ICAAC 2006 - Antiretroviral Drug Resistance in Patients With HIV

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(c) medscapeAntiretroviral drug therapy (ART) of HIV continues to improve, with current regimens offering greater convenience, tolerability, and even the ability to retain activity when resistance has developed, compared with the first highly active ART (HAART) regimens available a decade ago. The study of antiretroviral (ARV) drug resistance is crystallizing into distinct categories:

  • The prevalence and clinical implications of transmitted or primary HIV resistance;
  • the genetic mechanisms of drug resistance during initial treatment failure;
  • the implications of cross-resistance for salvage therapy with drugs belonging to previously used drug classes; and
  • the optimal use of new drug classes for treatment of persons in whom previous regimens failed.

Although only a small proportion of presentations at the 46th ICAAC were devoted to HIV drug resistance, there were several abstracts that extended current knowledge in each of these categories.

Primary Resistance to ARVs

There have been many small studies of the prevalence of HIV-1 drug resistance in previously untreated persons in the United States and Europe. Some of these studies have included only persons presenting with primary or acute HIV-1 infection; most have included previously untreated persons with chronic infection of unknown duration. The largest study in the United States is an ongoing surveillance program conducted by the US Centers for Disease Control and Prevention (CDC) in which newly HIV-1-diagnosed persons have samples tested for genotypic resistance to HIV-1 reverse transcriptase inhibitors (RTIs) and protease inhibitors (PIs). At this year's ICAAC, Ross and coworkers[1] described the prevalence of primary drug resistance in a second large US population -- previously untreated persons in the United States screened for clinical trials conducted by GlaxoSmithKline, Research Triangle Park, North Carolina. From 2000 to 2005, 2035 patients in 33 states underwent genotypic resistance testing. The overall percentage of patient samples with genotypic resistance to 1 or more drug classes increased from 5% and 10% in 2000 and 2001 to 14% and 16% in 2004 and 2005. Resistance rates to nonnucleoside RTIs (NNRTIs) increased from 2% at the start of the study to 10% by the end of the study. These results are highly similar to the 14% overall resistance to at least 1 class of ARV and 9% NNRTI resistance for the years 2003-2004 that were reported by the CDC at the 2005 Conference on Retroviruses and Opportunistic Infections (CROI).[2] In the analyses reported by Ross,[1] the highest rates of resistance were reported in whites from states in the western part of the United States.

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