The spectrum and frequency of reduced antiretroviral drug susceptibility with primary HIV infection in the United States.
authors
Little S, Daar E, Keiser P, D'Aquila R, Connick E, Hellmann N, Petropoulos C, Koup R, Rosenberg E, Walker B, Richman D.
publication
6th National Conference on HIV and Opportunistic Infections. 31 Jan-4 Feb 1999, Chicago, IL.
ABSTRACT
We performed antiretroviral (ARV) susceptibility testing for reverse transcriptase and protease inhibitors for 69 subjects from 5 sites (San Diego, Los Angeles, Dallas, Denver, Boston) in the US with HIV seroconversion within the preceding 12 months and <> 7 days of prior ARV therapy (additional specimens are under analysis). Plasma samples were obtained a mean of 55 days after estimated HIV seroconversion and evaluated by the ViroLogic assay for evidence of reduced drug susceptibility (range 2.5 to >300 fold) compared to the control virus (pNL4-3). The percentage of subjects with reduced susceptibility to the nucleoside and non-nucleoside inhibitors of reverse transcriptase (NRTI and NNRTI) and protease (PI) was NRTI 3%, NNRTI 17%, PI 13%, and Any Drug 28%. Although reduced susceptibility to the NNRTIs (NVP, DLV, and EFV) was 17%, levels of resistance were lower than have previously been reported among NVP-treated patients with the Y181C substitution. Reduced susceptibility to one PI was observed in 7 subjects and to all 4 PIs tested (SQV, IDV, RTV, NFV) in 2 subjects. Reduced susceptibility to one drug (N=12) or more than one drug (N=7) was demonstrated in 28% of the study population. Genotypic analysis will be performed to determine whether these changes result from known resistance mutations or natural polymorphisms. These findings may have clinical implications for primary therapy decisions.
