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The relationship between genotypic sensitivity score and treatment outcomes in late stage HIV disease after supervised HAART
Author(s) -
Castor Delivette,
Vlahov David,
Hoover Donald R.,
Berkman Alan,
Wu Ying Feng,
Zeller Barbara,
Brechtl John,
Hammer Scott M.
Publication year - 2009
Publication title -
journal of medical virology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.782
H-Index - 121
eISSN - 1096-9071
pISSN - 0146-6615
DOI - 10.1002/jmv.21500
Subject(s) - regimen , medicine , viral load , proportional hazards model , odds ratio , immunology , disease , human immunodeficiency virus (hiv) , drug resistance , oncology , biology , microbiology and biotechnology
This study investigated the effect of resistance testing quantified through a genotypic sensitivity score (GSS) on virologic, immunologic, and clinical responses among patients with late stage HIV‐1 disease receiving supervised highly active antiretroviral therapy (HAART). Newly admitted patients received drug resistance testing (n = 198) and then HAART supervised by residential health‐care facilities nurses. After initiating a resistance testing‐informed HAART regimen, patients were followed for HIV‐1 RNA suppression (<50 copies/ml), mean change in CD4 + T‐cells, new AIDS defining category C opportunistic conditions and death. GSS was constructed using the HAART regimen prescribed after resistance testing and data derived from IAS‐USA consensus mutations table with modification. Regressions with generalized estimating equations for robust estimation of standard errors and Cox proportional hazards regression estimated independent associations between GSS and treatment responses. After adjusting for adherence, initial log 10 HIV‐1 RNA levels, and other covariates, patients with a GSS ≥3 had significantly greater HIV‐1 RNA suppression (adjusted odds ratio (AOR) 2.32; 95% CI 1.14, 4.75). HIV‐1 RNA levels were lower among patients with ≥95% adherence, but the effect of GSS on viral suppression was not modified by adherence. Self‐rated health status, and baseline CD4 + T‐cell counts independently predicted HIV‐1 RNA suppression. GSS did not predict mean change in CD4 + cells/mm 3 (236 vs. 233, P = 0.92), occurrence of new AIDS defining category C conditions or death. These data support resistance testing‐guided therapy as an independent predictive factor to improve virologic responses in treatment‐experienced patients. J. Med. Virol. 81:1323–1335, 2009. © 2009 Wiley‐Liss, Inc.