FROM THE LANCET
Phase 3 clinical results show an oral, two-drug antiretroviral therapy (ART) of dolutegravir and rilpivirine to be an effective and safe alternative to a triple-drug current antiretroviral regimen (CAR) for maintaining virologic suppression of HIV-1 in adults.
Josep M Llibre, MD, from the department of infectious diseases at the Pujol University Hospital Germans Trias in Barcelona and his colleagues conducted a phase 3, randomized, parallel-group ( SWORD-1 and SWORD-2 ), multicenter, noninferiority investigation. The pooled, open-label study reported on a total of 1,028 individuals, median age 43 years, who met a base criteria of stable viral suppression (viral load fewer than 50 copies/mL) by a first or second CAR regimen consisting of two nucleoside reverse transcriptase inhibitors (NRTIs) plus a third drug (nonnucleoside reverse transcriptase inhibitors, integrase strand transfer inhibitors, or a protease inhibitor) for a minimum of 6 months at time of screening. The overall population was 80% white, with women making up 22% of the pooled populations. Random assignment with stratification according to class, age, and planned substudy participation resulted in 512 participants continuing their CAR regimen and an intention-to-treat population of 516 participants switching to the oral, once-daily, two-drug dolutegravir/rilpivirine regimen (dolutegravir 50 mg plus rilpivirine 25 mg).
Analysis of pooled SWORD1 and SWORD2 trials at the primary 48-week endpoint showed 95% of the participants for both the intent-to-treat, two-drug dolutegravir/rilpivirine therapy and the population maintaining their standard triple-drug CAR therapy continued to have successful viral suppression as evidenced by viral loads of fewer than 50 copies/mL. This result together with an adjusted treatment difference of –2.2% (95% confidence interval, –3.0 to 2.5) supports a noninferiority with a predefined margin of –8% of the dolutegravir/rilpivirine therapy to CAR for viral suppression as reported in the Lancet .
Reports of at least one adverse event by week 48 were slightly higher for the dolutegravir/rilpivirine therapy group (77%) when compared with those in the CAR group (71%). The most commonly experienced adverse effects were nasopharyngitis (10% each for dolutegravir/rilpivirine and CAR) and headache (8% for dolutegravir/rilpivirine vs. 5% for CAR). However, adverse effects were associated with higher withdrawals from the dolutegravir/rilpivirine therapy group, compared with the CAR group (3% vs. less than 1%, respectively) by the primary 48-week endpoint.
“Once-daily oral dolutegravir/rilpivirine therapy would be the first oral two-drug regimen that provides patients with an alternative to guideline-preferred triple-drug regimens, avoids major NRTI [nucleoside reverse transcriptase inhibitor] toxicities, has limited potential for drug-drug interactions, and does not increase lipid concentrations or inflammatory biomarkers,” according to Dr. Llibre and his colleagues.
The authors disclosed associations with financial and regulatory sponsor ViiV Healthcare and partner participation by Janssen Pharmaceutica NV in the development of the dolutegravir/rilpivirine two-drug regimen.
Source: Llibre JM et al. Lancet. 2018 Jan 10. doi: 10.1016/S0140-6736(17)33095-7 .
