Modern antiretroviral treatment is safe and effective, but researchers continue the quest for regimens that are more tolerable and convenient.

 

Gilead Sciences is testing a new once-daily single-tablet regimen containing its HIV capsid inhibitor lenacapavir and the integrase inhibitor bictegravir, best known as a component of Biktarvy. The ARTISTRY-1 trial enrolled over 500 heavily treatment-experienced people on complex regimens containing up to 11 pills a day. Switching to the new combination pill was statistically noninferior to staying on a multi-tablet regimen. In ATRISTRY-2, the new combo worked as well as Biktarvy.

 

Merck is working on another once-daily combination pill containing the non-nucleoside reverse transcriptase inhibitor doravirine and islatravir, the first nucleoside reverse transcriptase translocation inhibitor. Islatravir hit a snag in 2021 when participants in earlier trials experienced declines in CD4 or total lymphocyte counts, but scientists determined that the doses were too high, so subsequent trials tested doravirine plus a lower dose of islatravir. Researchers previously reported that people who switched from Biktarvy or another daily oral regimen were equally likely to maintain viral suppression on the new combo pill. Merck recently announced that the doravirine/islatravir pill is also safe and effective for people starting HIV treatment for the first time.

 

Finally, Gilead and Merck are developing a once-weekly combo pill containing lenacapavir and islatravir. Phase II data presented at the European AIDS Conference showed that people who switched from daily Biktarvy to separate lenacapavir and islatravir pills maintained viral suppression at 96 weeks. The companies are now testing lenacapavir/islatravir in a combination pill that could become the longest-acting regimen that doesn’t require injections.

 

“Developing new effective, convenient regimens for those left behind by advances in medical research is necessary to close the unmet HIV treatment gap,” says ARTISTRY-1 investigator Chloe Orkin, MBBCh, of Queen Mary University of London.