HIV Treatment as Prevention: Models, Data, and Questions - Towards Evidence-Based Decision-Making

doi:10.1371/JOURNAL.PMED.1001259

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HIV Treatment as Prevention: Models, Data, and Questions - Towards Evidence-Based Decision-Making

Journal Article•DOI•

HIV Treatment as Prevention: Models, Data, and Questions - Towards Evidence-Based Decision-Making

Peter Vickerman¹•Institutions (1)

University of Bristol¹

01 Jul 2012-PLOS Medicine (Public Library of Science)-Vol. 9, Iss: 7

TL;DR: It is hoped that this article will provide a foundation upon which greater collaborations between disciplines will be formed, and will afford deeper insights into the key factors involved, to help strengthen the support for evidence-based decision-making in HIV prevention.

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Abstract: Antiretroviral therapy (ART) for those infected with HIV can prevent onward transmission of infection, but biological efficacy alone is not enough to guide policy decisions about the role of ART in reducing HIV incidence. Epidemiology, economics, demography, statistics, biology, and mathematical modelling will be central in framing key decisions in the optimal use of ART. PLoS Medicine, with the HIV Modelling Consortium, has commissioned a set of articles that examine different aspects of HIV treatment as prevention with a forward-looking research agenda. Interlocking themes across these articles are discussed in this introduction. We hope that this article, and others in the collection, will provide a foundation upon which greater collaborations between disciplines will be formed, and will afford deeper insights into the key factors involved, to help strengthen the support for evidence-based decision-making in HIV prevention.

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Journal Article•DOI•

Modeling infectious disease dynamics in the complex landscape of global health.

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Hans Heesterbeek¹, Roy M. Anderson², Viggo Andreasen³, Shweta Bansal⁴, Daniela De Angelis, Christopher Dye, Ken T. D. Eames⁵, W. John Edmunds⁵, Simon D. W. Frost⁶, Sebastian Funk⁴, T. Déirdre Hollingsworth⁷, T. Déirdre Hollingsworth⁸, Thomas House⁷, Valerie Isham⁹, Petra Klepac⁶, Justin Lessler¹⁰, James O. Lloyd-Smith¹¹, C. Jessica E. Metcalf¹², Denis Mollison¹³, Lorenzo Pellis⁷, Juliet R. C. Pulliam¹⁴, Juliet R. C. Pulliam¹⁵, Mick G. Roberts¹⁶, Cécile Viboud¹⁵ - Show less +20 more•Institutions (16)

Utrecht University¹, Imperial College London², Roskilde University³, Georgetown University⁴, University of London⁵, University of Cambridge⁶, University of Warwick⁷, University of Liverpool⁸, University College London⁹, Johns Hopkins University¹⁰, University of California, Los Angeles¹¹, University of Oxford¹², Heriot-Watt University¹³, University of Florida¹⁴, John E. Fogarty International Center¹⁵, Massey University¹⁶

13 Mar 2015-Science

TL;DR: The development of mathematical models used in epidemiology are reviewed and how these can be harnessed to develop successful control strategies and inform public health policy, using the West African Ebola epidemic as an example.

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Abstract: Despite some notable successes in the control of infectious diseases, transmissible pathogens still pose an enormous threat to human and animal health. The ecological and evolutionary dynamics of infections play out on a wide range of interconnected temporal, organizational, and spatial scales, which span hours to months, cells to ecosystems, and local to global spread. Moreover, some pathogens are directly transmitted between individuals of a single species, whereas others circulate among multiple hosts, need arthropod vectors, or can survive in environmental reservoirs. Many factors, including increasing antimicrobial resistance, increased human connectivity and changeable human behavior, elevate prevention and control from matters of national policy to international challenge. In the face of this complexity, mathematical models offer valuable tools for synthesizing information to understand epidemiological patterns, and for developing quantitative evidence for decision-making in global health.

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514 citations

Journal Article•DOI•

HIV treatment as prevention: Systematic comparison of mathematical models of the potential impact of antiretroviral therapy on HIV incidence in South Africa

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Jeffrey W. Eaton¹, Leigh F. Johnson², Joshua A. Salomon³, Till Bärnighausen³, Till Bärnighausen⁴, Eran Bendavid⁵, Anna Bershteyn, David E. Bloom³, Valentina Cambiano⁶, Christophe Fraser¹, Jan A. C. Hontelez⁴, Salal Humair⁷, Salal Humair³, Daniel J. Klein, Elisa F Long⁸, Andrew N. Phillips⁶, Carel Pretorius, John Stover, Edward Allen Wenger, Brian G. Williams⁹, Timothy B. Hallett¹ - Show less +17 more•Institutions (9)

Imperial College London¹, University of Cape Town², Harvard University³, University of KwaZulu-Natal⁴, Stanford University⁵, University College London⁶, Lahore University of Management Sciences⁷, Yale University⁸, Stellenbosch University⁹

10 Jul 2012-PLOS Medicine

TL;DR: In this article, the authors compared the predictions of several mathematical models simulating the same ART intervention programmes to determine the extent to which models agree about the epidemiological impact of expanded ART.

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Abstract: Background: Many mathematical models have investigated the impact of expanding access to antiretroviral therapy (ART) on new HIV infections. Comparing results and conclusions across models is challenging because models have addressed slightly different questions and have reported different outcome metrics. This study compares the predictions of several mathematical models simulating the same ART intervention programmes to determine the extent to which models agree about the epidemiological impact of expanded ART. Methods and Findings: Twelve independent mathematical models evaluated a set of standardised ART intervention scenarios in South Africa and reported a common set of outputs. Intervention scenarios systematically varied the CD4 count threshold for treatment eligibility, access to treatment, and programme retention. For a scenario in which 80% of HIV-infected individuals start treatment on average 1 y after their CD4 count drops below 350 cells/ml and 85% remain on treatment after 3 y, the models projected that HIV incidence would be 35% to 54% lower 8 y after the introduction of ART, compared to a counterfactual scenario in which there is no ART. More variation existed in the estimated long-term (38 y) reductions in incidence. The impact of optimistic interventions including immediate ART initiation varied widely across models, maintaining substantial uncertainty about the theoretical prospect for elimination of HIV from the population using ART alone over the next four decades. The number of person-years of ART per infection averted over 8 y ranged between 5.8 and 18.7. Considering the actual scale-up of ART in South Africa, seven models estimated that current HIV incidence is 17% to 32% lower than it would have been in the absence of ART. Differences between model assumptions about CD4 decline and HIV transmissibility over the course of infection explained only a modest amount of the variation in model results. Conclusions: Mathematical models evaluating the impact of ART vary substantially in structure, complexity, and parameter choices, but all suggest that ART, at high levels of access and with high adherence, has the potential to substantially reduce new HIV infections. There was broad agreement regarding the short-term epidemiologic impact of ambitious treatment scale-up, but more variation in longer term projections and in the efficiency with which treatment can reduce new infections. Differences between model predictions could not be explained by differences in model structure or parameterization that were hypothesized to affect intervention impact. Please see later in the article for the Editors’ Summary.

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361 citations

Journal Article•DOI•

Antiretroviral treatment of HIV-1 prevents transmission of HIV-1: where do we go from here?

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Myron S. Cohen¹, M. Kumi Smith¹, Kathryn E. Muessig¹, Timothy B. Hallett², Kimberly A. Powers¹, Angela D. M. Kashuba¹ - Show less +2 more•Institutions (2)

University of North Carolina at Chapel Hill¹, Imperial College London²

02 Nov 2013-The Lancet

TL;DR: Evidence is growing that wider, earlier initiation of ART could reduce population-level incidence of HIV, and ongoing community-based prospective trials of early ART are likely to help to establish the population- level benefit of ART, and-if successful-to galvanise treatment as prevention.

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225 citations

Journal Article•DOI•

Immunodeficiency at the start of combination antiretroviral therapy in low-, middle-, and high-income countries.

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Dorita Avila, Keri N. Althoff, Catrina Mugglin, Kara Wools-Kaloustian, Manuel Koller, François Dabis, Denis Nash, Thomas Gsponer, Somnuek Sungkanuparph, Catherine C. McGowan, Margaret T May¹, David A. Cooper, Cleophas Chimbetete, Marcelo Wolff, Ann C. Collier, Hamish McManus, Mary-Ann Davies, Dominique Costagliola, Brenda Crabtree-Ramírez, Romanee Chaiwarith, Angela Cescon, Morna Cornell, Lameck Diero, Praphan Phanuphak, Adrien Sawadogo, Jochen Ehmer, Serge Eholié, Patrick C.K. Li, Matthew P. Fox, Neel R. Gandhi, Elsa González, Christopher K C Lee, Christopher J. Hoffmann, Andrew Kambugu, Olivia Keiser, Rossana Ditangco, Hans Prozesky, Fiona C Lampe, Nagalingeswaran Kumarasamy, Mari M. Kitahata, Emmanuel Lugina, Rita Lyamuya, Saphonn Vonthanak, Valeria Fink, Antonella d'Arminio Monforte, Paula M. Luz, Yi Ming Arthur Chen, Albert Minga, Jordi Casabona¹, Albert Mwango, Jun Yong Choi, Marie-Louise Newell, Elizabeth A. Bukusi, Kapella Zacharia Ngonyani, Tuti Parwati Merati, Juliana A. Otieno, Mwebesa B. Bosco, Sam Phiri, Oon T Ng, Kathryn Anastos, Jürgen K. Rockstroh, Ignacio Santos, Shinichi Oka, Geoffrey Somi, Christoph Stephan, Ramón Teira, Deo Wabwire, Gilles Wandeler, Andrew Boulle, Peter Reiss, Robin Wood, Benjamin H. Chi, Carolyn Williams, Jonathan A C Sterne¹, Matthias Egger - Show less +71 more•Institutions (1)

University of Bristol¹

01 Jul 2013-Journal of Acquired Immune Deficiency Syndromes

TL;DR: Median CD4 cell counts at the start of cART increased 2000–2009 but remained below 200 cells/&mgr;L in LIC and MIC and below 300 cells/ &mgr:L in HIC.

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Abstract: OBJECTIVE To describe the CD4 cell count at the start of combination antiretroviral therapy (cART) in low-income (LIC), lower middle-income (LMIC), upper middle-income (UMIC), and high-income (HIC) countries. METHODS Patients aged 16 years or older starting cART in a clinic participating in a multicohort collaboration spanning 6 continents (International epidemiological Databases to Evaluate AIDS and ART Cohort Collaboration) were eligible. Multilevel linear regression models were adjusted for age, gender, and calendar year; missing CD4 counts were imputed. RESULTS In total, 379,865 patients from 9 LIC, 4 LMIC, 4 UMIC, and 6 HIC were included. In LIC, the median CD4 cell count at cART initiation increased by 83% from 80 to 145 cells/μL between 2002 and 2009. Corresponding increases in LMIC, UMIC, and HIC were from 87 to 155 cells/μL (76% increase), 88 to 135 cells/μL (53%), and 209 to 274 cells/μL (31%). In 2009, compared with LIC, median counts were 13 cells/μL [95% confidence interval (CI): -56 to +30] lower in LMIC, 22 cells/μL (-62 to +18) lower in UMIC, and 112 cells/μL (+75 to +149) higher in HIC. They were 23 cells/μL (95% CI: +18 to +28 cells/μL) higher in women than men. Median counts were 88 cells/μL (95% CI: +35 to +141 cells/μL) higher in countries with an estimated national cART coverage >80%, compared with countries with <40% coverage. CONCLUSIONS Median CD4 cell counts at the start of cART increased 2000-2009 but remained below 200 cells/μL in LIC and MIC and below 300 cells/μL in HIC. Earlier start of cART will require substantial efforts and resources globally.

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154 citations

Journal Article•DOI•

Evaluation of the impact of immediate versus WHO recommendations-guided antiretroviral therapy initiation on HIV incidence: the ANRS 12249 TasP (Treatment as Prevention) trial in Hlabisa sub-district, KwaZulu-Natal, South Africa: study protocol for a cluster randomised controlled trial.

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Collins Iwuji¹, Joanna Orne-Gliemann², Frank Tanser¹, Sylvie Boyer², Sylvie Boyer³, Richard J Lessells⁴, Richard J Lessells¹, John Imrie⁵, John Imrie¹, Till Bärnighausen¹, Till Bärnighausen⁶, Claire Rekacewicz, Brigitte Bazin, Marie-Louise Newell⁷, Marie-Louise Newell¹, François Dabis² - Show less +12 more•Institutions (7)

University of KwaZulu-Natal¹, French Institute of Health and Medical Research², Aix-Marseille University³, University of London⁴, University College London⁵, Harvard University⁶, University of Southampton⁷

23 Jul 2013-Trials

TL;DR: This trial aims to provide proof-of-principle evidence regarding the effectiveness of Treatment-as-Prevention in reducing HIV incidence at the population level.

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Abstract: BACKGROUND: Antiretroviral therapy (ART) suppresses HIV viral load in all body compartments and so limits the risk of HIV transmission. It has been suggested that ART not only contributes to preventing transmission at individual but potentially also at population level. This trial aims to evaluate the effect of ART initiated immediately after identification/diagnosis of HIV-infected individuals, regardless of CD4 count, on HIV incidence in the surrounding population. The primary outcome of the overall trial will be HIV incidence over two years. Secondary outcomes will include i) socio-behavioural outcomes (acceptability of repeat HIV counselling and testing, treatment acceptance and linkage to care, sexual partnerships and quality of life); ii) clinical outcomes (mortality and morbidity, retention into care, adherence to ART, virologic failure and acquired HIV drug resistance), iii) cost-effectiveness of the intervention. The first phase will specifically focus on the trial's secondary outcomes. METHODS/DESIGN: A cluster-randomised trial in 34 (2 × 17) clusters within a rural area of northern KwaZulu-Natal (South Africa), covering a total population of 34,000 inhabitants aged 16 years and above, of whom an estimated 27,200 would be HIV-uninfected at start of the trial. The first phase of the trial will include ten (2 × 5) clusters. Consecutive rounds of home-based HIV testing will be carried out. HIV-infected participants will be followed in dedicated trial clinics: in intervention clusters, they will be offered immediate ART initiation regardless of CD4 count and clinical stage; in control clusters they will be offered ART according to national treatment eligibility guidelines (CD4 <350 cells/μL, World Health Organisation stage 3 or 4 disease or multidrug-resistant/extensively drug-resistant tuberculosis). Following proof of acceptability and feasibility from the first phase, the trial will be rolled out to further clusters. DISCUSSION: We aim to provide proof-of-principle evidence regarding the effectiveness of Treatment-as-Prevention in reducing HIV incidence at the population level. Data collected from the participants at home and in the clinics will inform understanding of socio-behavioural, economic and clinical impacts of the intervention as well as feasibility and generalizability. TRIAL REGISTRATION: Clinicaltrials.gov: NCT01509508; South African Trial Register: DOH-27-0512-3974.

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118 citations

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Journal Article•DOI•

Prevention of HIV-1 Infection with Early Antiretroviral Therapy

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Myron S. Cohen¹, Ying Q. Chen², Marybeth McCauley³, Theresa Gamble³, Mina C. Hosseinipour¹, Nagalingeswaran Kumarasamy, James Hakim⁴, Johnstone Kumwenda⁵, Beatriz Grinsztejn⁶, José Henrique Pilotto, Sheela Godbole, Sanjay Mehendale, Suwat Chariyalertsak⁷, Breno Santos, Kenneth H. Mayer⁸, Irving F. Hoffman¹, Susan H. Eshleman⁵, Estelle Piwowar-Manning⁵, Lei Wang², Joseph Makhema⁹, Lisa A. Mills¹⁰, Guy de Bruyn¹¹, Ian Sanne¹¹, Joseph J. Eron¹, Joel E. Gallant⁵, Diane V. Havlir¹², Susan Swindells¹³, Heather J. Ribaudo⁹, Vanessa Elharrar¹⁴, David N. Burns¹⁴, Taha E. Taha⁵, Karin Nielsen-Saines¹⁵, David D. Celentano⁵, Myron Essex⁹, Thomas R. Fleming¹⁶ - Show less +31 more•Institutions (16)

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

10 Aug 2011-The New England Journal of Medicine

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.

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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...

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5,871 citations

Journal Article•DOI•

Prevention of HIV-1 infection with early antiretroviral therapy

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Michael Rayment

01 Jul 2012-Journal of Family Planning and Reproductive Health Care

TL;DR: The exciting evidence generated by this paper – that antiretroviral treatment of HIV-1 infection definitively reduces the risk of onward transmission of the virus by 96% – was rightly dubbed Science magazine's ‘Breakthrough of the Year’ in 2011.

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Abstract: MS Cohen, YQ Chen, M McCauley N Engl J Med 2011 365:493–505. The exciting evidence generated by this paper – that antiretroviral treatment of HIV-1 infection definitively reduces the risk of onward transmission of the virus by 96% – was rightly dubbed Science magazine's ‘Breakthrough of the Year’ in 2011.1 ,2 It has long been known that the probability of sexual transmission of HIV is strongly correlated with concentrations of HIV in blood and genital fluids.3 ,4 Effective antiretroviral therapy (ART) produces prolonged and sustained suppression of HIV replication in these compartments, reducing the amount of free virus.5 ,6 Thus, there has long been a …

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4,259 citations

"HIV Treatment as Prevention: Models..." refers background or methods in this paper

...The biological efficacy data provided by the HPTN 052 trial [11] is only one piece of this puzzle....
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...This finding was shown in the HPTN 052 trial [11] (Box 1), which was chosen as the Science magazine breakthrough of the year for 2011 [12]....
[...]
...The findings of the HPTN 052 trial [11] demonstrated the biological efficacy of treatment in reducing infectiousness in heterosexual individuals who receive the best care and monitoring that is possible....
[...]

Journal Article•DOI•

Preexposure Chemoprophylaxis for HIV Prevention in Men Who Have Sex with Men

[...]

Robert M. Grant, Javier R. Lama, Peter L. Anderson¹, Vanessa McMahan, Albert Y. Liu², Lorena Vargas, Pedro Goicochea, Martin Casapia, Juan Vicente Guanira-Carranza³, Maria Esther Ramirez-Cardich³, Orlando Montoya-Herrera, Telmo Fernandez, Valdilea G. Veloso⁴, Susan Buchbinder, Suwat Chariyalertsak⁵, Mauro Schechter⁶, Linda-Gail Bekker⁷, Kenneth H. Mayer⁸, Esper G. Kallas⁹, K. Rivet Amico, Kathleen Mulligan², Lane R. Bushman¹, Robert J. Hance, Carmela Ganoza³, Patricia Defechereux, Brian S. Postle, Furong Wang², J. Jeff McConnell, Jia-Hua Zheng¹, Jeanny Lee, James F. Rooney, Howard S. Jaffe, Ana Martinez¹⁰, David N. Burns¹⁰, David V. Glidden² - Show less +31 more•Institutions (10)

University of Colorado Denver¹, University of California, San Francisco², Asociación Civil Impacta Salud y Educación³, Oswaldo Cruz Foundation⁴, Chiang Mai University⁵, Federal University of Rio de Janeiro⁶, University of Cape Town⁷, Brown University⁸, University of São Paulo⁹, National Institutes of Health¹⁰

29 Dec 2010-The New England Journal of Medicine

TL;DR: Oral FTC-TDF provided protection against the acquisition of HIV infection among the subjects and Detectable blood levels strongly correlated with the prophylactic effect.

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Abstract: The study subjects were followed for 3324 person-years (median, 1.2 years; maximum, 2.8 years). Of these subjects, 10 were found to have been infected with HIV at en rollment, and 100 became infected during follow-up (36 in the FTC–TDF group and 64 in the placebo group), indicating a 44% reduction in the incidence of HIV (95% confidence interval, 15 to 63; P = 0.005). In the FTC–TDF group, the study drug was detected in 22 of 43 of seronegative subjects (51%) and in 3 of 34 HIV-infected subjects (9%) (P<0.001). Nausea was reported more frequently during the first 4 weeks in the FTC–TDF group than in the placebo group (P<0.001). The two groups had similar rates of serious adverse events (P = 0.57). Conclusions Oral FTC–TDF provided protection against the acquisition of HIV infection among the subjects. Detectable blood levels strongly correlated with the prophylactic effect. (Funded by the National Institutes of Health and the Bill and Melinda Gates Foun dation; ClinicalTrials.gov number, NCT00458393.)

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4,247 citations

"HIV Treatment as Prevention: Models..." refers background in this paper

...Abbreviations: ART, antiretroviral therapy; MSM, men who have sex with men....
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...This could in part explain the apparent lack of preventive efficacy of ART in epidemics among MSM, as explored in Australia and elsewhere by Wilson [17] and in other examples examined by Kumi Smith et al. [16]....
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...First, it was shown that a 1% tenofovir vaginal microbicide gel reduced HIV acquisition in women in South Africa [6], and this was followed by a trial demonstrating that daily oral co-formulated tenofovir and emtricitabine reduced the risk of HIV acquisition in men who have sex with men (MSM) [7]....
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...In this collection, Wilson [17] describes the examples of Australia and France, among other settings, where, despite high testing rates and coverage of treatment among MSM, HIV incidence has not decreased....
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...This is in contrast to what models suggest should have occurred if the assumptions about treatment as prevention from heterosexual studies are applied to MSM populations....
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Journal Article•DOI•

Vaccination with ALVAC and AIDSVAX to Prevent HIV-1 Infection in Thailand

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Supachai Rerks-Ngarm¹, Punnee Pitisuttithum, Sorachai Nitayaphan, Jaranit Kaewkungwal, Joseph Chiu, Robert Paris, Nakorn Premsri, Chawetsan Namwat, Mark de Souza, Elizabeth Adams, Michael Benenson, Sanjay Gurunathan, Jim Tartaglia, John G. McNeil, Donald P. Francis, Donald Stablein, Deborah L. Birx, Supamit Chunsuttiwat, Chirasak Khamboonruang, Prasert Thongcharoen, Merlin L. Robb, Nelson L. Michael, Prayura Kunasol, Jerome H. Kim - Show less +20 more•Institutions (1)

Thailand Ministry of Public Health¹

16 Dec 2009-The New England Journal of Medicine

TL;DR: This ALVAC-HIV and AIDSVAX B/E vaccine regimen may reduce the risk of HIV infection in a community-based population with largely heterosexual risk and offer insight for future research.

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Abstract: In the intention-to-treat analysis involving 16,402 subjects, there was a trend toward the prevention of HIV-1 infection among the vaccine recipients, with a vaccine efficacy of 26.4% (95% confidence interval [CI], −4.0 to 47.9; P = 0.08). In the perprotocol analysis involving 12,542 subjects, the vaccine efficacy was 26.2% (95% CI, −13.3 to 51.9; P = 0.16). In the modified intention-to-treat analysis involving 16,395 subjects (with the exclusion of 7 subjects who were found to have had HIV-1 infection at baseline), the vaccine efficacy was 31.2% (95% CI, 1.1 to 52.1; P = 0.04). Vaccination did not affect the degree of viremia or the CD4+ T-cell count in subjects in whom HIV-1 infection was subsequently diagnosed. Conclusions This ALVAC-HIV and AIDSVAX B/E vaccine regimen may reduce the risk of HIV infection in a community-based population with largely heterosexual risk. Vaccination did not affect the viral load or CD4+ count in subjects with HIV infection. Although the results show only a modest benefit, they offer insight for future research. (ClinicalTrials.gov number, NCT00223080.)

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2,960 citations

"HIV Treatment as Prevention: Models..." refers background in this paper

...There have also been some indications that a vaccine candidate (RV144) provides some short-term protection against infection [9]....
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Journal Article•DOI•

Effectiveness and Safety of Tenofovir Gel, an Antiretroviral Microbicide, for the Prevention of HIV Infection in Women

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Quarraisha Abdool Karim¹, Salim S. Abdool Karim², Salim S. Abdool Karim¹, Salim S. Abdool Karim³, Janet A. Frohlich³, Anneke Grobler³, Cheryl Baxter³, Leila E. Mansoor³, Ayesha B. M. Kharsany³, Sengeziwe Sibeko³, Koleka Mlisana¹, Zaheen Omar³, Tanuja N. Gengiah³, Silvia Maarschalk³, Natasha Arulappan³, Mukelisiwe Mlotshwa³, Lynn Morris, Douglas Taylor⁴ - Show less +14 more•Institutions (4)

University of KwaZulu-Natal¹, Columbia University², Centre for the AIDS Programme of Research in South Africa³, FHI 360⁴

03 Sep 2010-Science

TL;DR: Tenofovir in a vaginal gel formulation shows significant protection against HIV infection in a randomized control trial, and could potentially fill an important HIV prevention gap, especially for women unable to successfully negotiate mutual monogamy or condom use.

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Abstract: The Centre for the AIDS Program of Research in South Africa (CAPRISA) 004 trial assessed the effectiveness and safety of a 1% vaginal gel formulation of tenofovir, a nucleotide reverse transcriptase inhibitor, for the prevention of HIV acquisition in women. A double-blind, randomized controlled trial was conducted comparing tenofovir gel (n = 445 women) with placebo gel (n = 444 women) in sexually active, HIV-uninfected 18- to 40-year-old women in urban and rural KwaZulu-Natal, South Africa. HIV serostatus, safety, sexual behavior, and gel and condom use were assessed at monthly follow-up visits for 30 months. HIV incidence in the tenofovir gel arm was 5.6 per 100 women-years (person time of study observation) (38 out of 680.6 women-years) compared with 9.1 per 100 women-years (60 out of 660.7 women-years) in the placebo gel arm (incidence rate ratio = 0.61; P = 0.017). In high adherers (gel adherence > 80%), HIV incidence was 54% lower (P = 0.025) in the tenofovir gel arm. In intermediate adherers (gel adherence 50 to 80%) and low adherers (gel adherence < 50%), the HIV incidence reduction was 38 and 28%, respectively. Tenofovir gel reduced HIV acquisition by an estimated 39% overall, and by 54% in women with high gel adherence. No increase in the overall adverse event rates was observed. There were no changes in viral load and no tenofovir resistance in HIV seroconverters. Tenofovir gel could potentially fill an important HIV prevention gap, especially for women unable to successfully negotiate mutual monogamy or condom use.

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2,365 citations

"HIV Treatment as Prevention: Models..." refers background in this paper

...The following people attended the meeting and meet International Committee of Medical Journal Editors authorship criteria for this article: Till Bärnighausen, Harvard School of Public Health, and Africa Centre for Health and Population Studies; Stephen Becker, Bill & Melinda Gates Foundation; Eran Bendavid, Stanford University; Anna Bershteyn, Intellectual Ventures; John Blandford, US Centers for Disease Control and Prevention; Marie-Claude Boily, Imperial College London; David Burns, US National Institute of Allergy and Infectious Diseases; Valentina Cambiano, University College London; Myron S. Cohen, University of North Carolina at Chapel Hill; Íde Cremin, Imperial College London; Wim Delva, South African Department of Science and Technology/ National Research Foundation Centre of Excellence in Epidemiological Modelling and Analysis, University of Stellenbosch, and Ghent University; Christopher Dye, World Health Organization; Jeffrey W. Eaton, Imperial College London; Matthias Egger, University of Bern; Christophe Fraser, Imperial College London; Noya Galai, Johns Hopkins University; Geoff Garnett, Bill & Melinda Gates Foundation; Peter D. Ghys, Joint United Nations Programme on HIV/AIDS; Timothy B. Hallett, Imperial College London; Laura Heaton, US Census Bureau; Charles B. Holmes, Office of the US Global AIDS Coordinator; Jan Hontelez, Erasmus University; Britta Jewell, Imperial College London; Olivia Keiser, University of Bern; Daniel Klein, Intellectual Ventures; Viviane Lima, University of British Columbia; Elisa Long, Yale University; Rob Lyerla, Office of the US Global AIDS Coordinator; Christiaan Marais, HEXOR; Fei Meng, Hasselt University; Gesine Meyer-Rath, Boston University; William C. Miller, University of North Carolina at Chapel Hill; Nicholas Muraguri, Kenya National AIDS & STI Control Programme; Brooke E. Nichols, Erasmus Medical Center; Karima R. Nigmatulina, Intellectual Ventures; Mead Over, Center for Global Development; Nancy Padian, Office of the Key Points N It has been established that ART for those infected with HIV can prevent onward transmission of infection, but biological efficacy alone is not enough to confirm the impact that ART could have on the HIV epidemic, or to show how best to use ART to reduce incidence of HIV....
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...However, these assumptions can be contrasted with recent real world experience in which the HIV testing rate was 52% in the crosssectional, nationally representative South African National HIV Prevalence, Incidence, Behaviour and Communication Survey [3], and the repeat testing rate of individuals in an intensive community-mobilising intervention was 28% [28]....
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...All models suggested that the existing treatment scale-up in South Africa should have already reduced new infections (incidence in 2011 is estimated to be 17%–32% lower than if there had been no ART [15])....
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...In South Africa, a country with one of the largest HIV epidemics, 3% of the young men and women who were 19 years old and uninfected at the time of the last conference will now be infected [3]....
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...First, it was shown that a 1% tenofovir vaginal microbicide gel reduced HIV acquisition in women in South Africa [6], and this was followed by a trial demonstrating that daily oral co-formulated tenofovir and emtricitabine reduced the risk of HIV acquisition in men who have sex with men (MSM) [7]....
[...]