Methadone Reduced Nevirapine Pharmacokinetic Parameters in People Living With HIV in Malaysia

@#Introduction: The HIV epidemic in Malaysia predominantly affects males (90% of total HIV cases) mostly intravenous drugs users. Nevirapine-based of highly active antiretroviral therapy (HAART) once- or twice-daily dosage improve accessibility and effectiveness of antiretroviral treatment for HIV positive intravenous drug users (IDUs) receiving methadone maintenance treatment. Studies reported that concomitant administration of nevirapine with methadone reduced methadone plasma concentration. Since methadone and nevirapine were both known to be the substrate for cytochrome 2B6 (CYP 2B6), concomitant use of both drugs may affect nevirapine concentration too. However, methadone effect on nevirapine concentration is still unclear. This is a cross sectional study which reports how methadone co-administration affects the pharmacokinetic parameters of nevirapine in people living with HIV (PLHIV). Methods: 112 patients receiving nevirapine-based antiretroviral drugs were recruited. Seventeen were maintained with methadone without withdrawal symptoms. High-performance liquid chromatography was used to measure plasma nevirapine concentrations. Nevirapine population pharmacokinetics was modelled with a non-parametric approach using Pmetrics software. Result: According to univariate analysis, concurrent methadone administration increased the clearance of nevirapine by 25.3% (p = 0.046). Multivariate analysis showed that methadone medication was independently linked with lower nevirapine concentrations and area-under-curve (Cmin was reduced by 15.2%, p = 0.011, Cmax 19.5%; p = 0.003, AUC12 16.2%; p = 0.021 respectively). Conclusion: This study provides in-vivo evidence of methadone co-administration reducing nevirapine exposure. Since a low concentration of nevirapine will lead to treatment failure, monitoring is essential for PLHIV using both medications at the same time.

Tualang Honey Potentially Delay Deterioration in Haematological and Immunological Parameters in Asymptomatic, Treatment-naïve HIV-infected Patients

@#Introduction: This report aimed to assess the effects of administration of Tualang honey for six months duration on the haematological and immunological parameters in treatment-naïve HIV-infected patients who were asymptomatic. Methods: This was a randomised, controlled, open-labelled study. A total of 95 asymptomatic HIV-positive subjects with low CD4 counts of 250-600 cells/mm3 and not on antiretroviral therapy were recruited. Tualang honey was administered at 20 g each, once daily (HLD; total of 20 g honey), twice daily (HID; total of 40 g honey) or thrice daily (HHD; total of 60 g honey) for six months period. Control (CT) group did not receive any honey supplementation. Haematological and immunological parameters were measured at baseline, three-month and six-month follow-up. The differences within the group (time effect) and between the groups (regardless of time) for all four groups were analysed using Repeated Measures ANOVA followed by a post-hoc test. Results: A significant reduction in total white blood cell, neutrophil and lymphocyte counts were observed at six-month follow-up in CT and HLD groups when compared to baseline. The immunological parameters showed similar trend of reduction in the CT and HLD groups. Meanwhile, the measured parameters were relatively maintained in HID and HHD groups at six-month period when compared to baseline. Conclusion: Tualang honey supplementation at intermediate and high doses for six months delay the deterioration of haematological and immunological parameters in asymptomatic, treatment-naïve HIV subjects.