High Rates of Polypharmacy-Associated Adverse Events Seen in Those Aging With HIV

People aging with HIV have more drug–drug interactions compared with those without HIV, according to results of an observational study.

Results of an observational study revealed that for each additional medication, people aging with HIV have more drug­–drug interactions compared with those without HIV.

Findings, published in The Lancet Healthy Longevity, also showed that after adjusting for known non–antiretroviral therapy (ART) drug–drug interactions, each additional non-ART medication confers excess risk of hospitalization among those aging with HIV, the authors explained.

Polypharmacy—typically defined as the simultaneous use of 5 or more medications—is common among older adults in North America and Europe and is associated with hospital admission and mortality in a dose-response manner, in addition to other adverse events.

For individuals aging with HIV, polypharmacy poses a host of challenges as these individuals “typically have polypharmacy a decade earlier than uninfected individuals” and “have excess physiological frailty, making them more susceptible to the adverse effects of medications,” the researchers wrote.

The greater the number of medications taken concomitantly, the higher the risk of harmful interactions with other medications and substances. Although ART extends survival, medications must be taken for life and “have an exceptionally large number of drug–drug interactions,” they added.

To better understand the association between hospitalization and all known pairwise drug interactions (KPDIs) in this population, the researchers used data from DrugBank, which contains information on all US FDA-approved drugs and was last updated in 2018.

The current analysis is an extension of a previous study and includes those “aging with HIV receiving ART who had suppressed HIV-1 RNA and people without HIV who were receiving at least 1 prescription medication from the US Veterans Affairs Healthcare System (VA) in the fiscal year of 2009 (Oct 1, 2008, to Sept 30, 2009).”

Individuals were followed up with until March 2019 for hospitalization and all-cause mortality, while analyses were restricted to medications filled on a chronic basis (at least 90 consecutive days allowing for a 30-day refill window). The researchers utilized the Veterans Aging Cohort Study (VACS) Index 2.0 to adjust for frailty (scored 0 to 100) with higher scores indicating a greater risk of mortality due to physiological injury.

A total of 9186 people living with HIV and 37,930 individuals without HIV were included in the final study; the majority of patients were male and aged 50 to 64 years.

Analyses revealed:

  • Compared with a random sample of medications, real-world pattern of medication counts and combinations were associated with 5 to 6 times more KPDIs (eg, for a combination of 6 medications, the KPDI count was 1.09 in the random sample, 5.49 in the HIV-negative population, and 7.13 in those living with HIV)
  • Among people aging with HIV, the median (interquartile range) CD4 count was 511 (346-720) cells/mm3
  • Non-ART medication counts were lower for people aging with HIV than those without HIV (mean [SD] count, 3 [3] vs 4 [3])
  • People aging with HIV had higher VACS Index 2.0 scores, suggesting greater physiological frailty than those without HIV (mean score, 50 [15] vs 33 [11])
  • For each additional observed medication, people aging with HIV had approximately 2.94 additional KPDIs and comparators had approximately 2.67 additional KPDIs
  • Adjustment for demographics, physiological frailty, and KPDI Index reduced the association between medication count and risk of hospitalization for people aging with HIV (HR, 1.08; 95% CI, 1.07-1.09 reduced to HR, 1.06; 95% CI, 1.05-1.07) and those without HIV (HR, 1.08; 95% CI, 1.07-1.08 reduced to, HR 1.04; 95% CI, 1.03-1.05)

People living with HIV also had higher rates of hospitalization and mortality. Overall, findings suggest “people aging with HIV might be more susceptible to harm from polypharmacy than those without HIV, both due to KPDIs and other mechanisms of injury,” the authors said.

Furthermore, they found that “when an individual was on a large number of medications, the harmful effects of polypharmacy appeared to outweigh benefit.”

As individuals with HIV were taking a lower number of non-HIV medications than those without ART, the authors hypothesized HIV-care providers are already concerned about polypharmacy.

Measures of medication count reflected in the analysis were conservative, as they only included those dispensed within the VA, marking a limitation to the study. The nature of drug interactions is also highly variable and investigators were not able to evaluate interactions between alcohol or other substances. Unadjusted confounding may have also affected the results.

Future analyses including more women patients should be carried out in health care systems to yield more generalizable findings, the researchers said.

“Sophisticated informatics tools are needed to better guide drug selection and deprescribing to avoid excess hospitalizations and mortality due to polypharmacy,” they concluded.


Justice AC, Gordon KS, Romero J, et al. Polypharmacy-associated risk of hospitalization among people ageing with and without HIV: an observational study. Lancet Healthy Longev. Published online October 1, 2021. doi:10.1016/S2666-7568(21)00206-3