A combination of two once-daily oral antiretrovirals, cabotegravir and rilpivirine, maintained HIV suppression for 5.5 years after a six-month lead-in period, according to a presentation at the recent IDWeek 2019 conference in Washington, DC.
Dr David Margolis of ViiV Healthcare presented the latest findings from the phase 2b LATTE (Long-Acting Antiretroviral Treatment Enabling) trial, which evaluated the safety and efficacy of oral cabotegravir plus rilpivirine as a simple two-drug maintenance regimen for people who had achieved viral suppression using a standard three-drug combination.
Cabotegravir is a next-generation integrase inhibitor being developed by ViiV. Rilpivirine is an approved drug from the NNRTI drug class, marketed as Edurant and a component of the Eviplera or Complera, Juluca and Odefsey co-formulations.
Findings from this study set the stage for testing long-acting injectable formulations of cabotegravir and rilpivirine administered monthly or every other month. Researchers tested the oral versions first because the long-acting formulations cannot easily be removed from the body in case of adverse events. The US Food and Drug Administration is expected to make a decision soon about approval of the monthly injectable regimen.
The LATTE study enrolled 243 previously untreated people living with HIV. Almost all were men (in part because hormonal contraception was not allowed), about two-thirds were white, about 30% were black and the median age was approximately 33.
During a 24-week induction phase, participants were randomly assigned to one of three once-daily doses of oral cabotegravir (10, 30 or 60mg) plus a then-standard backbone of two NRTIs: about 60% used tenofovir disoproxil fumarate/emtricitabine (Truvada) while the rest used abacavir/lamivudine (Kivexa or Epzicom). If viral load was below 50 copies/ml at week 24, they replaced the two NRTIs with oral rilpivirine as a maintenance regimen. A control group received efavirenz (Sustiva) plus two NRTIs. Follow-up in the randomised part of the study continued through week 96.
At 96 weeks, participants assigned to take any dose of cabotegravir could opt to receive the selected 30mg oral dose plus rilpivirine in an open-label phase. Ultimately, those who maintained viral suppression for the full 312-week follow-up period were eligible to roll over into another study evaluating the long-acting injectable formulations.
In 2014, Dr Margolis presented 48-week findings showing that 82% of participants who switched to oral cabotegravir plus rilpivirine maintained an undetectable viral load, compared with 71% of those who used efavirenz. At 96 weeks, the corresponding response rates were 76% and 63%. Looking only at those who started maintenance therapy, 86% maintained viral suppression.
The latest results, through the end of the open-label phase, showed that 66% of participants taking cabotegravir plus rilpivirine maintained viral suppression at week 312. More of the original participants had dropped out by this point – a quarter had no available virological data – which largely explained the decline in the response rate. Eight people experienced protocol-defined virological treatment failure, most of whom had evidence of new mutations conferring resistance to integrase inhibitors, NNRTIs or both.
Treatment was generally safe and well tolerated. At week 312, just two of the 160 participants (1%) experienced serious drug-related adverse events and eight (5%) stopped treatment due to adverse events, most of which did not appear to be attributable to the drugs.
As follow-up in LATTE was continuing, researchers went on to evaluate the long-acting injectable formulations of cabotegravir and rilpivirine in new studies. As reported at this year's Conference on Retroviruses and Opportunistic Infections, the injectable regimen was shown to be highly effective in Phase III clinical trials, both for people starting treatment for the first time and for those switching from another regimen with an undetectable viral load.
Margolis D et al. Long term efficacy, safety and durability of CAB and RPV as two drug oral maintenance therapy – LATTE week 312 results. IDWeek, Washington, DC, abstract 2840, 2019.