Efavirenz levels and 24-week efficacy in HIV-infected patients with tuberculosis receiving highly active antiretroviral therapy and rifampicin.
BACKGROUND
Concomitant use of efavirenz and rifampicin is common for treatment of HIV and tuberculosis. Plasma efavirenz levels can be reduced by rifampicin, but the appropriate daily dosage of efavirenz is unclear.


METHODS
HIV-infected patients with active tuberculosis, receiving rifampicin > 1 month, were randomized to receive stavudine and lamivudine plus efavirenz 600 or 800 mg daily. Plasma efavirenz levels were measured (at 12 h after dosing and on day 14) by high-performance liquid chromatography. Plasma HIV RNA was assessed at 16 and 24 weeks after antiretroviral therapy.


RESULTS
Baseline characteristics were comparable in the 84 patients (two groups of 42). Median plasma efavirenz levels were 3.02 mg/l (range, 0.07-12.21) in the 600 mg group and 3.39 mg/l (range, 1.03-21.31) in the 800 mg group (P = 0.632). Plasma efavirenz levels were < 1 mg/l in 3 of 38 (7.9%) patients in the 600 mg group and in none of the 800 mg group (P = 0.274). Approximately 40 and 45% of patients had efavirenz levels > 4 mg/l, respectively. There was no significant difference in time to HIV RNA < 50 copies/ml (P = 0.848).


CONCLUSIONS
Median plasma efavirenz levels were comparable among both groups. Efavirenz 600 mg/day should be sufficient for most Thai HIV-infected patients receiving rifampicin with body weight approximately 50 kg. These results may not be applicable to other ethic populations who have higher body weights. However, the study of long-term virological and immunological outcomes is needed and under further investigation.
Manosuthi
Weerawat
W
Ramathibodi Hospital, Mahidol University, Bangkok, Thailand. drweerawat@hotmail.com
Sungkanuparph
Somnuek
S
Thakkinstian
Ammarin
A
Vibhagool
Asda
A
Kiertiburanakul
Sasisopin
S
Rattanasiri
Sasivimol
S
Prasithsirikul
Wisit
W
Sankote
Jongkol
J
Mahanontharit
Apicha
A
Ruxrungtham
Kiat
K
D017088:AIDS-Related Opportunistic Infections / Q000097:blood / Q000188:drug therapy*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000480:Alkynes; D019380:Anti-HIV Agents / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000904:Antibiotics, Antitubercular / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D048588:Benzoxazines; D003521:Cyclopropanes; D004305:Dose-Response Relationship, Drug; D005260:Female; D015497:HIV-1; D006801:Humans; D008297:Male; D008875:Middle Aged; D010078:Oxazines / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D012367:RNA, Viral / Q000097:blood; D012293:Rifampin / Q000627:therapeutic use*; D016896:Treatment Outcome; D014376:Tuberculosis / Q000097:blood / Q000188:drug therapy*
D000480:Alkynes; D019380:Anti-HIV Agents; D000904:Antibiotics, Antitubercular; D048588:Benzoxazines; D003521:Cyclopropanes; D010078:Oxazines; D012367:RNA, Viral; C098320:efavirenz; D012293:Rifampin