Indicators for Potential Drug-Drug Interactions Identified Among People Living With HIV

New data show the prevalence of potential drug-drug interactions varies according to the drug use pattern considered, with people living with HIV using multiple illegal drugs being at the highest risk.

The prevalence of potential drug-drug interactions (pDDIs) is significant in people living with HIV (PLHIV) who use drugs, according to new study results published in PLoS ONE.

The prevalence of pDDIs also varies according to the drug use pattern considered, with people using multiple drugs, or polydrug users, being at the highest risk.

Antiretroviral therapy (ART) agents pose a high risk for pDDIs. According to the study, ART agents mainly induce, inhibit, or are a substrate of cytochrome P450 enzymes, particularly isozyme CYP3A4, and could lead to pDDIs in PLHIV who both use illicit drugs and are on ART. The study authors also pointed out that not all ART or illicit drugs are associated with higher risk of pDDIs.

“While the prevalence of pDDIs associated with medication used concomitantly with ART because of associated comorbidities has been well described, with reported rates ranging between 34.9% and 89.2%, there is still a dearth of data on pDDIs between ART drugs and illicit drugs,” the authors said.

Part of a larger research project, this study by the Interdisciplinary Spanish AIDS Society analyzed multiple aspects of illicit drug use by PLHIV across 12 regions in Spain from 36 institutions There was a total sample of 694 PLHIV taking ART and illicit drugs, with drug type, frequency, and mode of consumption during the last year being the 3 variables used to measure illicit drug use.

Overall, the study used 6 main variables:

  • Use of illicit drugs and other substances
  • pDDIs between illicit and ART drugs
  • Awareness, beliefs, intentional nonadherence, and communication with health care providers on the use of drugs and potential pDDIs
  • Adherence to ART
  • Health-related quality of life
  • Health and use-of-health care-system–related variables

After excluding 38 participants due to lack of information, 335 (51.1%) participants exhibited pDDIs between their ART regimen and the illegal drugs they were consuming or had consumed in the previous year. The researchers identified 708 significant or contraindicated pDDIs, with only 1 pDDI being considered a contraindicated combination, and the mean (SD) number of pDDIs per patient was 2.1 (1.7).

Of 656 PLHIV, 220 (33.5%) consumed 1 illicit drug, 128 (19.5%) consumed 2 drugs, 93 (14.2%) consumed 3 drugs, 48 (7.3%) consumed 4 drugs, and 167 (25.5%) consumed 5 or more drugs.

Cannabis, cocaine, nitrates, and MDMA were among the most commonly used illicit drugs, and cannabis, cocaine, MDMA, and GHB/GBL exhibited a higher prevalence of pDDIs. Nitrates were the only drugs to not result in pDDIs.

The results suggest the prevalence of pDDIs is significant in PLHIV who use drugs and that the prevalence differs according to the drug use pattern considered. The results also show that experiencing pDDIs could lead to intentional nonadherence.

“Although we did not find any impact of pDDIs on other health-related variables, longitudinal studies should be undertaken to determine whether pDDIs could have an impact on the long-term health status of PLHIV,” the authors said.

PLHIV people with HIV at the highest risk of pDDIs according to their drug use pattern and monitor their treatment.

“An awareness, recognition, and the correct management of pDDIs are important in optimizing the medical and pharmaceutical care administered to PLHIV and could help to prevent a loss of efficacy of the drugs administered, as well as any adverse events that they may cause,” the authors said. “Therefore, it is essential to provide practitioners responsible for the care of patients with adequate training and the support tools required to easily access validated information.”


Castro-Granell V, Garin N, Jaen A, Cenoz S, Galindo MJ, Fuster-RuizdeApodaca MJ. Prevalence, beliefs and impact of drug-drug interactions between antiretroviral therapy and illicit drugs among people living with HIV in Spain. PLoS ONE. Published online November 19, 2021. doi:10.1371/journal.pone.0260334