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

Background: HIV-positive individuals (HIV+) on antiretrovirals commonly take enough other medications to cross a threshold for polypharmacy but little is known about associated outcomes. We asked whether non-antiretroviral 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 antiretrovirals with suppressed HIV-1 RNA and uninfected individuals received at least one medication. We calculated average non-antiretroviral medication count for fiscal year 2009. As there is no established threshold for non-antiretroviral polypharmacy, we considered more than two and at least five medications. We followed for hospitalization and mortality (fiscal year 2010-2015), adjusting for age, sex, race/ethnicity and VACS Index.
Results: Among 9473 HIV+ and 39 812 uninfected individuals respectively, non-antiretroviral 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, more than two (hazard ratio 1.51, 95% CI 1.46-1.55) and at least five non-antiretrovirals (hazard ratio 1.52, 95% CI 1.49-1.56) were associated with hospitalization with no interaction by HIV status. Risk of mortality associated with more than two non-antiretrovirals interacted with HIV status (P = 0.002), but not for at least five (adjusted hazard ratio 1.43, 95% CI 1.36-1.50). For both groups and both outcomes, average medication count demonstrated an independent, dose response, association.
Conclusion: Neither severity of illness nor demographics explain a dose response, association of non-antiretroviral polypharmacy with adverse health outcomes among HIV+ and uninfected individuals.