The single-tablet regimen B/F/TAF (bictegravir/emtricitabine/tenofovir alafenamide, Biktarvy) works well for African Americans living with HIV, including those with a history of treatment failure or some preexisting resistance, according to two research presentations at the IDWeek 2020 conference in late October.
Both presentations reported on 48-week data from BRAAVE 2020, a phase 3 study evaluating a switch from stable triple-combination therapy to B/F/TAF among people with HIV who were virologically suppressed and who identified as African American or Black. The study was sponsored by Gilead, the maker of B/F/TAF. [Editor’s note: Gilead is an ad sponsor on TheBodyPro, but this article—just like everything we publish—is created independently by our editorial team based on our assessment of its importance to our readers.]
Full 24- and 48-week safety and efficacy results were presented by lead investigator Debbie P. Hagins, M.D., the medical director of the Chatham CARE Center in Savannah, Georgia. Perhaps the most striking aspect of the study was its demographic focus. “Sites were selected essentially to mirror the prevalence of HIV among African Americans,” said Hagins, who presented the data in a virtual poster presentation with prerecorded audio.
“African Americans continue to have the highest rates of HIV and AIDS in the U.S.,” Hagins noted. “While up to one third of [HIV treatment-]naive and 26% of treatment-experienced participants were African American or Black who participated in phase 3 studies with B/F/TAF, they remain underrepresented in HIV clinical research,” she explained.
Study Enrollment Specifics for BRAAVE 2020
The study enrolled adults who identified as African American, Black, or mixed race including Black, at 82 sites in 56 cities and towns with a high prevalence of HIV among African Americans. The sites spanned 23 states (as well as the District of Columbia) throughout the Northeast (Massachusetts, New Jersey, New York, Pennsylvania), Southeast (Alabama, Florida, Georgia, Louisiana, Mississippi, Missouri, North Carolina, South Carolina, Tennessee), Midwest (Illinois, Indiana, Michigan, Minnesota, Ohio, Wisconsin), Southwest (Nevada, Texas), and Pacific West (California, Washington).
Participants who were virologically suppressed (HIV RNA <50 copies/mL) on their current antiretroviral regimen (n=495) were randomly assigned 2:1 to either an immediate switch to open-label B/F/TAF at baseline (n=330) or a delayed switch to B/F/TAF at 24 weeks (n=165). To enroll in the study, participants had to be virologically suppressed for at least six months on a regimen of two NRTIs plus a third drug, and they had to have renal sufficiency as indicated by an eGFR ≥50 mL/min. Participants could have preexisting resistance mutations to NNRTIs, PIs, and NRTIs (provided that they did not have K65R, ≥3 TAMs, or T69 insertions), but they could not have preexisting integrase inhibitor (INSTI) resistance mutations.
The median age was 49 years. Participants who were classified female at birth comprised 31% of the B/F/TAF group and 33% of the group that stayed on their baseline regimen (SBR). “There was an effort to engage participation in a broad diversity of African Americans and Blacks, not only to have heterosexual males and females, but also men who have sex with men, transgender persons, and those of Hispanic and Latinx ethnicity,” Hagins said.
Cisgender participants were 96% in both arms. Sexual orientation was divided into four categories: gay or bisexual and male at birth (49% and 41%, respectively); heterosexual and female at birth (29% and 32%); heterosexual and male at birth (19% and 25%); and gay or bisexual female at birth (1% and 2%).
Median CD4 counts were 747 cells/mm3 for the B/F/TAF arm and 758 cells/mm3 for the SBR arm. Median eGFR (by Cockcroft-Gault) were 110 mL/min for the B/F/TAF arm and 107 mL/min for the SBR arm.
A Particular Focus on Baseline HIV Drug Resistance
Very important to this trial was the baseline resistance profile of the participants.
When B/F/TAF was approved by the U.S. Food and Drug Administration in 2018, it was indicated both as initial therapy for treatment-naive people living with HIV and as a switch regimen for those who had been virologically suppressed for at least three months, had no history of treatment failure, and had no known resistance mutations to any of the components of B/F/TAF.
While a previous study showed that B/F/TAF works as a switch regimen in those with archived NRTI resistance—notably including the M184V/I mutation that confers resistance to the emtricitabine component of B/F/TAF—the use of the regimen in those with a history of known resistance remains investigational.
In BRAAVE 2020, the proportion of participants with preexisting resistance was:
- For NRTI resistance overall, 13% in the B/F/TAF arm and 16% in the SBR arm.
- For the M184V/I mutation specifically, 9% in the B/F/TAF arm and 12% in the SBR arm.
- For NNRTI resistance, 21% in the B/F/TAF arm and 19% in the SBR arm.
- For PI resistance, 11% in the B/F/TAF arm and 15% in the SBR arm.
As for baseline regimens, 61% were on an INSTI-based regimen, 30% were on an NNRTI-based regimen, and 9% were on a PI-based regimen. NRTI backbones were F/TAF (67%), F/TDF (18%), or ABC/3TC (14%).
BRAAVE 2020 Findings: High Virologic Suppression at 24 and 48 Weeks
At 24 weeks, less than 1% of participants on B/F/TAF and 2% of those who stayed on their baseline regimen had detectable HIV RNA (defined as ≥50 copies/mL), while 96% of those on B/F/TAF and 95% of those who stayed on their baseline regimen were virologically suppressed.
At 48 weeks, the proportions were:
- 1% detectable among those who switched to B/F/TAF at baseline
- 0% detectable among those who switched to B/F/TAF at 24 weeks
- 95% undetectable for those in the immediate B/F/TAF arm
- 97% undetectable for those in the delayed B/F/TAF arm
Virologic data were missing for 4% across both study arms.
Participants with NRTI resistance, including M184V/I, remained virologically suppressed on B/F/TAF, and no treatment-emergent resistance was observed in any arm of the study. Adverse events were similar between the two treatment groups.
Study Results in Context: BRAAVE 2020
This was a noninferiority study—that is, while the study demonstrated that, for African Americans who were virologically suppressed on antiretroviral therapy, switching to B/F/TAF was noninferior to remaining on their previous regimen, it was not designed to prove that either approach—sticking or switching—was better than the other in terms of virologic outcomes.
There are, however, reasons beyond the study itself to infer that switching may be a good idea. As current U.S. HIV treatment guidelines state, switching from an effective antiretroviral treatment regimen to an alternative regimen may be advisable if the person on antiretrovirals is having issues with side effects, drug interactions, food interactions, pill burden, or cost. In addition, the guidelines state that an alternative regimen may be advisable in order to switch from a regimen containing tenofovir disoproxil fumarate (TDF, Viread) to one containing tenofovir alafenamide (TAF), or from a regimen containing dolutegravir (DTG, Tivicay), elvitegravir (EVG, Vitekta), or raltegravir (RAL, Isentress) to one containing bictegravir (BIC).
“Black and African Americans in this country have the highest rates of new HIV infections every year compared to other races,” Hagins said in a statement on the study findings released by Gilead. “Adding to that burden are other inequalities such as lack of health insurance, difficulties navigating the health care system, and poverty; all of which contribute to higher rates of drug resistance,” she added. “As drug resistance builds, treatment options become more limited, sometimes leading to less desirable, but often necessary, complicated treatment regimens.”
In general, treatment complexity undermines adherence. “These data from BRAAVE 2020, designed with community input to understand specific treatment responses of Black and African Americans, show B/F/TAF is an effective regimen for Black Americans, including those with a history of some drug resistance,” Hagins concluded.