Effectiveness of efavirenz-based regimens in young HIV-infected children treated for tuberculosis: a treatment option for resource-limited settings.
BACKGROUND
Antiretroviral treatment (ART) options for young children co-infected with HIV and tuberculosis are limited in resource-poor settings due to limited data on the use of efavirenz (EFV). Using available pharmacokinetic data, an EFV dosing schedule was developed for young co-infected children and implemented as the standard of care at Macha Hospital in Southern Province, Zambia. Treatment outcomes in children younger than 3 years of age or weighing less than 10 kg receiving either EFV-based ART plus anti-tuberculous treatment or nevirapine-based (NVP) ART were compared.


METHODS
Treatment outcomes were measured in a cohort of HIV-infected children seeking care at Macha Hospital in rural Zambia from 2007 to 2010. Information on the diagnosis and treatment of tuberculosis was abstracted from medical records.


RESULTS
Forty-five children treated for tuberculosis initiated an EFV-based regimen and 69 children initiated a NVP-based regimen, 7 of whom also were treated for tuberculosis. Children receiving both regimens were comparable in age, but children receiving EFV started ART with a lower CD4(+) T-cell percentage and weight-for-age z-score. Children receiving EFV experienced increases in both CD4(+) T-cell percentage and weight-for-age z-score during follow-up, such that levels were comparable to children receiving NVP after two years of ART. Cumulative survival after 12 months of ART did not differ between groups (NVP:87%;EFV:80%;p = 0.25). Eleven children experienced virologic failure during follow-up.The adjusted hazard ratio of virologic failure comparing EFV to NVP was 0.25 (95% CI:0.05,1.24) and 0.13 (95% CI:0.03,0.62) using thresholds of 5000 and 400 copies/mL, respectively.Five children receiving EFV were reported to have had convulsions after ART initiation compared to only one child receiving NVP (p = 0.04).


CONCLUSIONS
Despite poorer health at ART initiation, children treated for tuberculosis and receiving EFV-based regimens showed significant improvements comparable to children receiving NVP-based regimens. EFV-based regimens should be considered for young HIV-infected children co-infected with tuberculosis in resource-limited settings.
Macha Research Trust, Macha Hospital, Choma, Zambia.
Janneke H
JH
van Dijk
Catherine G
CG
Sutcliffe
Francis
F
Hamangaba
Christopher
C
Bositis
Douglas C
DC
Watson
William J
WJ
Moss
D000480:Alkynes; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D048588:Benzoxazines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D002648:Child; D002675:Child, Preschool; D060085:Coinfection; D003521:Cyclopropanes; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality / Q000821:virology; D006801:Humans; D008297:Male; D017211:Treatment Failure; D016896:Treatment Outcome; D014376:Tuberculosis / Q000276:immunology; D019562:Viral Load
D000480:Alkynes; D019380:Anti-HIV Agents; D048588:Benzoxazines; D003521:Cyclopropanes; C098320:efavirenz