Antiretroviral therapy interruptions: impact on HIV treatment and transmission

Gueorgui Dubrocq,1,2 Natella Rakhmanina3–5 1Division of Pediatric Infectious Diseases, Baylor Scott & White McLane Children’s Medical Center, Temple, TX, USA; 2Department of Pediatrics, Baylor Scott & White McLane Children’s Medical Center, Temple, TX, USA; 3Division of Pediatric Infectious Diseases, Children’s National Health System, Washington, DC, USA; 4Department of Pediatrics, The George Washington University School of Medicine and Health Sciences, Washington, DC, USA; 5Elizabeth Glaser Pediatric AIDS Foundation, Washington, DC, USA Introduction: Successful management of pediatric and adult human immunodeficiency virus (HIV) disease includes lifelong administration of antiretroviral therapy (ART). The need for the continuous use of antiretroviral drugs throughout the life course poses a challenge to children, adolescents, and adults living with HIV and their caregivers. Historically, treatment interruptions have been viewed as a negative therapeutic strategy. Recently, however, treatment interruptions or treatment reduction strategies have become a focus of investigations as innovative approaches to the long-term management of HIV disease. Current challenges with treatment interruptions include identifying an appropriate timeframe for length of interruptions and identifying HIV patient populations in whom the treatment interruption can be successful.Objective: In this review, we aimed at summarizing recent studies of planned and unplanned treatment interruptions in children and adults living with HIV.Materials and methods: We searched two databases (PubMed and Cochrane Controlled Trials Register) using keywords (HIV OR AIDS OR acquired immunodeficiency syndrome OR HIV-1 OR antiretroviral) AND (treatment interruption OR planned interruption OR therapeutic interruption OR unplanned interruption), for published randomized and nonrandomized clinical trials and observational cohort studies in children and adults (from birth to 99 years of age) in global settings covering a period from 2012 to 2018. In this review, only the studies that contained pediatric and adolescent populations with baseline immunological, ­virological, and clinical characteristics and outcomes after treatment interruption were included.Results: A total of 174 eligible citations from the two databases were identified. We identified 10 prospective treatment interruption studies on children (five studies) and adults (five studies) during 2012–2018 with a total of 863 pediatric and 273 adult subjects. Collectively, recent studies on children and adults with HIV infection suggest that treatment interruptions with proper monitoring can be successful by instituting well-defined immunological and virological parameters or thresholds such as CD4 count, CD4%, and HIV RNA viral load that identify low-risk populations with treatment failure. In addition to standard virological and immunological outcome measurements, selected biomarkers that help detect early immune activation may also be useful in the monitoring of treatment interruption.Conclusion: Treatment interruptions in adult and especially pediatric patients with well-controlled HIV disease may provide an alternative opportunity to optimize long-term HIV management by minimizing drug-associated toxicity and improving long-term adherence and quality of life. Keywords: HIV, antiretroviral therapy, treatment interruption