ABSTRACT: Purpose: We performed antiretroviral (ARV) susceptibility testing for reverse transcriptase (RT) inhibitors and protease inhibitors (PIs) for 133 subjects from five sites (San Diego, Los Angeles, Dallas, Denver and Boston) in the USA with HIV seroconversion within the preceding 12 months and 57 days of prior ARV therapy.
Methods: Baseline plasma samples were obtained a mean of 56 days after estimated HIV seroconversion from patients identified between 1990 and 1998. The ViroLogic PhenoSense HIV assay was used to assess ARV drug susceptibility (reduced susceptibility range 2.5 to >300-fold) compared to the control virus (pNL4-3) and population-based ABI sequence analysis was used to evaluate viral genotype.
Results: A major reduction in susceptibility (>10-fold) was observed in 3% of subjects: 2% to a nucleoside RT inhibitor (NRTI), 1% to a non-nucleoside RT inhibitor (NNRTI) and 2% to a protease inhibitor (PI). Sequence analysis of these samples showed multiple primary drug resistance mutationsn (T215Y, M184V, L90M, M46I, V82T, I84V) in the background of numerous secondary mutations. A moderate reduction in susceptibility (>2.5-10-fold) to one or more drug was observed among 29% of subjects (NRTI 4%, NNRTI 18%, PI 11%). The observed reductions in susceptibility to the NNRTI class were generally at lower levels than previously reported among nevirapine-treated patients with the Y181C substitution. Sequence analysis of these samples showed numerous polymorphisms, but no primary drug resistance mutations. The frequency of samples with reduced susceptibility to the PIs did not change during the study period, although both patients with a major reduction in susceptibility were identified in July 1998.
Conclusions: Routine resistance testing is necessary to identify and optimally treat patients with a major reduction in susceptibility to one or more antiretroviral agents. The high prevalence of moderate reductions in drug susceptibility may have treatment implications in newly infected patients; further studies are needed to clarify the clinical significance of such reductions in susceptibility.
