Steady-state nevirapine, lamivudine and stavudine levels in Malawian HIV-infected children on antiretroviral therapy using split Triomune 30 tablets.
BACKGROUND
Children remain under-represented in national antiretroviral treatment (ART) programmes in settings with limited resources and high HIV prevalence. In Malawi, an increasing number of HIV-infected children have been started on ART with split tablets of an adult fixed-dose combination drug in the past few years. In 2006, the national paediatric ART regime was changed from Triomune 40 (T40) to Triomune 30 (T30).


METHODS
This was a cross-sectional study conducted at the paediatric ART clinic in Blantyre (Malawi) from September 2006 to July 2007. Children taking T30 for > 6 weeks from each dosing weight band (<5, 5-<8, 8-<12, 12-<14, 14-<19, 19-<26, 26-<30 and > or = 30 kg) were recruited. Plasma drug concentration, CD4+ T-cell count and HIV viral load were measured.


RESULTS
A total of 74 children were analysed. The median nevirapine (NVP) concentration was 7.35 mg/l. A therapeutic NVP plasma level > 3 mg/l was found in 62 (87.8%) children. A subtherapeutic NVP level (< 3 mg/l) occurred significantly more often in children treated with T30 doses between one-quarter tablet once daily and one-half tablet twice daily (P=0.035). Median prescribed NVP dose was 342 mg/m(2)/day, but 13 (17.6%) children received a dose below the recommended dose of 300 mg/m(2)/day. Compared with a historical control, the median prescribed NVP dose was increased (from 243 to 342 mg/m(2)/day).


CONCLUSIONS
Our findings indicate that with the Malawian T30-based ART regime, the majority (87.8%) of children in the study group achieved a therapeutic NVP level. However, treatment remains suboptimal especially for young children receiving T30 dosages less than or equal to one-half tablets twice daily and child appropriate formulations are warranted.
General Paediatrics, Royal Hospital for Sick Children, Edinburgh, UK. goenke.poerksen@luht.scot.nhs.uk
Goenke
G
Poerksen
Louisa
L
Pollock
Peter
P
Moons
Emily
E
Chesshyre
David
D
Burger
Saye
S
Khoo
Elizabeth
E
Molyneux
D000293:Adolescent; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000097:blood* / Q000627:therapeutic use; D018791:CD4 Lymphocyte Count; D002648:Child; D002675:Child, Preschool; D003430:Cross-Sectional Studies; D004304:Dosage Forms; D004334:Drug Administration Schedule; D004338:Drug Combinations; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007223:Infant; D019259:Lamivudine / Q000008:administration & dosage / Q000097:blood* / Q000627:therapeutic use; D008295:Malawi; D008297:Male; D019829:Nevirapine / Q000008:administration & dosage / Q000097:blood* / Q000627:therapeutic use; D018119:Stavudine / Q000008:administration & dosage / Q000097:blood* / Q000627:therapeutic use; D013607:Tablets / Q000008:administration & dosage / Q000627:therapeutic use; D016896:Treatment Outcome; D019562:Viral Load
D019380:Anti-HIV Agents; D004304:Dosage Forms; D004338:Drug Combinations; D013607:Tablets; C516355:stavudine, lamivudine, nevirapine drug combination; D019259:Lamivudine; D019829:Nevirapine; D018119:Stavudine