Evolving uses of oral reverse transcriptase inhibitors in the HIV-1 epidemic: from treatment to prevention
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REVIEW
Open Access
Evolving uses of oral reverse transcriptase inhibitors in the HIV-1 epidemic: from treatment to prevention Ravindra K Gupta1*, David A M C Van de Vijver2, Sheetal Manicklal3 and Mark A Wainberg4 Abstract The HIV epidemic continues unabated, with no highly effective vaccine and no cure. Each new infection has significant economic, social and human costs and prevention efforts are now as great a priority as global antiretroviral therapy (ART) scale up. Reverse transcriptase inhibitors, the first licensed class of ART, have been at the forefront of treatment and prevention of mother to child transmission over the past two decades. Now, their use in adult prevention is being extensively investigated. We describe two approaches: treatment as prevention (TasP) the use of combination ART (2NRTI and 1NNRTI) following HIV diagnosis to limit transmission and pre-exposure prophylaxis (PrEP) –the use of single or dual oral agents prior to sexual exposure. Prevention of mother-to-child transmission using NRTI has been highly successful, though does not involve sustained use of NRTI to limit transmission. Despite theoretical and preliminary support for TasP and PrEP, data thus far indicate that adherence, retention in care and late diagnosis are the major barriers to their successful, sustained implementation. Future advances in drug technologies will be needed to overcome the issue of drug adherence, through development of drugs that involve both less frequent dosing as well as reduced toxicity, possibly through specific targeting of infected cells.
Review Introduction
The HIV epidemic has been devastating in its magnitude and devastation [1], despite the availability of effective antiretroviral therapy (ART). There are a number of reasons for this, including lack of access to ART for the majority of infected individuals until relatively recently [2] and low rates of uptake of HIV testing [3]. The global scale up of ART has gathered considerable momentum with an estimated 8 million individuals currently treated, and corresponding reductions in morbidity and mortality have been documented [4,5]. By contrast, in the absence of an effective vaccine and/ or cure, transmission has continued largely unabated over the last two decades, particularly in sub Saharan Africa, where 67% [6] of all HIV infections are to be found. Male circumcision has demonstrated around 50% protection in limiting transmission [7], although logistical and ethical * Correspondence: [email protected] 1 Division of Infection and Immunity, University College, 90 Gower St, London WC1E 6BT, UK Full list of author information is available at the end of the article
barriers may limit its public health impact. Topical microbicides have shown some promise, with vaginal microbicide gel containing tenofovir (TFV) conferring 39% protection in one study [8]. CAPRISA used tenofovir only (as TFV and not as TDF). Clearly, more effective prevention tools are needed. Prevention of mother to child transmission has proved highly effective when implemented
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