title: 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 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.
  
  
  CONCLUSIONS
  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.affiliation: 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.
authors.forename: David C
authors.initials: DC
authors.lastname: Boettiger
authors.forename: Linda
authors.initials: L
authors.lastname: Aurpibul
authors.forename: Dina Mukiarti
authors.initials: DM
authors.lastname: Hudaya
authors.forename: Siew M
authors.initials: SM
authors.lastname: Fong
authors.forename: Pagakrong
authors.initials: P
authors.lastname: Lumbiganon
authors.forename: Vonthanak
authors.initials: V
authors.lastname: Saphonn
authors.forename: Khanh H
authors.initials: KH
authors.lastname: Truong
authors.forename: Rawiwan
authors.initials: R
authors.lastname: Hansudewechakul
authors.forename: Lam V
authors.initials: LV
authors.lastname: Nguyen
authors.forename: Viet C
authors.initials: VC
authors.lastname: Do
authors.forename: Torsak
authors.initials: T
authors.lastname: Bunupuradah
authors.forename: Kulkanya
authors.initials: K
authors.lastname: Chokephaibulkit
authors.forename: Nik Khairulddin
authors.initials: NK
authors.lastname: Nik Yusoff
authors.forename: Nagalingeswaran
authors.initials: N
authors.lastname: Kumarasamy
authors.forename: Dewi Kumara
authors.initials: DK
authors.lastname: Wati
authors.forename: Kamarul Azahar
authors.initials: KA
authors.lastname: Razali
authors.forename: Azar
authors.initials: A
authors.lastname: Kariminia
mesh_terms: D000293:Adolescent; D000900:Anti-Bacterial Agents / Q000008:administration & dosage; D044966:Anti-Retroviral Agents / Q000009:adverse effects / Q000627:therapeutic use*; D019072:Antibiotic Prophylaxis; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects / Q000379:methods*; D001208:Asia; D002648:Child; D002675:Child, Preschool; D064420:Drug-Related Side Effects and Adverse Reactions; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy*; D006801:Humans; D007223:Infant; D008297:Male; D044342:Malnutrition; D016896:Treatment Outcome; D015662:Trimethoprim, Sulfamethoxazole Drug Combination / Q000008:administration & dosage
chemical_list: D000900:Anti-Bacterial Agents; D044966:Anti-Retroviral Agents; D015662:Trimethoprim, Sulfamethoxazole Drug Combination
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