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Single-Pill DTG/3TC Effective in
Suppressed People for 48 Weeks: SALSA
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IAS 2021, 11th IAS Conference on HIV Science, July 18-21, 2021
Mark Mascolini
Switching from a suppressive antiretroviral combination to single-pill dolutegravir/lamivudine (DTG/3TC) proved virologically noninferior to continuing a 3- or 4-drug regimen, according to 48-week results of the randomized SALSA trial [1]. The findings support results of the TANGO study in people switching from a suppressive regimen containing tenofovir alafenamide (TAF). In the GEMINI studies of antiretroviral-naive people, fixed-dose DTG/3TC proved noninferior to DTG plus tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) in attaining and maintaining a viral load below 50 copies [3].
SALSA aimed to broaden the scope of TANGO, which considered switching only from TAF-based regimens, to switching from any common 3- or 4-drug antiretroviral combination in adults. Participants needed at least two confirmed viral loads below 50 copies while taking 2 nucleos(t)ide reverse transcriptase inhibitors (NRTIs) plus a nonnucleoside, a boosted protease inhibitor, or an integrase inhibitor for at least 3 months. Enrollees could have no record of virologic failure and no documented NRTI or integrase inhibitor resistance.
Researchers evenly randomized 493 people from 17 countries to maintain their current regimen or switch to DTG/3TC. The primary endpoint was the proportion of people with a viral load at or above 50 copies at week 48 by FDA snapshot analysis.
Before treatment began, the DTG/3TC group was similar to the control group in age (median 45 years in both groups), proportion of participants of African heritage (18% and 19%), proportion of Asians (13% and 16%), proportion of whites (61% and 58%), and proportion with a CD4 count at or above 350 (91% and 93%). People assigned to DTG/3TC included a larger fraction of women (44% vs 34%).
The same proportions in the DTG/3TC arm and the control arm entered the trial taking a nonnucleoside (50%), an integrase inhibitor (40%), or a protease inhibitor (10%). Slightly larger proportions took TDF (44% in each arm) than TAF (34% on DTG/3TC and 37% in the control arm).
After 48 weeks randomization to DTG/3TC proved noninferior to maintaining the initial regimen in proportion with a viral load above 50 copies (less than 1% and 1%; adjusted difference -0.8%, 95% confidence interval [CI] -2.4% to 0.8%). Proportions with a viral load below 50 copies at week 48 were 94% with DTG/3TC and 93% with continued multidrug therapy. In a per-protocol analysis, 1 of 222 people (0.5%) in the DTG/3TC arm and 3 of 234 (1.3%) in the control arm had a 48-week viral load at or above 50 copies (adjusted difference -0.8%, 95% CI -2.5% to 0.9%). No one in either study arm had a confirmed virologic withdrawal through 48 weeks. As a result, the researchers observed no resistance mutations.
Among people randomized to DTG/3TC, drug-related adverse events affecting 3% or more of participants included weight increase (14 people, 6%), insomnia (7 people, 3%), and dizziness (7 people, 3%). Four people (2%) assigned to DTG/3TC had a drug-related adverse event leading to withdrawal from the study (2 insomnia, 1 alcohol abuse, and 1 anxiety), compared with 1 person (less than 1%) in the control arm (suicidal thoughts). Nobody in either group had a serious drug-related adverse event.
Adjusted average change in weight from baseline to week 48 measured 2.1 kg in the DTG/3TC group and 0.6 kg in the control group. Respective adjusted average changes in body mass index were 0.7 kg/m2 and 0.2 kg/m2.
Through 48 weeks of study, small changes in kidney (proximal tubular renal) function and bone markers favored the DTG/3TC group. Changes in the standard kidney marker estimated glomerular filtration rate (eGFR) by cystatin C and lipids were similar in the two study arms. Changes in three inflammation markers—C-reactive protein, interleukin-6, and soluble CD163—did not differ significantly between the two groups. People randomized to DTG/3TC had a significantly greater 48-week drop in another inflammation marker, CD14 (P = 0.002).
SALSA investigators proposed that these findings build on earlier TANGO results [2] supporting DTG/3TC as a reasonable switch option for people taking an effective 3- or 4-drug antiretroviral combination.
References
1. Llibre JM, Brites CA, Cheng CY, et al. Switching to the 2-drug regimen of dolutegravir/lamivudine (DTG/3TC) fixed-dose combination (FDC) is non-inferior to continuing a 3-drug regimen through 24 weeks in a randomized clinical trial (SALSA). IAS 2021, 11th IAS Conference on HIV Science, July 18-21, 2021. Abstract OALB0303.
2. van Wyk J, Ajana F, Bisshop F, et al. Efficacy and safety of switching to dolutegravir/lamivudine fixed-dose 2-drug regimen vs continuing a tenofovir alafenamide-based 3- or 4-drug regimen for maintenance of virologic suppression in adults living with human immunodeficiency virus type 1: phase 3, randomized, noninferiority TANGO study. Clin Infect Dis. 2020;71:1920-1929. doi: 10.1093/cid/ciz1243. https://academic.oup.com/cid/article/71/8/1920/5697294
3. Cahn P, Madero JS, Arribas JR, et al. Durable efficacy of dolutegravir plus lamivudine in antiretroviral treatment-naive adults with HIV-1 infection: 96-week results from the GEMINI-1 and GEMINI-2 randomized clinical trials. J Acquir Immune Defic Syndr. 2020;83:310-318. doi: 10.1097/QAI.0000000000002275.
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