to develop resistance with Raltegravir. It has high risk of drug drug interactions. But is useful in patients who need a higher barrier to resistance
Which study compared Dolutegravir and atazanavir/r and what did they find
ARIA Study
Higher rates of virological failure and grade 3/4 adverse events along with lower virological success in the atazanvir/r arm so should only be used if patient needs a PI and Darunavir/r cannot be taken
What did studies compared TDF and TAF conclude
TAF associated with less bone and renal disease but only of clinical importance in those with established disease already or at risk of these conditions already
Summarise the evidence for use of abacavir in people with CVD risk factors
A systematic review and meta analysis found an overall relative risk of 1.54 for acute myocardial infarction and 1.61 for all CVD from RECENT exposure to abacavir. The finding from cumulative exposure were less clear. So avoid starting abacavir in those with an estimated CVD risk of more than 10%
What should you start in a patient that is ART naive with evidence of TDR
Back bone of TDF or TAF plus 3TC/FTC plus one of the following
1. Dolutegravir
2. Bictegravir
3. Boosted Darunavir
When should integrase resistance testing be considered?
1.if any major mutations to other drug classes are detected
2.if the diagnosis is made in pregnancy
3. If there are other reasons to suspect transmitted integrase resistance (source)
What should you start in the context of rapid ART initiation?
TDF or TAF with 3Tc or FTC
Plus
Dolutegravir, Bictegravir or boosted Darunavir
