The main objective of this application is to investigate the prevalence and progression of neuroendocrinologic and neurological complications associated with HIV-infection in South India. The first case of HIV-infection was reported in1987 from the Christian Medical College, (CMC) Vellore, India the site of this proposed research project. Over the years, HIV-infection has spread aggressively and there are estimated to be at least 4.1 million HIV-infected individuals in India. It is estimated that during the next 5-10 years the number of infected individuals in India may exceed the present prevalence of the entire world and pose an international public health threat. Surprisingly, up to 25 percent of infected individuals in India have co-infections of both HIV-1 and 2. Immediately after infection, HIV crosses the blood-brain-barrier and is localized in very high concentrations in the hippocampus and to variable degrees in other areas of the brain. Since the hippocampus plays an important role in regulating various endocrine systems, memory and other neurological functions, this application proposes to investigate longitudinally the prevalence of abnormalities in these systems as associated with the progression of HIV-1 & HIV-2 co-infection as well as with HIV-1 or HIV-2 mono-infections in the catchment area of CMC. This study will follow N= 240 individuals; HIV-1/2 co-infected, N= 60; HIV-1+, N=60; HIV-2+, N=60; and HIV-seronegative individuals, N=60. Both men and women, age 20-45, will be enrolled and followed for up to 3 years at six -month intervals. Abnormalities in the endocrine systems will be investigated via norepinephrine, epinephrine, ACTH and cortisol responses to an alpha-adrenergic challenge, AM and PM plasma levels of endocrines and CSF levels of cytokines and hormones. Using path analytic procedures, endocrine functions will be tested as mediators of the progression of neuropsychiatric and neuropsychology impairments determined using standardized cognitive test batteries. The data will be useful in designing interventions and for instituting an effective health policy.