This study was conducted to investigate a report of positive test results with DMPA on an HIV rapid test. Suspecting HIV contamination, the Zambian Ministry of Health initiated a product withdrawal pending full evaluation.DMPA was evaluated for compliance to product specifications. Contamination with HIV and blood components was investigated with PCR and human IgG ELISA. The performance of Genie II, Unigold™ and Determine™ HIV rapid tests was evaluated using DMPA.DMPA was found compliant with product specifications and negative for HIV and human IgG. DMPA impaired the performance of HIV rapid tests resulting in false-positive/indeterminant results. Rapid test results using polysorbate 80 (formulation component of DMPA) mimicked results obtained with DMPA.The DMPA sample was negative for HIV and human IgG. Formulation components may have led to the interpretation of false-positive results, reinforcing the need to validate the sample type used in any test. DMPA use was reinstated in Zambia, minimizing the public health impact that resulted from the initial rapid test results.