Research in context
Evidence before this study
We searched PubMed, with combinations of the search terms “integrase strand transfer inhibitor” (INI), “integrase inhibitor”, “non-nucleoside reverse transcriptase inhibitor”, “raltegravir”, “dolutegravir”, “elvitegravir”, “rilpivirine”, “two drug HIV therapy”, “long acting”, and “HIV pre-exposure prophylaxis”, with no restrictions on language or publication date. Several small retrospective and uncontrolled studies using INIs plus non-nucleoside reverse transcriptase inhibitors (NNRTIs) as dual HIV-1 therapy have been reported. Results from these studies suggested long-term viral suppression from well tolerated regimens, which warranted further investigation and confirmation in larger randomised controlled studies. Longacting parenteral versions of cabotegravir and rilpivirine are being developed with promising preclinical and clinical pharmacology profiles.
Added value of this study
LATTE 24-week induction results confirm rapid and robust viral suppression with cabotegravir plus dual nucleoside reverse transcriptase inhibitors (NRTIs), a profile that has been well established for other drugs within the INI class. The two-drug maintenance regimen of cabotegravir plus rilpivirine showed viral suppression for an additional 72 weeks similar to the three-drug regimen of efavirenz plus dual NRTIs with similar safety and tolerability and an impressive resistance profile. Results from the LATTE study confirm, for the first time within a randomised controlled trial, the safety and durability of a two-drug INI plus NNRTI regimen after induction therapy in an antiretroviral-naive adult population.
Implication of all the available evidence
Current three-drug combination antiretroviral therapy regimens might result in treatment modification or interruption because of side-effects, toxicities, or complicated administration profiles. New HIV-1 antiretroviral agents need to be developed with a focus on improved safety, efficacy, and resistance profiles, and more convenient administration to enable patient adherence. In view of the potential for long-term side-effects of dual NRTIs and pharmacologically boosted protease-inhibitor regimens, a well tolerated, simplified two-drug therapy that offers sustained viral suppression while avoiding these classes might be particularly desirable within the ageing population with HIV infection and in patients with comorbidities, including renal and cardiovascular disease. Results from LATTE are fundamental for further assessment of parenteral formulations of cabotegravir and rilpivirine towards the increase in treatment options for patients and health-care providers.