Relative sensitivities of licensed nucleic acid amplification tests for detection of viremia in early human immunodeficiency virus and hepatitis C virus infection.

BACKGROUND: Screening donors for human immunodeficiency virus (HIV) and hepatitis C virus (HCV) RNA is primarily performed on minipools (MPs) with one of two commercial nucleic acid amplification tests (NAT; Roche Molecular Systems; or Gen-Probe/Chiron). We compared these assays with respect to detection of RNA in early HIV and HCV infection. STUDY DESIGN AND METHODS: Twelve HIV plasma donor panels (116 serial samples) and 12 HCV panels (180 serial samples) were selected to optimally represent early viremia. Initial testing was performed in singlicate or triplicate on separately coded aliquots, both neat and at dilutions corresponding to MP screening (1:16 for Gen-Probe; 1:24 for Roche); 20 additional replicates were performed when discordant results were observed. Odds ratios (ORs) comparing detection of RNA by different assays were derived with logistic regression models. Differences in window-period closure and yields of assays in MP or individual-donation (ID) format were estimated. RESULTS: Differences in detection rates between Roche and Gen-Probe NAT assays were small and only observed with samples with very-low-level viremia. ORs for detecting RNA by the Gen-Probe versus the Roche assay were significant for HIV if conducted on MPs (1.8; 95% confidence interval [CI], 1.3-2.5) but not neat (1.0; 95% CI, 0.72-1.4). Odds of detecting HCV RNA were higher if the Gen-Probe assay was conducted either neat (2.3; 95% CI, 1.6-3.2) or on MPs (4.0; 95% CI, 2.8-5.8). These differences translated to <1 day window-period closure and

Absence of HBV and HCV, HTLV-I and -II, and human herpes virus-8 activation after allogeneic RBC transfusion in patients with advanced HIV-1 infection.

BACKGROUND: The Viral Activation Transfusion Study was a prospective, randomized, double-blind comparison of transfusion with WBC-reduced versus non-WBC-reduced RBCs to HIV+ patients. The primary study characterized the effect of transfusion on HIV and CMV activation by monitoring viral load changes. The present study analyzed HBV, HCV, HTLV-I and -II, and human herpes virus-8 (HHV-8) viral load before and after transfusion to evaluate the further hypothesis that global immune stimulation following allogeneic RBC transfusion results in activation and increased viral proliferation of chronic viral infections other than HIV and CMV. STUDY DESIGN AND METHODS: Baseline samples from 519 to 523 subjects were screened for HBV, HCV, HTLV-I and -II, and HHV-8 infection, and baseline, serial weekly, and quarterly blood samples from infected subjects in the non-WBC-reduced arm were evaluated for changes from baseline in viral nucleic acid and ALT levels. RESULTS: Seroprevalence of HBV, HCV, HTLV-I and -II, and HHV-8 was 68, 25, 5, and 30 percent, respectively. No significant induction of HBV, HCV, HHV-8, or HTLV-I and -II viral replication following allogeneic transfusion of non-WBC-reduced blood was observed. A significant, albeit small, association was observed between transfusion and ALT. CONCLUSIONS: Based on these results and our previous finding that no adverse effect on HIV and CMV viral load and disease progression results from allogeneic transfusion, no evidence is found to support the selective use of WBC-reduced blood components for HIV-infected patients.

Comparative yield of HCV RNA testing in blood donors screened by 2.0 versus 3.0 antibody assays.

BACKGROUND: Two HCV antibody tests (EIA 2.0 [EIA2], Abbott; and the Version 3.0 ELISA [EIA3], Ortho) are currently licensed for screening of US blood donors. Testing of donors for HCV RNA allows comparison of the sensitivities of the two antibody-screening assays. STUDY DESIGN AND METHODS: All allogeneic blood donations at 13 US test sites were screened for HCV RNA by testing plasma minipools using an investigational assay (COBAS AmpliScreen HCV test, v2.0, Roche Molecular Systems). Some sites screened for HCV antibody by EIA2 and some used EIA3. The frequency of RNA-positive and antibody-negative (RNA-pos and Ab-neg) donations among donors screened by each antibody assay was compared. Antibody appearance was assessed in a donor follow-up study. RESULTS: A total of 5.51 x 10(6) donations were screened for HCV RNA. Of these, 2.27 million were screened for antibody by EIA2, and 3.24 million by EIA3. Twenty-three donations were HCV RNA-pos and Ab-neg. The frequency of RNA-pos and Ab-neg donations was higher among donations screened by EIA2 (1 in 134,000), compared to those screened by EIA3 (1 in 540,000) (p = 0.001). Of the 17 RNA-pos and Ab-neg donations identified by test sites that used EIA2, 14 were retested by EIA3 and 10 (71%) were reactive. Most RNA-pos and Ab-neg donors appear to be in the process of seroconversion. Donors that were initially EIA2-negative and EIA3-reactive showed a more prolonged pattern of seroconversion compared to those that were initially nonreactive by both antibody assays. Four donors were EIA2-negative, EIA3-reactive, and RIBA-indeterminate (c33c) for at least 90 days, 1 for more than 317 days. CONCLUSION: EIA3 would have detected the majority of RNA-positive donations missed by EIA2. Some RNA-positive donors are EIA2-negative and EIA3-reactive for a prolonged period of time.