Introduction

In extensively treatment experienced and multidrug resistant HIV-1 patients, maintaining lifelong HIV-1 suppression is crucial thus there is need for simple, effective, and well-tolerated antiretroviral therapy (ART) combinations. Darunavir (DRV) boosted with ritonavir (DRV/r) or cobicistat (DRV/c) and dolutegravir (DTG) have demonstrated efficacy in patients with limited therapeutic options.

Aim

To evaluate  efficacy and safety of DTG plus DRV/c as a once-daily maintenance strategy vs continuing the previous ART in patients who were highly treatment experienced with HIV-1 resistant to drugs but not integrase inhibitors (INSTIs) or DRV

Patient profile

• HIV-infected adultswith confirmed HIV-1 RNA <50 copies/mL for >6 months
• Prior treatment with at least 3 antiretroviral drugs
• History of drug resistance mutations against at least 2 antiretroviral classes but remaining fully susceptible to DRV and integrase inhibitors

Methods

• Randomized, open label, noninferiority, multicentre study.

• The primary endpoint was the proportion of patients with HIV-1 RNA 50 copies/mL at week 48 relative to time to loss of virologic response, with a noninferiority margin set at -12.5%
• Virologic failure was defined as confirmed HIV-1 RNA >50 copies/mL or a single determination of HIV-1 RNA >50 copies/mL followed by antiretroviral therapy discontinuation.

Results

• No significant differences in virologic efficacy in the Time to loss of virologic response (TLOVR) or FDA snapshot analyses

  Figure 1 Virological outcomes at week 48 as per TLOVR or FDA snapshot analysis

  

• In SOC group, 2 virologic failures vs none was observed in the 2D group.
• Three and 5 participants in the 2D and SOC groups experienced blips during the follow-up period (P=.480)
• At 48 weeks, mean ART adherence was similar between groups (100% in the 2D group vs 99.6% in the SOC group, P= .334)
• At week 48, median CD4+ change from baseline in cell/mm³ count was -1.0 cells/mm³ in the 2D arm and 0.4 cells/mm³ in the SOC arm (P=.130)

Table 1: Mean changes in Lipids, Creatinine

• At least 1 adverse event was reported in 91.1% in 2 D group vs 72.7% in SOC group.
• In 2D arm, a total of 111 adverse events were reportedvs 81 in the SOC arm (P= .002)
• No serious adverse events, AIDS-defining events, or deaths were reported during the study.

Conclusion

• In highly treatment experienced patients with resistance to at least 2 antiretroviral classes but fully active DRV and INSTIs, dual therapy with DRV/c plus DTG maintains viral suppression in patients who are well suppressed and adherent to ART.
• DRV/c plus DTG may be considered a once-daily therapy option only for well-selected patients.

Reference

Open Forum Infect Dis. 2023 Oct 31;10(11):ofad542