Systematic Review of the Use of Dried Blood Spots for Monitoring HIV Viral Load and for Early Infant Diagnosis

Abstract

BackgroundDried blood spots (DBS) have been used as alternative specimens to plasma to increase access to HIV viral load (VL) monitoring and early infant diagnosis (EID) in remote settings. We systematically reviewed evidence on the performance of DBS compared to plasma for VL monitoring and EID.Methods and FindingsThirteen peer reviewed HIV VL publications and five HIV EID papers were included. Depending on the technology and the viral load distribution in the study population, the percentage of DBS samples that are within 0.5 log of VL in plasma ranged from 52–100%. Because the input sample volume is much smaller in a blood spot, there is a risk of false negatives with DBS. Sensitivity of DBS VL was found to be 78–100% compared to plasma at VL below 1000 copies/ml, but this increased to 100% at a threshold of 5000 copies/ml. Unlike a plasma VL test which measures only cell free HIV RNA, a DBS VL also measures proviral DNA as well as cell-associated RNA, potentially leading to false positive results when using DBS. The systematic review showed that specificity was close to 100% at DBS VL above 5000 copies/ml, and this threshold would be the most reliable for predicting true virologic failure using DBS. For early infant diagnosis, DBS has a sensitivity of 100% compared to fresh whole blood or plasma in all studies.ConclusionsAlthough limited data are available for EID, DBS offer a highly sensitive and specific sampling strategy to make viral load monitoring and early infant diagnosis more accessible in remote settings. A standardized approach for sampling, storing, and processing DBS samples would be essential to allow successful implementation.Trial RegistrationPROSPERO Registration #: CRD42013003621.

Evaluation of the Aptima HIV-1 Quant Dx Assay using plasma and dried blood spots

“…Furthermore, the large number of virus load tests that will be necessary to support the UNAIDS goals will likely require the use of a variety of testing strategies, including monitoring suppression through centralized testing of dried blood spots (DBS). The DBS approach allows increased accessibility of virus load testing in remote, lowresource settings, as DBS are simple and inexpensive to both collect and transport (28). Moreover, modeling data suggest that virus load monitoring using DBS provides a mechanism for the cost-effective delivery of ART in low-resource settings (29).…”

Expanding the role of diagnostic and prognostic tools for infectious diseases in resource-poor settings

“…Technological advances have supported this shift. For example, the reach of centralized laboratory testing can be extended through the use of specimen collection and stabilization technologies in combination with sample transport systems; such as the use of dried blood spots for HIV levels, malaria parasite detection and serology [6][7][8] . In addition, new portable and integrated technologies can allow testing at primary health facilities, providing greater access to care and adoption 9 .…”

HIV-1 RNA testing of pooled dried blood spots is feasible to diagnose acute HIV infection in resource limited settings

“…[14][15][16] Many studies have demonstrated that dried blood spots (DBS) are useful for infant HIV diagnosis and monitoring plasma HIV viral loads with an excellent analytical performance. [17][18][19] However, no data is available for a DBS testing pooling strategy to diagnose acute and early adult HIV infections. In this study, we investigated whether pooled dried blood spot (DBS) testing might be a feasible method to identify acute HIV infection in a moderate risk HVCT setting.…”