Background and Methods:  To evaluate factors associated with improved survival among HIV-infected persons with extensive antiretroviral treatment (ART) experience we analyzed data from 1116 participants in the HIV Outpatient Study (HOPS) seen from January 1, 1994 to June 30, 2003, with > 4 years of ART, > 6 months with agents from each of the 3 major ART categories:  NRTI, NNRTI, and PI. CD4⁺ cell counts/mm³ (CD4), time on ART and highly active antiretroviral therapy (HAART), treatment interruptions, and plasma HIV viral load measurements as log₁₀ copies/cc plasma were compared among those who died vs those who survived.

Results:  Of 1116 heavily treatment-experienced (HTE) participants by our definition, followed a mean of 45 months post meeting HTE definition, 82 (7.3%) died. Mean post-HTE f/u was 37 months for deaths vs 46 months for survivors. Mean time on ART was shorter for death (7.1 years) vs survival (7.8 years, p = 0.03). Death had a lower mean CD4 at time of ART initiation (216 cells) than survival (330 cells, p <0.0001). Mean nadir CD4 for death was lower (74 cells) than for survival (194 cells, p <0.0001). Percentage of ART time spent receiving HAART was less for death (57.0%) than for survival (70.3%, p <0.0001). Deaths were more likely to have had non-HAART (usually mono- or dual-NRTI) as first ever ART than survivals (89.0% vs 76.8%, p = 0.01). Deaths were more likely to have had a treatment interruption (73.2%) than survivals (52.1%, p <0.0001). Mean number of ART drugs received was greater for death (10.2) than for survival (8.9, p = 0.0001). In multivariate analyses the following were independently associated with mortality:  higher viral load at HTE (Odds Ratio for death (OR) = 1.5, 3.6, and 8.7, respectively, for successively higher viral load categories vs undetectable, p (trend) <0.0001); lower CD4 at HTE (OR=0.98 per 10 CD4 cell increment, p = 0.02); older age at HTE (OR = 1.52 per each 10 year increment, p = 0.004); non-HAART as initial ART (OR = 2.33 vs HAART, p = 0.03); injection drug use (OR = 2.26 vs non-IDU, p = 0.02);  public insurance (OR = 1.78 vs. private, p = 0.03).

Conclusions:  Among HTE persons, improved survival was associated with:  having started ART at a higher CD4; having received HAART as initial ART; having spent a greater proportion of time on ART receiving HAART; not having undergone a treatment interruption post-ART initiation; not having used injection drugs; having private insurance; younger age; and having maintained better HIV suppression and higher CD4 counts after becoming HTE.

Keywords: survival; ART-experienced; factors