The management of antiretrovirals in Africa: a pilot study for a randomised controlled trial of treatment initiation strategies in HIV-1 infected persons in Africa. (360G-Wellcome-075393_B_04_A)

There is now a major worldwide initiative to fund and implement antiretroviral therapy (ART) programmes in developing countries, including the estimated 28 million persons with HIV living in sub-Saharan Africa. There is, however, little empiric evidence on which to base a rational strategy for implementing ART. Absence of such information the likelihood of this initiative failing is high. This proposal aims to conduct a pilot study to assess the feasibility of a large multi-site trial that will compare two strategies for initiating ART in sub-Saharan Africa. The pilot study and the main trial will build upon the infrastructure that has been established by the Africa Centre in the Hlabisa District, and at the proposed international sites in Uganda and Zimbabwe. The main study will enrol 3,600 HIV-infected patients in a randomised controlled trial comparing two strategies for starting therapy in a 5-year trial. One strategy - called the laboratory monitoring strategy (LMS) - would, as in industrialised countries, regularly monitor CD4 counts in HIV-infected individuals and initiate ART when the CD4 count is =200/µL. The comparator strategy called the clinical monitoring strategy (CMS) - is to use clinical monitoring of patients, and only initiate treatment when HIV-infected individuals return to clinic with symptoms and have a CD4 count =200/µL. The primary study outcome will be survival after 4 years of follow-up. The aims of the pilot study are: 1) To assess feasibility of recruiting subjects to attend for study screening and the impact of stigma on recruitment. 2) To assess the feasibility of subject screening, the informed consent process, and follow up. 3) To assess the feasibility of providing tuberculosis preventative therapy (TBPT) for all subjects. 4) To assess the feasibility of providing antiretroviral therapy (ART) to study subjects. The pilot study aims to enrol at least 200 subjects over a 12 month period at the Africa Centre. The study will be integrated into the health service operations at the site, which will include the provision of ART to patients with CD4 counts < 200/uL.