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.