Switching from efavirenz- to dolutegravir-based ART second-line achieved good rates of suppression: first results from the VISEND study

In the VISEND study, looking at second-line ART, participants with viral load <1000 copies/mL at time of switch, receiving tenofovir alafenamide/emtricitabine/dolutegravir (TAFED) and tenofovir disoproxil fumarate/lamivudine/dolutegravir (TLD) showed similar efficacy, with low rates of virologic failure at week 36. [1]

Participants with >1,000 copies/mL at the time of switch showed slightly higher rates of suppression with TLD compared to other treatment arms. These data were shown at AIDS 2020.

In ART programmes in sub-Saharan Africa, people taking NNRTI-based first-line regimens are being switched to TLD, often without recent viral load results.

The ongoing VISEND study is looking at virologic outcomes among ART-treated adults switched from tenofovir disoproxil fumarate/lamivudine or emtricitabine/efavirenz (TLE or TEE) or less frequently nevirapine-containing regimens to TLD or TAFED with and without virologic suppression at the time of switch. There was no resistance testing before switching.

Participants with viral load <1,000 copies/mL were randomised to either TLD or TAFED: arm A. Those with viral >1,000 copies/mL were randomised to TLD, TAFED, zidovudine/lamivudine + ritonavir-boosted lopinavir or atazanavir (AZT/3TC + LPV/r or ATV/r): arm B.

Study visits are: baseline, week 4, 12, 24, 48, 72, 96 and 144. The primary treatment failure endpoint is week 24 and 48 viral load >50 copies/mL. The investigators reported week 36 efficacy (Observed data analysis) and safety data at the virtual conference.

Participants in arm A were approximately 42 years old at baseline and in arm B they were about 38 years. Over 60% of VISEND participants are women.

A total of 1,126 participants were randomised to arm A (n=419) and arm B (n=707). In arm A, the percentage of participants with viral load <50 copies/mL was 90% and 87% for TLD and TAFED. In arm B, the percentage with viral load <50 copies/mL was 78%, 72% and 70% for TLD, TAFED and LPV/r or ATV/r, respectively.

In arm A weight change was +1.8 kg and +0.4 kg for TAFED and TLD (p<0.05). In arm B this was +2.7 kg, +1.9 kg and +1.3 kg for TAFED, TLD and LPV/r or ATV/r, respectively (p<0.05 for differences TAFED and TLD vs LPV/r or ATV/r).

comment

Switching to TLD and maintaining NRTI backbone second-line (as well as in people stable on TLE or TEE or with unknown viral load results) is becoming more common in low- and middle-income countries. The switch is partly supported by results from DAWNING, although this trial included viral load and resistance testing before switch. [2]

Currently, in the era of COVID-19, many treatment changes are happening without viral load testing (even in settings were this was usually standard) so these data from VISEND are reassuring.

Weight gain with dolutegravir, particularly in regimens with TAF has come to be expected.