Longitudinal Study Of Ocular Complications Research Articles

Secular trends in opportunistic infections, cancers and mortality in patients with AIDS during the era of modern combination antiretroviral therapy.

The aim of the study was to estimate the incidence of, determine risk factors for, and investigate the consequences of opportunistic infections (OIs) and malignancies among patients with the acquired immune deficiency syndrome (AIDS) in the era of modern combination antiretroviral therapy (cART). Three enrolment periods (1998-2002, 2003-2005 and 2006-2012), corresponding to changes in predominant cART regimens, were compared among 1889 participants enrolled in a prospective cohort study, the Longitudinal Study of Ocular Complications of AIDS (LSOCA). Incidences of AIDS-related OIs and cancers were estimated. Multivariate logistic and Cox regression models were used to determine the effect of demographic and clinical characteristics on OIs and mortality. Between participants enrolled in the 1998-2002 and 2006-2012 enrolment periods, the incidence of OIs decreased from 27 per 1000 person-years (PY) to 11 per 1000 PY (P < 0.001), and mortality decreased from 41 per 1000 PY to 18 per 1000 PY (P < 0.0001), corresponding to improvements in cART regimens. Improvements in cART regimens led to a progressive decline in the incidence of OIs and mortality between 1999 and 2013 among patients with AIDS in the era of modern cART.

Evaluation of the United States Public Health Service Guidelines for Discontinuation of Anticytomegalovirus Therapy After Immune Recovery in Patients With Cytomegalovirus Retinitis

To evaluate United States Public Health Service (USPHS) guidelines for discontinuing anticytomegalovirus (CMV) therapy in patients with AIDS who have immune recovery and quiescent retinitis after initiating highly active antiretroviral therapy. Cohort study of patients with CMV retinitis (Longitudinal Study of Ocular Complications of AIDS). Participants had CMV retinitis and CD4+ T-cell counts of 50 cells/μL or fewer enrolled from 1998 through 2009 who demonstrated sustained immune recovery (2 consecutive CD4+ T-cell counts of 100 cells/μL or more at least 6 months apart) and inactive retinitis. Participants were classified into 2 groups according to anti-CMV treatment after immune recover: (1) continued anti-CMV therapy and (2) discontinued therapy. We evaluated survival, visual acuity, and CMV retinitis activity; we used propensity scores to adjust for confounding factors for these analyses. Of 152 participants reviewed, 71 demonstrated immune recovery, 37 of whom discontinued therapy and 34 of whom continued therapy. At immune recovery, participants continuing therapy tended to be older (44 vs 40 years; P = .09), have bilateral retinitis (53% vs 32%; P = .10), and have lower CD4+ T-cell counts (148 vs 207 cells/μL; P < .001). There were no statistical differences in any of the clinical outcomes (death, retinitis progress, visual acuity, or incidence of bilateral retinitis). Both groups lost visual acuity during follow-up, on average 1.2 letters per year (P < .01). Discontinuation of anti-CMV therapy after immune recovery did not increase the risk of poor outcomes. These results support the current guidelines for discontinuation of anti-CMV therapy after achievement of sustained immune recovery.

Interviewer versus self-administered health-related quality of life questionnaires - Does it matter?

BackgroundPatient-reported outcomes are measured in many epidemiologic studies using self- or interviewer-administered questionnaires. While in some studies differences between these administration formats were observed, other studies did not show statistically significant differences important to patients. Since the evidence about the effect of administration format is inconsistent and mainly available from cross-sectional studies our aim was to assess the effects of different administration formats on repeated measurements of patient-reported outcomes in participants with AIDS enrolled in the Longitudinal Study of Ocular Complications of AIDS.MethodsWe included participants enrolled in the Longitudinal Study of Ocular Complications in AIDS (LSOCA) who completed the Medical Outcome Study [MOS] -HIV questionnaire, the EuroQol, the Feeling Thermometer and the Visual Function Questionnaire (VFQ) 25 every six months thereafter using self- or interviewer-administration. A large print questionnaire was available for participants with visual impairment. Considering all measurements over time and adjusting for patient and study site characteristics we used linear models to compare HRQL scores (all scores from 0-100) between administration formats. We defined adjusted differences of ≥0.2 standard deviations [SD]) to be quantitatively meaningful.ResultsWe included 2,261 participants (80.6% males) with a median of 43.1 years of age at enrolment who provided data on 23,420 study visits. The self-administered MOS-HIV, Feeling Thermometer and EuroQol were used in 70% of all visits and the VFQ-25 in 80%. For eight domains of the MOS-HIV differences between the interviewer- and self- administered format were < 0.1 SD. Differences in scores were highest for the social and role function domains but the adjusted differences were still < 0.2 SD. There was no quantitatively meaningful difference between administration formats for EuroQol, Feeling Thermometer and VFQ-25 domain scores. For ocular pain (VFQ-25), we found a statistically significant difference of 3.5 (95% CI 0.2, 6.8), which did, however, not exceed 0.2 SD. For all instruments scores were similar for the large and standard print formats with all adjusted differences < 0.2 SD.ConclusionsOur large study provides evidence that administration formats do not have a meaningful effect on repeated measurements of patient-reported outcomes. As a consequence, longitudinal studies may not need to consider the effect of different administration formats in their analyses.

Excess Mortality in Patients with AIDS in the Era of Highly Active Antiretroviral Therapy: Temporal Changes and Risk Factors

Excess mortality has decreased among human immunodeficiency virus (HIV)-infected patients but without evidence of a decrease among patients with AIDS. We assessed temporal changes in excess mortality and elucidated risk factors for excess mortality in patients with AIDS diagnosed in the era of highly active antiretroviral therapy (HAART). We included 1188 patients of the Longitudinal Study of Ocular Complications in AIDS who were aged 25-64 years at enrollment and who received a diagnosis of AIDS after 1995. We calculated excess mortality as the age-, year-, and sex-adjusted difference in mortality rates between patients with AIDS and persons in the US general population during the period 1999-2007. We used a relative survival model to identify risk factors for excess mortality. There were a mean of 50 excess deaths per 1000 person-years (95% confidence interval [CI], 44-57 excess deaths per 1000 person-years) during 1999-2007. Excess mortality almost halved, with an annual decrease of 8.0% per year (95% CI, 3.0%-12.7%; P = .002) but remained high at 36 excess deaths per 1000 person-years in 2007. Viral load >400 copies/mL (compared with <or= 400 copies/mL; risk ratio, 3.4; 95% CI, 2.3-5.0), CD4(+) count <200 cells/μL (compared with >or= 200 cells/μL; risk ratio, 2.7; 95% CI, 1.9-3.9), and cytomegalovirus retinitis (risk ratio, 1.6; 95% CI, 1.2-2.1) were the strongest risk factors for excess mortality. Excess mortality among patients with AIDS was nearly halved in the HAART era and most strongly linked to stage of HIV disease. These results reflect the continuing improvements in AIDS management but also highlight that excess mortality remains ∼5 times higher in patients with AIDS than in HIV-infected patients without AIDS.

Mitochondrial Haplogroups Are Associated With Risk of Neuroretinal Disorder in HIV-Positive Patients

Although highly active antiretroviral therapy has improved survivorship dramatically and decreased the incidence of cytomegalovirus retinitis among patients with AIDS, other ophthalmic complications continue to occur. One complication observed in approximately 12% of HIV-infected patients is a presumed neuroretinal disorder (NRD), manifested as decreased contrast sensitivity and associated with vague subjective complaints of hazy vision. Pathologically, patients with AIDS even without ocular opportunistic infections have loss of optic nerve axons, suggestive of mitochondrial dysfunction. We explored whether variation in mitochondrial DNA was associated with time to NRD in HIV-infected patients in the Longitudinal Study of Ocular Complications of AIDS cohort. Within the Western European, or "N", mitochondrial DNA macrohaplogroup, haplogroup J, was associated with 80% decrease in the risk of progression to NRD during the study (hazard ratio = 0.20, P = 0.039) and suggested an independent association with protection against NRD in a cross-section of all patients taken at enrollment (1.5% vs. 8.9% in patients with vs. without haplogroup J, respectively, P = 0.05). These data suggest that mitochondrial genotype may influence propensity to develop HIV-associated NRD in patients with AIDS.

Factors affecting attrition in a longitudinal study of patients with AIDS

Anecdotal data have suggested that retention of HIV-infected patients with immune recovery in longitudinal studies may be difficult as they resume normal activities. This study evaluated risk factors for attrition among patients with AIDS in a cohort study in the era of highly active antiretroviral therapy. Patients with AIDS enrolled in the Longitudinal Study of Ocular Complications of AIDS were evaluated every three months with demographic, clinical and laboratory data collected. Lost to follow-up was defined as any patient who missed all study visits and could not be contacted for 12 consecutive months, who had not died and who did not re-enter the study at a later date. Of the 1,052 patients studied, 77 (7.3%) were lost to follow-up (rate = 0.03/person year). In the multivariate analysis, factors associated with attrition were CD4+ T-cell count category (hazard ratio (HR) = 2.03; 95%CI: 1.01, 4.24; P=0.05 for CD4+ count ≤ 50 cells/µL and HR = 1.96; 95%CI: 1.12, 3.40; P=0.02 for CD4+ count 51–200 cells/µL) and detectable HIV viral load (HR = 1.29; 95%CI: 1.07, 1.53; P<0.001 for HIV viral load >400 copies/mL). These data suggest that patients with compromised immunologic status are at an increased risk for being lost to follow-up.

Long-term Study of Intraocular Pressure Changes in Patients with Human Immunodeficiency Virus Treated with Highly Active Antiretroviral Therapy

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. Retrospective analysis of patient data collected from 1997 through 2004. Cohort of patients from one eye center, including patients from the Longitudinal Study of Ocular Complications of Acquired Immunodeficiency Syndrome. 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. Intraocular pressure in relation to changes in CD4 cell counts. 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). 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.