Impact of Non-B HIV-1 Subtype on second line Protease Inhibitor Regimens in Africa (INSPIRE)
To identify in non-B subtype HIV-1 infections in Africa the potential contribution to HIV drug resistance (HIVDR) by mutations in other genes (gag, env) than those targeted by anti-retroviral therapy (pol, protease). This project leverages the established PASER and AFRICOS cohorts that previously determined HIVDR in Africa.
HIV-1 non-B subtypes and recombinant variants, which are responsible for 90% of the 35 million infections worldwide, have a high genetic variability compared to subtype B isolates, and this high genetic diversity may influence the resistance pathways to current and newer antiretroviral (ARV) drugs. Naturally occurring polymorphisms affect ARV response in subtype B viruses. The impact of these polymorphisms on drug resistance and treatment success within the context of non-B HIV-1 strains is not well understood. Two-thirds of 2nd line treatment failures among Nigerian patients with very good pharmacy record-derived adherence confirmed by plasma drug levels had emergent mutations in the HIV-1 gag gene. The purpose of this study is to evaluate HIV-1 drug resistance outside the classical targets (i.e., pol gene). The mutations identified in Env confer broad resistance to multiple classes of ARVs. This study seeks to determine the virological basis for treatment failure in patients where resistance is not predicted by standard genotypic tests and correlate HIV resistance genotypes, phenotypes and clinical outcomes in patients infected with non-B HIV-1 subtypes.
AIGHD Research Lead
Tobias Rinke de Wit and Seth Inzaule
- University of Maryland School of Medicine, U.S.A.
- University of Cambridge, Cambride, England : Military HIV Research Program (MHRP), African Cohort Study (AFRICOS)
- Centre for Proteomic and Genomic Research (CPGR), Cape Town, South Africa HIV Dynamics and Replication Program (HIV DRP),
- National Cancer Institute Stanford School of Medicine, California, U.S.A.
Marloes Nijboer (email@example.com)
NIH (National Institutes of Health)
United States of America