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Controlled Antiretroviral Drug Release Systems for Systemic HIV Pre-exposure Prophylaxis


Background: The HIV/AIDS pandemic remains among our greatest public health challenges. More than a quarter century after the description of the first cases of AIDS, HIV has spread to virtually every country in the world infecting 65 million people and killing 25 million. The ongoing high incidence of HIV infection and the incomplete coverage with basic HIV prevention tools underscore the need for new, highly effective biomedical HIV interventions to complement existing prevention strategies. In the absence of a vaccine, the administration of antiretroviral (ARVs) drugs before HIV exposure (pre-exposure prophylaxis or PrEP) has gained considerable attention as a strategy to protect high-risk HIV-negative people from becoming infected. PrEP is a proven concept for other infectious diseases such as malaria, and multiple lines of evidence suggest that it might also be a feasible strategy to prevent HIV infection. ARVs drugs effectively prevent HIV transmission at birth, during breastfeeding, and after occupational exposure, and as topical gels can prevent vaginal transmission. Several clinical trials with daily oral PrEP are now ongoing in high-risk populations. A reasonable next step would be to evaluate more practical, less costly drug delivery systems for humans.?

Public Health Impact: Mathematical models estimate that over the next 10 years an effective PrEP program with daily ARVs could prevent 2.7 to 3.2 million of the 11 million new HIV-1 infections projected to occur in sub-Saharan Africa. Model simulations have also shown that an effective PrEP program could substantially reduce the incidence of HIV transmission in populations at high risk of infection in the United States. This potentially significant public health benefit of PrEP requires a very high efficacy of the drugs and a high degree of adherence to the PrEP regimen. However, prophylactically giving people daily ARVs drugs may be costly and impractical, even if confined to a high-risk population. Thus, special emphasis should be made on evaluating long-acting drug delivery systems including injectable biopolymers that entrap and slowly release ARVs systemically over prolonged (weeks-months) periods of time. If effective, these systems could substantially decrease the frequency of ARV dosing, improve adherence, and minimize costs. PrEP with long-acting drug formulations may also provide an attractive prevention strategy against postnatal HIV acquisition in breast-fed babies.?

Examples of specific research areas of interest include, but are not limited to: ? The development of novel long-acting drug delivery systems for systemic PrEP including injectable bio polimers that entrap and slowly release ARVs. Designs should include systems for controlled release of attractive drug candidates for PrEP including HIV reverse transcriptase, entry, and integrase inhibitors. Initial studies may incorporate drug pharmacokinetic and efficacy studies in non-human primates. Experimental design may include ways to measure drug levels in blood and tissues and explore correlates of protection. Studies should be designed with the long-term goal of providing information that will guide human clinical trials.

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