Prevalence and management of drug-drug interactions with antiretroviral treatment in 2069 people living with HIV in rural Tanzania: a prospective cohort study

Abstract

Objectives: Widespread access to antiretroviral therapy (ART) has substantially increased life expectancy in sub-Saharan African countries. As a result, the rates of comorbidities and use of co-medications among people living with HIV are increasing, necessitating a sound understanding of drug-drug interactions (DDIs). We aimed to assess the prevalence and management of DDIs with ART in a rural Tanzanian setting.

Methods: We included consenting HIV-positive adults initiating ART in the Kilombero and Ulanga Antiretroviral Cohort (KIULARCO) between January 2013 and December 2016. DDIs were classified using www.hiv-druginteractions.org as red (contra-indicated), amber (potential clinical relevance requiring dosage adjustment/monitoring), yellow (weak clinical significance unlikely to require further management) or green (no interaction). We assessed management of amber DDIs by evaluating monitoring of laboratory or clinical parameters, or changes in drug dosages.

Results: Of 2069 participants, 1945 (94%) were prescribed at least one co-medication during a median follow-up of 1.8 years. Of these, 645 (33%) had at least one potentially clinically relevant DDI, with the highest grade being red in nine (< 1%) and amber in 636 (33%) participants. Of the 23 283 prescriptions, 19 (< 1%) and 1745 (7%) were classified as red and amber DDIs, respectively. Overall, 351 (2%) prescriptions were red DDIs or not appropriately managed amber DDIs.

Conclusions: Co-medication use was common in this rural sub-Saharan cohort. A third of participants had DDIs requiring further management. Of the 9% of participants with not appropriately managed DDIs, most were with cardiovascular and analgesic drugs. This highlights the importance of physicians' awareness of DDIs for their recognition and management.

Keywords: HIV infection; drug-drug interaction; drug-drug interaction management; sub-Saharan Africa.

Figure 1

Prevalence of drug–drug interactions (DDIs) at a patient and prescription level in 2069 patients. Percentages refer to the total number of patients with co‐medications and prescriptions, respectively. Numbers are per patient and per prescription whereby one prescription equals the same drug given at several visits.

Figure 2

Prescribed co‐medications and prevalence of drug–drug interactions (DDIs) within each therapeutic class. The figure displays prescribed co‐medications classified by therapeutic class. The distribution of DDI categories is represented within each therapeutic class. (1) Prescriptions of analgesics included 272 prescriptions of nonsteroidal anti‐inflammatory drugs (NSAIDs), 176 of paracetamol and 14 of opioid analgesics. (2) Prescriptions of antibiotics included 10 013 prescriptions of cotrimoxazole, 2362 of antituberculosis drugs, 2294 of isoniazid preventive therapy, 1125 of other antibiotics and eight of antibiotics/anti‐helmintics (tinidazole). (3) Prescriptions of cardiovascular drugs included 85 prescriptions of acetylsalicylic acid 100 mg, 136 of β‐blockers, 574 of calcium channel blockers, 1320 of diuretics and 586 of Angiotensin converting enzyme(ACE)/angiotensin II inhibitors. (4) Prescriptions of psychiatric drugs included 176 prescriptions of antidepressants, 13 of sedatives/anxiolytics and 90 of neuroleptics. (5) Other prescriptions included 25 prescriptions of benzyl benzoate, 14 of salbutamol, 13 of trihexyphenidyl, 12 of oral rehydration salt, four of aminobenzoic acid, three of metformin, three of silver nitrate, three of zinc oxide, two of aminophylline, one of boric acid, one of chlorhexidine, one of hydroxypropylmethylcellulose, one of norethisterone, one of pancreas lipase, one of sildenafil and one of tetanus vaccine/antitoxin.