Evaluation of HIV-1 Drug Resistance among Antiretroviral Treatment Na?ve and Experienced Patients Attending Urban and Peripheral Rural Treatment Centers in Cameroon. PROJECT ABSTRACT The global burden of HIV/AIDS infection worldwide is a major concern for all countries, but represents a specific challenge for fragile economies and health systems in resource-limited settings (RLS), and more specifically in Sub-Saharan Africa. Although major progresses have been achieved over the past three decades, especially in terms of development of drugs and drug-combinations, access to antiretroviral treatment (ART) in the developing world is still challenging. To address these challenges, several initiatives have been developed, including specific guidelines for ART initiation and switch in the context of RLS. These guidelines developed by the World Health Organization (WHO) and partners recommend a simplify approach that requires no or few biological markers for treatment initiation and switch and are thus quite different from current recommendations in industrialized countries, where several biological and virological markers including viral load and drug resistance evaluations are routinely used. Under such circumstances, there is thus a risk that resistance to treatment will emerge rapidly among patients who are receiving treatment in RLS, but also in those who are recently infected and are treatment-free, through transmission of resistant viruses. The current application aims at determining the frequency of transmitted HIV-1 drug resistant strains in newly infected patients and monitor HIVDR emergence and related program factors in urban and rural ART sites in Cameroon in order to provide adequate recommendations to program managers and decision makers on how to improve access to ART in Cameroon and other RLS. More specifically, we will (i) determine the frequency of transmitted HIV-1 drug resistant strains in recently infected, treatment-na?ve individuals in urban and rural areas in Cameroon, (ii) estimate the proportion of patient with successful treatment outcome after 12 to 36 months ART and identify factors associated with treatment failure, (iii) identify drug resistance mutations and mutation patterns that circulate in the population, (iv) assess the feasibility and reliability of field-friendly tools as dried blood specimens for the purpose of viral load testing and drug resistance genotyping, (v) evaluate the current HIV-1 molecular epidemiology in Cameroon and finally (vi) assess programmatic factors potentially associated with the prevention or emergence of HIVDR and provide recommendations to national authorities. The study is planned for two years, and will cover almost all Cameroonian regions from the north part of the country, to the south areas. The obtained results will be essential to guide the ART-program in Cameroon on how to improve not only access to treatment, but also the quality of ongoing and future treatment. Improving access and quality of ART in RLS is essential to use more efficiently, the limited available resources and also prevent an uncontrolled spread of resistant viruses that can highly affect current achievements. To meet these objectives, the study will be conducted by a highly experienced team in the field of HIV research in Africa, the Research Center for Emerging Diseases in Cameroon (CREMER), specialized in HIV genetic diversity and associated consequences, HIV drug resistance and HIV origin. The CREMER Virology Laboratory is a WHO accredited reference laboratory for the surveillance of HIV-1 drug resistance. )
The following application aims at addressing critical challenges associated to the expanded access to antiretroviral treatment in resource-limited countries including the risks of a rapid and uncontrolled emergence of drug resistance.