This application is for the renewal of the Study to Help the AIDS Research Effort (SHARE), which is the Baltimore-Washington DC site of the Multicenter AIDS Cohort Study (MACS). The MACS was funded by NIAID and NCI in 1983, with sites in Baltimore-Washington, Chicago, Pittsburgh, and Los Angeles to study the natural history of HIV infection in men who have sex with men. With the advent of effective combination antiretroviral therapy (cART), the MACS became also a study of the treated history of HIV infection, including the relationship between long-term controlled HIV infection and chronic diseases associated with aging. MACS participants, including 1808 enrolled in SHARE, have been followed semiannually since 1984 and have provided questionnaire data, physical exam data, laboratory data (including HIV serostatus, T cell subset measurements, and HIV viral load measurements), and a large repository of plasma, serum, cryopreserved peripheral blood mononuclear cells, and other specimens. Evaluating and following the prevalent and incident cases of HIV infection in SHARE and the MACS has provided key insights into risk factors for infection with HIV, monitoring and mechanisms of progression of HIV infection once it is established, host defense against HIV, genetic factors affecting HIV pathogenesis, and use, efficacy, and adverse effects of different types of therapy for HIV and related illnesses. SHARE and MACS are currently recruiting new participants who are receiving more recent cART regimens that are more potent, safer, and more convenient than older regimens, and which are initiated earlier in the course of HIV infection; this recruitment will be completed by the end of the current funding period in March, 2014. The specific aims of SHARE for the 2014-9 renewal period reflect those of the MACs and are to determine: the effect of evolving, earlier initiated c ART regimens on HIV-induced inflammation and immune dysfunction; the occurrence of and risk factors for emerging, non-AIDS-defining, high morbidity outcomes according to HIV infection and new c ART regimens; the determinants for incidence, progression and survival of malignancies, both AIDS- and non-AIDS-defining; the biologic and physiologic effects of treated HIV infection on the aging process; the relationships of substance use and psychosocial factors of aging in HIV infection with adherence, coping skills, resiliency, depression and quality of life and genetic factors associated with resistance to and control of HIV infection. SHARE will contribute to these goals through leadership of eight MACS working groups focusing on these topics, and through local studies focusing on liver disease, energy metabolism, cytomegalovirus infection, and regulation of immune activation and inflammation. These aims can be achieved only through continued follow-up of this extremely well-characterized cohort. SHARE and the MACS should continue to play a leading role in studies that will foster better treatments and prevention of HIV infection.