An Empirical Evaluation of Pharmacokinetic Drug Interactions Between Antiretroviral Agents and Antituberculosis Drugs in Co-infected Patients in Rivers State

HIV-tuberculosis co-infection is common in Nigeria, and pharmacokinetic drug interactions between antiretroviral and antituberculosis drugs, particularly rifampicin induction of CYP450 enzymes, can significantly compromise treatment efficacy. This study empirically evaluated pharmacokinetic interactions between antiretroviral agents and antituberculosis drugs in HIV-TB co-infected patients at two tertiary hospitals in Port Harcourt and Obio-Akpor, Rivers State. A cross-sectional pharmacokinetic study was conducted in 48 HIV-TB co-infected adults receiving concurrent ART and TB treatment. Blood samples were collected at defined intervals to measure efavirenz and lopinavir plasma concentrations during and after rifampicin co-administration. Plasma concentrations were determined by HPLC and compared against established therapeutic plasma concentration ranges. Drug interaction magnitude was assessed by comparison with published reference values. Subtherapeutic plasma efavirenz concentrations were observed in 39.6 percent of patients, primarily attributed to rifampicin induction. Lopinavir concentrations fell below the minimum effective concentration in 58.3 percent of patients receiving standard lopinavir/ritonavir doses with rifampicin, consistent with significant induction-based interaction. Dose-doubling of lopinavir/ritonavir in a subset of patients restored adequate concentrations in 71.4 percent. Co-infection with hepatitis B significantly exacerbated lopinavir underexposure. The study provides original empirical pharmacokinetic data from a Nigerian HIV-TB population, demonstrating the clinical significance of rifampicin-antiretroviral interactions and supporting dose adjustment protocols for co-infected patients.

Keywords: drug interactions, antiretroviral therapy, antituberculosis drugs, HIV-TB co-infection, Rivers State