15th International AIDS Conference Bangkok, Thailand - July 11-16, 2004

Int Conf AIDS 2004 Jul 11-16; 15:(abstract no. WeOrB1294)

Haubrich RH, Hernandez J, Bates M, Thompson M, Margolis D, Pappa K, Yau L, Schooley R
University of California, San Diego, San Diego, CA, United States

BACKGROUND: Reduced RC has been correlated with decreased disease progression in minimally treated and CD4 maintenance in experienced patients.

METHODS: Isolates from ART experienced subjects entering ESS40006 were assessed using genotype, phenotype and RC [ViroLogic] while on a failing PI-based ART regimen prior to an ARV switch. Pearson correlation and stepwise multiple linear regression were used to explore the relationship between RC and HIV resistance and disease status.

RESULTS: 59 isolates from subjects exposed to NRTIs, NNRTIs and PIs and 26 isolates from NNRTI-naïve subjects were analyzed. In the NNRTI experienced group, RC was linearly correlated with genotypic susceptibility scores (GSS based on IAS 2003 guidelines, p=0.03) and baseline HIV-1 RNA (p<0.001); and inversely correlated with baseline CD4 count (p<0.001) and the sum of fold change [FC] at baseline (log10, p<0.0001). The presence of the M184V mutation (p=0.002), TAMs (p=0.03), and PR mutations at codon 82 (p=0.001) significantly reduced RC. Significant associations were also found between the number of NRTIs, NNRTIs, PIs, or ARVs above the biological/clinical cut-off and RC (p<0.03). In a multivariate regression model, RC was significantly associated with baseline HIV-1 RNA (p=0.004), the presence of the M184V mutation (p=0.002), and PR mutations at codon 82 (p=0.004). Findings were less significant in the NNRTI naïve group. Other factors (PSS, other mutations, duration of prior ART, APV hypersusceptibility) were not associated with RC nor was RC predictive of week 24 CD4 or HIV RNA changes. Conclusion Phenotypic (number of agents) and genotypic resistance (the M184V mutation, TAMs, and PR mutations at 82) were associated with decreased RC in experienced subjects. RC was directly correlated with viral load and inversely correlated with CD4 counts, suggesting that decreased RC due to viral resistance may be associated with preservation of CD4 numbers.

040711
WeOrB1294

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