BackgroundDrug-drug interactions (DDIs) between antiretroviral therapy (ART) and commonly used co-medications in HIV patients, especially women, impact treatment efficacy and patient safety.ObjectiveThis study aimed to study the prevalence and types of drug-drug interactions (DDIs) between antiretroviral therapy drugs (ARTs) and comedications among a female population with HIV. Additionally, the study investigates the association of these DDIs with ART medication changes and treatment adherence.MethodsThis cross-sectional study included 632 adult women living with HIV (WLHIV). Data was retrospectively extracted from patient files. Drug.com interaction checker website was used to assess DDIs between ART and non-ART medications. Changes to the ART regimen previously attributed to ART side effects or patient non-adherence were considered drug changes.ResultsA total of 429 WLHIV (mean age: 44.05 ± 9.50) were eligible. The prevalence of DDIs between ART and non-ART medications was 21.4%, with 4.7% minor, 18.4% moderate, and 8.9% major interactions. The highest prevalence of DDI was among cardiovascular medication users (71.7%), followed by central nervous system drugs (69.2%). Changing medications resulted in a decrease in DDIs, with significant reductions in total and minor interactions. Participants without DDIs had better adherence to ART. DDI between ART and non-ART medications was significantly associated with ART drug change, even after accounting for side effects attributed to ARTs, indicating an independent twofold association (OR = 1.99, CI 1.04–3.77). Moreover, further adjustments for HIV viral load and CD4 + cell count did not change the significance of the association (OR = 2.01, CI 1.03–3.92).ConclusionDDIs in WLHIV impact adherence to ART. Altering ART may not be directly related to ART side effects, but rather primarily due to interactions with non-ART medications. Modifying non-ART drug regimens can reduce the likelihood of DDIs.