In a late-breaker presentation at the 2017 Conference on Retroviruses and Opportunistic Infections (CROI) in Seattle, data from the SWORD 1 & 2 studies showed that a two-drug regimen of dolutegravir (Tivicay, DTG) + rilpivirine (Edurant, RPV) suppressed HIV as well as various regimens of three or more drugs in people on long-term treatment. This is somewhat remarkable given that the new regimen does not appear to need a booster or an NRTI backbone or protease inhibitor to fully suppress HIV.
Both studies enrolled a total of 1,024 people who had been on their first or second regimen with an undetectable viral load at least a year but with no history of drug resistance or failure. The average time on treatment was four years and average CD4 count at study entry was about 625. Average age was 43, more than 3 out of 4 were men, and 4 out of 5 were white. People with hepatitis B could not enroll.
The studies equally assigned people to either stay on their suppressive 3- or 4-drug regimens or switch to the DTG (integrase inhibitor) + RPV (NNRTI) regimen at study entry. After 52 weeks, the first group will also switch to the DTG + RPV regimen.
The presentation showed that, after the first 48 weeks, 95% of those in both groups maintained undetectable viral loads below 50 copies. There were very slight numerical differences in SWORD 1 (96% for both) vs. SWORD 2 (94% for both), but were statistically not significant.
One person in the DTG + RPV group who was eventually not taking their regimen as prescribed developed detectable viral load and an NNRTI mutation before getting back under 50 copies by re-starting DTG + RPV. No integrase inhibitor mutations were seen in either group.
Serious side effects were uncommon and equal between the groups. A higher rate of mild to moderate side effects were reported in the DTG + RPV group (17%) compared to 2% in the other group. It will be interesting to contrast this difference again after the next switch at 52 weeks to the initial switch.
As for changes in blood fats, very similar rates were seen across both groups for total cholesterol, HDL and LDL cholesterol, total HDL ratio and triglycerides. However, changes in markers of bone health were slightly but significantly better in the DTG + RPV group.
This is very promising news to see a two-drug maintenance regimen suppress HIV at rates similar to 3- and 4-drug regimens. A combination pill will be formulated for another study, which will include more treatment experienced individuals. Researchers will continue to follow
these SWORD 1 & 2 study participants through 148 weeks.
JM Libre, et al. Phase III SWORD 1&2: Switch to DTG+RPV maintains virologic suppression through 48 wks. 2017 CROI, Seattle. Abstract 44LB.