Awachana Jiamsakul1, Stephen J Kerr1,2,3, Oon Tek Ng4, Man Po Lee5, Romanee Chaiwarith6, Evy Yunihastuti7, Kinh Van Nguyen8, Thuy Thanh Pham9, Sasisopin Kiertiburanakul10, Rossana Ditangco11, Vonthanak Saphonn12, Benedict L H Sim13, Tuti Parwati Merati14, Wingwai Wong15, Pacharee Kantipong16, Fujie Zhang17, Jun Yong Choi18, Sanjay Pujari19, Adeeba Kamarulzaman20, Shinichi Oka21, Mahiran Mustafa22, Winai Ratanasuwan23, Boondarika Petersen24, Matthew Law1, Nagalingeswaran Kumarasamy25. 1. The Kirby Institute, UNSW Australia, Sydney, Australia. 2. HIV-NAT, The Thai Red Cross AIDS Research Centre, Bangkok, Thailand. 3. Department of Global Health, Academic Medical Center, University of Amsterdame, Amsterdam Institute for Global Health and Development, Amsterdam, The Netherlands. 4. Department of Infectious Diseases, Tan Tock Seng Hospital, Singapore City, Singapore. 5. Queen Elizabeth Hospital, Hong Kong, China. 6. Research Institute for Health Sciences, Chiang Mai University, Chiang Mai, Thailand. 7. Working Group on AIDS, Faculty of Medicine, University of Indonesia/Cipto Mangunkusumo Hospital, Jakarta, Indonesia. 8. National Hospital for Tropical Diseases, Hanoi, Vietnam. 9. Bach Mai Hospital, Hanoi, Vietnam. 10. Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand. 11. Research Institute for Tropical Medicine, Manila, Philippines. 12. National Center for HIV/AIDS, Dermatology & STDs and University of Health Sciences, Phnom Penh, Cambodia. 13. Hospital Sungai Buloh, Sungai Buloh, Malaysia. 14. Faculty of Medicine Udayana University & Sanglah Hospital, Bali, Indonesia. 15. Taipei Veterans General Hospital, Taipei, Taiwan. 16. Chiangrai Prachanukroh Hospital, Chiang Rai, Thailand. 17. Beijing Ditan Hospital, Capital Medical University, Beijing, China. 18. Division of Infectious Diseases, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea. 19. Institute of Infectious Diseases, Pune, India. 20. University of Malaya Medical Centre, Kuala Lumpur, Malaysia. 21. National Center for Global Health and Medicine, Tokyo, Japan. 22. Hospital Raja Perempuan Zainab II, Kota Bharu, Malaysia. 23. Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand. 24. TREAT Asia, amfAR - The Foundation for AIDS Research, Bangkok, Thailand. 25. YRGCARE Medical Centre, Chennai, India.
Abstract
OBJECTIVES: 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.
OBJECTIVES: 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.
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