Triple-Therapy HIV Combination Demonstrates Efficacy in Treatment-Naive Patients

Gilead's experimental combination therapy observed to reduce HIV RNA in adult patients.

Gilead Sciences recently announced positive results from two phase 3 clinical trials examining the safety and efficacy of a triple-drug cocktail for use in treatment-naïve patients with HIV-1.

The drug is a fixed-dose combination of bictegravir (BIC) 50-mg, an investigational integrase strand transfer inhibitor (INSTI), and emtricitabine/tenofovir alafenamide (FTC/TAF) 200/25-mg, a dual-nucleoside reverse transcriptase inhibitor (NRTI) backbone, according to a press release.

In the ongoing clinical trials, the BIC/FTC/TAF combination was observed to be non-inferior to combination treatments of dolutegravir (DTG) plus a dual-NRTI backbone.

The new data from studies 1489 and 1490 were presented at the 9th IAS Conference on HIV Sciences.

“Physicians continue to look for treatment regimens with simple, convenient dosing that can sustain virologic suppression with a safety profile that is appropriate for most HIV patients,” said lead author of study 1489 Joel Gallant, MD, MPH. “Combinations of an integrase inhibitor plus a dual-NRTI backbone have become a standard of care for initial treatment of HIV. In clinical trials, the investigational regimen of BIC/FTC/TAF has been well tolerated with low rates of discontinuations due to adverse events, a high barrier to resistance and few drug interactions.”

Included in study 1489 were 629 treatment-naïve adults with HIV who were randomized 1:1 to receive BIC/FTC/TAF or abacavir/dolutegravir/lamivudine (ABC/DTG/3TC) 600/50/300-mg.

At 48 weeks, 92.4% of patients treated with BIC/FTC/TAF and 93% of patients taking ABC/DTG/3TC achieved HIV RNA levels less than 50 copies/mL, which was the primary efficacy endpoint, according to the release.

Another analysis explored how the combination treatments effected bone mineral density (BMD) and renal function. Mean percentage changes in BMD from baseline to 48 weeks were -0.83% for the BIC/FTC/TAF regimen and -0.60% for ABC/DTG/3TC in lumbar spine, according to the release. For total hip, the mean percentage change in BMD from baseline was -0.78% for BIC/FTC/TAF and -1.02% for ABC/DTG/3TC.

The authors did not observe differences in changes from baseline in estimated glomerular filtration rate, proteinuria, or lipids.

The most common adverse events included nausea (10% for BIC/FTC/TAF, 23% for ABC/DTG/3TC), diarrhea (13% for both treatments), and headache (11% for BIC/FTC/TAF, 14% for ABC/DTG/3TC), according to the release.

Included in study 1490 were 645 treatment-naïve patients who were randomized to receive BIC/FTC/TAF or DTG+FTC/TAF.

At 48 weeks, 89.4% of patients treated with BIC/FTC/TAF and 92.9% of patients treated with DTG+FTC/TAF achieved HIV RNA less than 50 copies/mL, according to the study.

“These data reinforce the safety and efficacy profile consistently seen in other trials evaluating regimens based on the FTC/TAF combination,” said lead author of study 1490 Paul Sax, MD. “These results suggest that the combination of bictegravir with FTC/TAF has the potential to be appropriate for a broad range of HIV patients, including those with mild to moderate renal impairment.”

The authors reported that no patients developed resistance to either treatment. Additionally, lipid changes were not significantly different between the groups.

The most common adverse events were headache and diarrhea, with rates similar between both groups, according to the release.

“The phase 3 findings presented at IAS 2017 demonstrate that a single-tablet combination of bictegravir with the FTC/TAF backbone may deliver an important novel triple-therapy HIV treatment,” said Norbert W. Bischofberger, PhD, executive vice president, Research and Development and chief scientific officer at Gilead. “These data in treatment-naïve patients, and data from two additional Phase 3 studies in treatment-experienced patients, formed the basis of our regulatory applications in the United States and the European Union.”