Non antiretroviral polypharmacy and adverse health outcomes among HIV-infected and uninfected individuals.

BACKGROUND: HIV positive individuals (HIV+) on antiretrovirals (ARV) commonly take enough other medications to cross a threshold for polypharmacy but little is known about associated outcomes. We asked whether non-ARV polypharmacy is associated with hospitalization and mortality and whether associations differ by HIV status.

METHODS: Data on HIV+ and uninfected individuals in the US Veterans Affairs Healthcare System were analyzed. Eligible HIV+ were on ARVs with suppressed HIV-1 RNA and uninfected individuals received at least one medication. We calculated average non-ARV medication count for FY 2009. Since there is no established threshold for non-ARV polypharmacy, we considered >2 and ≥5 medications. We followed for hospitalization and mortality (FY 2010-2015), adjusting for age, gender, race/ethnicity and VACS Index.

FINDINGS: Among 9,473 HIV+ and 39,812 uninfected individuals respectively, non-ARV polypharmacy was common (>2: 67%, 71%; ≥5: 34%, 39%). VACS Index discriminated risk of hospitalization (c-statistic: 0.62, 0.60) and mortality (c-statistic: 0.72, 0.70) similarly in both groups. After adjustment, >2 (HR 1.51, 95% CI 1.46, 1.55) and ≥5 non-ARVs (HR 1.52, 95%CI 1.49, 1.56) were associated with hospitalization with no interaction by HIV status. Risk of mortality associated with >2 non-ARV interacted with HIV status (p = 0.002), but not for ≥5 (adjusted HR 1.43, 95% CI 1.36, 1.50). For both groups and both outcomes, average medication count demonstrated an independent, dose response, association.

INTERPRETATION: Neither severity of illness nor demographics explain a dose response, association of non-ARV polypharmacy with adverse health outcomes among HIV+ and uninfected individuals.