Introduction

The combination of bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) is a recommended regimen for HIV-1 treatment.

Aim

To report long-term outcomes for B/F/TAF in patients enrolled in two studies who were originally assigned to B/F/TAF through 240 weeks

Patient Profile

Adults living with HIV-1 with no prior treatment experience and HIV-1 RNA viral levels >500 copies/mL

Methods

• This is an integrated analysis of two phase 3 studies (study -1489 and 1490) evaluating the safety and efficacy of bictegravir, emtricitabine, and tenofovir alafenamide as initial therapy, after 240 weeks
• Study 1489: Patients were randomized 1:1 ratio to once daily treatment with either B/F/TAF (50/200/ 25 mg) or DTG/ABC/3TC (50/600/300 mg).
• Study 1490: Patients were randomized (1:1) to once daily treatment with B/F/TAF (50/ 200/25 mg) or DTG 50 mg + F/TAF (200/25 mg)
• After 144 weeks, 634 participants from both studies were randomized to and initated treatment with B/F/TAF; 506/634 entered the optional open-label extension phase; and 444/506 completed 240 weeks of treatment

Study Outcomes

• Efficacy outcomes at week 240 were the percentages of participants with available data with virologic suppression (HIV-1 RNA <50 copies/mL) at Week 240 using missing = excluded and missing = failure methods.
• Other secondary efficacy outcomes included changes from baseline in CD4+ cell count, percentage changes from baseline in hip and lumbar spine bone mineral density, Renal safety assessments, changes in fasting lipids and Adverse event incident rates at week 240.

Results

• At 240 weeks, virologic suppression (HIV-1 RNA <50 copies/mL) was reported in 98.6% of participants who continued assigned treatment and 1.4% (6/432) with virologic failure as per missing = excluded analysis
• As per missing = failure analysis, 67.2% who initiated B/F/TAF had documented virologic suppression through 5 Years.

  Figure 1: Virologic outcomes through 240 weeks

   

• Mean change in CD4+ count from baseline was +338 cells /µL
  • The mean (SD) CD4+ count among 415 participants evaluated was 785 (282.4) cells /µL.
• No treatment-emergent resistance to B/F/TAF was detected.

  Safety

• Diarrhea (21.5%), headache (18.5%), and nasopharyngitis (18.1%) were the most common adverse events among all participants who initiated B/F/TAF
• Treatment related discontinuation was reported in 1.6% (n = 10/634) of participants (n = 5 with events considered drug-related).
• At week 240, total cholesterol increased by 21 mg/dL from baseline; 19 mg/dL for low density lipoprotein (LDL) cholesterol, 4 mg/dL for high density lipoprotein (HDL) cholesterol, and 10 mg/dL for triglycerides; change in total cholesterol:HDL

  ratio was 0.1

• Median weight change from baseline was +6.1 kg (2.0, 11.7).
• In Study 1489, hip and spine bone mineral density mean percent changes from baseline were <0.6%.
• There were no renal adverse events related discontinuations

Conclusion

B/F/TAF demonstrated sustained high rates of virologic suppression with no treatment-emergent resistance and rare drug discontinuations due to adverse events

Reference

eClinicalMedicine 2023;59: 101991