Susceptibility to Antiretroviral Drugs of CRF01_AE, CRF02_AG, and Subtype C Viruses from Untreated Patients of Africa and Asia: Comparative Genotypic and Phenotypic Data

Abstract

Non-B HIV-1 viruses are predominant in developing countries where access to antiretroviral drugs (ARVs) is progressively being intensified. It is important to obtain more data on the susceptibility of these viruses to available ARVs. CRF01_AE, CRF02_AG, and subtype C strains of HIV-1 obtained from untreated patients from Vietnam, Cote d'Ivoire, and India were analyzed for their in vitro susceptibility to NRTIs, NNRTIs, PIs, and an entry inhibitor (T-20) using a recombinant viral assay (PHENOSCRIPT). The corresponding viruses, which had been previously sequenced in reverse transcriptase (RT), protease (prot), plus envelope (env) C2/V3 genes and had therefore been fully characterized, were further sequenced in env HR1 + HR2 regions. CRF01_AE isolates are sensitive to NRTIs and NNRTIs with the exception of one isolate that exhibits a decreased susceptibility to NNRTIs associated with a I135T substitution in RT. CRF02_AG and subtype C viruses are sensitive to NRTIs and NNRTIs but some CRF02_AG isolates tend to be resistant to abacavir, potentially related to associated substitutions of RT at positions 123 (D123N) plus 135 (I135V). Whereas all but one CRF01_AE isolates are fully susceptible to PIs, some CRF02_AG and, more frequently, some subtype C isolates are resistant to atazanavir. The role of substitutions in prot at positions of secondary resistance mutations 20, 36, 63, and 82 is raised with a potentially crucial role of the V82I substitution. Finally, all viruses tested, regardless of the CRF or subtype, are fully susceptible to T-20.