Introduction

Bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) (50/200/25 mg) is approved for use in adults globally and is recommended in international HIV guidelines as a first-line treatment and as a switching option for individuals who have achieved virologic suppression

Aim

Evaluate the efficacy and safety of 96 weeks of B/F/TAF treatment in participants who switched from dolutegravir (DTG)-based therapy on completion of the blinded phase at 144weeks.

Patient Profile

Participants from studies 1489 and 1490 who completed 144 weeks of DTG-based ART and were switched to B/F/TAF

Methods

• Studies 1489 and 1490 were phase 3 randomized, double-blind, active-controlled trials assessing first-line therapy for HIV-1.
• After 144 weeks of treatment with either a dolutegravir (DTG)-based regimen or a regimen of bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF), participants had the option to enter a 96-week open-label extension (OLE) with B/F/TAF.
• In total, out of the 519 participants switched from DTG-based regimen (DTG/ abacavir/lamivudine or DTG+F/TAF) to B/F/TAF across Studies 1489 and 1490, 457 individuals entered the 96th week of the open-label extension
• Viral suppression (defined as HIV-1 RNA <50 copies/ml) ,changes in CD4 cell count, treatment-emergent resistance, safety following the switch from a DTG-based regimen to B/F/TAF were evaluated

Results

• At OLE Week 96, participants who switched to B/F/TAF exhibited high rates of virologic suppression, achieving 99.5% in those switching from DTG/abacavir/lamivudine and 99.1% in those switching from DTG + F/TAF.

  Figure 1: Rates of virologic suppression in participants who switched from DTG Based regimens

  

  M=E, missing= excluded; M= F, missing=failure

  Immunological Outcomes

• In participants who switched to B/F/TAF from DTG/ABC/3TC, the median changes in CD4 cell count were -6 cells/µl at both OLE Week 48 and Week 96
• Conversely, those who switched from DTG + F/TAF to B/F/TAF experienced median increases in CD4 cell count of +14 cells/µl at Week 48 and +3 cells/µl at Week 96

Safety

• Drug related adverse events after switching were reported in 21 participants , with diarrhea, weight gain, and headache occurring most commonly.
• No cases of proximal renal tubulopathy, drug-related Grade 4 adverse events, or serious adverse events were reported.
• Treatment-related adverse events related discontinuation were observed in 2 participants.

  Table 1 : Adverse events during OLE (Weeks 144–240)

  	Switch from DTG/ABC/3TC to B/F/TAF (N =254)	Switch from DTG+F/TAF to B/F/TAF (N =265)
  Any AE, n	214	215
  Drug-related AE, n	13	8
  >2 participants in either group or overall, n
  Diarrhea	3	0
  Weight increased	2	1
  Headache	1	1
  Grade 3 or 4 drug-related AE, n	0	1
  Any SAE	19	32
  Drug-related SAE	0	0
  Discontinued B/F/TAF due to drug-related AE	2	0
  Deaths	2	3

   

• Participants who switched from DTG/ABC / 3TC exhibited significant greater weight gain than those who switched from DTG+F/ TAF
  • participants who switched from DTG/ ABC/3TC had greater weight changes than those who switched from DTG+F/ TAF.
  • Median at Week 240was +2.4 kgversus +1.3 kg.
• Median weight change from the blinded phase baseline to OLE Week 96 was numerically similar across treatment groups.

Conclusion

• Participants who switched to B/F/TAF from a regimen containing DTG achieved sustained high levels of virologic suppression without the emergence of resistance.
• The treatment was well tolerated, and no new safety concerns were observed during B/F/TAF therapy.

Reference

AIDS 2024, 38: 983–991