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Another Benefit to Starting ART Early: Lower Risk for Resistance

Among patients who experienced virologic rebound in this observational cohort study, risk for resistance was decreased in those who initiated ART at CD4 counts >350 cells/mm³.

In the debate about when to start antiretroviral therapy (ART) in patients with relatively high CD4-cell counts, one common concern is that such a strategy will lead to increased risk for resistance, thereby limiting future drug options. Using data from the HIV Outpatient Study (HOPS), investigators assessed the incidence of resistance mutations among patients who started treatment at various CD4-cell–count thresholds.

The analysis included all HOPS patients who entered the study treatment naive or initiated ART in 1999 or later, started ART with a potent combination regimen, had at least two subsequent study visits, and had a complete treatment history. Out of 760 such patients, 683 achieved initial virologic suppression, with 243 subsequently experiencing virologic rebound. Among this group, 78 patients (32%) underwent genotype resistance testing at or after rebound: 46 who had started ART at CD4 counts <200 cells/mm³, 14 who had started at 200–349 cells/mm³, and 18 who had started at >350 cells/mm³.

Major resistance mutations were seen more frequently among patients who initiated ART at CD4 counts <200 and 200–349 cells/mm³ (50% in each group) than among those who started at >350 cells/mm³ (22%; P=0.062). The trend was similar for each of the individual drug classes, with the results most striking for NRTI-associated mutations (48%, 31%, and 11%, respectively; P=0.005).

Comment: Although limited by the relatively small number of patients who underwent resistance testing, this study adds to other cohort data suggesting that early ART initiation does not appear to increase the risk for resistance — indeed, the incidence may be decreased in patients starting therapy at the highest CD4-cell counts. As noted by the authors, biological factors, behavioral factors, or both may underlie this difference. The restriction of the study population to only those patients who achieved initial virologic suppression decreases the potential for confounding by level of adherence.

— Paul E. Sax, MD

Published in AIDS Clinical Care July 13, 2009

Citation(s):

Uy J et al. Initiation of HAART at higher CD4 cell counts is associated with a lower frequency of antiretroviral drug resistance mutations at virologic failure. J Acquir Immune Defic Syndr 2009 Aug; 51:450.

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• earlyl institution of HAART and resistance risk
  Ann Harvey, Richmond, CA, 17 Jul 2009 3:13 PM EST
  The concern for increased risk for resistance sith early institution of HAART has to do with the number of years... [more]