BHIVA What To Start

Question 1

What are the 4 options recommended as initial treatment for MOST people living with HIV

Answer 1

1. Bictegravir/emtricitabine/TAF
2. 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%

Question 2

What ART is recommended in certain clinical situations (there are 4)

Answer 2

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)

Question 3

Which clinical trials compare Dolutegravir vs efavirenz

Answer 3

Advance
NAMSAL
Single

Question 4

Summarise the ADVANCE trial

Answer 4

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

Question 5

Summarise the NAMSAL trial

Answer 5

Large double blind RCT
Abacavir/3Tc/ Dolutegravir and TDF/FTC/efavirenz
VL outcomes favouring Dolutegravir 74% vs 69%

Question 6

Summarise the SINGLE study

Answer 6

Large double blind RCT
Compared abacavir/3TC and Dolutegravir to TDF/FTC/efavirenz
VL advantage and less adverse events in Dolutegravir arm

Question 7

Which clinical trials compare Dolutegravir and bictegravir

Answer 7

GS-1490 and GS 1489

Question 8

What were the conclusions of GS1490 and GS1489

Answer 8

Non inferiority for virological success
No difference in serious adverse events

Question 9

Which studies looked at the two drug regimen Dolutegravir/lamivudine as first line treatment

Answer 9

GEMINI 1 and 2

Question 10

Summarise the GEMINI studies

Answer 10

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

Question 11

In which individuals is DTG/3TC not recommended as initial treatment

Answer 11

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

Question 12

Studies evaluating the use of Doravirine

Answer 12

DRIVE-ahead and DRIVE-forward

Question 13

Summarise Drive ahead and Drive forward

Answer 13

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%)

Question 14

What was the outcome of Drive ahead and Drive forward

Answer 14

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

Question 15

Which study compared Raltegravir to Dolutegravir and what were there conclusions?

Answer 15

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

Question 16

Which study compared Darunavir/ritonavir to Dolutegravir and what were the findings

Answer 16

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.

Question 17

Which study compared Darunavir/r with Raltegravir and what did they find?

Answer 17

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

Question 18

Which study compared Dolutegravir and atazanavir/r and what did they find

Answer 18

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

Question 19

What did studies compared TDF and TAF conclude

Answer 19

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

Question 20

Summarise the evidence for use of abacavir in people with CVD risk factors

Answer 20

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%

Question 21

What should you start in a patient that is ART naive with evidence of TDR

Answer 21

Back bone of TDF or TAF plus 3TC/FTC plus one of the following
1. Dolutegravir
2. Bictegravir
3. Boosted Darunavir

Question 22

When should integrase resistance testing be considered?

Answer 22

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)

Question 23

What should you start in the context of rapid ART initiation?

Answer 23

TDF or TAF with 3Tc or FTC
Plus
Dolutegravir, Bictegravir or boosted Darunavir