Topical prophylaxis for HIV prevention in women: becoming a reality

Abstract

Strategies to protect against sexual transmission of HIV include the development of products formulated for topical application, which limit the toxicities associated with systemic oral pre-exposure prophylaxis. Following several clinical trial failures, attention is now focused on antiretroviral (ARV) agents. Highly potent ARV topical formulations provide a female-controlled, targeted, and feasible option for HIV prevention. A recently completed tenofovir gel trial was the first to demonstrate significant protection against HIV acquisition. Topical ARVs have the advantage of delivering high concentration of drug at the site of transmission of HIV, with low systemic absorption. Sustained-release formulations, such as intravaginal rings, will likely improve adherence and can be designed to provide controlled and continuous delivery of ARV combinations. Further studies to test alternative dosing strategies and pharmacokinetic/pharmacodynamic relationships in the genital tract will provide valuable information as the field strives to improve upon the promising tenofovir gel trial results.

Fig. 1

Antiretroviral (ARV) microbicides and mechanism of action within the female genital tract. ARVs inhibit HIV infection of target cells at various steps including viral attachment (1), fusion (2), and reverse transcription (3). CCR5, chemokine (C–C) motif receptor 5; mAbs, monoclonal antibodies; NNRTI, nonnucleoside reverse transcriptase inhibitor; NRTI, nucleotide reverse transcriptase inhibitor; RANTES, regulated upon activation, normal T-cell expressed and secreted