a large window period for identification of acute infection [1–5], others relied on patient recall of symptoms associated with acute retroviral syndrome [6]. Still other studies focused on one particular aspect of acute HIV infection, such as clinical signs and symptoms [7], without placing the clinical presentation in the context of virological and immunological responses. Furthermore, the majority of these studies were conducted in developed countries where both the context for the research and the viral subtypes are markedly different from those that are found in southern Africa and the developing world. The only prospective acute infection study that was conducted in Africa identified acute infections within a period averaging 1.1 months but was limited by its focus on clinical manifestations of acute infection [8]. As a prospective observational cohort study, this study will also provide a methodology for setting up and managing an observational cohort requiring frequent visits over an extended period of time against within a very challenging, resource-constrained environ- ment with participants who tend to be highly mobile and difficult to contact by conventional means. To our knowledge, this acute infection study will be the first in southern Africa to document acute infection in a prospective cohort with extensive follow-up on the natural history of HIV-1 subtype C infection. The aim of this paper is to provide a preliminary description of the demographic and clinical charac- teristics of the cohort of HIV-uninfected participants, the challenges in administering the cohort, and some of the successful strategies employed to overcome these obstacles. This paper provides important information with respect to the establishment of high-risk cohorts for acute HIV infection and other prospective observational studies. Establishment of cohorts in developing country setting have unique challenges which differ between locations and populations. Our cohort consists primarily of high risk HIV-uninfected women working as female sex workers, recruited from a large urban area. This cohort is of high potential impact as forms part of a larger acute infection study which measures virological, immunological and clinical events in acute and early infection. Results from this study are likely to provide valuable information to inform vaccine trials, as well as understanding host, immunological and virological correlates of disease progression in subtype C infection. This paper provides important information with respect to the establishment of high- risk cohorts for acute HIV infection and other prospective observational studies. Materials and Methods The CAPRISA 002 Acute Infection Study is being conducted at the Doris Duke Medical Research Institute (DDMRI) at the Nelson R Mandela School of Medicine of the University of KwaZulu-Natal in Durban, South Africa. The goal of this study is to identify acute HIV infection and, by prospectively following participants with acute infection, provide thorough information on the natural history of HIV-1 subtype C infection. Cohort Development Building on participatory research methods developed for earlier work in similar cohorts [9–11], a network of ten community liaison persons (CLPs) was established prior to initiation of the study to assist with study recruitment and retention efforts. Recruitment was based upon word-of-mouth and site visits by the CLPs. Initially we recruited directly within 5 kilometres of the clinic site, but CLPs did bring women in from as far as around 45 kilometres (approximately 3 to 28 miles). Most of the recruitment sites were associated with CAPRISA 002 Study transport links into the city, and so participants were able to access the existing system of public transport. Participants received reimbursement for time, effort and their transport expenses when they visited the clinic. We limited our recruitment radius so that no woman would have to use her own money. Women from the community who were at least 18 years old and either self-identified as female sex workers (FSWs) or reported having had at least three partners in the 3 months prior to recruitment were screened for participation in the study. Young women in urban South Africa are already at high risk for HIV infection [12], and our goal was to identify women who would theoretically be at the greatest risk of HIV acquisition. Women who were pregnant at the time of screening or who planned to travel away from the study site for more than 3 months were excluded from participation. The screening procedure for identifying HIV-negative women consisted of voluntary counselling and testing (VCT) followed by a blood collection for rapid HIV antibody testing and urine collection for pregnancy testing. If the first antibody test (Determine: Abbott Laboratories, Tokyo, Japan) was negative, the participant was enrolled into the HIV-negative cohort. If the first antibody test was positive, a second rapid antibody test (Capillus; Trinity Biotech, Jamestown, NY, USA) was adminis- tered. Those with a two positive antibody tests were referred for HIV follow-up care. Those with discordant antibody results were given a confirmatory HIV enzyme immunoassay (EIA) (BEP 2000; Dade Behring, Marburg, Germany) and were either enrolled into the HIV-negative cohort or referred for HIV follow-up care on the basis of those results. In order to maximize participant retention, the study visit schedule was thoroughly explained during the informed consent process and was re-emphasized at each study visit. Detailed locator information was collected and was reviewed at each subsequent visit and a secure participant-tracking database was established to facilitate visit scheduling and prompt follow-up for missed visits. Additionally, participants were compensated (100 South African Rand, ,$14USD, as approved by the ethics committee) for their transport to the study site and for their time at the clinic. To improve communication with the cohort, a web-based short message service (SMS) is used to send pre-approved cell phone text messages to willing participants. This system is used to remind participants who generally do not have access to fixed-line telephone services about their study appointments. The service is cost effective (0.33 South African Rand per message) and also provides an electronic record of all messages sent and whether or not they are received. If a participant misses a visit, the clinic nurse administrator attempts to call a participant for the first 3 days after the clinic visit. A SMS with the clinic contact number is also sent out on the second and third days. If these attempts at contact are unsuccessful by the second week, the study community liaison officer attempts person-to-person contact by travelling to the participant’s documented contact site as well as to the site from which the participant was originally recruited. In addition to the methods above, the study staff and community liaisons regularly communicate with the study community at large to increase awareness of HIV/AIDS and explain the purpose of HIV prevention research and the importance of completing research study visits. A Community Research Support Group (CRSG) comprised of the CLPs meets bi-monthly with study representatives to discuss and provide feedback on the progress of the study and to discuss challenges faced by the study team with regards to community and participant relations. PLoS ONE | www.plosone.org 2 April 2008 | Volume 3 | Issue 4 | e1954