Janssen Sciences Ireland UC (Janssen) announced positive results from the full data read out for two Phase III studies evaluating the safety and efficacy of switching virologically suppressed patients from a three- or four-drug antiretroviral regimen to the two-drug regimen of dolutegravir (ViiV Healthcare) and rilpivirine (Janssen). Full results were presented at the annual Conference on Retroviruses and Opportunistic Infections (CROI) in Seattle, WA.

If approved, this treatment could be the first two-drug regimen for HIV and could offer those living with HIV who are virally suppressed the option to switch to a regimen which does not include a nucleotide reverse transcriptase inhibitor (NRTI).

The dolutegravir and rilpivirine regimen achieved non-inferior viral suppression (HIV-1 RNA <50 c/mL) at 48 weeks compared with a three- or four-drug regimen in both pooled and individual analyses of the SWORD 1 and SWORD 2 studies (current antiretroviral therapy (CAR) 485/511 (95%), dolutegravir + rilpivirine 486/513 (95%) (adjusted difference -0.2%, (95% CI: [3.0%, 2.5%]), pooled analysis). Virologic suppression rates were similar between treatment arms. The median duration of antiretroviral treatment was just over four years at the time of entry into the studies. The most commonly reported (>5%) adverse events in the dolutegravir and rilpivirine arm were nasopharyngitis, headache, diarrhea and upper respiratory tract infection. For the CAR arm, the most commonly reported adverse events were nasopharyngitis, upper respiratory tract infection, back pain, headache and diarrhea. The studies are ongoing for 148 weeks.

"The SWORD Phase III results represent an important step forward in our efforts to deliver a two-drug regimen that may help simplify dosing regimens and reduce pill burden for people living with HIV," says Lawrence M. Blatt, Global R&D Head, Infectious Diseases & Vaccines, Janssen.  "As HIV is increasingly treated as a life-long condition, we remain committed to ongoing research and development of further medicines to treat HIV more simply and to help all those living with HIV to achieve an undetectable viral load and have an improved quality of life."

Virologic failure rates were <1% in the DTG+RPV arm and 1% in the three- or four- antiretroviral-drug arm. No integrase strand inhibitor (INSTI) resistance-associated mutations were reported. Protocol-defined virologic failure with a non-nucleoside reverse-transcriptase inhibitor (NNRTI) resistance-associated mutation (RAMs; K101K/E) was reported in only one patient in the DTG+RPV arm in the context of documented non-adherence, but with no impact on regimen efficacy as the subject re-suppressed on dolutegravir and rilpivirine prior to withdrawal from the study.

The overall rate of serious adverse events was comparable between treatment groups (DTG+RPV: 27, CAR: 21). As would be expected when switching from a stable regimen to a new regimen (in most cases containing two new drugs), more adverse events were reported and led to withdrawal from the study in the DTG+RPV arm (DTG+RPV: 21, CAR: 3).

The safety profiles for dolutegravir and rilpivirine in these studies were consistent with the product labelling for each medicine.