METHODOLOGY: Cord blood samples from a pilot screening programme for congenital hypothyroidism in 1995 at Ipoh city and surrounding district hospitals were screened anonymously for HIV 1 and 2. HIV status was determined using chemiluminescent technology. Positive samples were retested using the Genelavia Mixt assay.
RESULTS: A total of 4927 samples were tested. The ethnic breakdown included 51.7% Malays, 18.9% Chinese, 14.3% Indian, 2.3% Others and 12.9% unknown. The geographical distribution of samples was 73.9% urban, 24.2% rural and 1.9% unknown. The seroprevalence of HIV positivity was 3.25 per 1000 deliveries (95% CI: 1.92-5.16). Seroprevalence was higher for samples from rural and Malay mothers.
CONCLUSION: The high seroprevalence in this study suggests that the spread of HIV is far wider than that anticipated by mandatory national reporting. It also supports antenatal screening and the use of antiretroviral therapy as an important strategy to reduce perinatal transmission.
METHODS: Nevirapine population pharmacokinetics was modelled with Pmetrics. A total of 708 observations from 112 patients were included in the model building and validation analysis. Evaluation of the model was based on a visual inspection of observed versus predicted (population and individual) concentrations and plots weighted residual error versus concentrations. Accuracy and robustness of the model were evaluated by visual predictive check (VPC). The median parameters' estimates obtained from the final model were used to predict individual nevirapine plasma area-under-curve (AUC) in the validation dataset. The Bland-Altman plot was used to compare the AUC predicted with trapezoidal AUC.
RESULTS: The median nevirapine clearance was of 2.92 L/h, the median rate of absorption was 2.55/h and the volume of distribution was 78.23 L. Nevirapine pharmacokinetics were best described by one-compartmental with first-order absorption model and a lag-time. Weighted residuals for the model selected were homogenously distributed over the concentration and time range. The developed model adequately estimated AUC.
CONCLUSIONS: In conclusion, a model to describe the pharmacokinetics of nevirapine was developed. The developed model adequately describes nevirapine population pharmacokinetics in HIV-infected patients in Malaysia.
MATERIALS AND METHODS: A total of 112 patients were recruited and treated with nevirapine-based antiretroviral therapy. Plasma nevirapine and metabolite concentrations were assayed using high-performance liquid chromatography via liquid-liquid extraction.
RESULTS: Thirty-nine (34.8%) of the patients had no 3-OH NVP detected in their plasma while 2-OH NVP was detected in all patients. Metabolite concentrations were low compared to nevirapine. Positive correlations were observed between nevirapine and its metabolites, 2-OH NVP (P < 0.01) and 3-OH NVP (P = 0.012). Nevirapine concentration was decreased when concomitantly administered with methadone. Univariate analysis showed that ALT level, AST level, and detection of 3-OH NVP were associated with nevirapine pharmacokinetic parameters.
CONCLUSION: The variability of nevirapine pharmacokinetic parameters was caused by liver enzymes and the presence of 3-OH NVP metabolites. The presence of 3-OH NVP can probably be used to distinguished CYP2B6 activity and efficacy of nevirapine in patients with HIV infection.