People with suppressed HIV and the M184V/I viral mutation who switch medications to combined bictegravir, emtricitabine, and tenofovir alafenamide (B/F/TAF) appear to maintain viral suppression, reports an industry-sponsored analysis.
“M184V/I was detected in 10% of virologically suppressed clinical trial participants at study baseline. Switching to B/F/TAF demonstrated durable efficacy in maintaining viral suppression, including in those with preexisting M184V/I,” write senior study author Kirsten L. White, PhD, of Gilead Sciences, in Foster City, Calif., and colleagues in AIDS .
“Similarly high rates of virologic suppression were maintained in B/F/TAF-treated participants with or without preexisting M184V/I for at least 1 year with no emergent resistance,” they write.
Clinicians use the single-tablet B/F/TAF combination as an initial HIV therapy and as an approved replacement regimen when switching therapies in certain virologically suppressed people with HIV, the authors write.
Dr. White and her colleagues analyzed pooled data from 2,286 adult and 100 child participants in six randomized clinical trials investigating the safety and efficacy of switching to B/F/TAF in virologically suppressed (HIV-1 RNA < 50 copies/mL for 3 or 6 months) people with HIV. At screening, participants were on three-drug antiretroviral regimens.
Overall, 2,034 participants switched treatment regimens to B/F/TAF and had follow-up HIV-1 RNA data. Of these, 1,825 had baseline genotypic data, and preexisting M184V/I was detected in 182 (10%) of them.
All studies had postbaseline visits at weeks 4 and 12, and every 12 weeks thereafter, with B/F/TAF treatment lasting a median of 72 weeks. Plasma HIV-1 RNA levels were measured, and efficacy was assessed for all patients who switched to B/F/TAF.
The researchers assessed preexisting drug resistance by historical genotypes, baseline proviral DNA genotyping, or both, and they determined virologic outcomes by last available on-treatment HIV-1 RNA. They used stepwise selection in a multivariate logistic regression model to identify potential risk factors for M184V/I.
Virologic suppression well maintained
At the final on-treatment visit, 98% (179/182) of participants with preexisting M184V/I and 99% (2012/2034) of all B/F/TAF-treated participants had HIV-1 RNA less than 50 copies/mL, with no treatment-emergent resistance to B/F/TAF.
Factors linked with preexisting M184V/I in adults included being Black or Hispanic/Latinx, having baseline CD4+ cell count less than 500 cells/mL, advanced HIV disease, longer antiretroviral therapy, more prior third agents, and other resistance.
These results are important, Jana K. Dickter, MD, associate clinical professor in the division of infectious diseases at City of Hope in Duarte, Calif., told this news organization in an email.
added Dr. Dickter, who was not involved in the study. “This combination is recommended as an initial regimen by the U.S. Department of Health & Human Services.”
Easy to administer, well tolerated, and potent
Barbara Gripshover, MD, professor at Case Western Reserve University, Cleveland, and medical director of the special immunology unit of the Cleveland Medical Center, explained that “M184V/I is a common resistance mutation in patients who’ve had prior virologic failure on a lamivudine- or emtricitabine-containing regimen.”
“This study shows that, even in the presence of the M184V/I, switching virally suppressed persons to B/F/TAF provides continued durable virologic suppression,” Dr. Gripshover, who also was not involved in the study, said in an email.
Clinicians may comfortably switch patients to this regimen without fear of virologic failure, she added.
“Fixed-dose B/F/TAF, a potent, well-tolerated, single-tablet regimen, is a good switch option for persons on older regimens that contain either more pills, less tolerable agents, or ‘boosting’ agents that block cytochrome 3A4,” she noted. “Having a potent backbone agent is key.
“This is a good regimen due to its simplicity, tolerability, and potency,” Dr. Gripshover said, “and many patients exposed to older regimens may harbor archived M184V/I.
“The large number of subjects who had prior M184V/I and remained suppressed is convincing to me that B/F/TAF is durably effective in the presence of FTC resistance,” she concluded.
The study was supported by Gilead Sciences. Dr. White and 11 coauthors are employees and stock shareholders of Gilead, and three other coauthors report relevant financial relationships with Gilead and other pharmaceutical companies. One coauthor as well as Dr. Dickter and Dr. Gripshover report no relevant financial relationships.
A version of this article first appeared on Medscape.com.