Reassessing the hypothesis on STI control for HIV prevention
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ABSTRACT: Southern Africa continues to shoulder a disproportionate burden of the HIV epidemic with the number of new infections outstripping treatment initiation two- to threefold. Current prevention strategies have had a limited impact on the trajectory of the epidemic so far. The history of HIV prevention research is dominated by failed approaches, but recent developments have provided reason for hope. These include the successful male circumcision outcomes in trials in South Africa, Kenya and Uganda, the recent protective outcome of a tenofovir vaginal gel trial in South Africa and the proof that pre-exposure prophylaxis with oral combination tenofovir/emtricitabine can work in men. The latter positive outcome has however been shattered by the early closure of FEM-PrEP for futility. The challenge now is on how to best integrate emerging prevention methods with established strategies, recognising that some of the older methods have never been scaled up to saturation level.Tropical Medicine & International Health 06/2011; 16(9):1120-30. DOI:10.1111/j.1365-3156.2011.02807.x · 2.30 Impact Factor
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ABSTRACT: There is a pressing need for microbicides—vaginally applied drug delivery systems that create a pharmacological barrier to HIV—to prevent the male-tofemale sexual transmission of HIV. Numerous antiretroviral agents with a wide range of mechanisms of inhibiting HIV are under development. Delivery systems are required that complement the antiviral agents through maximizing their safety, efficacy and user adherence within cost constraints such that they are affordable in resource poor nations with high HIV prevalence. To this end, three drug delivery systems were engineered for microbicide application in this thesis. The first delivery system was designed to promote uniform distribution and retention of the antivirals in the vaginal lumen, and provide semen triggered delivery into semen—the carrier of HIV in male-to-female sexual transmission. The delivery system consisted of a temperature and pH sensitive gel composed of a terpolymer of N-isopropylacrylamide, acrylic acid and butyl methacrylate. The neutralization of acidic pH in the vagina upon exposure to semen was used as the trigger to release the active agents from the terpolymer gel. The thermosensitive design employed was such that the delivery vehicle is applied as a liquid at room temperature to allow uniform coating, and gels postapplication to promote retention. In vitro characterizations under simulated physiological conditions confirmed that the designed system was liquid at room temperature, gels as the temperature is increased from room to body temperature, and provides burst release of active agents upon exposure to semen fluid simulant. The second and third systems were intravaginal rings (IVRs) for sustained delivery of dapivirine, a potent inhibitor of HIV replication after the virus has entered the host cells. A sustained delivery of replication inhibitors is pursued to allow enough time for antiviral drugs to diffuse into the vaginal epithelium and ensure that inhibitory concentrations are established before the viral attack. Monolithic IVRs were fabricated from biomedical grade polyurethanes and degradable polyurethanes synthesized with hydrolytically labile ester groups in the polymer backbone. The ability of the utilized polyurethane matrix to provide a zero-order delivery of dapivirine enabled a monolithic design that can be manufactured using a cost-effective melt extrusion procedure. The inexpensive IVR design loaded with a potent drug and with the high user adherence associated with IVRs offer a promising solution for an effective microbicide.
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ABSTRACT: For generalised HIV/AIDS sub-Saharan African epidemics emphasis has been placed on the three established pillars of HIV prevention: condom promotion and distribution, Voluntary Counselling and Testing (VCT) and treatment of other sexually transmitted infections (STIs). Experiences in several countries support the positive results of Ugandan prevention politics called Abstinence, Be faithful, Condom (ABC), based on Primary Behaviour Change (PBC). Polemics tending to label this approach as “confessional based” have been recently intensified after Pope Benedict XVI recalled how the sole use of condoms cannot be considered the solution for HIV/AIDS in Africa. An honest and scientific approach to the dramatic reality of HIV/AIDS in Africa may yet require a reconsideration of the Western positions towards HIV prevention, accepting the potential challenge of a multifaceted strategy that uses all valid approaches, with particular regard to PBC: the elusive goal of vaccine, the simplistic trust in condoms, or acritical enthusiasm in drugs (either as therapy, postexposure or preventive treatment), mathematical modelling. All these are pieces of a complex puzzle. Synergy between treatment and prevention needs to be implemented in a realistic way, never forgetting that behaviour change is a process, not an event, involving human freedom and will. The need of a really participating community, with a prevention coming from below to the top and not from external over-imposing criteria, is also mandatory. Per fronteggiare l’epidemia da HIV nell’Africa sub sahariana ci si è a lungo basati sui tre cosiddetti “pilastri della prevenzione”: la promozione e la distribuzione di profilattici, la consulenza e il test volontario e il trattamento delle infezioni a trasmissione sessuale. Esperienze in diversi paesi supportano i risultati positivi della politica di prevenzione ugandese denominata “ABC” (Abstinence, Be-faithful, Condom), basata sulla modifica dei comportamenti sessuali (Primary Behavioural Change, PBC). Alcune polemiche, tendenti ad etichettare questo approccio come “confessionale”, si sono recentemente intensificate dopo che Papa Benedetto XVI ha ricordato come l’esclusivo uso del condom non può essere considerato la soluzione per il problema HIVAIDS in Africa. In questo lavoro vengono brevemente esaminati i principali indirizzi attuali di prevenzione, mostrando l’importanza dell’impatto del cambiamento comportamentale e del condom, la possibilità di ampliare la terapia antiretrovirale a scopo di prevenzione oltre che di trattamento ed infine le controversie delle opzioni della profilassi pre-esposizione e post esposizione. Un approccio onesto e scientifico alla drammatica realtà della epidemia da HIV in Africa richiede di rivedere la posizione occidentale verso la prevenzione, accettando la sfida di una strategia multiforme che utilizzi tutti i validi approcci, con particolare riguardo alla modifica dei comportamenti. L’attuale elusività di un efficace vaccino, la semplicistica fiducia nel preservativo o l’acritico entusiasmo nei farmaci, i modelli matematici: tutti questi sono solo singoli pezzi di un complesso puzzle. La sinergia tra trattamento e prevenzione deve essere attuata in modo realistico, non dimenticando mai che il cambiamento del comportamento è un processo dinamico, non un evento istantaneo, che coinvolge la libertà e la volontà umana. La necessità di una comunità veramente coinvolta, per una prevenzione che parte da un convincimento di base e non per la spinta di pressioni esterne, risulta di fondamentale importanza.08/2009; 7(2):70-76. DOI:10.1007/s12682-009-0019-9