Purpose: To characterize a longitudinal relationship between highly active antiretroviral therapy immune recovery as defined by an increase in CD4 cell counts and any associated changes in intraocular pressure (IOP) in both patients with and patients without a history of cytomegalovirus (CMV) retinitis and to determine if human immunodeficiency (HIV)-induced reduction in IOP is reversible. Design: Retrospective analysis of patient data collected from 1997 through 2004. Participants: Cohort of patients from one eye center, including patients from the Longitudinal Study of Ocular Complications of Acquired Immunodeficiency Syndrome. Methods: Linear regression analyses were conducted within the CMV and non-CMV groups to determine the change in IOP per 100- unit change in CD4 count. Average changes in IOP per change in CD4 count were compared between the CMV and the non-CMV groups using a Wilcoxon rank-sum test. Linear regression analyses were conducted within the CMV and non-CMV groups to determine the linear relationship between the 12- month change in IOP per 12- month 100- unit change in CD4 count. Main Outcome Measure: Intraocular pressure in relation to changes inCD4 cell counts. Results: Compared with the non-CMV group, the median IOP change per change in CD4 count was not statistically different from the CMV group (0.9 vs. 1.7 mmHg/100 CD4 cells, respectively; P=0.20). Analysis of the linear relationship between the 12- month change in IOP and the 12- month change in CD4 count within both the CMV and non-CMV groups showed a strong linear relationship: 67% of the variability in a 12- month IOP change for the CMV group (P<0.0001) and 36% of the variability in a 12- month IOP change for the non-CMV group (P<0.001). Conclusions: Reduction in T-lymphocyte count in HIV infection is accompanied by a decrease in IOP in both CMV-infected and non-CMV-infected eyes, and immune recovery is associated with an increase in IOP. Purpose: To characterize a longitudinal relationship between highly active antiretroviral therapy immune recovery as defined by an increase in CD4 cell counts and any associated changes in intraocular pressure (IOP) in both patients with and patients without a history of cytomegalovirus (CMV) retinitis and to determine if human immunodeficiency (HIV) -induced reduction in IOP is reversible Design:. Retrospective analysis of patient data collected from 1997 through 2004. Participants: Cohort of patients from one eye center, including patients from the Longitudinal Study of Ocular Complications of Acquired immunodeficiency Syndrome. Methods: Linear regression analyzes were performed within the CMV and non-CMV groups to determine the change in IOP per 100-unit change in CD4 count. CMV groups using a Wilcoxon rank-sum test. Linear regression analyzes were conducted within the CMV and non-CMV groups to determine the linear relationship between the 12-month change in IOP per 12- month 100-unit change in CD4 count. Main Outcome Measure: Intraocular pressure in relation to changes in CD4 cell counts. Results: Compared with the non-CMV group, the median IOP change per change in CD4 count was not statistically different from the CMV group (0.9 vs. 1.7 mmHg / 100 CD4 cells, respectively; P = 0.20). Analysis of the linear relationship between the 12- month change in IOP and the 12- month change in CD4 count within both the CMV and non-CMV groups showed a strong linear relationship: 67% of the variability in a 12- month IOP change for the CMV group (P <0.0001) and 36% of the variability in a 12 - month IOP change for the non-CMV group (P <0.001). Conclusions: Reduction in T-lymphocyte count in HIV infection is accompanied by a decrease in IOP in both CMV-infected and non-CMV-infected eyes, and immune recovery is associated with an increase in IOP.