The human immunodeficiency virus (HIV) was discovered in 1982, but treatment strategies were not introduced until 5 years later. Early regimens consisted of one or two drugs and often led to treatment failure. Since the advent in 1995 of highly active antiretroviral therapy (HAART), which consists of at least three agents, a dramatic improvement has been seen in the number of patients attaining undetectable viral loads, improved CD4 counts, and improved survival. However, early HAART often consisted of drugs with complex dosing schedules, strict food requirements, treatment-limiting adverse effects, and the need to take 16–20 pills/day. These treatment barriers often led to patient non-adherence, with subsequent treatment failure and development of resistant strains. Our project will focus on HIV drug resistance, viral diversity, pathogenesis and therapeutic aspects of HIV infection. It will range from basic aspects of virology as the pursuit of the identification and characterization of the mechanisms of resistance to new antiretroviral drugs, to more applied clinical research themes as implication of minority variants on virological response to treatment and to the design of clinical trials in North and South countries evaluating new therapeutic strategies in HIV infection.
More specifically, our project will be structured in 6 parts: (i) epidemiology of resistance to antiretroviral drugs at the national and international levels, (ii) mechanisms of resistance to antiretroviral drugs for both HIV-1 (molecular bases of resistance and impact of minor resistance viral species) and HIV-2 (resistance to new anti HIV-2 agents), (iii) pathogenesis (characterization and quantification of HIV-2 reservoir, role of the accessory genes such as nef and vpx, immune aspects) and new treatments of HIV-2 infection, (iv) new strategies for use of antiretroviral drugs in the North and in the South countries, (v) pharmacology of antiretroviral drugs and (vi) innovation in drug discovery with in silico analyses including comparison of drug binding sites on HIV molecules, simulation of interactions and virtual screening approaches.