Clinicians are well aware of the changing natural history of HIV infection in regions where antiretroviral therapy is accessible. Clinical investigations of HIV in the first 20 years of the epidemic focused on the diagnosis, treatment and prevention of opportunistic infections. While there has always been a need to improve management strategies, effective approaches were developed for most opportunistic infections, although the quality and duration of survival were short until antiretroviral therapy became effective and durable. As patients have live longer, morbidity due to comorbidities related to viral diseases (HCV, HBV, HPV, CMV), metabolic disorders, chronic inflammation, and neoplastic processes have become more prevalent. Health care systems have had to augment and expand their screening programs for such morbidities, and develop more comprehensive health care for HIV infected patients who survive with these co morbidities. Washington, D.C. is an example of a city which is realigning its resources to focus on these emerging comorbidities and to integrate care. Data on these comorbidities provide insight into research challenges that must be met.