At the 2017 Conference on Retroviruses and Opportunistic Infections (CROI), results from the LATTE study showed that the 2-drug regimen of the integrase inhibitor cabotegravir (CAB) + the NNRTI rilpirivine (RPV, Edurant) suppressed HIV levels as well as a 3-drug efavirenz (Sustiva) regimen through 144 weeks. The first 96 weeks were partially blinded to establish a proper CAB dose, with the additional weeks of data coming from open-label CAB at the selected dose of 30mg per day. Both CAB and RPV are also candidates for long-acting injected drugs, and the results of LATTE are helping to inform the development of the long-acting products, which will be dosed either every one or two months.
As people with HIV live longer, there’s a desire to reduce pill burden and to find easier-to-take, effective regimens. Maintenance regimens have a place in HIV treatment once stable HIV suppression has been established. In another presentation at CROI, the oral combination of dolutegravir (Tivicay) + rilpivirine is also being explored as a maintenance regimen.
LATTE is a Phase II study where roughly 60 people who were new to treatment were randomized to receive either efavirenz + a backbone of 2 NRTIs or one of three different doses of CAB (10mg, 30mg, or 60mg) + 2 NRTIs. At 24 weeks, those on CAB with viral loads <50 copies then switched their 2 NRTIs for RPV, thereby reducing their dosing to two drugs. At week 96, the efavirenz group stopped the study while the three CAB groups were allowed to go onto an open-label phase with the 30mg CAB dose + RPV.
Of the 243 people who were enrolled at the beginning, 96% were male, 38% were non-white and 14% had viral loads >100,000. A total of 138 continued into the open-label phase of weeks 96 to 144.
Among those who started the maintenance regimen of CAB + RPV at week 24, 76% remained suppressed <50 copies HIV RNA at week 144 This analysis included all who continued in the open-label 30mg part of the study, no matter the dose they originally took. Roughly 8% had not reached an undetectable level. Viral failures and drug resistance did occur, with mutations to CAB and RPV in some, but most were found in those on the 10mg maintenance dose between weeks 24 and 96.
Serious side effects were reported in 9% of people on CAB + RPV, affecting a third of them to stop the study. Mild to serious lab changes occurred in 17%, with serious changes in creatine kinase (8%), ALT (1%), lipase (4%) and total neutrophils (3%).
CAB + RPV as maintenance therapy will move into further study with an injected maintenance regimen of both drugs.
DA Margolis, et al. Long-Term Safety and Efficacy of CAB and RPV as 2-Drug Oral Maintenance Therapy. 2017 CROI, Seattle. Abstract 442.