Initiation of HAART at CD4 cell counts 350 cells/mm3 is associated with a lower prevalence of antiretroviral resistance mutations at virologic failure
Objectives: Determine prevalence of antiretroviral (ARV) drug resistance according to the CD4 cell count at which HAART was initiated among persons failing treatment.
Methods: We examined data from participants in the HIV Outpatient Study, a prospective observational cohort of HIV-infected patients seen at ten HIV-specialty clinics in the United States. We included antiretroviral-naïve patients enrolled after January 1, 1999 (when genotypic HIV resistance testing [GT] became generally available) whose viral load (VL) was suppressed following initiation of HAART and who then had GT performed due to later virologic rebound (VL >1,000 copies/mL). Among these patients, we assessed the prevalence of major resistance mutations (per IAS-USA guidelines) at first GT stratified by the CD4 cell count at which HAART was initiated. Two-sided p-values for trend were calculated with the Cochrane-Armitage Exact Test.
Results: Among 8,224 patients with evaluable data, 78 met inclusion criteria. Patients initiating at CD4 cell counts <200 cells/mm3 were older, had higher baseline VL, and were more likely to have been treated with protease inhibitors.
| ||CD4 cell count at HAART initiation (median months to virologic failure)|| |
|Major genotype mutation detected||0-199 cells/mm3 (11.8)||200-349 cells/mm3 (11.3)||³350 cells/mm3 (23.2)||p-value|
|Any mutation (N=78)||23/46 (50%)||7/14 (50%)||4/18 (22%)||0.076|
|NRTI mutation among NRTI-exposed (n=77)||22/46 (49%)||4/13 (31%)||2/18 (11%)||0.007|
|NNRTI mutation among NNRTI-exposed (n=37)||10/20 (50%)||3/7 (43%)||1/10 (10%)||0.051|
|PI mutation among PI-exposed (n=48)||9/32 (28%)||1/8 (13%)||0/8 (---)||0.103|
Conclusions: Patients who initiated HAART at CD4 cell counts >350 cells/mm3 were half as likely to develop any major resistance mutation than patients who started at <200 cells/mm3 despite a 2-fold greater exposure to ARVs at time of virologic failure. The prevalence of NRTI and NNRTI resistance mutations was almost five-fold different between patients in these two CD4 strata. Although our analyses were limited by small sample size, the same trends were seen in all ARV classes.
4th IAS Conference on HIV Pathogenesis, Treatment and Prevention
"UyJ., et al.
Initiation of HAART at CD4 cell counts 350 cells/mm3 is associated with a lower prevalence of antiretroviral resistance mutations at virologic failure.
4th IAS Conference on HIV Pathogenesis, Treatment and Prevention: