Introduction: Blood transfusion is an essential life-saving intervention in the healthcare delivery. Mandatory screening of donor units helps prevent transfusion-transmissible infections, such as Human Immunodeficiency Virus (HIV).

Aim: The purpose of this study was to use Nucleic Acid-Amplification Testing (NAAT) to screen for the presence of HIV-1 in blood-banked samples labelled as “safe for transfusion” per serological testing algorithm.

Materials and Methods: This hospital-based cross-sectional diagnostic study was conducted in May 2016 on serologically tested donor blood units in the Koforidua Regional Hospital blood bank. One hundred (100) donor samples were analysed using the COBAS® AmpliPrep/COBAS® TaqMan® HIV-1 Qual Test for the detection of HIV-1 RNA and proviral DNA. results: Of the 100 donor samples that tested sero-negative for HIV-1 and 2 using the antibody screening kit, four (4) samples (4%) were reactive by NAAT. Blood donors who came for donation were only males and majority (90%) were between the ages of 17-27 years. Additionally, all the NAAT HIV-1 positive samples were from participants in the 17-27 year group. conclusion: NAAT demonstrated that a significant number of HIV-infected individuals are misdiagnosed at Ghanaian pointsof-care. This finding has necessitated the need for inclusion of NAAT in donor blood screening in areas prevalent for HIV-1 in Ghana, considering the risk involved in using the licensed antibody test provided by the health authorities. In cases where NAAT screening may not be feasible, newer tests that have greater sensitivity compared to the FDA-licensed 3rd generation EIA which only detects HIV antibodies can be adopted.