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AIDS. 2018 Mar 27;32(6):739-749. doi: 10.1097/QAD.0000000000001756.

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

Author information

Veterans Affairs Connecticut Healthcare System, Yale University School of Medicine and Public Health, West Haven, Connecticut.
Washington DC Veterans Affairs Medical Center and George Washington University School of Medicine and Health Sciences, Washington, DC.
Department of Medicine (Infectious Diseases), Department of Biostatistics and Epidemiology, Center for Clinical Epidemiology and Biostatistics, Center for Pharmacoepidemiology Research and Training, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
Emory University School of Medicine, Atlanta, Georgia.
VA Connecticut Healthcare System and Yale School of Nursing, West Haven, Connecticut.
Icahn School of Medicine at Mount Sinai, New York City, New York, USA.



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.


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.


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.


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

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