title: Effects of unplanned treatment interruptions on HIV treatment failure - results from TAHOD.
abstract: OBJECTIVE
  Treatment interruptions (TIs) of combination antiretroviral therapy (cART) are known to lead to unfavourable treatment outcomes but do still occur in resource-limited settings. We investigated the effects of TI associated with adverse events (AEs) and non-AE-related reasons, including their durations, on treatment failure after cART resumption in HIV-infected individuals in Asia.
  
  
  METHODS
  Patients initiating cART between 2006 and 2013 were included. TI was defined as stopping cART for >1 day. Treatment failure was defined as confirmed virological, immunological or clinical failure. Time to treatment failure during cART was analysed using Cox regression, not including periods off treatment. Covariables with P < 0.10 in univariable analyses were included in multivariable analyses, where P < 0.05 was considered statistically significant.
  
  
  RESULTS
  Of 4549 patients from 13 countries in Asia, 3176 (69.8%) were male and the median age was 34 years. A total of 111 (2.4%) had TIs due to AEs and 135 (3.0%) had TIs for other reasons. Median interruption times were 22 days for AE and 148 days for non-AE TIs. In multivariable analyses, interruptions >30 days were associated with failure (31-180 days HR = 2.66, 95%CI (1.70-4.16); 181-365 days HR = 6.22, 95%CI (3.26-11.86); and >365 days HR = 9.10, 95% CI (4.27-19.38), all P < 0.001, compared to 0-14 days). Reasons for previous TI were not statistically significant (P = 0.158).
  
  
  CONCLUSIONS
  Duration of interruptions of more than 30 days was the key factor associated with large increases in subsequent risk of treatment failure. If TI is unavoidable, its duration should be minimised to reduce the risk of failure after treatment resumption.
authors.affiliation: The Kirby Institute, UNSW Australia, Sydney, Australia.
authors.forename: Awachana
authors.initials: A
authors.lastname: Jiamsakul
authors.affiliation: The Kirby Institute, UNSW Australia, Sydney, Australia.|HIV-NAT, The Thai Red Cross AIDS Research Centre, Bangkok, Thailand.|Department of Global Health, Academic Medical Center, University of Amsterdame, Amsterdam Institute for Global Health and Development, Amsterdam, The Netherlands.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Kerr
authors.affiliation: Department of Infectious Diseases, Tan Tock Seng Hospital, Singapore City, Singapore.
authors.forename: Oon Tek
authors.initials: OT
authors.lastname: Ng
authors.affiliation: Queen Elizabeth Hospital, Hong Kong, China.
authors.forename: Man Po
authors.initials: MP
authors.lastname: Lee
authors.affiliation: Research Institute for Health Sciences, Chiang Mai University, Chiang Mai, Thailand.
authors.forename: Romanee
authors.initials: R
authors.lastname: Chaiwarith
authors.affiliation: Working Group on AIDS, Faculty of Medicine, University of Indonesia/Cipto Mangunkusumo Hospital, Jakarta, Indonesia.
authors.forename: Evy
authors.initials: E
authors.lastname: Yunihastuti
authors.affiliation: National Hospital for Tropical Diseases, Hanoi, Vietnam.
authors.forename: Kinh
authors.initials: K
authors.lastname: Van Nguyen
authors.affiliation: Bach Mai Hospital, Hanoi, Vietnam.
authors.forename: Thuy Thanh
authors.initials: TT
authors.lastname: Pham
authors.affiliation: Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
authors.forename: Sasisopin
authors.initials: S
authors.lastname: Kiertiburanakul
authors.affiliation: Research Institute for Tropical Medicine, Manila, Philippines.
authors.forename: Rossana
authors.initials: R
authors.lastname: Ditangco
authors.affiliation: National Center for HIV/AIDS, Dermatology & STDs and University of Health Sciences, Phnom Penh, Cambodia.
authors.forename: Vonthanak
authors.initials: V
authors.lastname: Saphonn
authors.affiliation: Hospital Sungai Buloh, Sungai Buloh, Malaysia.
authors.forename: Benedict L H
authors.initials: BL
authors.lastname: Sim
authors.affiliation: Faculty of Medicine Udayana University & Sanglah Hospital, Bali, Indonesia.
authors.forename: Tuti Parwati
authors.initials: TP
authors.lastname: Merati
authors.affiliation: Taipei Veterans General Hospital, Taipei, Taiwan.
authors.forename: Wingwai
authors.initials: W
authors.lastname: Wong
authors.affiliation: Chiangrai Prachanukroh Hospital, Chiang Rai, Thailand.
authors.forename: Pacharee
authors.initials: P
authors.lastname: Kantipong
authors.affiliation: Beijing Ditan Hospital, Capital Medical University, Beijing, China.
authors.forename: Fujie
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Division of Infectious Diseases, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea.
authors.forename: Jun Yong
authors.initials: JY
authors.lastname: Choi
authors.affiliation: Institute of Infectious Diseases, Pune, India.
authors.forename: Sanjay
authors.initials: S
authors.lastname: Pujari
authors.affiliation: University of Malaya Medical Centre, Kuala Lumpur, Malaysia.
authors.forename: Adeeba
authors.initials: A
authors.lastname: Kamarulzaman
authors.affiliation: National Center for Global Health and Medicine, Tokyo, Japan.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Oka
authors.affiliation: Hospital Raja Perempuan Zainab II, Kota Bharu, Malaysia.
authors.forename: Mahiran
authors.initials: M
authors.lastname: Mustafa
authors.affiliation: Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand.
authors.forename: Winai
authors.initials: W
authors.lastname: Ratanasuwan
authors.affiliation: TREAT Asia, amfAR - The Foundation for AIDS Research, Bangkok, Thailand.
authors.forename: Boondarika
authors.initials: B
authors.lastname: Petersen
authors.affiliation: The Kirby Institute, UNSW Australia, Sydney, Australia.
authors.forename: Matthew
authors.initials: M
authors.lastname: Law
authors.affiliation: YRGCARE Medical Centre, Chennai, India.
authors.forename: Nagalingeswaran
authors.initials: N
authors.lastname: Kumarasamy
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage* / Q000009:adverse effects* / Q000627:therapeutic use; D001208:Asia; D018791:CD4 Lymphocyte Count; D018450:Disease Progression; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D008297:Male; D055118:Medication Adherence / Q000523:psychology; D008875:Middle Aged; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012307:Risk Factors; D013997:Time Factors; D017211:Treatment Failure; D016896:Treatment Outcome; D019562:Viral Load; D016903:Drug Monitoring
chemical_list: D019380:Anti-HIV Agents
keywords: Asia; Asie; HIV; VIH; adverse events; antiretroviral; antirretroviral; antirétroviral; effets indésirables; eventos adversos; interrupción del tratamiento; interruptions de traitement; treatment interruptions