Antiretrovirals to prevent HIV infection: Pre-and postexposure prophylaxis

Division of Infectious Disease, University of North Carolina at Chapel Hill, 130 Mason Farm Road, CB #7030, Chapel Hill, NC 27599, USA.
Current Infectious Disease Reports (Impact Factor: 1.68). 08/2008; 10(4):323-31. DOI: 10.1007/s11908-008-0052-5
Source: PubMed


More than 3 million people are now receiving antiretroviral therapy (ART) worldwide. Currently, the indications for ART depend primarily on CD4 count, blood viral burden, and clinical signs and symptoms suggesting advanced HIV disease. However, interest is increasing in ART's preventive potential. Postexposure prophylaxis following both occupational and nonoccupational exposure to HIV is the standard-of-care in many settings. Observational and ecologic studies suggest that ART administered to HIV-infected people reduces transmission within serodiscordant couples. Pre-exposure prophylaxis to prevent HIV infection is a potentially safe and intermittent intervention for very high-risk people, and clinical trials to evaluate this preventive strategy are underway. The prevention benefits of ART may begin to affect the decision of when to start therapy and add a much-needed strategy to current HIV prevention efforts.

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    • "HIV viral load is the key determinant of viral transmission, as demonstrated clearly in observational studies of sexual transmission among HIV-discordant couples; in those studies, no transmission was seen when the index case had a plasma viral load below 1,000 copies HIV ribonucleic acid (RNA)/mL [25,26]. By reducing plasma viral load to undetectable levels (<50 copies HIV RNA/mL), it is assumed that ART will also suppress viral burden in the genital tract to levels at which transmission is unlikely to occur [27,28], although genital shedding of HIV can sometimes occur even when plasma viraemia is suppressed [29]. While vertical HIV transmission occurs via a different route, proof of concept is provided by trials of PMTCT, which have demonstrated that HIV transmission from mother to child before, during, or after delivery is largely prevented by ART [10-12]. "
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    ABSTRACT: Effective interventions to reduce HIV incidence in sub-Saharan Africa are urgently needed. Mathematical modelling and the HIV Prevention Trials Network (HPTN) 052 trial results suggest that universal HIV testing combined with immediate antiretroviral treatment (ART) should substantially reduce incidence and may eliminate HIV as a public health problem. We describe the rationale and design of a trial to evaluate this hypothesis. A rigorously-designed trial of universal testing and treatment (UTT) interventions is needed because: i) it is unknown whether these interventions can be delivered to scale with adequate uptake; ii) there are many uncertainties in the models such that the population-level impact of these interventions is unknown; and ii) there are potential adverse effects including sexual risk disinhibition, HIV-related stigma, over-burdening of health systems, poor adherence, toxicity, and drug resistance.In the HPTN 071 (PopART) trial, 21 communities in Zambia and South Africa (total population 1.2 m) will be randomly allocated to three arms. Arm A will receive the full PopART combination HIV prevention package including annual home-based HIV testing, promotion of medical male circumcision for HIV-negative men, and offer of immediate ART for those testing HIV-positive; Arm B will receive the full package except that ART initiation will follow current national guidelines; Arm C will receive standard of care. A Population Cohort of 2,500 adults will be randomly selected in each community and followed for 3 years to measure the primary outcome of HIV incidence. Based on model projections, the trial will be well-powered to detect predicted effects on HIV incidence and secondary outcomes. Trial results, combined with modelling and cost data, will provide short-term and long-term estimates of cost-effectiveness of UTT interventions. Importantly, the three-arm design will enable assessment of how much could be achieved by optimal delivery of current policies and the costs and benefits of extending this to UTT.Trial registration: NCT01900977.
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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.
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