Comprehensive mapping of clinically relevant resistance against coreceptor antagonists in HIV-1 non-B subtypes.

The HIV-1 envelope interacts with two receptors to enter its target cell: a primary receptor CD4 and a coreceptor, CCR5 or CXCR4. Recently maraviroc, a drug that interacts with the CCR5 coreceptor, was licensed for clinical use. As its therapeutic success greatly depends on the absence of X4 and R5X4 viral strains, patients have to be screened in advance for the presence of these natural resistant forms. This would prevent the subscription of a suboptimal antiviral regimen that could result into virological failure and resistance development against co-prescribed drugs within the regimen. The commercial and labor intensive phenotypic coreceptor test that was used within the clinical trials, is going to be replaced by more simple genotypic approaches in clinical practive, as already done for the other drug classes. The current models that predict coreceptor use from the viral envelope genotype are constructed on subtype B viruses. Because there are indications that the current models are not as sensitive and specific for non-B subtypes as for subtype B, we want to determine the subtype-dependent characteristics of coreceptor use. Additionally, we want to compare the epidemiology of co-receptor use in therapy-naïve and - experienced patients infected with non-B subtypes and compare it with subtype B infections.

Keywords:HIV, Coreceptor, Genotype, Resistance

Disciplines:Laboratory medicine, Diagnostics, Medicinal products, Public health care, Public health sciences, Public health services