Taking large numbers of medications in addition to antiretroviral therapy (ART) is associated with an increased risk of hospitalisation and death for HIV-positive individuals, investigators from the US Department of Veterans Affairs report in AIDS. Taking at least two medications in addition to triple ART was associated with a 50% increase in the risk of hospitalisation and 20% increase in mortality risk. But the investigators found that taking large numbers of therapies – polypharmacy – had a similar association with adverse health outcomes in matched HIV-negative controls.
“In this large cohort of HIV+ and demographically similar uninfected individuals, non-antiretroviral polypharmacy demonstrates a dose-response association with hospitalization and mortality and neither severity of illness nor demographic factors explain these associations,” write the authors. “Short of a randomized trial, these results provide important evidence that non-antiretroviral polypharmacy contributes to adverse health events among those aging with and without HIV infection.”
Improvements in treatment and care mean that most HIV-positive individuals now have an excellent life expectancy, and increasing numbers of people are surviving into older age. Diseases associated with ageing are responsible for much of the illness now observed in individuals with HIV, with many people taking medications for the treatment of these conditions, in addition to their antiretroviral therapy.
In the general population, taking five or more therapies is classified as polypharmacy and has been associated with a range of adverse health outcomes.
Investigators from the Department of Veterans Affairs – one of the largest HIV care providers in the US – wanted to see if non-antiretroviral polypharmacy was associated with an increased risk of hospitalisation and death.
They designed a prospective study involving HIV-positive antiretroviral-treated people and closely matched controls.
There were two definitions of non-ART polypharmacy: taking at least two medications, and taking five or more medications.
Data on polypharmacy were collected for 2009 and its association with hospitalisation and death was examined in the period 2010 to 2015. When examining these associations, the investigators took into account potential confounders.
The study population consisted of 9473 HIV-positive and 39,812 HIV-negative individuals. Just under two-thirds were aged between 50 and 64 years and almost all were men. The HIV-positive people had a median CD4 cell count of 515 cells/mm3.
Several common co-morbidities were equally distributed among the HIV-positive and HIV-negative individuals, including uncontrolled hypertension (21%), hyperlipidemia (42%) and mental health disorders (27%).
Overall, illnesses were more severe among people with HIV than their HIV-negative peers. During the five years of follow-up individuals with HIV were more likely than HIV-negative people to be hospitalised (58% vs 55%) or die (17% vs 14%).
Factors associated with polypharmacy were similar regardless of HIV status, including older age, hypertension, diabetes, coronary heart disease, chronic obstructive pulmonary disease and elevated blood lipids.
In adjusted analysis, after controlling for disease severity and demographic factors, polypharmacy was associated with an approximately 50% increase in the risk of hospitalisation, regardless of HIV status (two or more medications (HR = 1.51; 95% CI, 1.47-155; five or more, HR = 1.52; 95% CI, 1.49-1.56). Each additional non-antiretroviral increased the risk of hospitalisation by 8% (HR = 1.08; 95% CI, 1.08-1.08).
Polypharmacy was also associated with a significant increase in mortality risk. Taking at least two medications increased the risk of death by 20% for HIV-positive people and 49% for HIV-negative individuals. Treatment with five or more therapies was associated with a 43% increase in mortality risk, regardless of HIV infection status.
“Accounting for demographics and severity of illness, both HIV+ and uninfected individuals experience increased risk of hospitalization and mortality when exposed to increasing counts of non-antiretroviral medication,” conclude the authors. “Future research is needed to determine the impact of eliminating medications not essential for quality of life and survival among those aging with HIV infection.”
Justice AC et al. Nonantiretroviral polypharmacy and adverse health outcomes among HIV-infected and uninfected individuals. AIDS, 32: 739-49, 2018.