The success of antiretroviral therapy (ART) has transformed HIV infection into a chronic disease, reducing AIDS-related illnesses to a secondary concern in many parts of the world. However, ART does not fully restore immune health, leading to a new set of HIV-associated complications, including cardiovascular disease and cancer. These complications are associated with cumulative toxicities from long-term antiretroviral exposure, causing metabolic disturbances and end-organ damage. The healthcare systems in resource-limited regions, particularly sub-Saharan Africa, are ill-equipped to manage the chronic care required for HIV patients, which includes addressing multiple co-morbidities. The aging population of HIV-infected individuals will further exacerbate these challenges, necessitating the development of sustainable chronic care models. While a cure for HIV remains a distant goal, recent clinical observations suggest that interventions such as stem cell transplants and early aggressive therapy may offer hope. Biomedical research must focus on understanding and reversing the chronic inflammation associated with HIV, while integrating non-communicable disease and tuberculosis services into chronic care.The success of antiretroviral therapy (ART) has transformed HIV infection into a chronic disease, reducing AIDS-related illnesses to a secondary concern in many parts of the world. However, ART does not fully restore immune health, leading to a new set of HIV-associated complications, including cardiovascular disease and cancer. These complications are associated with cumulative toxicities from long-term antiretroviral exposure, causing metabolic disturbances and end-organ damage. The healthcare systems in resource-limited regions, particularly sub-Saharan Africa, are ill-equipped to manage the chronic care required for HIV patients, which includes addressing multiple co-morbidities. The aging population of HIV-infected individuals will further exacerbate these challenges, necessitating the development of sustainable chronic care models. While a cure for HIV remains a distant goal, recent clinical observations suggest that interventions such as stem cell transplants and early aggressive therapy may offer hope. Biomedical research must focus on understanding and reversing the chronic inflammation associated with HIV, while integrating non-communicable disease and tuberculosis services into chronic care.