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Pharmacokinetics of Nevirapine and Rifampicin in TB/HIV Co-infected Patients in Burkina Faso
Alberto Matteelli*1, N Saleri1,3, M Regazzi2, P Villani2, V Bonkoungou3, J Simpore3, A Carvalho1, M Cusato2, G Carosi1, and M Dembele3
1Inst of Infectious and Tropical Diseases, Univ of Brescia, Italy; 2Inst of Pharmacology, IRCCS, San Matteo, Pavia, Italy; and 3Natl TB Prgm, Ministry of Hlth, Burkina Faso
Background: Nevirapine (NVP) is part of
first-line antiretroviral regimens (HAART) of most resource-limited countries.
Rifampicin (RFM), an essential component of any anti-tuberculosis (anti-TB) regimen,
significantly reduces NVP plasma levels. We have determined the full pharmacokinetic
curves of NVP and RFM in patients on combined therapy in Burkina Faso.
Methods: We enrolled patients with
documented HIV-1 infection, CD4+ T lymphocyte <100 cells /cm3,
no previous history of HAART and TB diagnosis according to national guidelines.
Standard anti-TB therapy (2 RHZE/4 RH) and standard HAART (fixed dose
combination of stavudine, lamivudine, and NVP) were used in all cases. HAART
was started within 30 days from anti-TB therapy; NVP was given as 200 mg once daily
for 2 weeks, then 200 mg twice dai1y. We plotted 3 NVP pharmacokinetic curves: after
4 weeks of RFM+NVP (T1); after 10 weeks of RFM+NVP (T2); and 4 weeks after
termination of anti-TB therapy (T3). RFM pharmacokinetic curves were: at
steady state before NVP (T0); after 4 weeks of RFM+NVP (T1); and after 10 weeks
of RFM+NVP (T2). NVP and RFM parameters were measured by high-performance
liquid chromatography (HPLC) in plasma samples at 0, 1, 2, 4, 6, 8, 12 hours
after drug intake.
Results: From May 2006 to April 2007, 16
subjects were enrolled. The median value of the area under the curve (AUC) of
NVP was reduced by 27.7% at T1 compared with NVP alone (T3) (44.1 µg/mL/h vs
61.0 µg/mL/h; p = 0.018). The reduction virtually disappeared at T2 (3.7%,
AUC of 58.8 µg/mL/h). Values of Ctrough <3 µg/mL were observed in
33.3%, 30.8% and 12.5% of cases at T1, T2, and T3 (NVP alone), respectively. The
median AUC values of RFM were low at T0 (11.9 µg/mL/h), but increased of 57.3%
at T1 (18.6 µg/mL/h; p = 0.01) and of 74.1 % at T2 (20.6 µg/mL/h; p
= 0.001). Efficacy of TB and HIV treatment were not hampered by combined
therapy.
Conclusions: RFM determined a reduction of
the AUC of NVP in TB/HIV co-infected patients that was rapidly reversible and
virtually disappeared after 10 weeks of combined therapy. The AUC of RFM was
lower then previously described in TB/HIV co-infected patients but increased
significantly during combined treatment. These data warrant the implementation
of larger clinical trials on the association of NVP and RFM with tolerability
and efficacy end-points.
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