Background: Ready acceptance of the first news of HIV-positive diagnosis is a known personal and public health safety-net. Its beneficial effects include prompt commencement and sustenance of HIV-positive treatment and care, better management of transmission risk, and disclosure of the HIV-positive status to significant others. Yet, no known study has explored this topic in Ghana; despite Ghana’s generalised HIV/AIDS infection rate. Existing studies have illuminated the effects of such reactions on affected significant others; not the infected.Methods: This paper studied qualitatively the initial reactions of 26 persons living with HIV/AIDS upon receiving the initial news of their diagnosis. Sample selection was combined purposive and random, from two hospitals in a district in Ghana heavily affected by HIV/AIDS. The paper applied the theory of hopelessness.Results: As expected, the vast majority of respondents reacted to the initial announcement of their HIV-positive infection with a myriad of negative psychosocial reactions, including thoughts of committing suicide. A few, however, received the news with resignation. For the vast majority of respondents, having comorbidities from AIDS prior to the diagnosis primarily shaped their initial reactions to it. This was followed by having/having had an HIV-positive spouse/partner, and exposure to health education on HIV/AIDS on TV particularly. Receiving counselling from healthcare workers mostly facilitated their transitioning to self-acceptance of their HIV-positive status.Conclusions: Although the first news of an HIV-positive diagnosis was immobilising to most respondents, the trauma faded, paving the way for beneficial public health actions. The findings do not wholly support earlier propositions of the theory of hopelessness. Rather, results indicate that both internal and external insecurities can trigger hopelessness in persons living with HIV/AIDS. The results imply the critical need for continuous education on HIV/AIDS by public health advocates, using mass media, particularly, TV. This should continuously emphasise the need for voluntary counseling and testing and the fact that once infected, prevention of further transmission, and immediate seeking and adhering to healthcare are important. These can prevent comorbidities and death from HIV infection. Healthcare workers in VCTs should empathise with persons who are informed of their HIV-positive status for the first time.