Journal
EXPERT OPINION ON DRUG METABOLISM & TOXICOLOGY
Volume 6, Issue 1, Pages 55-68Publisher
TAYLOR & FRANCIS LTD
DOI: 10.1517/17425250903393752
Keywords
drug interactions; efavirenz; HIV; nevirapine; rifampicin; tuberculosis
Funding
- NIH [NIH K23 AI071760]
- Life-span/Tufts/Brown Center for AIDS Research [5D437W000237]
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [K23AI071760] Funding Source: NIH RePORTER
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Importance of the field: HIV/tuberculosis (TB) co-infection is common and associated with high mortality. Simultaneous highly active antiretroviral therapy during TB treatment is associated with substantial survival benefit but drug-drug interactions complicate NNRTI dosing. Areas covered in this review. We reviewed the impact of rifampicin-containing TB therapy on the NNRTIs pharmacokinetics and clinical outcome. PubMed database was searched from 1966 to July 2009 using the terms efavirenz, rifampicin, nevirapine, pharmacokinetics, pharmacogenetics, HIV, TB, CYP2B6, CYP3A4 and metabolism. References from identified articles and abstracts from meetings were also reviewed. What the reader will gain: A comprehensive review of the literature on this subject including pharmacokinetic and clinical studies. Most studies were small, observational or underpowered to detect the true effect of rifampicin on NNRTI-based therapy. None of the studies were controlled for genetic factors and there were limited data on children. Take home message: There were insufficient data to make definitive recommendations about dose adjustment of the NNRTIs during rifampin-containing therapy. Current data suggest that the standard dose of efavirenz or nevirapine is adequate in most HIV/TB co-infected adults. However, more research is needed in pediatric populations as well as to define role of drug-gene interactions.
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