Cleveland, Ohio The Arts' laboratory in Cleveland is located on the 10th floor of the Biomedical Research Building and is well equipped with all the instrumentation required for molecular virology studies. In addition, the Center for AIDS Research at CWRU provides additional infrastructure including a biosafety level 2 and 3 laboratory. The Arts' laboratory is currently funded by grants from the NIAID and NICHD, NIH. We currently have two post-doctoral fellows, two research assistants, and four graduate students but this number continues to fluctuate. Collaborations have been established with several research groups around the world including Dr. Solomon at the National AIDS Center in Argentina, Drs. Holmes and Prof. Phillips at University of Oxford, Dr. Mullins and a team of scientists at University of Washington, Dr. Vanham at the Institute of Tropical of Medicine in Antwerp, Belgium. However, our closest interactions are with the Joint Clinical Research Centre in Kampala, Uganda (Dr. Peter Mugyenyi, Director and Dr. Cissy Kityo, Research Coordinator). General Research Interests Heterogeneity of human immunodeficiency virus type 1 (HIV- 1) has a significant impact on viral fitness, disease progression in the patient, emergence of drug resistance, and development of an effective vaccine. Although encompassing a broad range of topics, all of our research projects are related to HIV-1 genetic diversity. We have recently observed that the replicative capacity or fitness of HIV-1 is very strong predictor of disease progression. HIV-1 fitness and diversity appears to increase during disease, which suggests the Red Queen Hypothesis may be in play. Several divergent HIV subtypes co-circulate in throughout the world. We now have evidence that subtype C, which dominates the HIV-1 epidemic may actually be less fit. This observation provides evidence for HIV-1 attenuation in the epidemic. As part of a program project, we are testing the anti-HIV activity of beta chemokine analogs (e.g. AOP-RANTES). This project involves testing these drugs against divergent, primary HIV- 1 strains, isolated throughout the world. We are trying to characterize the mechanism of inhibition by these chemokine analogs by studying HIV-1 binding to CD4 and CCR5. A beta chemokine analog may be employed as vaginal viricide to prevent HIV infections in developing countries. Treatment with antiretrovirals results in the emergence of drug resistant HIV- 1 isolates. In many instances, these drug resistant isolates may pre-exist and even predominate in the intrapatient HIV population prior to treatment. We are studying the baseline and emergence of drug resistant HIV- 1 isolates in HIV-infected Ugandans. Co-infection of a human host with two different strains of HIV-1 will lead to recombination. In parts of the world where two subtypes co-circulate, intersubtype HIV-1 recombinants are becoming prevalent and hampering the development of effective HIV-1 vaccines. Our studies focus on the molecular mechanisms involved in intersubtype HIV-1 recombinations as well as the fitness of these recombined isolates Mailing address: Division of Infectious Disease Biomedical Research Building, Room 1010 Case Western Reserve University School of Medicine 10900 Euclid Ave. Cleveland, OH 44106

Kampala, Uganda CWRU-JCRC Virology laboratory in Kampala, Uganda Location and structure This virology laboratory was established in 1999 with support from the Fogarty International AIDS Training Program, the Center for AIDS Research, and NIH grant funds from Dr. Arts. The laboratory is located at the Joint Clinical Research Centre, a medical clinic and center directed by Dr. Peter Mugyenyi and supported by the Ugandan Ministry of Defense, Ministry of Health, and Makerere University. This state-of-the-art laboratory is equipped with instrumentation for molecular biology studies including an automated sequencer, PCR thermocyclers, and gel electrophoresis equipment. Currently, the laboratory employees an on-site director, Korey Demers and two research assistants, Fred Kyeyune and Stanley Bulima. General Research Interests The research interests of this laboratory basically mirrors the overall objectives of the Arts Laboratory. However, this laboratory also performs various clinical assays including viral loads.