Simpler HIV treatment, with only 2 drugs, keeps viral loads suppressed
Antiretroviral therapy (ART) using just two approved drugs—dolutegravir and rilpivirine —kept HIV suppressed for a year in people with undetectable viral load who switched from a three- or four-drug combo, according to a presentation at the Conference on Retroviruses and Opportunistic Infections (CROI) this week in Seattle.
As people with HIV face the prospect of lifelong treatment, researchers continue the search for antiretroviral options that are better tolerated, easier to take, and cheaper—but without losing any of the effectiveness of standard multi-drug therapy.
The integrase inhibitor dolutegravir (Tivicay) is a good candidate for treatment simplification because it has potent activity against HIV and a high barrier to resistance. Both dolutegravir and the NNRTI rilpivirine (Edurant) are well tolerated and have few drug-drug interactions.
Josep Llibre, MD, from University Hospital Germans Trias in Barcelona presented findings from the SWORD-1 and SWORD-2 trials, which assessed whether dolutegravir plus rilpivirine could maintain viral suppression in treatment-experienced people who switched from a three- or four-drug regimen.
Previous smaller studies have shown that dual therapy is promising. For instance, as researchers reported at last year’s International AIDS Conference, dolutegravir plus the inexpensive nucleoside reverse transcriptase inhibitor lamivudine (Epivir) suppressed HIV in most people starting ART in a pilot study called PADDLE.
The SWORD studies, however, are the first large Phase 3 trials to show that a two-drug combination can work as well as regimens containing more drugs.
SWORD-1 and SWORD-2 were identical international studies. Together they included 1,024 people with HIV who had been on standard ART with undetectable viral load for at least a year and had no history of virological treatment failure or evidence of drug resistance.
More than three-quarters were men, most were white, the median age was 43 years, and the baseline CD4 count was approximately 600 cells/mm3. At study entry they were on regimens containing at least three drugs: an integrase inhibitor (20%), NNRTI (54%), or protease inhibitor (26%) plus two NRTIs. About three-quarters used tenofovir disoproxil fumarate (TDF).
Participants were randomly assigned to either switch to once-daily dolutegravir plus rilpivirine or stay on their current regimen.
Most people in both treatment groups maintained viral suppression: 95% of people taking dolutegravir plus rilpivirine and 95% of people who did not change their drug regimen still had viral suppression below 50 copies/mL at 48 weeks. This showed that switching to the dual regimen was “non-inferior” to staying on the current combination.
Development of drug resistance, which can lead to treatment failure, is one concern when using regimens with fewer drugs. But in the SWORD studies, virological failure was rare (1% or less in both groups). One person taking dolutegravir plus rilpivirine developed a NNRTI resistance mutation, but no participants developed integrase resistance mutations.
Treatment was generally safe and well tolerated. The most common adverse events were sore throat, headache, upper respiratory tract infections, and diarrhea. Switching to the dual regimen had a beneficial effect on laboratory biomarkers of bone health, likely because many people stopped taking TDF, which is known to cause bone loss.
Although the frequency of more severe adverse events was similar in the two arms (2% vs <1%), there were more mild to moderate events in the dolutegravir plus rilpivirine arm (17% vs 2%). Joseph Eron, MD, suggested at a CROI press conference that this may reflect the fact that people who switch drugs often blame common symptoms like a headache on new medications.
In today’s HIV treatment market, a majority of people can take regimens consisting of one pill once daily, so newly developed options must be equally convenient. ViiV Healthcare and Janssen have collaborated to co-formulate dolutegravir and rilpivirine into a small once-daily pill, and future trials will use this single-tablet regimen.
Liz Highleyman is a freelance medical writer and editor of HIVandHepatitis.com.