Introduction

Efavirenz-based regimens, once standard, are now less preferred due to neuropsychiatric adverse effects and long-term toxicity, though still common in resource-limited settings for their low cost and proven efficacy. Bictegravir (BIC), with high potency, safety, and strong resistance barrier, is ideal for regimen simplification, but evidence for switching from EFV/FTC/TDF to BIC/FTC/TAF in suppressed patients has been lacking.

Aim 

Evaluate the efficacy and safety outcomes of a treatment switch from EFV/FTC/TDF given once daily (OD) or on alternate days (ATAD) to BIC/FTC/TAF in virologically suppressed people with HIV (PWH).

Patient

Adults (≥18 years) with HIV-1, virologically suppressed for ≥24 weeks.

Eligibility Criteria

• HIV-RNA <50 copies/mL for ≥24 weeks.
• On EFV/FTC/TDF (once daily or alternate days) for ≥24 weeks.
• No major resistance mutations to NRTI, NNRTI, PI, or INSTI.
• Creatinine clearance ≥50 mL/min.

Methods 

• Single-arm, prospective, open-label, non-randomized Phase IV trial
• 234 virologically suppressed PWHwere enrolled in the study. 
  1. 175 participants (74.8%) switched from EFV/FTC/TDF once daily OD 
  2. 59 participants (25.2%) switched from EFV/FTC/TDF ATAD regimen
• Follow-up Visits: Weeks 4, 8, 12, 24, 36, and 48 
• Primary Endpoint: Proportion of participants with HIV-RNA <40 copies/mL at 24 weeks
• Secondary Endpoints
  1. HIV-RNA <40 copies/mL at 48 weeks
  2. Discontinuation rates
  3. Drug resistance development
  4. Clinical and laboratory adverse events
  5. Changes in CD4 count, HIV-DNA, lipid profile, renal function

Results

Virologic Success

• The switch to BIC/FTC/TAF demonstrated high virologic efficacy and durability over 48 weeks.
  1. At 24 weeks, 212 / 234 participants (90.6%,) had HIV-RNA <40 copies/mL. 
  2. At 48 weeks, 217 / 234 participants (92.7%,) maintained HIV-RNA <40 copies/mL in the ITT analysis. 
  3. Virological failure occurred in three participants, all of whom resuppressed without changing antiretroviral therapy. 
  4. No major resistance mutations were detected in participants with virological failure. 
  5. The per-protocol (PP) analysis showed similar results, with 93.4% suppression at 48 weeks. 
  6. Treatment discontinuation due to adverse events or other reasons was 5.1% in ITT and 4.8% in PP populations. 

Figure 1: Virological outcomes with BIC/FTC/TAF at 48 weeks.

Immunologic Response

• After 48 weeks, the CD4 cell count increased by an average of 58.76 cells/mm³ overall (P < 0.001). 
  1. In participants switching from EFV/FTC/TDF once daily (OD), the CD4 count increased by 51.96 cells/mm³ (P < 0.001). 
  2. In participants switching from EFV/FTC/TDF alternate days (ATAD), the CD4 count increased by 79.37 cells/mm³ (P = 0.011), which was significantly greater than the OD group (P = 0.026). 
• The CD4/CD8 ratio showed a slight decrease of –0.04 ( P = 0.002) across all groups. 

Metabolic Changes

• Serum creatinine increased slightly by +0.12 mg/dL (P < 0.001). 
• Total cholesterol decreased by –8.45 mg/dL (P = 0.002). 
• HDL cholesterol decreased by –4.66 mg/dL (P < 0.001). 
• There were no significant changes in LDL cholesterol, triglycerides, glycemia, AST, or ALT (P ≥ 0.321). 
• Body weight increased by +1.51 kg at 24 weeks (P < 0.001) & +2.04 kg at 48 weeks (P < 0.001), with slightly higher gains in the OD group compared to the ATAD group.

Safety

• 106 clinical adverse events (mostly mild) were reported during study.
• No statistically significant changes in femoral BMD, lumbar BMD, and beta 2-microglobulin were detected from BL to week 48

Analysis of the HIV medical outcomes survey (MOS-HIV) questionnaire

• Most patients reported "excellent" or "very good" quality of life on the MOS-HIV questionnaire at BL, and very few had limitations in daily living activities with the current regimen.
  1. 14/70 at baseline , 16/64 at week 4, 10/58 at week 24, and 15/52 at week 48.

Conclusion

• This study   demonstrated that BIC/FTC/TAF as a viable switching strategy for PWH currently on an OD or alternating-day regimen of EFV/FTC/TDF. 
• BIC/FTC/TAF should be considered where resources allow, generic low-dose EFV-based regimens may remain appropriate in select settings for individuals who tolerate them and maintain virologic control.

Reference 

Int. J. Infect. Dis 2025;158: 107961