Evaluation of FDA licensed HIV assays using plasma from Cameroonian blood donors

Abstract

Several diagnostic assays for the detection of HIV infection have been approved and licensed by the FDA for blood donor screening. However, the performance of these assays is unknown when testing genetically divergent blood specimens. To evaluate the performance of these assays with diverse HIV strains, we chose to study specimens collected from blood donors in Cameroon where genetic diversity and recombinant variants are prevalent. In this study, we tested 240 human plasma specimens collected from two blood centers in Cameroon. These samples were screened initially in Cameroon for antibody to HIV using a rapid assay. We also performed sequencing to determine subtype. Our evaluation has demonstrated that HIV infection in most HIV plasma samples could be detected by most of the US FDA licensed diagnostic assays. With the exception of a few specimens, HIV-1 p24 antigen was not detected in any of the samples. In addition, some nucleic acid tests (NAT) assays were not able to detect a few serologic reactive samples and all new variants including some CRF02_AG variants.

Review of status of HIV strain diversity in the United States

“…The early nucleic acid-based assays (NAT) used to monitor viral loads in HIV-1 infected patients were impacted by the genetic variability between HIV-1 subtypes resulting in under quantification of or failure to detect some non-B viruses [Swanson et al, 2000[Swanson et al, , 2005Geelan et al, 2003;Harris et al, 2005;Lee et al, 2006]. While the high genetic diversity in HIV-1 continues to pose a challenge for NAT, at least one real-time HIV-1 viral load assay has been designed to address this issue [Swanson et al, 2006a[Swanson et al, ,b, 2007.…”

HIV variants and hepatitis B surface antigen mutants: Diagnostic challenges for immunoassays

“…Recombination between subtypes and groups adds to the overall diversity of HIV-1 [Brennan et al, 2006;McCutchan, 2006]. In some regions (e.g., Cameroon and Thailand), recombinant strains referred to as circulating recombinant forms (CRFs), have become the predominant form of HIV-1 [Brennan et al, 2006;Lee et al, 2006]. The high degree of genetic diversity observed for HIV-1 presents a challenge to developers of assays designed for screening, diagnosis, and patient monitoring.…”

“…Identification and characterization of several new group N infections were described. Two papers [Brennan et al, 2006;Lee et al, 2006] present data on Cameroonian blood donors that revealed the presence of a high level of HIV-1 variation with five subtypes, six CRFs, numerous unique recombinant forms and group O (combined data from the two papers). The majority of the donors were infected with a recombinant HIV-1 strain, CRF02_AG, a mosaic of viral subtypes A and G.…”

“…Genetic variation was also shown to influence performance of nucleic acid based assays. Two papers [Brennan et al, 2006;Lee et al, 2006] showed that nucleotide polymorphisms within primer and probe sites can impact the ability to detect or accurately quantify divergent HIV-1 strains. The papers presented at this meeting clearly indicated that the continued evolution and ever-changing global distribution of HIV will continue to present important challenges for assays designed to screen, diagnose, and monitor this viral infection.…”

Field Evaluation of Calypte’s AWARETM Blood Serum Plasma (BSP) and Oral Mucosal Transudate (OMT) Rapid Tests for Detecting Antibodies to HIV-1 and 2 in Plasma and Oral Fluid

“…Rapid test kits have been shown in certain settings to be incapable of detecting infections by some genetic subtypes of the HIV-1 [7-9]. This calls for the need to regularly update diagnostic principles and methods, and the continuous evaluation of test kits to make sure that they can detect the newly emerging viral strains.…”