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J Clin Microbiol 2018 Jul 26;56(8):e02045-17

Comparison of detection limits of 4th generation combination HIV antigen/antibody, p24 antigen and viral load assays on diverse HIV isolates.

Stone M, Bainbridge J, Sanchez AM, Keating SM, Pappas A, Rountree W, Todd C, Bakkour S, Manak M, Peel SA, Coombs RW, Ramos EM, Shriver MK, Contestable P, Nair SV, Wilson DH, Stengelin M, Murphy G, Hewlett I, Denny TN, Busch MP, EQAPOL Program


BACKGROUND: Detection of acute HIV infection is critical for HIV public health and diagnostics. Clinical 4th generation antigen-antibody (Ag/Ab) combination (combo) and p24 Ag immunoassays have enhanced detection of acute infection compared to Ab alone assays, but require ongoing evaluation with currently circulating diverse subtypes. Genetically and geographically diverse HIV clinical isolates were used to assess clinical HIV diagnostic, blood screening and next generation assays. METHODS: Blinded 300 member panels of 20 serially diluted well-characterized antibody negative HIV isolates were distributed to manufacturers and end-user labs to assess relative analytic sensitivity of currently approved and pre-approved clinical HIV 4th generation Ag/Ab combo or p24 Ag alone immunoassays across diverse subtypes. The limits of virus detection (LODs) were estimated for different subtypes relative to confirmed viral loads. RESULTS: Analysis of immunoassay sensitivity was benchmarked against confirmed viral load measurements on the blinded panel. Based on the proportion of positive results on 300 observations all Ag/Ab combo and standard sensitivity p24 Ag assays performed similarly and within half log LODs, illustrating similar breadth of reactivity and diagnostic utility. Ultrasensitive p24 Ag assays achieved dramatically increased sensitivities, while the rapid combo-assays performed poorly. CONCLUSIONS: Similar performance of the different commercially available 4th gen assays on diverse subtypes supports their use in broad geographic settings with locally circulating HIV clades and recombinant strains. Next generation pre-clinical ultrasensitive p24 Ag assays achieved dramatically improved sensitivity, while p24 Ag detection by rapid 4th gen assays performed poorly.

Category: Journal Article
PubMed ID: #29793968 DOI: 10.1128/JCM.02045-17
PubMed Central ID: #PMC6062817
Includes FDA Authors from Scientific Area(s): Biologics
Entry Created: 2018-04-22 Entry Last Modified: 2018-08-12