Dried fluid spots for HIV type-1 viral load and resistance genotyping: a systematic review

Background: Dried spots on filter paper made of whole blood (dried blood spots; DBS), plasma (dried plasma spots; DPS) or serum (dried serum spots) hold promise as an affordable and practical alternative specimen source to liquid plasma for HIV type-1 (HIV-1) viral load determination and drug resistance genotyping in the context of the rapidly expanding access to antiretroviral therapy (ART) for HIV-1-infected individuals in low- and middle-income countries. This report reviews the current evidence for their utility. Methods: We systematically searched the English language literature published before 2009 on Medline, the websites of the World Health Organization and US Centers for Disease Control and Prevention, abstracts presented at relevant international conferences and references from relevant articles. Results: Data indicate that HIV-1 viral load determination and resistance genotyping from DBS and DPS is feasible, yielding comparable test performances, even after storage. Limitations include reduced analytical sensitivity resulting from small analyte volumes (approximately 3.5 log(10) copies/ml at 50 mu l sample volume), nucleic acid degradation under extreme environmental conditions, impaired efficiency of nucleic acid extraction, potential interference of archived proviral DNA in genotypes obtained from DBS and the excision of spots from the filters in high-volume testing. Conclusions: This technology offers the advantages of a stable specimen matrix, ease of sample collection and shipment. The current sensitivity in drug resistance testing is appropriate for public health surveillance among pretreatment populations. However, consistently improved analytical sensitivity is needed for their routine application in the therapeutic monitoring of individuals receiving ART, particularly at the onset of treatment failure