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

被引:28
作者
Kwara, Awewura [1 ,2 ]
Ramachandran, Geetha [3 ]
Swaminathan, Soumya [3 ]
机构
[1] Brown Univ, Warren Alpert Med Sch, Providence, RI 02906 USA
[2] Miriam Hosp, Providence, RI 02906 USA
[3] TB Res Ctr, Madras, Tamil Nadu, India
关键词
drug interactions; efavirenz; HIV; nevirapine; rifampicin; tuberculosis; HIV-INFECTED PATIENTS; NEVIRAPINE PLASMA-CONCENTRATIONS; ACTIVE ANTIRETROVIRAL THERAPY; CYP2B6 983T-GREATER-THAN-C POLYMORPHISM; EFAVIRENZ-CONTAINING REGIMENS; CYTOCHROME P4502B6 CYP2B6; PRIMARY HUMAN HEPATOCYTES; SUB-SAHARAN AFRICA; POPULATION PHARMACOKINETICS; HIV-1-INFECTED INDIVIDUALS;
D O I
10.1517/17425250903393752
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:55 / 68
页数:14
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