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Abstract
EVOLVING PATTERNS OF HIV-1 RESISTANCE TO ANTIRETROVIRAL AGENTS IN NEWLY INFECTED INDIVIDUALS
SIMON V, VANDERHOEVEN J, HURLEY A, LOUIE M, PARKIN N, BODEN D, MARKOWITZ M, RAMRATNAM B, DAWSON K
Background: We and others have reported that the prevalence of the transmission of drug resistant HIV-1 variants has increased over the past 2 years. Here we analyze changes in resistance patterns observed during 1995-2000.
Methods: 142 newly infected individuals (NI’s 1995-1998: n=74; 1999-2000: n=68) were referred to the ADARC (133 NYC area, 15 other urban centers). Baseline plasma samples were analyzed using RT-PCR and an ABI sequencer and/or the TRUEGENE HIV-1 assay (VGI, Canada). The phenotype was determined by a recombinant assay (PhenoSense, ViroLogic, Ca).
Results: Viral variants harboring resistance-associated mutations in PR (primary mutations) and/or RT genes (M41L, T69D; K70R, K103N, V118I; V179E/D, M184V, L210W; T215Y; T215S/D, K219Q) were detected in 18% of subjects (1995-1998: 9/74 12%; 1999-2000: 16/68; 24%). MDR viruses (2- or 3-drug class) were present in 5 NI’s (3.5%). Differences in frequency of mutations in PR were found at positions L90M (1 vs. 4%) and K20R (1 vs. 12%); M36I (1 vs. 19%); A71V/T (1 vs. 13%) and I93L (34 vs. 18%). In RT the frequency of NNRTI (K103N) and AZT related mutations doubled (M41L, L210W, T215Y). The 3TC mutation M184V in contrast was only detected in 1995-1998 (4%). Amino acid substitutions in RT only found in 1999-2000 were T69D (4.5%), T215S/D (6%) and T215A/V (3%). Neither T69D nor T215S/D/A/V were associated with reduced drug susceptibility. The prevalence of viral variants with >5 fold reduced susceptibility to any drug did not change over time (1995-1998: 8%; 1999-2000: 9%).
Conclusion: For the years 1999-2000 we found an increased number of both transmitted drug resistant HIV-1 variants and viruses with altered genotypes in RT but wild-type phenotypes. An absence of the M184V mutation was also seen for this period. We hypothesize that these findings may reflect transmission by previously treated individuals who have discontinued therapy allowing for the evolution of HIV-1 variants in the absence of drug pressure.
The 1st. IAS Conference on HIV Pathogenesis and Treatment
Abstract no.
122
Suggested Citation
"SIMONV, et al.
EVOLVING PATTERNS OF HIV-1 RESISTANCE TO ANTIRETROVIRAL AGENTS IN NEWLY INFECTED INDIVIDUALS.
Oral Presentation:
The 1st. IAS Conference on HIV Pathogenesis and Treatment
:
Abstract no.
122"
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