title: Treatment Outcomes and Resistance Patterns of Children and Adolescents on Second-Line Antiretroviral Therapy in Asia.
abstract: Data on pediatric treatment outcomes and drug resistance while on second-line antiretroviral therapy (ART) are needed to guide HIV care in resource-limited countries.
  
  
  
  HIV-infected children <18 years who were switched or switching to second-line ART after first-line failure were enrolled from 8 sites in Indonesia, Thailand, and Vietnam. Genotyping was performed at virologic failure (VF; HIV-RNA >1000 copies/mL). Cox proportional hazards regression was used to evaluate factors predicting VF.
  
  
  
  Of 277 children, 41% were female. At second-line switch, age was 7.5 (5.3-10.3) years, CD4 count was 300 (146-562) cells per cubic millimeter, and percentage was 13 (7-20%); HIV-RNA was 5.0 (4.4-5.5) log10 copies per milliliter. Second-line regimens contained lamivudine (90%), tenofovir (43%), zidovudine or abacavir (30%), lopinavir (LPV/r; 91%), and atazanavir (ATV; 7%). After 3.3 (1.8-5.3) years on second-line ART, CD4 was 763 (556-1060) cells per cubic millimeter and 26% (20-31%). VF occurred in 73 (27%), with an incidence of 7.25 per 100 person-years (95% confidence interval [CI]: 5.77 to 9.12). Resistance mutations in 50 of 73 children with available genotyping at first VF included M184V (56%), ≥1 thymidine analogue mutation (TAM; 40%), ≥4 TAMs (10%), Q151M (4%), any major LPV mutation (8%), ≥6 LPV mutations (2%), and any major ATV mutation (4%). Associations with VF included age >11 years (hazard ratio [HR] 4.06; 95% CI: 2.15 to 7.66) and HIV-RNA >5.0 log10 copies per milliliter (HR 2.42; 95% CI: 1.27 to 4.59) at switch and were seen more commonly in children from Vietnam (HR 2.79; 95% CI: 1.55 to 5.02).
  
  
  
  One-fourth of children developed VF while on second-line ART. However, few developed major mutations to protease inhibitors.
authors.affiliation: *HIV-NAT, Thai Red Cross AIDS Research Centre, Bangkok, Thailand;†TREAT Asia/amfAR-The Foundation for AIDS Research, Bangkok, Thailand;‡Infectious Disease Department, Children's Hospital 1, Ho Chi Minh City, Vietnam;§US Military HIV Research Program, Walter Reed Army Institute of Research/Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD;‖Infectious Disease Department, Children's Hospital 2, Ho Chi Minh City, Vietnam;¶Infectious Disease Department, National Hospital of Pediatrics, Hanoi, Vietnam;#Division of Infectious Diseases, Department of Pediatrics, Khon Kaen University, Khon Kaen, Thailand;**Cipto Mangunkusumo General Hospital, Jakarta, Indonesia;††Faculty of Medicine and Research Institute for Health Sciences, Chiang Mai University, Chiang Mai, Thailand;‡‡Department of Pediatrics, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand;§§The Kirby Institute, University of New South Wales, Sydney, Australia; and‖‖Department of Global Health, Academic Medical Center, University of Amsterdam, Amsterdam Institute for Global Health and Development, Amsterdam, the Netherlands.
authors.forename: Wasana
authors.initials: W
authors.lastname: Prasitsuebsai
authors.forename: Sirinya
authors.initials: S
authors.lastname: Teeraananchai
authors.forename: Thida
authors.initials: T
authors.lastname: Singtoroj
authors.forename: Khanh Huu
authors.initials: KH
authors.lastname: Truong
authors.forename: Jintanat
authors.initials: J
authors.lastname: Ananworanich
authors.forename: Viet Chau
authors.initials: VC
authors.lastname: Do
authors.forename: Lam Van
authors.initials: LV
authors.lastname: Nguyen
authors.forename: Pope
authors.initials: P
authors.lastname: Kosalaraksa
authors.forename: Nia
authors.initials: N
authors.lastname: Kurniati
authors.forename: Tavitiya
authors.initials: T
authors.lastname: Sudjaritruk
authors.forename: Kulkanya
authors.initials: K
authors.lastname: Chokephaibulkit
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Kerr
authors.forename: Annette H
authors.initials: AH
authors.lastname: Sohn
mesh_terms: D000293:Adolescent; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D002648:Child; D002675:Child, Preschool; D015224:Dideoxynucleosides; D024921:Drug Resistance, Multiple, Viral / Q000187:drug effects* / Q000276:immunology; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000453:epidemiology / Q000276:immunology; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D007214:Indonesia / Q000453:epidemiology; D019259:Lamivudine; D008297:Male; D011446:Prospective Studies; D019438:Ritonavir; D013785:Thailand / Q000453:epidemiology; D016896:Treatment Outcome; D014744:Vietnam / Q000453:epidemiology; D019562:Viral Load; D015215:Zidovudine; D000099227:Abacavir
chemical_list: D019380:Anti-HIV Agents; D015224:Dideoxynucleosides; D019259:Lamivudine; D019438:Ritonavir; D015215:Zidovudine; D000099227:Abacavir