Identification of Potential Clinically Significant Drug Interactions in HIV-infected Patients

A Comprehensive Therapeutic Approach

C Iniesta-Navalón; JJ Franco-Miguel; JJ Gascón-Cánovas; L Rentero-Redondo


HIV Medicine. 2015;16(5):273-279. 

In This Article

Abstract and Introduction


Objectives The aim of the study was to determine the prevalence of potential clinically significant drug interactions (CSDIs) in HIV-positive individuals and to identify associated risk factors.

Methods A cross-sectional study was conducted including all HIV-infected out-patients attending the Pharmacy Service of a regional reference hospital in Murcia, south-eastern Spain. The complete treatment was screened for possible CSDIs using the Spanish College of Pharmacists' online software resource, bot. Additionally, the severity level of the CSDIs involving antiretroviral (ARV) drugs was compared with that established in the specific antiretroviral database Multivariate logistic regression was used to identify associated risk factors.

Results Two hundred and sixty-eight patients were included in the study. A total of 292 potential drug interactions were identified, of which 102 (34.9%) were CSDIs, of which 52.9% involved ARV drugs. Seven therapeutic drug classes were involved in 75% of CSDIs (protease inhibitors, benzodiazepines, nonsteroidal anti-inflammatory drugs, nonnucleoside reverse transcriptase inhibitors, corticosteroids, antithrombotics and proton pump inhibitors). Factors independently associated with CSDIs were treatment with more than five drugs [odds ratio (OR) 15.1; 95% confidence interval (CI) 6.3–36.2], and treatment with a protease inhibitor (OR 5.3; 95% CI 2.4–11.74).

Conclusions The findings of this study suggest that the prevalence of clinically relevant drug–drug interactions is high in HIV-infected patients, and could represent a major health problem. Awareness, recognition and management of drug interactions are important in optimizing the pharmaceutical care of HIV-infected patients and helping to prevent adverse events and/or loss of efficacy of the drugs administered.


As a result of improved antiretroviral therapy (ART), the expected lifespan of HIV-positive individuals has increased dramatically, but comorbidities such as cardiovascular disease, hyperlipidaemia, hypertension, diabetes, osteoporosis, renal disease and non-AIDS-related cancers are increasingly common.[1] Because of this comorbidity, a wide variety of drugs (e.g. antidepressives or antibacterials) are used alongside antiretroviral drugs. However, the combination of such drugs presents the potential for drug–drug interactions (DDIs), an important cause of adverse drug reactions (ADRs).

Drug–drug interactions are one of the main health problems associated with drug use: around 5% of drug use-related side effects in primary care may be caused by DDIs.[2] Clinically significant drug interactions (CSDIs) involving antiretroviral agents have been reported in 30–41.2% of HIV-positive patients in the USA,[3] and 20–23% in the Netherlands.[4] Several studies have suggested a positive correlation between increased age and increased risk for drug interactions in HIV-positive patients.[5] However, most studies focus on interactions involving at least one antiretroviral (ARV) drug and ignore those that involve non-ARV drugs, despite the fact that such drugs may be responsible for undesirable side effects, which may reduce adherence to treatment with a consequent decrease in effectiveness.

The recognition and management of drug interactions are important in optimizing the pharmaceutical care of HIV-infected patients by helping to prevent adverse events and/or loss of efficacy of the administered drugs.[7–9] Awareness and knowledge of these risk factors may prove helpful as clinicians attempt to identify and manage drug interactions for patients receiving ART.[3]

Because of its importance to public health, this is a topic that has gained prominence in recent years but, despite this, to the best of our knowledge, few studies have focused on the prevalence of DDIs in the overall treatment of HIV-positive individuals. In this study, our goals were to determine the prevalence of potential CSDIs in HIV-positive individuals, and to identify any associated risk factors.