With oral antiretroviral therapy, HIV has become a manageable chronic illness. However, UNAIDS targets for virologic suppression have not yet been attained in many low-income and middle-income countries (LMICs). Long-acting drug formulations hold promise to improve treatment outcomes. In this rapidly evolving area of research, we aim to review recent literature on the treatment of HIV with long-acting agents and identify implementation considerations for LMICs.

Randomized controlled trials have shown that monthly long-acting injectable cabotegravir (CAB) and rilpivirine (RPV) is noninferior to oral ART, and 2-monthly CAB/RPV is noninferior to monthly injections. However, few people from LMICs were included. A modelling study predicts that in sub-Saharan Africa, injectable CAB/RPV is best targeted to those with poor adherence (HIV viral load >1000 copies/ml) in whom cost-effectiveness is greatest and risk of contributing to further resistance is no greater than continuation of oral ART. Other promising agents, such as lenacapavir are under investigation and may prove particularly useful in heavily treatment-experienced adults.

Long-acting regimens are a promising advance in HIV treatment. By extending the dosing interval, increasing convenience and being discreet these regimens may reduce HIV treatment challenges. However, there are multiple implementation considerations in LMICs including the need for exclusion of hepatitis B, cold chain, oral bridging in case of missed dosing and switching during tuberculosis therapy. Efficacy and safety data are also awaited for settings without routine access to baseline resistance testing or regular viral load monitoring and for special populations, such as pregnancy, children and the elderly.