| The high mutation rate of HIV in combination with its poor proofreading capacity provides a low threshold for the selection of resistant virus upon drug selective pressure. The use of HAART aims to reduce the replication of virus to such levels that the emergence of resistant virus is prevented. However, even among persons treated with appropriate highly active antiretroviral treatment (HAART) regimens and with good adherence, it is inevitable that some degree of HIV drug resistance (HIVDR) will occur. Recently, through various initiatives worldwide, access to treatment has increased significantly for people living in resource-limited countries. Even though great concern exists about the development of resistance, most countries, like Rwanda, did not yet develop the capacity for assessing this. However, since resistance will jeopardize the efficacy of treatment programmes, the surveillance and monitoring of HIVDR should become part of HIV treatment programmes. INTERACT project 11 aims to further build sustainable capacity for HIVDR at the Laboratoire National de Réference (LNR) in Rwanda and to implement and apply this technique for surveillance of HIVDR in treated and untreated populations. Part A. Capacity building in HIVDR sequencing is most commonly used for the determination of HIVDR and provides information on an entire viral nucleotide sequence. A well-organized molecular diagnostic laboratory with highly specialized personnel for the processing of the samples, the use of dedicated equipment and the interpretation of the results is needed. Currently, the LNR is in the process of setting up HIVDR testing facilities. In the first part of the project, UMC Utrecht Virology (UMCU-Viro) will assist LNR with the capacity building for quality assured HIVDR testing. Where needed, UMCU-Viro will assist in the organization of the laboratory and the development of standard operation procedures. Through its contacts with WHO in the HIVResNet Laboratory Working Group and the UMCU-Viro based Unite-More project, UMCU-Viro will provide laboratory validation panels for internal Quality Assurance (QA)/Quality Control (QC), and will conduct external QA/QC. Access to sustainable data management system will be installed for HIVDR data. In order to provide sustainable human resources capacity building, the training of a Rwandan PhD student is foreseen who will be educated in GLP, HIVDR testing, subtyping, interpretation of results, etcetera. Also, scientific workshops will be organized on a yearly basis for the training and education of health care personnel, policy makers and laboratory personnel in the field of HIV drug resistance. Part B. Emergence of HIVDR in a population on first line HAART. In developed countries, HIVDR testing is used for the guidance of treatment decisions in the individual patient. Given the high cost of resistance testing, in resource limited settings HIVDR testing should be first used to provide Public Health data for the assessment of the efficacy of treatment programmes. Currently, the most prescribed first line HAART regimen in Rwanda consists of lamivudine, stavudine and nevirapine, in a fixed dose combination. Evaluation of treatment response is based on clinical or immunological parameters. However virologic failure, preceding clinical and immunological failure, is not assessed. This way, under the constant selective pressure of drugs, the virus could accumulate resistance. This part of the project aims to assess the incidence of virologic failure during first line HAART with lamivudine, stavudine and nevirapine in a fixed dose combination through regular viral load (VL) testing. Further, virus from patients expressing virological failure will be genotyped and subtyped and the percentage of strains carrying resistance will be determined. Socio-demographic information on the patients will be gathered and factors associated with treatment failure will be determined. For this objective, a cohort of 200 patients starting this treatment will be installed in the TRAC Clinic in Kigali (in collaboration with projects D and E). Part C. Transmission of HIVDR to newly infected individuals. Resistance can be transmitted from one patient to another. Research shows that this transmitted resistance can hamper the response to first line treatment. The first HAART provides the patient's best chance for a sustained treatment response. Therefore, the assessment of this phenomenon is important since it could jeopardize the efficacy of the ARV treatment program used in the country. In this third part of the project resistance in untreated patients will be studied. Strategies will be developed for surveillance of drug resistance in the general HIV infected population, comparing regions/populations where HAART was introduced to more remote populations, and to determine the transmission of drug resistance to newly diagnosed HIV infected individuals. This activity will adhere to the methodology developed by WHO HIVResNet in collaboration with the UMCU-Viro based Unite More program, to ensure maximum compatibility with other studies. |
