Antiretroviral Therapy in Severely Malnourished, HIV-infected Children in Asia

Background: Information on antiretroviral therapy (ART) use in HIVinfected children with severe malnutrition (SM) is lacking. We investigated long-term ART outcomes in this population. Methods: Children enrolled in the TREAT Asia Pediatric HIV Observational Database who had SM (weight-for-height or body mass index–for-age Z score less than ?3) at ART initiation were analyzed. Generalized estimating equations were used to investigate poor weight recovery (weight-for-age Z score less than ?3) and poor CD4% recovery (CD4% <25), and competing risk regression was used to analyze mortality and toxicity-associated treatment modification. Results: Three hundred fifty-five (11.9%) of 2993 children starting ART had SM. Their median weight-for-age Z score increased from ?5.6 at ART initiation to ?2.3 after 36 months. Not using trimethoprim–sulfamethoxazole prophylaxis at baseline was associated with poor weight recovery [odds ratio: 2.49 vs. using; 95% confidence interval (CI): 1.66–3.74; P < 0.001]. Median CD4% increased from 3.0 at ART initiation to 27.2 after 36 months, and 56 (15.3%) children died during follow-up. More profound SM was associated with poor CD4% recovery (odds ratio: 1.78 for Z score less than ?4.5 vs. ?3.5 to less than ?3.0; 95% CI: 1.08–2.92; P = 0.023) and mortality (hazard ratio: 2.57 for Z score less than ?4.5 vs. ?3.5 to less than ?3.0; 95% CI: 1.24–5.33; P = 0.011). Twenty-two toxicity-associated ART modifications occurred at a rate of 2.4 per 100 patient-years, and rates did not differ by malnutrition severity. Conclusion: Trimethoprim–sulfamethoxazole prophylaxis is important for the recovery of weight-for-age in severely malnourished children starting ART. The extent of SM does not impede weight-for-age recovery or antiretroviral tolerability, but CD4% response is compromised in children with a very low weight-for-height/body mass index-for-age Z score, which may contribute to their high rate of mortality. Key Words: severe malnutrition, antiretroviral therapy, children, Asia (Pediatr Infect Dis J 2016;35:e144–e151) The Joint United Nations Children’s Fund—World Health Organization (WHO)—World Bank Child Malnutrition Database estimates that 14.5% of children in South-East Asia are malnourished, of whom 5.2% are severely malnourished.1 It is also estimated that there are 210,000 HIV-infected persons aged <15 years living in the Asia Pacific area.2 Although food insecurity is more common in resource-limited parts of the region, the association between HIV infection and adverse nutritional outcomes has been reported in both resource-rich and resource-limited settings.3 In children aged 6–60 months, severe malnutrition (SM) can be defined as a weight-for-height Z score less than ?3 or a midupper arm circumference less than 115 mm, and in children aged 61 months to 14 years, a body mass index (BMI)-for-age Z score less than ?3.4 The optimal management of HIV in children with SM is not well defined. Expert opinion suggests that SM should be stabilized, and antiretroviral therapy (ART) initiated as soon as possible after stabilization.3,5 Yet information on the effectiveness and safety of antiretroviral drugs in this setting is lacking,3,6,7 and HIV-infected children with SM have a high risk of early mortality after starting ART.3,8–11 The aims of this study were to describe the prevalence and predictors of SM in HIV-infected children starting ART in Asia and to investigate how the extent of SM at ART initiation impacts treatment response. METHODS The study population consisted of HIV-infected patients enrolled in the TREAT Asia Pediatric HIV Observational Database (TApHOD). This cohort contributes to the International Epidemiologic Databases to Evaluate AIDS global consortium and has been described previously.12 Recruitment started in 2008. Up to March 2014, TApHOD included data from 5511 children who had ever received care from 1 of the 16 pediatric clinics in Cambodia (n = 1), India (n = 1), Indonesia (n = 2), Malaysia (n = 4), Thailand