What's New in HIV Treatment: A Report on Updates from IAS 2019

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Anton Pozniak, moderator for the IAS 2019 press conference about HIV treatment research, greeting an Educational Fund Scholarship recipient at the IAS Exhibition Booth.

The HIV treatment landscape is constantly evolving, with new and improved regimens easing the once-mighty burden of daily antiretroviral treatment, according to new data presented at the 10th International AIDS Society (IAS) Conference on HIV Science in Mexico City last week.

Two-drug therapy -- once considered a pipe dream because of the apparent risk of antiretroviral resistance -- may in fact be realistic for some patients, according to two major presentations at IAS. Meanwhile, researchers from France have tested the theory that it's safe for some patients to take short "breaks," essentially skipping a few doses of antiretroviral regimens each week. This strategy could improve patient safety by lowering the amount of drug patients are exposed to over their lifetimes.

And, new data on the investigational therapy MK-8591, an injectable nucleoside reverse transcriptase translocation inhibitor (NRTTI), demonstrated sustained viral response in combination with doravirine (Pifeltro, also called DOR), a recently approved NNRTI.

Pedro Cahn, M.D.

GEMINI and TANGO: A Second Wind for Two-Drug Therapy

Two studies presented at IAS found that the two-drug combination of dolutegravir (Tivicay, DTG) and lamivudine (3TC, Epivir) is effective at suppressing HIV and does not appear to lead to resistance.

According to a follow-up analysis of the phase 3 GEMINI studies (NCT02831673 and NCT02831764), dolutegravir/lamivudine was effective in people who had never previously been treated for HIV. The researchers reported results up to 96 weeks after treatment was initiated and didn't find any drug-resistant mutations.

TANGO, meanwhile, was yet another phase 3 trial that found that it was safe for patients to switch from a traditional three-drug regimen containing tenofovir alafenamide (TAF) to a two-drug regimen with just dolutegravir and lamivudine. By 48 weeks, none of the patients who had been switched to dual therapy had developed resistance.

"Dual therapy has shown to be effective," said Pedro Cahn, M.D., of Buenos Aires University Medical School in Argentina, speaking at a press conference at IAS.

"Now it is time," he said, "to rethink the position of dual therapy in international guidance."

Roland Landman, M.D.

ANRS QUATUOR Trial: Is Four Days as Good as Seven?

Conventional wisdom states that for HIV treatment to be effective, patients need to take their medication every day. Yet new data from the France-based ANRS QUATUOR study is challenging that notion. This study, which evaluated 647 patients whose HIV was well controlled by a triple-drug regimen, found that when some of those patients stopped taking pills for three days a week, they were no worse off than those who took their medication every day.

"We know from previous studies that viral rebound is not going to happen in three days," said Roland Landman, M.D., of the infectious diseases department at Bichat Hospital in Paris, who presented ANRS QUATUOR data at a press conference at IAS.

Landman, who calls this four-day strategy a "short-cycle approach" to treatment, says it opens up the possibility of offering certain patients "pill holidays" -- or short breaks over the weekend. Not only would this reduce patients' long-term exposure to HIV antiretrovirals, which carry some side effects, but it also would be more affordable for national health systems, he pointed out.

Full panel for HIV Treatment Research: New Drugs and More Efficient Regimens press conference

A Phase 2b Study of MK-8591 Plus Doravirine

The investigational drug MK-8591, in development by Merck, is an injectable nucleoside reverse transcriptase translocation inhibitor (NRTTI). When paired with doravirine, a recently approved NNRTI, it offered a similar rate of viral suppression at 48 weeks compared to once-daily treatment with doravirine, lamivudine, and tenofovir disoproxil fumarate (TDF).

The phase 2b study was designed in such a way that patients initially received MK-9591 alongside doravirine and lamivudine. After 24 weeks, those who achieved a low viral load were taken off lamivudine. Investigators found MK-8591 was well tolerated at each of the three doses tested -- 0.25 mg, 0.75 mg, or 2.25 mg. Overall, six patients experienced virologic failure -- five out of 90 in the MK-8591 group (5.6%), and one out of 31 in the doravirine/lamivudine/TDF group (3.2%). None of those patients had signs of resistance to the study drugs.

A smaller portion of patients in the MK-8591 group experienced drug-related adverse events (7.8%) compared to the doravirine/lamivudine/TDF group (19.4%).

Willem Francois Venter, M.D., F.C.P.

The ADVANCE Trial: More Good News for Dolutegravir

In another win for dolutegravir, the phase 3 ADVANCE trial found strong evidence that dolutegravir-based regimens work just as well as regimens that contain efavirenz (Sustiva, Stocrin), an NNRTI that is currently one of the most commonly used HIV medications in low- and middle-income countries.

According to the ADVANCE trial abstract, NNRTI drug resistance is a growing problem, affecting more than 10% of patients in South Africa.

The ADVANCE trial was a 96-week, open-label study of 1,053 HIV-positive patients in South Africa. It compared three different treatment combinations: TAF/emtricitabine (FTC, Emtriva)/dolutegravir, TDF/emtricitabine/dolutegravir, and TDF/emtricitabine/efavirenz. Investigators did not screen for baseline drug resistance, per South African treatment guidance.

"Both DTG and TAF have been licensed to generic manufacturers and are very cheap to make, so we would theoretically have a cheaper and safer regimen," said Willem Francois Venter, M.D., F.C.P., of Ezintsha, a research group of Wits Reproductive Health and HIV Institute in Johannesburg, South Africa, speaking at an IAS press conference.

Data presented at IAS were simultaneously published in the New England Journal of Medicine. At 48 weeks, the percent of patients with suppressed viral load was 84% in the TAF/emtricitabine/dolutegravir arm, 85% in the TDF/emtricitabine/dolutegravir arm, and 79% in the TDF/emtricitabine/efavirenz arm. Surprisingly, although there's been reported resistance to NNRTIs in South Africa, there were very low rates of virologic failure across all the treatment arms.