Adam W Bartlett1, Pagakrong Lumbiganon2, Nia Kurniati3, Tavitiya Sudjaritruk4, Thahira J Mohamed5, Rawiwan Hansudewechakul6, Penh S Ly7, Khanh H Truong8, Thanyawee Puthanakit9, Lam V Nguyen10, Kulkanya Chokephaibulkit11, Viet C Do12, Nagalingeswaran Kumarasamy13, Nik Khairulddin Nik Yusoff14, Moy S Fong15, Dewi K Watu16, Revathy Nallusamy17, Annette H Sohn18, Matthew G Law19. 1. Kirby Institute, University of New South Wales Sydney, New South Wales, Australia. Electronic address: abartlett@kirby.unsw.edu.au. 2. Department of Pediatrics, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand. 3. Cipto Mangunkusumo, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia. 4. Department of Pediatrics, Faculty of Medicine, and Research Institute for Health Sciences, Chiang Mai University, Chiang Mai, Thailand. 5. Pediatric Institute, Hospital Kuala Lumpur, Kuala Lumpur, Malaysia. 6. Chiangrai Prachanukroh Hospital, Chiang Rai, Thailand. 7. National Centre for HIV/AIDS, Dermatology and STDs, Phnom Penh, Cambodia. 8. Children's Hospital 1, Ho Chi Minh City, Vietnam. 9. Department of Pediatrics, Faculty of Medicine and Research Unit in Pediatric and Infectious Diseases, Chulalongkorn University, Bangkok, Thailand. 10. National Hospital of Pediatrics, Hanoi, Vietnam. 11. Department of Pediatrics, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand. 12. Children's Hospital 2, Ho Chi Minh City, Vietnam. 13. YRGCARE Medical Centre, CART CRS, Chennai, India. 14. Hospital Raja Perempuan Zainab II, Kelantan, Malaysia. 15. Hospital Likas, Kota Kinabalu, Malaysia. 16. Sanglah Hospital, Udayana University, Bali, Indonesia. 17. Penang Hospital, Penang, Malaysia. 18. TREAT Asia/amfAR - The Foundation for AIDS Research, Bangkok, Thailand. 19. Kirby Institute, University of New South Wales Sydney, New South Wales, Australia.
Abstract
PURPOSE: Antiretroviral monotherapy and treatment interruption are potential strategies for perinatally HIV-infected adolescents (PHIVA) who face challenges maintaining effective combination antiretroviral therapy (ART). We assessed the use and outcomes for adolescents receiving monotherapy or undergoing treatment interruption in a regional Asian cohort. METHODS: Regional Asian data (2001-2016) were analyzed to describe PHIVA who experienced ≥2 weeks of lamivudine or emtricitabine monotherapy or treatment interruption and trends in CD4 count and HIV viral load during and after episodes. Survival analyses were used for World Health Organization (WHO) stage III/IV clinical and immunologic event-free survival during monotherapy or treatment interruption, and a Poisson regression to determine factors associated with monotherapy or treatment interruption. RESULTS: Of 3,448 PHIVA, 84 (2.4%) experienced 94 monotherapy episodes, and 147 (4.3%) experienced 174 treatment interruptions. Monotherapy was associated with older age, HIV RNA >400 copies/mL, younger age at ART initiation, and exposure to ≥2 combination ART regimens. Treatment interruption was associated with CD4 count <350 cells/μL, HIV RNA ≥1,000 copies/mL, ART adverse event, and commencing ART age ≥10 years compared with age <3 years. WHO clinical stage III/IV 1-year event-free survival was 96% and 85% for monotherapy and treatment interruption cohorts, respectively. WHO immunologic stage III/IV 1-year event-free survival was 52% for both cohorts. Those who experienced monotherapy or treatment interruption for more than 6 months had worse immunologic and virologic outcomes. CONCLUSIONS: Until challenges of treatment adherence, engagement in care, and combination ART durability/tolerability are met, monotherapy and treatment interruption will lead to poor long-term outcomes.
PURPOSE: Antiretroviral monotherapy and treatment interruption are potential strategies for perinatally HIV-infected adolescents (PHIVA) who face challenges maintaining effective combination antiretroviral therapy (ART). We assessed the use and outcomes for adolescents receiving monotherapy or undergoing treatment interruption in a regional Asian cohort. METHODS: Regional Asian data (2001-2016) were analyzed to describe PHIVA who experienced ≥2 weeks of lamivudine or emtricitabine monotherapy or treatment interruption and trends in CD4 count and HIV viral load during and after episodes. Survival analyses were used for World Health Organization (WHO) stage III/IV clinical and immunologic event-free survival during monotherapy or treatment interruption, and a Poisson regression to determine factors associated with monotherapy or treatment interruption. RESULTS: Of 3,448 PHIVA, 84 (2.4%) experienced 94 monotherapy episodes, and 147 (4.3%) experienced 174 treatment interruptions. Monotherapy was associated with older age, HIV RNA >400 copies/mL, younger age at ART initiation, and exposure to ≥2 combination ART regimens. Treatment interruption was associated with CD4 count <350 cells/μL, HIV RNA ≥1,000 copies/mL, ART adverse event, and commencing ART age ≥10 years compared with age <3 years. WHO clinical stage III/IV 1-year event-free survival was 96% and 85% for monotherapy and treatment interruption cohorts, respectively. WHO immunologic stage III/IV 1-year event-free survival was 52% for both cohorts. Those who experienced monotherapy or treatment interruption for more than 6 months had worse immunologic and virologic outcomes. CONCLUSIONS: Until challenges of treatment adherence, engagement in care, and combination ART durability/tolerability are met, monotherapy and treatment interruption will lead to poor long-term outcomes.
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