Cabotegravir (long-acting dolutegravir analogue) is an HIV-1 integrase strand transfer inhibitor. According to a commentary, as a typical phase II study, "it is not powered for definitive conclusions about relative performance of experimental strategy and regimen, but the results are nonetheless radical and provocative in that they challenge the notion that:"
• dual therapy is not a realistic option compared with triple therapy.
• if dual therapy is an option, it must include a robust agent such as a boosted protease inhibitor.
• an induction–maintenance strategy won't be effective if it uses only two drugs
The commentators note this study will not go on to a phase 3 trial examining selected cabotegravir 30mg dose plus rilpivirine 25mg as oral combination therapy. The LATTE study was used to establish the proof of principle that this dual therapy combination is effective. As both drugs have long pharmacokinetic half-lives and are amenable to nanosuspension and intramuscular injection, the ongoing LATTE-2 trial is evaluating use of long-acting intramuscular cabotegravir 30mg plus rilpivirine 25mg as the first all injectable two-drug regimen. The two pharmaceutical companies have announced an agreement to coformulate these drugs into one tablet and a series of phase 3 studies to assess the clinical use of this oral two-drug alternative as a fixed-dose combination. The commentators suggest “the LATTE study might herald not only the beginning of a new era of longacting intramuscular injection as an option for long-term HIV management, but also the dawn of an effective and well tolerated two-drug N(t)RTI-sparing and protease-inhibitor-sparing single tablet regimen for long-term oral ART.”