ABSTRACT:
We determined the prevalence of resistant HIV-1 in newly infected individuals (NIs) by genetic analysis of reverse transcriptase (RT) and protease genes from 80 baseline plasma samples collected between July 1995 and April 1999. The subjects included mainly homosexual men (95%) from the New York Metro area (81%) and Los Angeles (14%). Plasma RNA from 80 subjects was tested by direct sequencing of three independent RT-PCR reactions. Drug-associated resistance mutations were identified for zidovudine (7.5%), lamivudine (5.0%), NNRTIs (7.5%) and PIs (2.5%). Multidrug resistant (MDR) virus was found in three (3.8%) individuals. Extensive protease gene polymorphism was observed at residues 63 (60.0%), 93 (35.0%), 10 (17.5%) and36 (5.0%).
Phenotypic testing was performed on 38 samples. The concordance between genotypic and phenotypic data was 100% resistant genotypes and 87.9% for non-resistant genotypes. Virus with three- to fivefold decreased susceptibility by phenotype to PIs and wild-type genotype was found in four cases. Limiting dilution PCR was performed on these isolates. None had a primary resistance mutation in protease. There was no difference in the incidence of protease gene polymorphisms between these isolates and viruses phenotypically susceptible to PIs. The clinical significance of baseline reduced susceptibility to antiretrovirals remains to be identified. The overall prevalence of resistant genotypes to any antiretroviral agent was 17.5%. The prevalence increased to 22.5% for virus resistant by either genotypic or phenotypic testing.
