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

Abstract

Background Information on antiretroviral therapy (ART) use in HIV-infected 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 BMI-for-age z-score <−3) at ART initiation were analyzed. Generalized estimating equations were used to investigate poor weight recovery (weight-for-age z-score <−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 cotrimoxazole prophylaxis at baseline was associated with poor weight recovery (OR 2.49 vs. using, 95%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 (OR 1.78 for z-score <−4.5 vs. −3.5 to <−3.0, 95%CI 1.08-2.92, p=0.023) and mortality (HR 2.57 for z-score <−4.5 vs. −3.5 to <−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. Discussion Cotrimoxazole 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/BMI-for-age z-score which may contribute to their high rate of mortality.

Nutritional, clinical and immunological status of children at HIV diagnosis in the continental region of Equatorial Guinea

“…The impact of this strategy may be higher in low‐income regions due to rarer availability of laboratory techniques that allow close monitoring of the response to ART. An advanced immunological stage or the presence of a high viral load has been associated with a poorer nutritional status . This agrees with the findings of this study, where the presence of acute underweight increased fourfold the risk of moderate‐severe immunodeficiency.…”

“…Although ART is effective in improving the nutritional status, a significant percentage of patients continue to be nutritionally deficient , so it seems appropriate to support the initiation of ART with a nutritional intervention. Malnourished patients show worse immune reconstitution after the initiation of ART than patients with a normal nutritional level .…”

Growth and pubertal development in HIV-infected adolescents

“…Recent studies have confirmed these general findings in Asia and many African countries (Table 2). Studies in Asia (primarily Thailand and China) have reported mean z-scores of −2.4 to −1.7 for HAZ and −2.6 to −1.1 for WAZ, with corresponding high prevalences of stunting and underweight [16–18].…”

“…In LRS, the increases in weight and height after ART initiation are somewhat more striking than those in HRS, with increases in mean z-scores after 2 years ranging from 0.4–1.0 in HAZ, and 0.4–1.5 in WAZ (see Table 2) [12,16–18,20]. McGrath reported a mean increase of 0.40 in HAZ and 1.03 in WAZ after 24 months on ART [11].…”

Impact of antiretroviral treatment on height evolution of HIV infected children

“…HIV infection in children has been associated with growth delays in terms of weight (wasting and underweight) and height (stunting) [1–9]. Antiretroviral treatments (ART) have been shown to have a positive impact on the evolution of the anthropometric parameters [8–13], but studies have mostly focused on the improvement of the weight-for-age z-score (WAZ) [9, 14–18]. Results of the several studies analyzing the effect of ART on height-for-age z-score (HAZ), a better indicator of the general development of children in the long term [19–23] are conflicting, some suggesting a favourable effect [24–27] and others not [28–32].…”