Background:  Use of HIV genotypic and phenotypic susceptibility testing (GPT) can optimize ART drug selection, HIV suppression and CD4 cell-count responses in HIV-1-infected patients. The effect of GPT use on survival is unknown.

Methods:  We analyzed data from HAART-experienced and ART-naive patients in the HIV Outpatient Study (HOPS), a multicenter, prospective, observational study of U.S. HIV-infected persons. Patients seen since January 1, 1999 with a plasma HIV RNA >1000 copies/mL were analyzed to identify predictors of GPT use and Cox proportional hazards models were used to compare survival rates among those who did versus those who did not undergo GPT.

Results:  Of 3202 patients, 1110 (34.6%) had GPT. Median follow-up was 3.3 years. Patients who had GPT were more likely to be white, men who have sex with men (MSM), have baseline CD4 <200 cells/mm³, history of AIDS-defining illness, private insurance, and HAART-experienced with protease inhibitors (all p <0.01). In univariate analyses, improved survival was associated with GPT use (incidence rate ratio = 0.38), and baseline covariates of age ≤40 years, white race, MSM, no history of injection drug use, CD4 ≥200 cells/mm³, viral load log₁₀ ≤4.0 copies/mL, ART-naive status, and private insurance (all p ≤0.01). In Cox analyses adjusting for significant univariate factors, GPT use remained associated with improved survival for the overall cohort (hazard ratio [HR] = 0.60, p <0.001), for HAART-experienced patients (n = 2107, 808 had GPT) (HR = 0.60, p = 0.002), and for triple ART class-experienced patients (n = 951, 534 had GPT) (HR = 0.56, p = 0.006). For ART-naive patients whose first ART was HAART (n = 592, 182 had GPT) (HR = 0.33, p = 0.077), GPT was most associated with improved survival for those with baseline CD4 <200 cells/mm³ (HR = 0.22, p <0.001). In HAART-experienced persons, those who did versus those who did not undergo GPT had a mean increase in CD4 count at 12 months post baseline of 159% vs 48%, respectively, p = 0.04. Survival was improved among patients who had either genotypic testing (GT) alone (n = 644) (HR = 0.44, p <0.001) or phenotypic testing (PT) alone (n = 147) (HR = 0.19, p <0.001), compared to those who had neither.

Conclusions:  In the HOPS, GPT use was strongly associated with improved survival. Benefit was seen in both HAART-experienced and ART-naive persons, particularly those with baseline CD4 count <200 cells/mm³, and was associated with both HIV GT and PT use. GPT-associated CD4 improvements corroborated survival benefits. GPT-guided HAART selection should be routinely considered.