Routine versus Targeted Viral Load Strategy among Patients Starting Antiretroviral in Hanoi, Vietnam

Abstract

Introduction HIV viral load (VL) testing is recommended by the WHO as the preferred method for monitoring patients on antiretroviral therapy (ART). However, evidence that routine VL (RVL) monitoring improves clinical outcomes is lacking. Methods We conducted a prospective, randomized controlled trial of RVL monitoring every six months versus a targeted VL (TVL) strategy (routine CD4 plus VL testing if clinical or immunological failure) in patients starting ART between April 2011 and April 2014 at Bach Mai Hospital in Hanoi. Six hundred and forty‐seven subjects were randomized to RVL (n = 305) or TVL monitoring (n = 342) and followed up for three years. Primary endpoints were death or WHO clinical Stage 4 events between six and thirty‐six months of ART and rate of virological suppression at three years. Results Overall, 37.1% of subjects were female, median age was 33.4 years (IQR: 29.5 to 38.6), and 47% had a CD4 count ≤100 cells/mm3 at time of ART initiation. Approximately 44% of study events (death, LTFU, withdrawal, or Stage 4 event) and 68% of deaths occurred within the first six months of ART. Among patients on ART at six months, death or Stage 4 event occurred in 3.6% of RVL and 3.9% of TVL (p = 0.823). Survival analysis showed no significant difference between the groups (p = 0.825). Viral suppression at 36 months of ART was 97.2% in RVL and 98.9% in TVL (p = 0.206) at a threshold of 400 copies/mL and was 98.0% in RVL and 98.9% in TVL (p = 0.488) at 1000 copies/mL. In ITT analysis, 20.7% in RVL and 21.9% in TVL (p = 0.693) were unsuppressed at 1000 copies/mL. Conclusions We found no significant difference in rates of death or Stage 4 events and virological failure in patients with RVL monitoring compared to those monitored with a TVL strategy after three years of follow‐up. Viral suppression rates were high overall and there were few study events among patients alive and on ART after six months, limiting the study's power to detect a difference among study arms. Nonetheless, these data suggest that the choice of VL monitoring strategy may have less impact on patient outcomes compared to efforts to reduce early mortality and improve ART retention.

Performance and Outcomes of Routine Viral Load Testing in People Living with HIV Newly Initiating ART in the Integrated HIV Care Program in Myanmar between January 2016 and December 2017

“…However, we speculate that this may have been due to clinicians requesting earlier VL testing based on the need to know, for example in pregnant women, or later VL testing based on patient clinical status. While previous studies have shown that routine VL monitoring results in earlier detection of virologic failure and earlier switching to second-line ART [ 21 , 22 ], a recent study in Vietnam showed no difference in rates of failure or death between routine and targeted VL testing [ 23 ].…”

Virological failure and treatment switch after ART initiation among people living with HIV with and without routine viral load monitoring in Asia

“…1 Department of Statistics, Faculty of Science, Kasetsart University, Bangkok, Thailand; 2 HIV-NAT, Thai Red Cross AIDS Research Centre, Bangkok, Thailand; 3 The Kirby Institute, UNSW, Sydney, New South Wales, Australia; 4 Sydney School of Public Health, The University of Sydney, Sydney, New South Wales, Australia; 5 BJ Government Medical College and Sassoon General Hospital, Pune, India; 6 Queen Elizabeth Hospital, Kowloon, Hong Kong SAR; 7 National Hospital for Tropical Diseases, Hanoi, Vietnam; 8 Chiang Mai University -Research Institute for Health Sciences, Chiang Mai, Thailand; 9 Division of Infectious Diseases and Tropical Medicine, Department of Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand; 10 National Center for HIV/AIDS, Dermatology & STDs, Phnom Penh, Cambodia; 11 Taipei Veterans General Hospital, Taipei, Taiwan; 12 Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand; 13 Chiangrai Prachanukroh Hospital, Chiang Rai, Thailand; 14 Beijing Ditan Hospital, Capital Medical University, Beijing, China; 15 Faculty of Medicine, Universitas Indonesia -Dr. Cipto Mangunkusumo General Hospital, Jakarta, Indonesia; 16 Chennai Antiviral Research and Treatment Clinical Research Site (CART CRS), VHS-Infectious Diseases Medical Centre, VHS, Chennai, India; 17 Institute of Infectious Diseases, Pune, India; 18 University Malaya Medical Centre, Kuala Lumpur, Malaysia; 19 Faculty of Medicine, Udayana University & Sanglah Hospital, Bali, Indonesia; 20 National Center for Global Health and Medicine, Tokyo, Japan; 21 Research Institute for Tropical Medicine, Muntinlupa City, Philippines; 22 Division of Infectious Diseases, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea; 23 Tan Tock Seng Hospital, Singapore; 24 Bach Mai Hospital, Hanoi, Vietnam; 25 Hospital Sungai Buloh, Sungai Buloh, Malaysia; 26 TREAT Asia, amfAR -The Foundation for AIDS Research, Bangkok, Thailand…”

“…However, previous studies report that PLHIV from sites with routine VL testing switched to second-line ART after virologic failure was confirmed [6][7][8][9]. Studies from Asia indicate that routing VL testing can improve clinical outcomes [6,9,10].…”

“…According to the World Health Organization (WHO) recommendations, routine VL testing should be conducted 6 and 12 months after ART initiation and every 12 months thereafter [ 3 ]. Previous studies indicate that VL tests can detect treatment failure earlier and more accurately than CD4 testing or clinical monitoring [ 4 , 5 , 6 ]. However, in resource‐limited settings, routine VL testing may not be readily available and switches to a second‐line regimen may occur immediately without evidence of virological failure (VF).…”

Prevalence of Advanced HIV Disease, Cryptococcal Antigenemia, and Suboptimal Clinical Outcomes Among Those Enrolled in Care in Vietnam

“…Among patients enrolled in a randomized controlled trial who initiated ART between April 2011 and 2014 at a large HIV clinic in Hanoi, Vietnam, the median CD4 cell count at enrollment in HIV care was 130 cells/mL, and 35.5% (230/647) of participants had AIDS-defining OIs. 4 The high proportion of patients with advanced disease at the time of testing, delayed linkage to care, and late ART initiation all contribute to suboptimal clinical outcomes-lower retention rates, high loss to follow-up (LTFU), death, and OIs. 5 Cryptococcal disease is common among patients with advanced HIV and is an independent predictor of cryptococcal meningitis (CM) and death in HIV-infected individuals with advanced disease.…”