Highly active antiretroviral treatment as prevention of HIV transmission: Review of scientific evidence and update

Antiretroviral Treatment and HIV Care Unit, Department of HIV/AIDS, World Health Organization, Geneva, Switzerland.
Current opinion in HIV and AIDS (Impact Factor: 4.68). 07/2010; 5(4):298-304. DOI: 10.1097/COH.0b013e32833a6c32
Source: PubMed


An estimated 33 million people are living with HIV and universal access remains a dream for millions of people. By the end of year 2008, four million people were on treatment; however, over five million needed treatment, and in 2007, there were 2.7 million new infections. Without significant improvement in prevention, we are unlikely to meet universal access targets including the growing demand for highly active antiretroviral treatment (HAART). This review examines HAART as a potential tool for preventing HIV transmission.
We discuss recent scientific evidence regarding the treatment and prevention gap, importance viral load and HIV transmission, HAART and HIV transmission, when to start, HIV counseling and testing, modeling results and next steps.
HAART has considerable treatment and prevention benefits and it needs to be considered as a key element of combination prevention. To explore HAART as an effective prevention strategy, we recommend further evaluation of human rights and ethical considerations, clarification of research priorities and exploration of feasibility and acceptability issues.

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    • "There is increasing recognition that a combination of prevention methods will be needed to bring HIV transmission under effective control in the most severely affected countries, and combination prevention programmes are being developed to meet this need [2,3]. These may involve the provision of proven prevention methods, such as male circumcision [4-7] and prevention of mother-to-child transmission (PMTCT) [8-12], a range of behavioural and biomedical interventions specially targeted at those most at risk of infection, and expanded testing and treatment for individuals found to be HIV-infected [13,14]. The potential role of earlier treatment as a preventive measure has been emphasised by an individually randomised trial showing that early treatment of HIV-infected individuals reduced transmission to their sexual partners by 96% [15]. "
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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.
    Trials 02/2014; 15(1):57. DOI:10.1186/1745-6215-15-57 · 1.73 Impact Factor
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    • "The advent of highly-active anti-retroviral therapy (HAART) based on protease inhibitors has greatly improved the treatment of HIV so that it is now a manageable disease [3]. Recent observations point to a decreasing incidence of some cancers in patients on protease inhibitors [4], with our previous work demonstrating inhibition of cell growth and induction of apoptosis in ovarian cancer [5]. "
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    ABSTRACT: Recent observations suggest a lower incidence of malignancies in patients infected with HIV during treatment with Highly Active Anti-Retroviral Therapy (HAART) utilizing protease inhibitors. We investigated the effects of ritonavir, a FDA approved HIV protease inhibitor, on proliferation of pancreatic ductal adeno-carcinoma (PDAC) cell lines. Human PDAC cell lines BxPC-3, MIA PaCa-2, and PANC-1 were propagated under standard conditions and treated with serial dilutions of ritonavir. Ritonavir inhibited cell growth in a dose-dependent manner as well as activated the intrinsic apoptotic pathway in human pancreatic ductal adenocarcinoma (PDAC) cell lines. We observed down-modulation of cell-cycle promoting and up-regulation of cell-cycle inhibitory genes; enhanced interaction of retinoblastoma protein (RB) with E2F-1 transcription factor; inhibition of phosphorylation of RB, resulting in sequestration of E2F-1 and subsequent down-regulation of S phase genes; decreased interaction of E2F-1 with its consensus binding sites; inhibition of cell motility and invasiveness; and inhibition of the AKT pathway. Our results demonstrate a potential use of ritonavir as part of combination chemotherapy for PDAC. Since ritonavir is FDA approved for HIV, drug repositioning for PDAC would limit the costs and reduce risks.
    Pharmaceuticals 01/2014; 7(1):46-57. DOI:10.3390/ph7010046
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    • "It was estimated that 34 million people worldwide were living with HIV/AIDS as of 2011, more than 1 million of whom were living in the United States [1]. While advancements made in highly active antiretroviral therapy (HAART) have dramatically increased survival time and quality of life for those infected with HIV, long term treatment is problematic for several reasons [2]. Among them are the necessity of life-long adherence to medication regimens, the potential for cumulative side-effects, emergence of drug-resistant mutants, and the unbearable cost for the majority of the world’s HIV-infected individuals [3,4]. "
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    ABSTRACT: Despite highly effective anti-retroviral therapy, HIV is thought to persist in patients within long-lived cellular reservoirs in the form of a transcriptionally inactive (latent) integrated provirus. Lentiviral latency has therefore come to the forefront of the discussion on the possibility of a cure for HIV infection in humans. Animal models of lentiviral latency provide an essential tool to study mechanisms of latency and therapeutic manipulation. Of the three animal models that have been described, the feline immunodeficiency virus (FIV)-infected cat is the most recent and least characterized. However, several aspects of this model make it attractive for latency research, and it may be complementary to other model systems. This article reviews what is known about FIV latency and chronic FIV infection and how it compares with that of other lentiviruses. It thereby offers a framework for the usefulness of this model in future research aimed at lentiviral eradication.
    Retrovirology 07/2013; 10(1):69. DOI:10.1186/1742-4690-10-69 · 4.19 Impact Factor
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