Sixty-three of 65 antiretroviral-naive people randomized to the integrase inhibitor bictegravir plus emtricitabine/tenofovir alafenamide (FTC/TAF) had a viral load below 50 copies after 48 weeks in a double-blind comparison with dolutegravir plus FTC/TAF . A 3-in-1 combination of bictegravir with FTC/3TC is in a phase 3 trial in naive people .
Bictegravir is a strand-transfer HIV integrase inhibitor with in vitro findings indicating limited drug-drug interactions. The phase 2 comparison with the integrase inhibitor dolutegravir plus FTC/TAF enrolled 98 treatment-naive people with a viral load at or above 1000 copies, a CD4 count above 200, and an estimated glomerular filtration rate (eGFR) at or above 70 mL/min . The primary endpoint was the proportion of people with a viral load below 50 copies at week 24 by the FDA snapshot algorithm.
Researchers randomized 65 people to bictegravir and FTC/TAF (plus dolutegravir placebo) and 33 to dolutegravir and FTC/TAF (plus bictegravir placebo). The bictegravir and dolutegravir groups had median ages of 30 and 36, more than 90% were men, and about 57% were white. Median pretreatment viral load was low at 4.41 log10 in the bictegravir group and 4.48 log10 in the dolutegravir group (about 25,700 and 30,200 copies). Proportions with a pretreatment load above 100,000 copies were 15% on bictegravir and 21% on dolutegravir.
Two people dropped out of the bictegravir arm, 1 because of an adverse event and 1 lost to follow-up. Two people quit the dolutegravir arm, 1 because of poor adherence and 1 lost to follow-up.
After 24 weeks 63 of 65 people randomized to bictegravir and 31 of 33 randomized to dolutegravir had a viral load below 50 copies (97% versus 94%, 95% confidence interval [CI] -8.5 to 14.2, P = 0.50). After 48 weeks of treatment, 63 of 65 assigned to bictegravir and 30 of 33 assigned to dolutegravir still had a viral load below 50 copies (97% versus 91%, 95% CI -6.0 to 18.8, P = 0.17). Average CD4 gains were 258 with bictegravir and 192 with dolutegravir.
One person in the bictegravir arm stopped treatment because of urticaria (a vascular skin reaction) after the week-24 visit; this person had a history of urticaria and atopic dermatitis. The researchers found no treatment-related serious adverse events in either study arm, and no one died. Through 48 weeks eGFR declined by 7.0 mL/min in the bictegravir arm and 11.3 mL/min in the dolutegravir arm. No one stopped treatment because of renal adverse events.
Besides the phase 3 trial in naive adults , trials are also under way to study bictegravir in virologically suppressed adults on atazanavir, darunavir, dolutegravir, E/C/F/TAF, or E/C/F/TDF and in virologically suppressed children and adolescents.
- Sax PE, DeJesus E, Crofoot G, et al. Randomized trial of bictegravir or dolutegravir with 10:45 FTC/TAF for initial HIV therapy. Conference on Retroviruses and Opportunistic Infections (CROI), February 13-16, 2017, Seattle. Abstract 41.
- ClinicalTrials.gov. Safety and efficacy of bictegravir/emtricitabine/tenofovir alafenamide versus abacavir/dolutegravir/lamivudine in HIV-1 infected, antiretroviral treatment-naive adults. ClinicalTrials.gov identifier NCT02607930. https://clinicaltrials.gov/ct2/show/NCT02607930
- ClinicalTrials.gov. Safety and efficacy of bictegravir + emtricitabine/tenofovir alafenamide versus dolutegravir + emtricitabine/tenofovir alafenamide in HIV-1 infected, antiretroviral treatment-naive adults. ClinicalTrials.gov identifier NCT02397694. https://clinicaltrials.gov/ct2/show/NCT02397694