Effect of nevirapine on the steady-state trough concentrations of atazanavir in HIV-infected patients receiving atazanavir/ritonavir.
METHODS
To evaluate the influence of nevirapine on atazanavir trough concentrations (Ctrough) in a group of HIV-infected patients, we performed an open-label pilot study enrolling patients receiving 300/100 mg atazanavir/ritonavir once daily for 2 weeks or longer. Nevirapine was added at a dose of 200 mg once daily from Days 0 to 14 and 200 mg twice daily from Days 14 to 28. Atazanavir and nevirapine plasma Ctroughs were determined at Days 0 and 28. Atazanavir Ctroughs were compared between Days 0 and 28. Atazanavir and nevirapine Ctroughs at Day 28 were compared with historical controls receiving either 400 mg atazanavir once daily or 200 mg nevirapine twice daily.


RESULTS
Fourteen patients were enrolled and 11 completed the study. The geometric mean (range) atazanavir Ctrough decreased from 0.631 mg/L (range, 0.235-1.87 mg/L) at Day 0 to 0.316 mg/L (range, 0.142-1.109 mg/L) at Day 28 to give a geometric mean ratio of 0.59 (95% confidence interval, 0.38-0.80; P = 0.026); nonetheless, the atazanavir Ctrough remained higher than the minimum effective concentration in 80% of the participants and higher than the median concentration in the control subjects receiving 400 mg atazanavir once daily without ritonavir (geometric mean ratio, 3.20; 95% confidence interval, 1.65-6.22; P = 0.001). The nevirapine Ctrough at Day 28 was slightly higher than in the historical controls on 200 mg nevirapine twice daily without atazanavir (geometric mean ratio, 1.46; 95% confidence interval, 1.04-2.06; P = 0.030).


CONCLUSIONS
We conclude that coadministration of 300/100 mg atazanavir/ritonavir once daily plus 200 mg nevirapine twice daily was safe and well tolerated but resulted in a decrease of atazanavir Ctrough by nearly half. Therefore, monitoring atazanavir Ctrough is recommended in patients treated with this drug combination, and increasing the atazanavir dose might be necessary.
Moltó
José
J
Lluita contra la Sida Foundation, HIV Unit, Hospital Universitari Germans Trias i Pujol, Badalona, Spain. jmolto@flsida.org
Deig
Elisabet
E
Valle
Marta
M
Maria Llibre
Josep
J
Miranda
Cristina
C
Cedeño
Samandhy
S
Valero
Silvia
S
Negredo
Eugenia
E
Clotet
Bonaventura
B
D019380:Anti-HIV Agents / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology; D000069446:Atazanavir Sulfate; D004347:Drug Interactions; D016903:Drug Monitoring; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D017320:HIV Protease Inhibitors / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D019829:Nevirapine / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology*; D009842:Oligopeptides / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use; D010865:Pilot Projects; D011725:Pyridines / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use; D019438:Ritonavir / Q000627:therapeutic use
D019380:Anti-HIV Agents; D017320:HIV Protease Inhibitors; D009842:Oligopeptides; D011725:Pyridines; D000069446:Atazanavir Sulfate; D019829:Nevirapine; D019438:Ritonavir