Investigational 2-Drug HIV Regimen Showing Promise

SEATTLE — A switch to a novel, once-daily, 2-drug regimen of dolutegravir plus rilpivirine may be as effective as a 3- or 4-drug current antiretroviral regimen (CAR) in HIV-1-infected patients, according to data from 2 identical open-label, multicenter, global, phase 3, noninferiority studies presented at CROI 2017. The 2-drug regimen demonstrated high efficacy and noninferiority to the continuation of CAR in virologically suppressed HIV-1-infected adults. No new safety concerns were observed.

The findings suggest the 2-drug combo offers the potential for reduction in cumulative antiretroviral therapy exposure without increasing risk for virologic failure. “A 2-drug regimen with dolutegravir and rilpivirine proved noninferior efficacy vs standard triple therapy in the main study endpoint at 48 weeks,” said Josep Llibre, MD, PhD, a senior consultant at the University Hospital Germans Trias, Badalona, Barcelona, Spain. “The rates of efficacy were very high (95%), and a low number of subjects discontinued due to toxicity.”

The researchers looked at 2 identical open-label, multicenter, global, phase 3, noninferiority studies (SWORD-1 and SWORD-2; ClinicalTrials.gov identifiers: NCT02429791 and NCT02422797, respectively) that evaluated the efficacy and safety of switching from a 3- or 4-drug CAR to dolutegravir plus rilpivirine once daily. All the patients had HIV-1 RNA <50 copies/mL (viral load <50 copies/mL) for at least 12 months, and none had a history of virologic failure.

There were 1024 patients: 513 received dolutegravir plus rilpivirine, and 511 received CAR. The analysis showed that at week 48, switching to the 2-drug combo was noninferior to continuing CAR in pooled analysis of both the intent-to-treat exposed population (95% vs 95%) and the per protocol population (96% vs 96%). Efficacy results were similar in SWORD-1 (95% vs 96% for CAR) and SWORD-2 (94% vs 95% for CAR).

“The study opens a new era of once-daily antiretroviral treatment in streamlined regimens with a 2-drug regimen which is booster free, nucleoside free, and protease inhibitor free,” Dr Llibre told Infectious Disease Advisor.

The findings from this study are encouraging because they suggest a new daily regimen could be adopted that has the potential for fewer drug interactions and potentially fewer long-term adverse effects. Dr Llibre said it is premature to apply these data to other HIV-1-infected patient populations, who may have significant coinfections or may not be virologically suppressed. “The study is a maintenance study, so this data should only be used in that scenario,” said Dr Llibre.

The median duration of antiretroviral treatment was just more than 4 years at the time of entry into the studies. The most commonly reported (>5%) adverse events in the dolutegravir and rilpivirine group were nasopharyngitis, headache, diarrhea, and upper respiratory tract infection. For the CAR group, the most commonly reported adverse events were nasopharyngitis, upper respiratory tract infection, back pain, headache, and diarrhea.

The studies are ongoing for 148 weeks. All the patients had previously achieved viral suppression on a 3- or 4-drug (integrase strand transfer inhibitor, nonnucleoside reverse transcriptase inhibitor, or protease inhibitor-based) antiretroviral regimen. These patients were randomly assigned to either stay on their 3- or 4-drug regimen or switch to a dolutegravir and rilpivirine regimen.

Virologic failure rates were less than 1% in the dolutegravir and rilpivirine group and 1% in the 3- or 4-antiretroviral-drug group. No nonnucleoside reverse transcriptase inhibitor resistance-associated mutations were reported.

Reference

Llibre JM, Hung C-C, Brinson C, et al. Phase III SWORD 1&2: switch to DTG+RPV maintains virologic suppression through 48 wks. Presented at: CROI 2017. Seattle, WA; February 13-16, 2017. Abstract 44LB.