title: Non-Nucleoside Reverse Transcriptase Inhibitor-Based Antiretroviral Therapy in Perinatally HIV-Infected, Treatment-Naïve Adolescents in Asia.
abstract: OBJECTIVE
  About a third of untreated, perinatally HIV-infected children reach adolescence. We evaluated the durability and effectiveness of non-nucleoside reverse-transcriptase inhibitor (NNRTI)-based antiretroviral therapy (ART) in this population.
  
  
  METHODS
  Data from perinatally HIV-infected, antiretroviral-naïve patients initiated on NNRTI-based ART aged 10-19 years who had ≥6 months of follow-up were analyzed. Competing risk regression was used to assess predictors of NNRTI substitution and clinical failure (World Health Organization Stage 3/4 event or death). Viral suppression was defined as a viral load <400 copies/mL.
  
  
  RESULTS
  Data from 534 adolescents met our inclusion criteria (56.2% female; median age at treatment initiation 11.8 years). After 5 years of treatment, median height-for-age z score increased from -2.3 to -1.6, and median CD4+ cell count increased from 131 to 580 cells/mm(3). The proportion of patients with viral suppression after 6 months was 87.6% and remained >80% up to 5 years of follow-up. NNRTI substitution and clinical failure occurred at rates of 4.9 and 1.4 events per 100 patient-years, respectively. Not using cotrimoxazole prophylaxis at ART initiation was associated with NNRTI substitution (hazard ratio [HR], 1.5 vs. using; 95% confidence interval [CI] = 1.0-2.2; p = .05). Baseline CD4+ count ≤200 cells/mm(3) (HR, 3.3 vs. >200; 95% CI = 1.2-8.9; p = .02) and not using cotrimoxazole prophylaxis at ART initiation (HR, 2.1 vs. using; 95% CI = 1.0-4.6; p = .05) were both associated with clinical failure.
  
  
  CONCLUSIONS
  Despite late ART initiation, adolescents achieved good rates of catch-up growth, CD4+ count recovery, and virological suppression. Earlier ART initiation and routine cotrimoxazole prophylaxis in this population may help to reduce current rates of NNRTI substitution and clinical failure.
authors.affiliation: Faculty of Medicine, The Kirby Institute, UNSW Australia, Sydney, New South Wales, Australia. Electronic address: dboettiger@kirby.unsw.edu.au.
authors.forename: David C
authors.initials: DC
authors.lastname: Boettiger
authors.affiliation: Department of Pediatrics, Faculty of Medicine, Research Institute for Health Sciences, Chiang Mai University, Chiang Mai, Thailand.
authors.forename: Tavitiya
authors.initials: T
authors.lastname: Sudjaritruk
authors.affiliation: Department of Pediatrics, Penang Hospital, Malaysia.
authors.forename: Revathy
authors.initials: R
authors.lastname: Nallusamy
authors.affiliation: Department of Pediatrics, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand.
authors.forename: Pagakrong
authors.initials: P
authors.lastname: Lumbiganon
authors.affiliation: Department of Pediatrics, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
authors.forename: Supattra
authors.initials: S
authors.lastname: Rungmaitree
authors.affiliation: Department of Pediatrics, Chiangrai Prachanukroh Hospital, Chiang Rai, Thailand.
authors.forename: Rawiwan
authors.initials: R
authors.lastname: Hansudewechakul
authors.affiliation: YRG CARE Medical Centre, CART CRS, Chennai, India.
authors.forename: Nagalingeswaran
authors.initials: N
authors.lastname: Kumarasamy
authors.affiliation: HIV-NAT, The Thai Red Cross AIDS Research Centre, Bangkok, Thailand.
authors.forename: Torsak
authors.initials: T
authors.lastname: Bunupuradah
authors.affiliation: National Centre for HIV/AIDS Dermatology and STDs, University of Health Sciences, Phnom Penh, Cambodia.
authors.forename: Vonthanak
authors.initials: V
authors.lastname: Saphonn
authors.affiliation: Department of Infectious Diseases, Children's Hospital 1, Ho Chi Minh City, Vietnam.
authors.forename: Khanh Huu
authors.initials: KH
authors.lastname: Truong
authors.affiliation: Department of Pediatrics, Hospital Raja Perempuan Zainab II, Malaysia.
authors.forename: Nik K N
authors.initials: NKN
authors.lastname: Yusoff
authors.affiliation: Department of Infectious Diseases, Children's Hospital 2, Ho Chi Minh City, Vietnam.
authors.forename: Viet Chau
authors.initials: VC
authors.lastname: Do
authors.affiliation: National Hospital of Pediatrics, Hanoi, Vietnam.
authors.forename: Lam V
authors.initials: LV
authors.lastname: Nguyen
authors.affiliation: Pediatric Institute, Hospital Kuala Lumpur, Kuala Lumpur, Malaysia.
authors.forename: Kamarul A M
authors.initials: KAM
authors.lastname: Razali
authors.affiliation: Hospital Likas, Kota Kinabalu, Malaysia.
authors.forename: Siew Moy
authors.initials: SM
authors.lastname: Fong
authors.affiliation: Department of Child Health, Cipto Mangunkusumo General Hospital, Jakarta, Indonesia.
authors.forename: Nia
authors.initials: N
authors.lastname: Kurniati
authors.affiliation: Faculty of Medicine, The Kirby Institute, UNSW Australia, Sydney, New South Wales, Australia.
authors.forename: Azar
authors.initials: A
authors.lastname: Kariminia
mesh_terms: D000293:Adolescent; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods; D001208:Asia; D018791:CD4 Lymphocyte Count; D002648:Child; D005260:Female; D006128:Growth; D015658:HIV Infections / Q000188:drug therapy* / Q000503:physiopathology / Q000635:transmission; D006801:Humans; D007231:Infant, Newborn; D018445:Infectious Disease Transmission, Vertical; D008297:Male; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use*; D015662:Trimethoprim, Sulfamethoxazole Drug Combination / Q000627:therapeutic use; D019562:Viral Load; D055815:Young Adult
chemical_list: D000900:Anti-Bacterial Agents; D018894:Reverse Transcriptase Inhibitors; D015662:Trimethoprim, Sulfamethoxazole Drug Combination
keywords: Antiretroviral therapy; Cotrimoxazole; HIV; Non-nucleoside reverse-transcriptase inhibitor; Perinatal HIV infection