Efficacy of bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) versus dolutegravir (DTG)-based 3-drug regimens in adults with HIV who have suboptimal antiretroviral adherence

Presenter: Kristen Andreatta, research scientist at Gilead Sciences, Inc., Foster City, CA

Presented October 13, 2023.

Levels of virologic suppression remained high in adult patients with HIV with suboptimal (< 85%) adherence to a regimen of bictegravir, emtricitabine, and tenofovir alafenamide (B/F/TAF), according to Kristen Andreatta, a research scientist at Gilead Sciences, Inc., Foster City, CA, United States. In contrast, virologic suppression was reduced in those with suboptimal adherence to a dolutegravir (DTG)-based 3-drug regimen, Andreatta said in an Infectious Disease Week 2023 poster presentation.

Adherence to daily oral antiretroviral therapy is important for sustaining HIV suppression, because it prevents emergence of drug resistance, improves HIV morbidity and mortality outcomes, and prevents transmission of HIV to others. The single-tablet regimen B/F/TAF is a guidelines-recommended (Department of Health and Human Services, International Antiviral Society-USA, and European AIDS Clinical Society) regimen for adults, adolescents and children weighing 14 kg or more with demonstrated efficacy and tolerability and a high barrier to resistance. Five studies of B/F/TAF,1–6 Andreatta noted, have shown the oral regimen to be noninferior to DTG plus 2 nucleoside reverse transcriptase inhibitors (NRTIs).

Andreatta and colleagues conducted a retrospective assessment of drug adherence and its effect on virologic outcomes in this series of  double-blind, placebo-controlled studies, among which HIV adult patients were treatment-naïve1–4 or virologically suppressed.5,6 All patients had been randomized 1:1 to B/F/TAF or DTG plus 2 NRTIs plus placebo in the form of multiple tablets, allowing for unbiased comparison of adherence between treatment groups, Andreatta said. Researchers evaluated adherence through pill counts, and virologic outcomes through assays of last on-treatment HIV-1 RNA.

Among the 2,622 participants (median age about 39.5 years), the proportions of participants in the 2 treatment groups with high (≥ 95%), intermediate (≥  85% to < 95%) or low (< 85%) adherence were similar for in the B/F/TAF group (high adherence 80.1%, intermediate adherence 16.4%, low adherence 3.5%) and the DTG-plus-2-NRTIs group (high adherence 76.9%, intermediate adherence 17.9%, low adherence 5.2%) at 48 weeks, and for weeks 96 and 144 as well. Andreatta emphasized that in the B/F/TAF group, rates of virologic suppression were similar in those with high adherence (98.8%) and intermediate adherence (98.1%) vs those with low adherence (95.7%; P = .12). In contrast, in the DTG-plus-2-NRTIs group, rates of virologic suppression were significantly higher in those with high adherence (98.7%) and intermediate adherence (98.3%) compared with low adherence (89.9%; P < .0001).

In the additional studies with follow-up extended to week 144,1–3 the same pattern persisted with similar virologic suppression for all levels of adherence (P = .45) with B/F/TAF, but with significantly reduced virologic suppression in the low-adherence (< 85%) DTG-plus-2-NRTIs group (P < .0001).

Andreatta said further that among the 9 participants with low adherence and HIV-1 RNA ≥ 50 copies/mL at their last visit through 48 weeks, 3 patients subsequently resuppressed the virus (1 in the B/F/TAF group, 2 in the DTG-plus-2-NRTIs group), 5 discontinued (all in the DTG-plus-2-NRTIs group), and 1 was lost to follow-up (in the B/F/TAF group).

Treatment-emergent M184V resistance was observed in 2 patients in the DTG-plus-2-NRTIs group; no treatment-emergent resistance was reported among B/F/TAF recipients.

Andreatta concluded that overall, most participants receiving either placebo-controlled B/F/TAF or DTG plus 2 NRTIs demonstrated at least 85% adherence. In those with suboptimal adherence, high levels of virologic suppression were maintained with B/F/TAF treatment. In those with suboptimal adherence to DTG plus 2 NRTIs, virologic suppression was reduced. She stated, “These data suggest that B/F/TAF is more effective than DTG plus 2 NRTIs in achieving and maintaining virologic suppression in participants with suboptimal (< 85%) adherence to study drug.”

REFERENCES

  1. Gallant J, Lazzarin A, Mills A, et al. Bictegravir, emtricitabine, and tenofovir alafenamide versus dolutegravir, abacavir, and lamivudine for initial treatment of HIV-1 infection (GS-US-380-1489): a double-blind, multicentre, phase 3, randomised controlled non-inferiority trial. Lancet 2017; 390(10107):2063–2072. doi:10.1016/S0140-6736(17)32299-7
  2. Sax PE, Pozniak A, Montes ML, et al. Coformulated bictegravir, emtricitabine, and tenofovir alafenamide versus dolutegravir with emtricitabine and tenofovir alafenamide, for initial treatment of HIV-1 infection (GS-US-380-1490): a randomised, double-blind, multicentre, phase 3, non-inferiority trial. Lancet 2017; 390(10107):2073–2082. doi:10.1016/S0140-6736(17)32340-1
  3. Orkin C, DeJesus E, Sax PE, et al. Fixed-dose combination bictegravir, emtricitabine, and tenofovir alafenamide versus dolutegravir-containing regimens for initial treatment of HIV-1 infection: week 144 results from two randomised, double-blind, multicentre, phase 3, non-inferiority trials. Lancet HIV 2020; 7(6):e389–e400. doi:10.1016/S2352-3018(20)30099-0
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  5. Molina JM, Ward D, Brar I, et al. Switching to fixed-dose bictegravir, emtricitabine, and tenofovir alafenamide from dolutegravir plus abacavir and lamivudine in virologically suppressed adults with HIV-1: 48 week results of a randomised, double-blind, multicentre, active-controlled, phase 3, non-inferiority trial [published correction appears in Lancet HIV. 2018 Jun 22;:]. Lancet HIV 2018; 5(7):e357–e365. doi:10.1016/S2352-3018(18)30092-4
  6. Sax PE, Rockstroh JK, Luetkemeyer AF, et al. Switching to bictegravir, emtricitabine, and tenofovir alafenamide in virologically suppressed adults with human immunodeficiency virus. Clin Infect Dis 2021; 73(2):e485–e493. doi:10.1093/cid/ciaa988

Disclosures: Andreatti is employed by and holds stocks/shares in Gilead.

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