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Initiation of HAART at Higher CD4 Cell Counts Is Associated With a Lower Frequency of Antiretroviral Drug Resistance Mutations at Virologic Failure

Uy, Jonathan MD*; Armon, Carl MSPH; Buchacz, Kate PhD; Wood, Kathy BSN; Brooks, John T MDthe HOPS Investigators

JAIDS Journal of Acquired Immune Deficiency Syndromes: August 2009 - Volume 51 - Issue 4 - p 450-453
doi: 10.1097/QAI.0b013e3181acb630
Brief Report: Clinical Science

Background: There are limited data on the risk of developing HIV drug resistance based on the CD4 cell count at which highly active antiretroviral therapy (HAART) is initiated.

Methods: We examined data from participants in the HIV Outpatient Study who initiated antiretroviral therapy with HAART in 1999 or later (when genotypic resistance testing became more commonly used in clinical practice and in the HIV Outpatient Study), achieved virologic suppression, and subsequently experienced virologic failure and received a genotypic assay for antiretroviral resistance mutations. We assessed the frequency of resistance mutations at virologic failure and the differences in the frequencies of mutations by the CD4 stratum at which HAART was initiated using the Cochran-Armitage exact test.

Results: Of 683 patients who achieved virologic suppression on a first HAART regimen, 243 had virologic failure and 78 of these had a genotype resistance test done. Among these patients, the frequency of any HIV resistance mutations was 50% among patients who started HAART at 0-199 CD4 cells per cubic millimeter or 200-349 CD4 cells per cubic millimeter compared with 22% among patients who started HAART at ≥350 CD4 cells per cubic millimeter (P = 0.062). The frequency of nucleoside reverse transcriptase inhibitor-associated mutations was 48%, 31%, and 11% among persons who initiated nucleoside reverse transcriptase inhibitor-containing HAART within these respective CD4 cell count strata (P = 0.005). We observed similar trends for nonnucleoside reverse transcriptase inhibitor-associated (P = 0.040) and protease inhibitor-associated (P = 0.063) mutations among persons initiating HAART containing these agents.

Conclusions: Patients failing HAART that was initiated at <350 CD4 cells per cubic millimeter had higher frequencies of resistance mutations to the classes of antiretrovirals to which they had been exposed than failing patients who initiated at ≥350 CD4 cells per cubic millimeter. Initiating HAART at higher CD4 cell counts may decrease the risk of developing treatment-limiting antiretroviral resistance.

From the *University of Illinois, Chicago, IL; †Cerner Corporation, Vienna, VA; and ‡Division of HIV/AIDS Prevention, Centers for Disease Control and Prevention, Atlanta, GA.

Received for publication August 22, 2008; accepted April 8, 2009.

Supported by Contract 200-2006-18797-Centers for Disease Control and Prevention.

Presented at the 4th IAS Conference on HIV Pathogenesis, Treatment, and Prevention, July 2007, Sydney, Australia. Poster WEPEB017.

Jonathan Uy is currently employed by Bristol-Myers Squibb. All other authors have no conflicts of interest.

The findings and conclusions in this report are those of the authors and do not necessarily represent the official views of the Centers for Disease Control and Prevention.

The investigation followed the guidelines of the US Department of Health and Human Services regarding protection of human subjects. The study protocol was approved and renewed annually by each participating institutions' ethical review board. All study participants provided written, informed consent.

Correspondence to: Jonathan Uy, MD, Associate Director, Virology Medical Strategy, Bristol-Myers Squibb, 777 Scudders Mill Road, Plainsboro, NJ 08536 (e-mail:

© 2009 Lippincott Williams & Wilkins, Inc.