METHODS: The HIV-CAUSAL Collaboration consisted of 12 cohorts from the United States and Europe of HIV-positive, ART-naive, AIDS-free individuals aged ≥18 years with baseline CD4 cell count and HIV RNA levels followed up from 1996 through 2007. We estimated hazard ratios (HRs) for cART versus no cART, adjusted for time-varying CD4 cell count and HIV RNA level via inverse probability weighting.
RESULTS: Of 65 121 individuals, 712 developed tuberculosis over 28 months of median follow-up (incidence, 3.0 cases per 1000 person-years). The HR for tuberculosis for cART versus no cART was 0.56 (95% confidence interval [CI], 0.44-0.72) overall, 1.04 (95% CI, 0.64-1.68) for individuals aged >50 years, and 1.46 (95% CI, 0.70-3.04) for people with a CD4 cell count of <50 cells/μL. Compared with people who had not started cART, HRs differed by time since cART initiation: 1.36 (95% CI, 0.98-1.89) for initiation <3 months ago and 0.44 (95% CI, 0.34-0.58) for initiation ≥3 months ago. Compared with people who had not initiated cART, HRs <3 months after cART initiation were 0.67 (95% CI, 0.38-1.18), 1.51 (95% CI, 0.98-2.31), and 3.20 (95% CI, 1.34-7.60) for people <35, 35-50, and >50 years old, respectively, and 2.30 (95% CI, 1.03-5.14) for people with a CD4 cell count of <50 cells/μL.
CONCLUSIONS: Tuberculosis incidence decreased after cART initiation but not among people >50 years old or with CD4 cell counts of <50 cells/μL. Despite an overall decrease in tuberculosis incidence, the increased rate during 3 months of ART suggests unmasking IRIS.
METHODS: We determined the frequency of opportunistic infections and tuberculosis in patients receiving vedolizumab in phase 3 clinical trials and post-marketing settings. We also evaluated adverse events reported in the post-marketing setting in patients with a history of or concurrent hepatitis B/C virus infection.
RESULTS: The incidence of opportunistic infections in patients receiving vedolizumab was 0.7 (GEMINI 1 and 2 clinical trials) and 1.0 (long-term safety study) per 100 patient-years, with 217 events reported in approximately 114,071 patient-years of exposure (post-marketing setting). Most opportunistic infections were nonserious and the majority of patients continued treatment with vedolizumab. Clostridium difficile was the most commonly reported infection, with an incidence rate of 0.5 per 100 patient-years (clinical trials). Tuberculosis was reported at 0.1 per 100 patient-years (clinical trials), with 7 events in the post-marketing setting. No tuberculosis-related deaths were reported in either setting. No cases of progressive multifocal leukoencephalopathy were reported. In 29 patients with a history of or concurrent hepatitis B/C infection in the post-marketing setting, no viral reactivation was observed.
CONCLUSIONS: Clinical trials and post-marketing data showed that the rate of serious opportunistic infections in patients receiving vedolizumab was low and most patients could continue vedolizumab treatment. The frequency of tuberculosis infection was also low and no hepatitis B/C viral reactivation was reported.