Sixteen HIV-infected children (6 males) receiving an EFV-containing ART regimen for at least two weeks from Government ART centres at Kilpauk Medical College and Hospital, Chennai; Government Rajaji Hospital, Madurai; and BJ Wadia Hospital, Mumbai; were recruited. The mean age was 101 months, mean CD4 count was 14% and mean body weight was 18.8 kg. None were on concurrent rifampicin-containing anti-TB treatment. The study was cleared by the Institutional Ethics Committee; informed written consent was obtained from parent/guardian. Twelve-hour plasma EFV concentration was determined by HPLC(2).

The mean 12-hour EFV concentration in the 16 children was 2.39 µg/mL (range: 0.72-7.82 µg/mL). The blood levels were within the therapeutic range (1 – 4 µg/mL) of EFV in 12, below 1.0 µg/mL in 1 and above 4.0 µg/mL in 3 children. The only child who had sub-therapeutic EFV concentration had not shown an increase in CD4 cell counts up to 36 months of treatment. Weight gain ranged from 0.3 to 19.5 kg during a treatment period of 1 to 93 months and clinical status showed improvement in all children.

The clinical recommendations for treatment of children with EFV are based on data obtained in adult patients(3). In this small group of children studied, the mean dose of EFV received was 14.6 mg/kg body weight, which is within the recommended dosing range (10.0 to 16.7 mg/kg). Hirt, et al.(4) suggested that pediatric dosing guidelines for EFV should be based on both age and body weight, since plasma clearance of EFV decreased significantly with age, due to higher activity of hepatic drug-metabolizing enzymes in younger children.

We found that the majority (15 out of 16 children) receiving EFV doses based on the NACO guidelines had 12-hour EFV concentrations within or above the therapeutic range. Three children with drug levels above the therapeutic limit did not have any obvious adverse effects due to EFV. Although these findings are encouraging, the small sample size limits the generalizability of the conclusions. Our study findings are consistent with those in Thai HIV-infected children(5), but differ with von Hentig, et al.(6) and Ren, et al.(7), who reported a higher proportion of children with sub-therapeutic plasma EFV. The difference could be due to ethnic variations and genetic factors which are known to influence EFV pharmacokinetics. Our limitations include the small sample size, lack of information on CYP2B6 516G>T polymorphism and post-ART viral load. However, our data provides some preliminary information that can be used to guide treatment policy for HIV-infected children in India.

Dr PK Bhavani, Dr Poorana Ganaga Devi, Ms P Vennila and HIV laboratory staff.

Funding: USAID through WHO, SEARO, New Delhi.

Competing interests: None.

1. National AIDS Control Organisation. Guidelines for HIV care and treatment in infants and children, November 2006. Available from http://www. nacoonline.org/quick-links/publication/treatment-care-support. Accessed on April 03, 2010.

2. Ramachandran G, Kumar AK, Swaminathan S, Venkatesan P, Kumaraswami V, Greenblatt DJ. Simple and rapid liquid chromatography method for determination of efavirenz in plasma. J Chromatogr B Analyt Technol Biomed Life Sci 2006; 835: 131-135.

3. van Leth F, Phanuphak P, Ruxrungtham K, Baraldi E, Miller S, Gazzard B, et al. Comparison of first-line antiretroviral therapy with regimens including nevirapine, efavirenz or both drugs, plus stavudine and lamivudine : a randomized open-label trial, the 2NN study. Lancet 2004; 363: 1253-1263.

4. Hirt D, Urien S, Olivier M, Pcyriere H, Nacro B, Diagbouga S, et al. Is the recommended dose of efavirenz optimal in young West African HIV-infected children? Antimicrob Agents Chemother 2009; 53: 4407-4413.

5. Puthanakit T, Tanbaiboon P, Aurpibul L, Cressey TR, Sirisanthana V. Plasma efavirenz concentrations and the association with CYP2B6 516G>T polymorphism in HIV-infected Thai children. Antivir Ther 2009; 14: 315-320.

6. von Hentig N, Koenigs C, Elanjikal S, Linde R, Dunsch D, Kreuz W, et al. Need for therapeutic drug monitoring in HIV-1 infected children receiving efavirenz doses according to international guidelines. Eur J Med Res 2006; 11: 377-380.