David C Boettiger1, Linda Aurpibul, Dina Mukiarti Hudaya, Siew M Fong, Pagakrong Lumbiganon, Vonthanak Saphonn, Khanh H Truong, Rawiwan Hansudewechakul, Lam V Nguyen, Viet C Do, Torsak Bunupuradah, Kulkanya Chokephaibulkit, Nik Khairulddin Nik Yusoff, Nagalingeswaran Kumarasamy, Dewi Kumara Wati, Kamarul Azahar Razali, Azar Kariminia. 1. From the *The Kirby Institute, UNSW Australia, Sydney, Australia; †Department of Pediatrics, Faculty of Medicine, Chiang Mai University and Research Institute for Health Sciences, Chiang Mai, Thailand; ‡Cipto Mangunkusumo General Hospital, Jakarta, Indonesia; §Hospital Likas, Kota Kinabalu, Malaysia; ¶Division of Infectious Diseases, Department of Pediatrics, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand; ‖National Centre for HIV/AIDS Dermatology and STDs, Phnom Penh, Cambodia; **Children's Hospital 1, Ho Chi Minh City, Vietnam; ††Chiangrai Prachanukroh Hospital, Chiang Rai, Thailand; ‡‡National Hospital of Pediatrics, Hanoi, Vietnam; §§Children's Hospital 2, Ho Chi Minh City, Vietnam; ¶¶HIV-NAT, the Thai Red Cross AIDS Research Centre, Bangkok, Thailand; ‖‖Department of Pediatrics, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand; ***Hospital Raja Perempuan Zainab II, Kelantan, Malaysia; †††YRGCARE Medical Centre, CART CRS, Chennai, India; ‡‡‡Sanglah Hospital, Udayana University, Bali, Indonesia; §§§Pediatric Institute, Hospital Kuala Lumpur, Kuala Lumpur, Malaysia; and ¶¶¶Members of TREAT Asia Pediatric HIV Observational Database are listed in Appendix.
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 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.
BACKGROUND: Information on antiretroviral therapy (ART) use in HIV-infectedchildren 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.
Authors: Robert E Black; Lindsay H Allen; Zulfiqar A Bhutta; Laura E Caulfield; Mercedes de Onis; Majid Ezzati; Colin Mathers; Juan Rivera Journal: Lancet Date: 2008-01-19 Impact factor: 79.321
Authors: Kunjal Patel; Miguel A Hernán; Paige L Williams; John D Seeger; Kenneth McIntosh; Russell B Van Dyke; George R Seage Journal: Clin Infect Dis Date: 2008-06-01 Impact factor: 9.079