Factors associated with mortality among persistently viraemic triple-antiretroviral-class-experienced patients receiving antiretroviral therapy in the HIV Outpatient Study (HOPS)

Abstract

Background: Identifying factors associated with mortality for HIV-infected patients with persistent viraemia despite antiretroviral (ARV) therapy may inform diagnostic and treatment strategies. Methods:We analysed data from viraemic triple-ARV-class-experienced HIV Outpatient Study patients seen during 1 January 1999 to 31 December 2012 who, despite treatment that included ARVs from three major drug classes [nucleoside analogue reverse transcriptase inhibitors, non-nucleoside analogue reverse transcriptase inhibitors and protease inhibitors (PIs)], had plasma HIV RNA levels [viral load (VL)] >1000 copies/mL ['triple ARV class failure' (TCF)]. The baseline was defined as the date of meeting the TCF criteria during 1999-2008. We identified factors associated with mortality using Cox regression. Results: Of 597 patients who met the TCF criteria (median follow-up after baseline 4.9 years), 115 (19.3%) died. Baseline factors associated with mortality were age per 10 years [hazard ratio (HR) 1.61, 95% CI 1.28-2.02], risk of HIV from use of injection drugs (HR 1.81, 95% CI 1.10-2.98), CD4+ Tcell count <200 cells/mm3 (HR 3.68, 95% CI 2.41-5.62), VL ≥5.0 log10 copies/mL (HR 2.91, 95% CI 1.88-4.49) and receiving a first combination ARV therapy regimen that was PI-based (HR 2.44, 95% CI 1.47-4.06); receiving a novel ARV agent during follow-up (HR 0.45, 95% CI 0.22-0.93) was protective. Genotypic resistance testing results were available for 274 (45.9%) of the TCF patients, of whom 47 (17.2%) died. In this group, factors associated with death were increasing age (HR 1.94, 95% CI 1.36-2.78, per 10 year increment), risk of HIV from use of injection drugs (HR 2.71, 95% CI 1.37-5.39), baseline VL ≥5.0 log10 copies/mL (HR 5.35, 95% CI 2.82-10.1) and receiving PI-based first combination ARV therapy regimen (HR 3.20, 95% CI 1.25-8.17). No HIV mutations or combinations of mutations were significantly associated with survival. Conclusions: Factors significantly associated with mortality risk among TCF patients who received ongoing ARV therapy included traditional clinical predictors but not the presence, type or number of HIV genetic mutations. The use of novel ARV drugs by these ARV therapy-experienced patientswas associated with an improved survival.