Dolutegravir with Darunavir/Cobicistat Safe to Prescribe in Treatment of HIV, Study Suggests

The world has come a long way in the fight against HIV; of course, one of the biggest advancements made came with the advent of antiretroviral therapy (ART), which offers infected individuals treatment options that would allow them to live longer, healthier lives, and helps reduce their risk of transmission.

Researchers are constantly working to improve treatment strategies in efforts to increase adherence, reduce associated toxicity and costs, and to try to stay ahead of resistant strains of the virus. As such, dual therapies that do not use nucleoside reverse transcriptase inhibitors (NRTIs, or sometimes referred to as “nukes”) are being explored and appear promising.

At the 25th Conference on Retroviruses and Opportunistic Infections (CROI), Emilie Elliot, from the Chelsea and Westminster Hospital in London, United Kingdom, presented a poster regarding research that explored the pharmacokinetics of dolutegravir (ViiV Healthcare's Tivicay) with and without darunavir/cobicistat (Janssen's Prezcobix) in healthy volunteers.

“The integrase inhibitor, dolutegravir (DTG), combined with boosted darunavir (DRV), both potent and with high resistance barriers, potentially offers a powerful yet safe and tolerable ART dual therapy regimen,” study authors write.

To explore this further, Dr. Elliot and her team conducted a phase 1, open label, cross over, pharmacokinetic (PK) study which took place over the course of 57 days. Healthy volunteers between the ages of 18 and 65 years were randomized into 2 groups:

Group 1: DTG 50mg administered on days 1 to 14 followed by a 7-day wash out period, DTG+DRV/c 50mg+800/150mg on days 22 to 35 (co-administration period), again, followed by a 7-day wash out, and lastly, DRV/c 800/150mg on days 43 to 56

Group 2: DRV/c 800/150mg administered on days 1 to 14 followed by a 7-day wash out period, DTG 50mg+DRV/c 800/150mg on days 22 to 35 (co-administration period), again, followed by a 7-day wash out, and lastly, DTG 50mg on days 43 to 56

In total, 25 volunteers were screened; of these volunteers, 20 attended baseline and 20 completed all PK phases (with 11 in group 1 and 9 in group 2), according to poster authors. One subject withdrew. The median age of participants was 33.5 years of age, 13 volunteers were female, and median BMI was 27. Of the 20 volunteers, 13 self-reported as Caucasian, 6 as Black African/Caribbean, and 1 as White and African. Dr. Elliot’s team found that the drugs studied were well-tolerated.

DTG geometric mean ratios (GMR, DTG+DRV/c versus DTG alone) and 90% confidence intervals (CI) for Cmax, AUC and C24h were 1.01 (0.92-1.11), 0.95 (0.87-1.04) and 0.9 (0.8-1.0), according to the poster. Furthermore, DRV GMR (DRV/c+DTG versus DRV/c alone) and 90%CI for Cmax, AUC and C24h were 0.90 (0.83-0.98), 0.93 (0.86-1.00) and 0.93 (0.78-1.11) and for cobicistat Cmax, AUC and C24h were 0.96 (0.89-1.04), 0.98 (0.88-1.08) and 0.98 (0.79-1.22).

None of the participants experienced grade 3 or 4 side effects; no laboratory abnormalities were observed.

“Concentrations of DTG during co-administration with DRV/c decreased by 10% and those of DRV with DTG by 7%. GM minimum concentrations (C₂₄) for both drugs stayed well above the protein-adjusted IC₉₀ (DTG) and EC₉₀ (DRV) at all time points,” the authors conclude, “suggesting this combination can be prescribed safely in the treatment of HIV-1, including in patients harboring resistance that benefit from optimal antiretroviral exposures.”