Research in context
Evidence before this study
To establish the background for this study, we searched PubMed publications on the topics of antiretroviral therapy and treatment adherence; long-acting injectable therapies; and the safety, efficacy, and pharmacokinetics of cabotegravir (GSK1265744) and rilpivirine using the keywords “antiretroviral therapy”, “treatment adherence”, “long-acting injectable therapies”, “cabotegravir”, “GSK1265744”, “rilpivirine”, and “TMC-2782”. We also located package inserts and government documents using internet search engines. All searches were updated as of March 7, 2017. A review of this literature shows an ongoing challenge in HIV therapy wherein suboptimal adherence to daily oral medication can lead to treatment failure or the emergence of viral resistance. To date, no long-acting injectable regimen is available to patients with HIV. Cabotegravir is an integrase strand transfer inhibitor with clinically demonstrated activity against the HIV-1 virus and a physiochemistry and pharmacokinetic profile amenable to its formulation and use as a long-acting agent. Rilpivirine is a non-nucleoside reverse transcriptase inhibitor approved as an oral agent for the treatment of HIV-1 infection in combination with other antiretrovirals; its physiochemistry is also appropriate for formulation as a long-acting agent. We did a randomised, open-label, parallel group, phase 2b study (LATTE-2) in patients with HIV-1 viral suppression on oral medication to evaluate the efficacy, safety, and tolerability of cabotegravir plus rilpivirine given as long-acting injections every 4 or 8 weeks, compared with daily oral cabotegravir taken with abacavir and lamivudine.
Added value of this study
The LATTE-2 study is the first to investigate the efficacy and safety of a long-acting injectable antiretroviral therapy for the treatment of HIV-1 infection. An option to treat HIV-1 without the use of daily oral medications represents a paradigm shift in the HIV-1 treatment landscape. The principal finding of the study is that among patients who were suppressed on an oral cabotegravir-based therapy, switching to a long-acting combination of cabotegravir and rilpivirine maintained virological suppression in 90% of patients overall through week 96 following 4-week or 8-week injectable administration at rates comparable to remaining on daily oral cabotegravir-based therapy. The complete week 96 dataset included here provides important evidence for both the durability of virological response and acceptability of intramuscular injections for chronic use with dual antiretroviral therapy in patients infected with HIV-1.
Implications of all the available evidence
To date, the class of integrase strand transfer inhibitors has shown a high level of virological efficacy in clinical studies, which has translated to global widespread successful use. The ability to employ one of these agents, in partnership with one other agent, as an effective long-acting injectable agent has the potential to address the challenges of adherence to daily medication faced by people living with HIV. The daily psychological burden of being discovered as HIV positive can be eased by less frequent or clinic-based medication dosing and might be a preferred option for some patients. Following the advent and proliferation of single-tablet regimens, which themselves constituted a leap forward in dosing convenience, long-acting injectables such as the cabotegravir plus rilpivirine regimen might represent the next revolution in HIV therapy by providing an option that circumvents the burden of chronic daily dosing.