A Multi-center, Double-blinded Randomized Trial for Genotype Based Personalized Prescription of Nevirapine

Genetic tests has been suggested to reduce side effects related to Nevirapine(NVP), a commonly prescribed component of highly active antiretroviral therapy(HAART) in developing countries. This clinical trials is designed to determine the efficacy and the cost-effectiveness of this approach in the developing countries setting.

NVP-based HAART and efavirenz(EFV)-based HAART will be provided through Thai national universal health coverage. Information of the prescribed drug will be collected, and monitoring for the compliance with the prescribed highly active antiretroviral therapy will be conducted.

Outcome measurements:

The primary objective of this study is to evaluate the reduction in incidences of NVP associated cutaneous side effects by genotype based personalized prescription. The volunteers will be monitored for any solicited and non-solicited adverse effects for 6 months after drug administration, with first 6 weeks intensive monitoring for cutaneous adverse reactions. Laboratory safety profiles (Complete Blood Count(CBC), Alanine transaminase(ALT), Aspartate transaminase(AST), Blood Urea Nitrogen(BUN), creatinine, direct bilirubin, total bilirubin, lactate dehydrogenase, alkaline phosphatase) will be assessed during the intensive monitoring period (6 weeks).

Statistical Methods:

Descriptive statistics will be used to evaluate the conduct of the study. Analysis variables will include overall follow-up rate, drug compliance, and events of protocol violation.

Laboratory and safety data will be presented using comparative statistics for each study group and compared within and between groups using standard parametric or non-parametric comparison tests, i.e., McNemar's test or paired t-test as appropriate.

Comparison of rate of cutaneous adverse reaction, hepatitis and severe cutaneous adverse reaction(SCAR) will be made with chi-square test. Variable that shown significant different between the "standard of care" or control group and the "genetic test" or intervention group will adjusted for the final analysis with Poisson logistic regression.

The overall rate of adverse events in all participants will be monitored whether the rate of adverse events is lower than the predefined criteria. The extension of trial may be considered based on the rate of adverse events.