Dose adjustment of the non-nucleoside reverse transcriptase inhibitors during concurrent rifampicin-containing tuberculosis therapy: one size does not fit all.
BACKGROUND
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Kwara
Awewura
A
Warren Alpert Medical School of Brown University and The Miriam Hospital, Providence, Rhode Island 02906, USA. akwara@lifespan.org
Ramachandran
Geetha
G
Swaminathan
Soumya
S
D000328:Adult; D000480:Alkynes; D000995:Antitubercular Agents / Q000627:therapeutic use*; D048588:Benzoxazines / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D002648:Child; D003521:Cyclopropanes; D004347:Drug Interactions; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy*; D006801:Humans; D019829:Nevirapine / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage* / Q000627:therapeutic use*; D012293:Rifampin / Q000627:therapeutic use*; D014376:Tuberculosis / Q000150:complications* / Q000188:drug therapy*
D000480:Alkynes; D000995:Antitubercular Agents; D048588:Benzoxazines; D003521:Cyclopropanes; D018894:Reverse Transcriptase Inhibitors; D019829:Nevirapine; C098320:efavirenz; D012293:Rifampin