INSTI-based Two-Drug Antiretroviral Effective for New HIV

AMSTERDAM — A once-a-day regimen of dolutegravir (Tivicay, GlaxoSmithKline) plus lamivudine suppresses HIV viral load in people new to treatment for up to a year, according to early results from the ongoing GEMINI studies.

"I don't think everyone should be treated with this regimen, but I do think it's a very safe and potent combination with less drug exposure for our patients," said investigator Pedro Cahn, MD, from Buenos Aires University Medical School in Argentina.

How the combination will do over the long term is "an open question," he added. "That's why we will be following the patients for 144 weeks. What we can say is that, as of 48 weeks, it's safe, it's effective, and it's noninferior."

The combination of dolutegravir, an integrase strand transfer inhibitor, plus lamivudine is not the first simplified drug regimen tested in people living with HIV. Most recently, the SWORD-1 and SWORD-2 studies tested dolutegravir plus rilpivirine for people with suppressed viral loads (Lancet. 2018;391:839-849).

GEMINI 1 (NCT02831673) and GEMINI 2 (NCT02831764) tested dolutegravir plus lamivudine in people new to HIV treatment.

Testing a Simplified Regimen

Whatever we can do to reduce the drug burden is "very welcome to both providers and patients," Cahn told Medscape Medical News. "It could also mean less exposure to drugs," he pointed out, and therefore "less toxicity and, potentially, less cost."

Cahn and his colleagues recruited 716 people for GEMINI 1 and 717 for GEMINI 2 from 21 countries. All were treatment-naive or had received HIV treatment for fewer than 10 days.

None of the participants had drug-resistant mutations or hepatitis B infection, most had viral loads below 500,000 copies/mL, and none were candidates for hepatitis C treatment. The majority of the participants were white, and 15% were women.

Participants were randomly assigned to receive the two-drug regimen of dolutegravir plus lamivudine or the three-drug regimen of dolutegravir plus the tenofovir and emtricitabine combination (Truvada, Gilead Sciences).

GlaxoSmithKline announced in June that the GEMINI studies had met their end points, but Cahn presented complete 48-week data for the first time here at the International AIDS Conference 2018.

NonInferior

The two regimens were comparable at 48 weeks.

Study	Two-Drug Regimen, %	Three-Drug Regimen, %
Table. Patients With Viral Loads Below 50 Copies/mL at 48 Weeks
GEMINI 1	90	93
GEMINI 2	93	94

Six patients did not respond to the two-drug therapy and four did not respond to the three-drug therapy. Increases in CD4 counts were higher with the two-drug regimen than with the three-drug regimen (224 vs 218), although the difference was not significant.

More patients in the two-drug group than in the three-drug group had two viral load tests above 200 copies/mL and were withdrawn from the study before 48 weeks (6 vs 4). However, none of these patients experienced treatment-emergent resistance.

Even in the 2% of patients in each group with baseline viral loads above 500,000 copies/mL, the difference in viral suppression was not significant.

"That is really the stress test for any combination that you want to test for, right?" Cahn asked the packed crowd that spilled out into the hall outside the conference room.

Not for Everyone

"These are really impressive findings," said Andrew Hill, PhD, from Liverpool University in the United Kingdom. "But those inclusion criteria require diagnostic tests that aren't available everywhere."

Another audience member asked about the issue of pregnancy and dolutegravir. Another criterion for participation in the trial, Cahn said, was that a woman could not be pregnant. The two women who became pregnant during the trial were withdrawn as soon as their pregnancy tests were positive.

Those babies "were born without any problems," he reported.

Alireza Farabi, MD, from the Ryan White clinic in Las Vegas, left the session excited to prescribe this combination to the right patients. "I can see myself prescribing this," he said.

However, I don't think this would be a good choice for patients who might be noncompliant, such as young people or people with drug-abuse issues and depression, he added.

This study was funded by ViiV Healthcare and GlaxoSmithKline. Cahn, Hill, and Farabi have disclosed no relevant financial relationships.

International AIDS Conference 2018: Abstract TUAB0107LB. Presented July 24, 2018.

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