Bictegravir-Containing Regimen Non-Inferior to Dolutegravir-Containing Regimens in HIV

Combination treatments well tolerated amongst study participants with HIV-1 infection.

The latest results from a pair of phase 3 studies showed that bictegravir, emtricitabine, and tenofovir alafenamide (BIC/FTC/TAF) combination treatment for HIV-1 infection was statistically non-inferior to dolutegravir-containing regimens in combination with a dual NRTI backbone.

The studies, 1489 and 1490, evaluated the safety and efficacy of a fixed-dose combination of 50 mg of BIC and 200 mg of emtricitabine and 25 mg of tenofovir, according to a press release.

A total of 629 treatment-naïve adults with HIV were included in the 1489 study. The participants were randomized 1:1 to receive BIC/FTC/TAF or abacavir/dolutegravir/lamivudine (ABC/DTG/3TC) in the doses 600 mg, 50 mg, and 300 mg, respectively.

The results of the study showed that 92.4% of patients in the BIC/FTC/TAF arm and 93% in the ABC/DTG/3TC arm achieved the primary endpoint of HIV-RNA levels less than 50 copies/mL at week 48.

In a separate analysis, the investigators examined the effect of the BIC/FTC/TAF and ABC/DTG/3TC regimens on the changes in bone mineral density (BMD) and measures of renal function.

The mean percentage changes in BMD from baseline to week 48 were -0.83% for BIC/FTC/TAF versus -0.60% for ABC/DTG/3TC in lumbar spine, and -0/78% for BIC/FTC/TAF versus -1.02% for ABC/DTG/3TC in total hip.

No differences between the regimens in changes from baseline to week 48 were observed for estimated glomerular filtration rate or proteinuria. No significantly different lipid changes were observed between the 2 arms, according to the release. None of the patients in either arm developed treatment-emergent resistance. Furthermore, discontinuations due to adverse events (AEs) were minimal in both treatment arms. The most common AEs were nausea, diarrhea, and headache.

“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,” Joel Gallant, MD, MPH, lead author of study 1489, said in a release. “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 discontinuation due to adverse events, a high barrier to resistance and few drug interactions.”

For the 1490 study, 645 treatment-naïve adults with HIV were randomized to receive BIC/FTC/TAF or DTG+FTC/TAF. At week 48, the results of the study showed that 89.4% of patients in the BIC/FTC/TAF arm and 92.9% of patients in the DTG+FTC/TAF achieved the primary endpoint of HIV-1 RNA levels less than 50 copies/mL.

No patients in either group developed treatment resistance to any of the regimens. Lipid changes were not significantly different between the 2 arms, and there were no renal discontinuations or cases of proximal renal tubulopathy, according to the release.

Discontinuations due to AEs in study 1490 were low in both treatment arms. The most common AEs were headache and diarrhea.

“These data reinforce the safety and efficacy profile consistently seen in other trials evaluating regimens based on the FTC/TAF combination,” Paul Sax, MD, lead author of study 1490, said in a release. “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 data were presented in 2 late-breaker sessions at the 9th Annual IAS Conference on HIV Science in Paris.

“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,” Norbort W. Bischofberger, PhD, executive vice president of Research and Development and chief scientific officer at Gilead, said in a release. “These data in treatment-naïve patients, and data from 2 additional phase 3 studies in treatment-experienced patients, formed the basis of our regulatory applications in the United States and the European Union.”

In addition to these findings, the ongoing studies 1844 and 1878 are evaluating BIC/FTC/TAF among virologically suppressed adult patients and are also part of the regulatory submissions in the United States and Europe.