Predictors of Treatment Failure in HIV-Positive Children Receiving Combination Antiretroviral Therapy: Cohort Data From Mozambique and Uganda

Delays detecting treatment failure and switching to second-line combination antiretroviral therapy (cART) are often observed in human immunodeficiency virus (HIV)-infected children of low-middle-income countries (LMIC).

An observational study included HIV-infected children attending the Beira Central Hospital (Mozambique) and the Nsambya Hospital, Home Care Department (Uganda) evaluated clinical and immunological failure according to World Health Organization (WHO) 2006 guidelines. Baseline predictors for cART failure and for drug substitution were explored in unadjusted and adjusted Cox proportional hazard models.

Two hundred eighteen of 740 children with at least 24 weeks follow-up experienced treatment failure (29%; 95% confidence interval [CI] 26-33), with crude incidence of 20.0 events per 100 person-years (95% CI 17.5-22.9). Having tuberculosis co-infection or WHO stage 4, or starting a nontriple cART significantly increased risk of failure. Two hundred two of 769 (26.3%) children receiving cART substituted drug(s), with crude incidence of 15.4 events per 100 person-years (95% CI 13.4-17.7). Drug toxicity (18.3%), drug availability (17.3%), and tuberculosis drugs interaction (52, 25.7%) were main reported reasons, while only 9 (4%) patients switched cART for clinical or immunological failure. Children starting lamivudine-zidovudine-nevirapine or lamivudine-stavudine-efavirenz or lamivudine-zidovudine-efavirenz were more likely to have substitute drugs. Increased substitution was found in children with mild immunosuppression and tuberculosis co-infection at cART initiation as well as poor adherence before drug substitution.

Considerable delay in switching to second-line cART may occur despite an observed high rate of failure. Factors including WHO clinical stage and tuberculosis co-infection should be evaluated before starting cART. Toxicity and drug adherence should be monitored to minimize drug substitution in LMIC.

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By: Costenaro P1, Penazzato M1, Lundin R1, Rossi G1, Massavon W2, Patel D1, Nabachwa S3, Franceschetto G1, Morelli E1, Bilardi D1, Nannyonga MM3, Atzori A4, Mastrogiacomo ML4, Mazza A5, Putoto G4, Giaquinto C1.

• 1Department of Pediatrics, University of Padova, Italy;
• 2Department of Pediatrics, University of Padova, Italy; St. Raphael of St. Francis Nsambya Hospital, Kampala, Uganda;
• 3St. Raphael of St. Francis Nsambya Hospital, Kampala, Uganda;
• 4Doctors With Africa CUAMM, Padova, Italy;
• 5Associazione Casa Accoglienza alla Vita Padre Angelo, Trento, Italy. 

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