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.
Highlights
The HIV epidemic has been devastating in its magnitude and devastation [1], despite the availability of effective antiretroviral therapy (ART)
The potential for treatment as prevention (TasP) to curb the epidemic is being explored following a report showing that transmission amongst discordant couples was reduced by 96% when the HIV infected partner initiated immediate antiretroviral therapy as compared to delaying treatment until a CD4
A recent study from South Africa has shown a reduction in new HIV infections in a high incidence area following ART scale up with two nucleoside reverse transcriptase inhibitors (NRTI) and one non-nucleoside reverse transcriptase inhibitor (NNRTI) [10]
Summary
The HIV epidemic has been devastating in its magnitude and devastation [1], despite the availability of effective antiretroviral therapy (ART). Combination ART (together with elective Caesarian section and absence of breastfeeding) proved to be highly efficacious in industrialised settings [108,109], cost and feasibility concerns coupled with lack of safety data from developing countries (risk of drug toxicity in mother, adverse pregnancy outcomes, and treatment interruption) limited the wider use of triple ARV prophylaxis. In RLS the disastrous impact of unsafe replacement feeding on child survival on the one hand [124] and breast milk transmission on the other have threatened the global success of pre- and perinatal prophylaxis regimens Emerging data from these settings provide compelling evidence that covering a recommended six month exclusive breastfeeding period either with maternal combination antiretroviral therapy or, where access to HAART is limited, extended daily infant nevirapine for 14 weeks or 6 months comparably suppresses HIV transmission rates to 1-5% at 6-12 months [130]. In a South African study, pregnant women were substantially more likely to be lost to follow-up than non-pregnant women for both pre-ART care and while on ART [136,137], and adherence is a concern with the potential development of drug resistance for both mother and infant [131,132]
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