Establishing a Cohort at High Risk of HIV Infection in South Africa: Challenges and Experiences of the CAPRISA 002 Acute Infection Study Francois van Loggerenberg1*, Koleka Mlisana1, Carolyn Williamson1,2, Sara C. Auld1,3, Lynn Morris1,4, Clive M. Gray1,4, Quarraisha Abdool Karim1,3, Anneke Grobler1, Nomampondo Barnabas1, Itua Iriogbe1, Salim S. Abdool Karim1,3 for the CAPRISA 002 Acute Infection Study Team 1 Centre for the AIDS Programme of Research in South Africa (CAPRISA), University of KwaZulu-Natal, Durban, South Africa, 2 Institute for of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa, 3 Columbia University, New York, New York, United States of America, 4 National Institute for Communicable Diseases, Johannesburg, South Africa Abstract Objectives: To describe the baseline demographic data, clinical characteristics and HIV-incidence rates of a cohort at high risk for HIV infection in South Africa as well as the challenges experienced in establishing and maintaining the cohort. Methodology/Principle Findings: Between August 2004 and May 2005 a cohort of HIV-uninfected women was established for the CAPRISA 002 Acute Infection Study, a natural history study of HIV-1 subtype C infection. Volunteers were identified through peer-outreach. The cohort was followed monthly to determine HIV infection rates and clinical presentation of early HIV infection. Risk reduction counselling and male and female condoms were provided. After screening 775 individuals, a cohort of 245 uninfected high-risk women was established. HIV-prevalence at screening was 59.6% (95% CI: 55.9% to 62.8%) posing a challenge in accruing HIV-uninfected women. The majority of women (78.8%) were self-identified as sex-workers with a median of 2 clients per day. Most women (95%) reported more than one casual sexual partner in the previous 3 months (excluding clients) and 58.8% reported condom use in their last sexual encounter. Based on laboratory testing, 62.0% had a sexually transmitted infection at baseline. During 390 person-years of follow-up, 28 infections occurred yielding seroincidence rate of 7.2 (95% CI: 4.5 to 9.8) per 100 person-years. Despite the high mobility of this sex worker cohort retention rate after 2 years was 86.1%. High co-morbidity created challenges for ancillary care provision, both in terms of human and financial resources. Conclusions/Significance: Challenges experienced were high baseline HIV-prevalence, lower than anticipated HIV- incidence and difficulties retaining participants. Despite challenges, we have successfully accrued this cohort of HIV- uninfected women with favourable retention, enabling us to study the natural history of HIV-1 during acute HIV-infection. Our experiences provide lessons for others establishing similar cohorts, which will be key for advancing the vaccine and prevention research agenda in resource-constrained settings. Citation: van Loggerenberg F, Mlisana K, Williamson C, Auld SC, Morris L, et al. (2008) Establishing a Cohort at High Risk of HIV Infection in South Africa: Challenges and Experiences of the CAPRISA 002 Acute Infection Study. PLoS ONE 3(4): e1954. doi:10.1371/journal.pone.0001954 Editor: Cesar Augusto Ugarte-Gil, Instituto de Medicina Tropical Alexander Von Humboldt, Peru Received November 30, 2007; Accepted February 27, 2008; Published April 16, 2008 Copyright: 2008 van Loggerenberg et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: CAPRISA received support for the CAPRISA 002 Acute Infection Study from the Comprehensive International Program of Research on AIDS (CIPRA) funded by the National Institute of Allergy and Infectious Disease (NIAID), National Institutes of Health (NIH) and the US Department of Health and Human Services (DHHS) (Grant#1 U19 AI51794). The funders supported the initial development of the protocol but had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist. * E-mail: loggerenbergf@ukzn.ac.za Introduction As we move into the third decade of the AIDS epidemic, the need to increase and improve the research being conducted in some of the hardest hit areas of the developing world has become increasingly clear. These regions pose unique challenges for scientific research as they are typically resource-poor settings with minimal existing infrastructure and populations that are not well integrated into a formal health care system. In order to conduct effective research into the HIV epidemic in southern Africa, it is critical to improve our ability to maintain longitudinal cohorts in the face of significant social, cultural, and logistical hurdles. In order to determine which host and viral factors during the acute and early phases of HIV-1 infection have a significant impact on the subsequent course of disease, the Centre for the AIDS Programme of Research in South Africa (CAPRISA) initiated the CAPRISA 002 Acute Infection Study. This study will characterize HIV-1 subtype C viral load set point in heterosexual infection in South Africa, the role of specific T cell immune responses in the control of replication, and the relationship between viral set point, CD4+ T cell count trajectory and disease progression. The design of this study overcomes several limitations of previous acute infection studies. While several earlier studies used PLoS ONE | www.plosone.org 1 April 2008 | Volume 3 | Issue 4 | e1954