Dried Blood Spots for Viral Load Monitoring in Malawi: Feasible and Effective

April Dried Blood Spots for Viral Load Monitoring in Malawi: Feasible and Effective Sarah E. Rutstein 0 1 Mina C. Hosseinipour 0 1 Deborah Kamwendo 0 1 Alice Soko 0 1 Memory Mkandawire 0 1 Andrea K. Biddle 0 1 William C. Miller 0 1 Morris Weinberger 0 1 Stephanie B. Wheeler 0 1 Abdoulaye Sarr 0 1 Sundeep Gupta 0 1 Frank Chimbwandira 0 1 Reuben Mwenda 0 1 Steve Kamiza 0 1 Irving Hoffman 0 1 Ronald Mataya 0 1 0 1 Department of Health Policy and Management, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States, 2 Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States, 3 University of North Carolina Project, Lilongwe, Malawi, 4 School of Public Health, Loma Linda University, Loma Linda, California, United States, 5 Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States, 6 Centers for Disease Control , Lilongwe, Malawi, 7 Ministry of Health , Lilongwe, Malawi, 8 College of Medicine , Blantyre , Malawi 1 Academic Editor: William A Paxton, Institute of Infection and Global Health , UNITED KINGDOM - Data Availability Statement: In keeping with U.S. National Institutes of Health guidance on protecting human subjects privacy, the study team will make all individual-level demographic, clinical, and laboratory data for enrolled ART patients available on request by contacting Malawi Ministry of Health through Mr. Frank Chimbwandira at the HIV Unit (email: ). As the analytical data set includes sensitive data regarding HIVinfection status for a vulnerable population of HIVinfected individuals, as well as health facility and other locator information that could be used to identify participants through deduction. To evaluate the feasibility and effectiveness of dried blood spots (DBS) use for viral load (VL) monitoring, describing patient outcomes and programmatic challenges that are relevant for DBS implementation in sub-Saharan Africa. We recruited adult antiretroviral therapy (ART) patients from five district hospitals in Malawi. Eligibility reflected anticipated Ministry of Health VL monitoring criteria. Testing was conducted at a central laboratory. Virological failure was defined as >5000 copies/ml. Primary outcomes were program feasibility (timely result availability and patient receipt) and effectiveness (second-line therapy initiation). We enrolled 1,498 participants; 5.9% were failing at baseline. Median time from enrollment to receipt of results was 42 days; 79.6% of participants received results within 3 months. Among participants with confirmed elevated VL, 92.6% initiated second-line therapy; 90.7% were switched within 365 days of VL testing. Nearly one-third (30.8%) of participants with elevated baseline VL had suppressed (<5,000 copies/ml) on confirmatory testing. Median period between enrollment and specimen testing was 23 days. Adjusting for relevant covariates, participants on ART >4 years were more likely to be failing than participants on therapy 14 years (RR 1.7, 95% CI 1.0-2.8); older participants were less likely to be failing (RR 0.95, 95% CI 0.92-0.98). There was no difference in likelihood of failure based on clinical symptoms (RR 1.17, 95% CI 0.65-2.11). Funding: MW.10.1433 (http://www.cdc.gov/ globalhealth/countries/malawi/) Public Health Evaluation of use of Dried Blood Spots for Viral Load Monitoring received by RM. The funder assisted in the early stages of study design, and AS and SG were involved in preparation of the manuscript. Funders were not involved in data collection, analysis or decision to publish. F30 MH098731 (http://www. nimh.nih.gov/index.shtml) Fellowship support for SER. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript." Competing Interests: The authors have declared that no competing interests exist DBS for VL monitoring is feasible and effective in real-world clinical settings. Centralized DBS testing may increase access to VL monitoring in remote settings. Programmatic outcomes are encouraging, especially proportion of eligible participants switched to secondline therapy. Viral load (VL) testing is the preferred method for monitoring antiretroviral therapy (ART) to identify potential adherence problems and treatment failures [1]. Compared to immunological (CD4 cell counts) or clinical staging, VL testing is more sensitive and specific for accurately diagnosing treatment failure, reducing premature or inappropriate switching to second line therapy [27]. Delaying treatment changes for patients failing first-line ART increases morbidity and mortality [8, 9] and may lead to accumulation of resistance mutations that compromise second-line ART response [1013]. With VL monitoring, failing patients are identified sooner [1418]. Additionally, the avoidance of premature switching prevents the loss of potential lifeyears on first-line therapy and costs associated with having patients on more expensive and complicated second-line regimens. These concerns are especially relevant in resource-limited settings where third-line options are not widely available. As recently revised ART guidelines expand treatment eligibility, potentially leading to >20 million HIV infected patients on ART in Africa alone, access to VL monitoring remains poor and identifying appropriate monitoring strategies in resource-limited settings is an urgent global health priority [19, 20]. The benefits of ART, specifically reducing transmission [21] and disease progression [22], are realized only if viral replication is suppressed [23]. Rates of virological failure in sub-Saharan Africa range from 6% to 53%, depending on failure threshold, clinical setting, and ART exposure time [14, 2431]. Pooled estimates from low- and middleincome countries at 12 months of ART exposure suggest 16% failure [29]. Despite the benefits of VL monitoring, numerous barriers impede scale-up in resourcelimited settings. Traditional VL tests used in developed countries are prohibitively expensive and complex for routine use in resource-limited settings because they require laboratory infrastructure for plasma processing, continuous cold-chain, and phlebotomy-trained providers. Point-of-care technologies are under evaluation but are not yet available [32]. The use of dried blood spot (DBS) for specimen collection and subsequent transport to centralized testing laboratories is an appealing alternative to plasma-based VL testing [1, 3340]. Malawi is one of many countries attempting to incorporate VL monitoring from DBS into ART care [41, 42]. Over 10 years after ART rollout, <1% of Malawian ART patients are on second-line regimens [42], which may reflect providers relying primarily on clinical staging criteria to diagnose treatment failure and subsequent under-diagnosis of virological failure. DBS program feasibility for routine VL monitoring in ART clinics, includ (...truncated)