Objective.To determine the effect of human immunodeficiency virus (HIV) infection on disease activity in rheumatoid arthritis (RA).Methods.A retrospective records review of patients who contracted HIV infection subsequent to RA diagnosis (HIV group), compared to an HIV-negative group of patients with RA (control group), for 28-joint Disease Activity Score (DAS28) scores at initial presentation (T0) and last clinic visit (TL), and at diagnosis of HIV infection (TH) in the HIV group.Results.Of 1712 patients with RA, 85 were HIV-positive (4.9%), 43 of them contracting HIV subsequent to RA diagnosis. The mean (SD) age, RA disease duration, and duration following diagnosis of HIV were 47.1 (10.1), 10.5 (8.4), and 2.9 (2.0) years, respectively, for the HIV group. Both the HIV and control groups showed similar improvement in joint counts and C-reactive protein (CRP) at visit TL, in spite of methotrexate (MTX) being withdrawn in most patients in the HIV group by visit TL (11.6% in the HIV group were still taking MTX vs 83.7% in the control group, p = 0.0002), but a minority (13.9%) had ongoing moderate to high disease activity at visit TL. In the HIV group, the mean DAS28-erythrocyte sedimentation rate (ESR) and DAS28-CRP scores were similar at baseline, but at visits TH and TL the mean DAS28-ESR scores were significantly higher than the mean DAS28-CRP scores (31% and 31.8%, p < 0.0005 and p < 0.004, respectively), mainly resulting from ESR increase following HIV seroconversion.Conclusion.Disease activity improved in most patients in the HIV group in spite of stopping the MTX as the “anchor drug.” The DAS28-ESR overestimates disease activity compared to the DAS28-CRP in the setting of HIV infection.