Initiation of HAART at higher CD4 cell counts is associated with a lower frequency of antiretroviral drug resistance mutations at virologic failure.

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 >or=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 >or=350 CD4 cells per cubic millimeter. Initiating HAART at higher CD4 cell counts may decrease the risk of developing treatment-limiting antiretroviral resistance.