Introduction

Dolutegravir and cobicistat-boosted darunavir (DTG+DRV/c) as dual regimen presents a promising alternative for HIV patients who exhibit resistance or intolerance to nucleoside reverse transcriptase inhibitors, particularly those with a history of treatment failure.

Aim

To evaluate efficacy  and tolerability of dual therapy with dolutegravir plus darunavir/ cobicistat in treatment-experienced patients with HIV

Patient Profile

Treatment-experienced patients with HIV who switched to the DTG+DRV/c regimen

Methods

• Retrospective analysis
• 40 treatment-experienced patients with HIV-1 transitioned to combination therapy of DTG+DRV/c (DTG 50 mg, DRV 800 mg, and cobicistat 150 mg, co-formulated once or twice daily)
• Patients were categorized into two groups based on the reasons for switching regimens:
  • Treatment failure group
  • Non-failure groups
• The primary endpoint was the proportion of patients with plasma HIV-RNA levels of <50 copies/mL at week 144 post-switch
• The secondary endpoints were safety and tolerability assessments.

Results

• The treatment failure group (n=17) initiated therapy with extremely high HIV RNA levels (>5 log₁₀ copies/ml), which rapidly decreased to undetectable levels (<1 log10 copies/ml) within a short duration.
• The treatment non-failure group (n=23) presented with persistently low HIV RNA levels (~1 log₁₀ copies/ml) throughout the initial 12-week period.
• The study demonstrated sustained virologic suppression in both groups throughout the 144-week study period, with both groups maintaining viral loads below the clinical threshold of 200 copies/mL, thereby confirming the efficacy of the treatment regimen.
• The treatment failure group-initiated therapy with CD4+ T cell counts approximately 250 cells/mm³, which increased steadily and approached 500 cells/mm3 by week 144, indicating ongoing immune restoration.
• The non-failure group maintained CD4+ T cells at a stable level around 500 cells/mm³, signifying sustained immune system stability.
• Most patients who changed or discontinued this regimen for various reasons maintained virologic suppression after 3 months, highlighting the effectiveness of the treatment program.
• The post-switch regimen was well-tolerated, with no notable changes observed in renal function, liver function, glucose levels, or lipid profiles.
• Most patients (85.0%, 34/40) demonstrated excellent tolerance to the regimen, indicating a high level of tolerability.

Conclusion

• DTG+DRV/c has been shown to be an efficacious and tolerable switch therapy regimen for HIV-infected patients with prior treatment experience, exhibiting durable benefits throughout up to 144 weeks of follow-up.
• This regimen has demonstrated adaptability across diverse patient populations and has been associated with significant virologic and immunologic improvements, particularly in individuals with a history of treatment failure.

Reference

Infect Chemother. 2024 Jun;56(2):247-255