High Coverage of ART Associated with Decline in Risk of HIV Acquisition in Rural KwaZulu-Natal, South Africa
22 Feb 2013-Science (American Association for the Advancement of Science)-Vol. 339, Iss: 6122, pp 966-971
TL;DR: This work used data from one of Africa's largest population-based prospective cohort studies (in rural KwaZulu-Natal, South Africa) to follow up a total of 16,667 individuals who were HIV-uninfected at baseline, observing individual HIV seroconversions over the period 2004 to 2011.
Abstract: The landmark HIV Prevention Trials Network (HPTN) 052 trial in HIV-discordant couples demonstrated unequivocally that treatment with antiretroviral therapy (ART) substantially lowers the probability of HIV transmission to the HIV-uninfected partner. However, it has been vigorously debated whether substantial population-level reductions in the rate of new HIV infections could be achieved in "real-world" sub-Saharan African settings where stable, cohabiting couples are often not the norm and where considerable operational challenges exist to the successful and sustainable delivery of treatment and care to large numbers of patients. We used data from one of Africa's largest population-based prospective cohort studies (in rural KwaZulu-Natal, South Africa) to follow up a total of 16,667 individuals who were HIV-uninfected at baseline, observing individual HIV seroconversions over the period 2004 to 2011. Holding other key HIV risk factors constant, individual HIV acquisition risk declined significantly with increasing ART coverage in the surrounding local community. For example, an HIV-uninfected individual living in a community with high ART coverage (30 to 40% of all HIV-infected individuals on ART) was 38% less likely to acquire HIV than someone living in a community where ART coverage was low (<10% of all HIV-infected individuals on ART).
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University of Washington1, South African Medical Research Council2, Fred Hutchinson Cancer Research Center3, FHI 3604, University of Zimbabwe5, Centre for the AIDS Programme of Research in South Africa6, Makerere University7, RTI International8, University of Pittsburgh9, Johns Hopkins University10, National Institutes of Health11, Université de Montréal12, Eastern Virginia Medical School13
TL;DR: None of the drug regimens evaluated reduced the rates of HIV-1 acquisition in an intention-to-treat analysis, and adherence to study drugs was low.
Abstract: BackgroundReproductive-age women need effective interventions to prevent the acquisition of human immunodeficiency virus type 1 (HIV-1) infection. MethodsWe conducted a randomized, placebo-controlled trial to assess daily treatment with oral tenofovir disoproxil fumarate (TDF), oral tenofovir–emtricitabine (TDF-FTC), or 1% tenofovir (TFV) vaginal gel as preexposure prophylaxis against HIV-1 infection in women in South Africa, Uganda, and Zimbabwe. HIV-1 testing was performed monthly, and plasma TFV levels were assessed quarterly. ResultsOf 12,320 women who were screened, 5029 were enrolled in the study. The rate of retention in the study was 91% during 5509 person-years of follow-up. A total of 312 HIV-1 infections occurred; the incidence of HIV-1 infection was 5.7 per 100 person-years. In the modified intention-to-treat analysis, the effectiveness was −49.0% with TDF (hazard ratio for infection, 1.49; 95% confidence interval [CI], 0.97 to 2.29), −4.4% with TDF-FTC (hazard ratio, 1.04; 95% CI, 0.73 to 1.4...
1,089 citations
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01 Jan 2014
854 citations
TL;DR: The role of immune activation in the pathogenesis of non-AIDS clinical events (major causes of morbidity and mortality in people on antiretroviral therapy) is receiving increased recognition and breakthroughs in the prevention of HIV important to public health include male medical circumcision.
687 citations
Haidong Wang1, Chelsea A. Liddell1, Matthew M Coates1, Meghan D. Mooney1 +228 more•Institutions (123)
TL;DR: Decreases since 2000 in under-5 mortality rates are accelerating in many developing countries, especially in sub-Saharan Africa, and rising income per person and maternal education and changes in secular trends led to 4·2 million fewer deaths.
684 citations
TL;DR: The epidemiology of HIV infection in sub-Saharan Africa, key drivers of the continued high incidence, mortality rates and priorities for altering current epidemic trajectory in the region are reviewed.
Abstract: Global trends in HIV infection demonstrate an overall increase in HIV prevalence and substantial declines in AIDS related deaths largely attributable to the survival benefits of antiretroviral treatment. Sub-Saharan Africa carries a disproportionate burden of HIV, accounting for more than 70% of the global burden of infection. Success in HIV prevention in sub-Saharan Africa has the potential to impact on the global burden of HIV. Notwithstanding substantial progress in scaling up antiretroviral therapy (ART), sub-Saharan Africa accounted for 74% of the 1.5 million AIDS related deaths in 2013. Of the estimated 6000 new infections that occur globally each day, two out of three are in sub-Saharan Africa with young women continuing to bear a disproportionate burden. Adolescent girls and young women aged 15-24 years have up to eight fold higher rates of HIV infection compared to their male peers. There remains a gap in women initiated HIV prevention technologies especially for women who are unable to negotiate the current HIV prevention options of abstinence, behavior change, condoms and medical male circumcision or early treatment initiation in their relationships. The possibility of an AIDS free generation cannot be realized unless we are able to prevent HIV infection in young women. This review will focus on the epidemiology of HIV infection in sub-Saharan Africa, key drivers of the continued high incidence, mortality rates and priorities for altering current epidemic trajectory in the region. Strategies for optimizing the use of existing and increasingly limited resources are included.
608 citations
References
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University of North Carolina at Chapel Hill1, Fred Hutchinson Cancer Research Center2, FHI 3603, University of Zimbabwe4, Johns Hopkins University5, Oswaldo Cruz Foundation6, Chiang Mai University7, Fenway Health8, Harvard University9, Kenya Medical Research Institute10, University of the Witwatersrand11, University of California, San Francisco12, University of Nebraska Medical Center13, National Institutes of Health14, University of California, Los Angeles15, University of Washington16
TL;DR: In this article, Antiretroviral therapy that reduces viral replication could limit the transmission of human immunodeficiency virus type 1 (HIV-1) in serodiscordant couples.
Abstract: Background Antiretroviral therapy that reduces viral replication could limit the transmission of human immunodeficiency virus type 1 (HIV-1) in serodiscordant couples. Methods In nine countries, we...
5,871 citations
TL;DR: A theoretical strategy of universal voluntary HIV testing and immediate treatment with ART, combined with present prevention approaches, could have a major effect on severe generalised HIV/AIDS epidemics.
1,948 citations
TL;DR: The reductionist approach reveals the importance of human Self peptides and their utility in enhancing drug delivery and imaging.
Abstract: Foreign particles and cells are cleared from the body by phagocytes that must also recognize and avoid clearance of "self" cells. The membrane protein CD47 is reportedly a "marker of self" in mice that impedes phagocytosis of self by signaling through the phagocyte receptor CD172a. Minimal "Self" peptides were computationally designed from human CD47 and then synthesized and attached to virus-size particles for intravenous injection into mice that express a CD172a variant compatible with hCD47. Self peptides delay macrophage-mediated clearance of nanoparticles, which promotes persistent circulation that enhances dye and drug delivery to tumors. Self-peptide affinity for CD172a is near the optimum measured for human CD172a variants, and Self peptide also potently inhibits nanoparticle uptake mediated by the contractile cytoskeleton. The reductionist approach reveals the importance of human Self peptides and their utility in enhancing drug delivery and imaging.
842 citations
TL;DR: Because CVL is temporally upstream of new HIV infections, jurisdictions should consider adding CVL to routine HIV surveillance to track the epidemic, allocate resources, and to evaluate the effectiveness of HIV prevention and treatment efforts.
Abstract: Background
At the individual level, higher HIV viral load predicts sexual transmission risk. We evaluated San Francisco's community viral load (CVL) as a population level marker of HIV transmission risk. We hypothesized that the decrease in CVL in San Francisco from 2004–2008, corresponding with increased rates of HIV testing, antiretroviral therapy (ART) coverage and effectiveness, and population-level virologic suppression, would be associated with a reduction in new HIV infections.
769 citations
TL;DR: A population-level association between increasing HAART coverage, decreased viral load, and decreased number of new HIV diagnoses per year is shown, which supports the proposed secondary benefit of HAART used within existing medical guidelines to reduce HIV transmission.
759 citations