Reversible reduction of nevirapine plasma concentrations during rifampicin treatment in patients coinfected with HIV-1 and tuberculosis.
BACKGROUND
Nevirapine (NVP) plasma levels are reduced in patients receiving rifampicin (RFM) for tuberculosis (TB) treatment. We determined variations over time of the pharmacokinetic parameters of NVP in patients who receive RFM.


METHODS
HIV-1-infected patients with CD4+ T-lymphocyte count <or=100 cells per microliter and TB diagnosis received standard anti-TB therapy and a fixed-dose combination of stavudine, lamivudine, and NVP. Full NVP pharmacokinetic curves were calculated at 4 (T1) and 10 weeks (T2) of combined therapy and at 4 (T3) and 26 weeks after termination of anti-TB therapy.


RESULTS
In 16 enrolled subjects, the median value of the area under the curve of NVP was reduced by 25.6% at T1 compared with NVP alone (43.7 vs. 58.7 microg x mL(-1) x h(-1); P = 0.02). The reduction was only 7.5% at T2 (54.3 vs. 58.7 microg x mL(-1) x h(-1); P = 0.17). The median C trough was reduced of 19.5% at T1 compared with T3 (3.3 vs. 4.2 microg/mL; P = 0.02) and of 7.1% at T2 compared with T3 (3.9 vs. 4.2 microg/mL; P = 0.17). The proportion of subjects with C trough values <or=3 microg/mL was 31.2% (5 of 16), 40.0% (6 of 15), and 7.7% (1 of 13) at T1, T2, and T3, respectively.


CONCLUSIONS
The reduction of the area under the curve of NVP during concomitant RFM treatment substantially decreases over time.
Matteelli
Alberto
A
Institute of Infectious and Tropical Diseases, University of Brescia, Brescia, Italy. amatteelli@bsnet.it
Saleri
Nuccia
N
Villani
Paola
P
Bonkoungou
Victor
V
Carvalho
Anna Cristina C
AC
Kouanda
Seni
S
Sanou
Marie J
MJ
Simporé
Jacques
J
Monno
Laura
L
Carosi
Giampiero
G
Regazzi
Mario
M
Dembele
Mathurin
M
D000328:Adult; D019380:Anti-HIV Agents / Q000097:blood* / Q000493:pharmacokinetics / Q000627:therapeutic use; D000904:Antibiotics, Antitubercular / Q000008:administration & dosage*; D018791:CD4 Lymphocyte Count; D005260:Female; D005500:Follow-Up Studies; D015658:HIV Infections / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D015497:HIV-1; D006801:Humans; D019259:Lamivudine / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D019829:Nevirapine / Q000097:blood* / Q000493:pharmacokinetics / Q000627:therapeutic use; D011446:Prospective Studies; D012293:Rifampin / Q000008:administration & dosage*; D018119:Stavudine / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use; D014376:Tuberculosis / Q000150:complications / Q000188:drug therapy*
D019380:Anti-HIV Agents; D000904:Antibiotics, Antitubercular; D019259:Lamivudine; D019829:Nevirapine; D018119:Stavudine; D012293:Rifampin