In antiretroviral-naive adults with HIV infection, the two-drug regimen was noninferior to a standard three-drug regimen.

Two-drug antiretroviral therapy (ART)regimens for ART-naive adults with HIV infection are of considerable interest.Now, investigators have conducted two identical randomized, controlled trials(GEMINI 1 and 2) to evaluate what is currently the most promising two-drugcombination — dolutegravir/lamivudine — for ART-naive HIV-positive adults.

SUMMARY AND COMMENT | INFECTIOUS DISEASES, HIV/AIDS

November 29, 2018

Wendy S. Armstrong, MD reviewing Cahn P et al. Lancet 2018 Nov 9

A total of 1441 participants wereassigned 1:1 to dolutegravir/lamivudine or a standard three-drug regimen:dolutegravir/tenofovir/emtricitabine. At enrollment, participants had viralloads of 1000 to 100,000 copies/mL (increased during the trial to an upperlimit of 500,000 copies/mL).

At 48 weeks, pooleddata from the intention-to-treat analysis demonstrated virologic suppression of<50 copies/mL in 91% in the two-drug group and 93% in the three-drug group,demonstrating non inferiority for the two-drug regimen. In subgroup analysis, no differences in rates of viral suppression were observed in those with viralloads >100,000 copies/mL, but rates of suppression were significantly lower in those with a baseline CD4 count <200 cell/mm3.

The latter group represented only 8%–9% of the total study population, and most endpoints did not represent virologic failure, limiting the interpretation of this finding.Among 10 patients who met criteria for virologic withdrawal (all with rebound),none developed mutations to agents in their treatment regimen.

COMMENT The GEMINI studies add support to the use of dolutegravir/lamivudine as a two-drug regimen for initial treatment of adults with HIV infection, with important caveats: The studies excluded patients with viral loads >500,000 copies/mL, and the performance in those with CD4 counts <200 remains uncertain. Additional 96- and 144-week data analyses are planned to assess durability and experience in “real-world” patients to further clarify the risks for resistance. If these promising results are maintained, the most important advantage of this regimen is the potential for dramatic cost savings with the use of branded dolutegravir and generic lamivudine, which could introduce much needed price competition to the ART market.