Prevalence of HIV-associated ophthalmic disease among patients enrolling for antiretroviral treatment in India: a cross-sectional study.

BACKGROUND: The ocular manifestations of HIV may lead to visual impairment or blindness. In India, patients typically initiate antiretroviral treatment (ART) with low CD4 cell counts when the risk of ocular complications may be high. The objective of this study was to determine the prevalence and types of HIV-associated ocular conditions in patients referred for ART in India. METHODS: This cross-sectional study was undertaken at a large public sector ART centre in Mumbai, India. Data collection including a standardised symptom screen, and an ophthalmic examination were performed on all consecutive patients satisfying the criteria for enrollment into the ART clinic irrespective of the presence or absence of ophthalmic/visual symptoms. RESULTS: Enrolled patients (n = 149) had a median CD4 cell count of 180 cell/microL (inter-quartile range [IQR], 106-253 cells/microL). The prevalence of HIV-associated ocular disease was 17.5% (95% CI, 11.2-23.6%) in all participants and 23.8% (95% CI: 14.5-33.1) in those with CD4 cell counts <200 cells/microL (n = 84). Only 7.7% of patients with HIV-associated ocular disease reported any eye symptoms in the standardised symptom screen. Objective visual impairment was detected in 20% of those with HIV-associated ocular disease compared to 6% in those without ocular manifestations (p = 0.02). Vitreoretinal disease was the most common manifestation, of which cytomegalovirus retinitis (CMVR) was the most frequent retinal infection (overall prevalence 8.7%, 95% CI: 4.1-13.3%). In a multivariable analysis, HIV-associated ocular disease was independently associated with a CD4 count <100 cells/microL (odds ratio [OR], 6.3, 95% CI: 1.5-25.9) and WHO clinical stages 3 and 4 (OR 9.4, 95% CI: 2.4-37.2). However, symptoms were not independently predictive of ocular disease. Sensitivity of ocular symptom screening was 7.7%, with a positive predictive value of 18% in this population. CONCLUSION: Over a fifth of unselected patients who are eligible for ART in this setting have HIV-related ocular disease of which CMVR is the most common form. Such patients may be at risk of developing ocular immune reconstitution phenomena during ART. Screening for ocular symptoms is not a reliable method to identify those with ocular morbidity and this highlights the need for routine ophthalmic screening prior to commencement of ART

Increased ocular lens density in HIV-infected individuals with low nadir CD4 counts in South Africa: evidence of accelerated aging.

BACKGROUND: HIV infection is thought to be associated with an increased risk of age-related morbidity and premature aging. Lens density increases with age and may function as a biomarker of aging. The relationship of lens density measurements with clinical and demographic characteristics in HIV-infected individuals in comparison with a matched population of HIV-seronegative individuals was investigated. METHODS: Case-control study of 490 adults aged greater than or equal to 30 years composed of 242 HIV-infected adults and 248 age- and sex-matched HIV-seronegative individuals. Lens density was assessed using lens densitometry (Pentacam) imaging. Measurements were divided into quartiles, and comparison of HIV status and HIV-related factors was assessed by multivariate and multinomial logistic regression. RESULTS: The mean age was 41.2 years in HIV-infected adults and 42.3 years in HIV-seronegative individuals (P = 0.14). Of the HIV-infected adults, 88% were receiving antiretroviral therapy (ART) (median duration, 58 months), and within this group, their median CD4 count was 468 cells per microliter and 84% had undetectable viral load. Although adjusted lens densities were similar by HIV serostatus, participants on ART and who had nadir CD4 counts less than 200 cells per microliter had a higher risk of high lens density compared with HIV-seronegative individuals (P trend = 0.04). Lens density was weakly associated with detectable HIV viremia despite ART, but not with current CD4 count. CONCLUSIONS: HIV-infected individuals on ART with nadir CD4 counts <200 cells per microliter had increased risk of higher lens density. Lens density may represent a novel biomarker of aging, providing insight into accelerated aging trajectories in HIV infection

Differing spectrum of HIV-associated ophthalmic disease among patients starting antiretroviral therapy in India and South Africa

Differences in the prevalence and spectrum of HIV-associated ophthalmic disease in Africa and Asia are not well documented. We studied two comparable cohorts of patients initiating antiretroviral therapy in Mumbai, India, and Cape Town, South Africa. The prevalence of HIV-associated ophthalmic disease was higher in the Indian population (17.5%) than in the South African population (12.1%). This was largely because of vitreo-retinal opportunistic infections (11.4%vs. 2.6%, respectively), notably cytomegalovirus retinitis. This difference persisted after adjusting for confounding factors (adjusted odds ratio = 11.32, 95% confidence interval: 2.67–48.13), confirming a marked geographical difference in the prevalence of HIV-associated retinal disease

Retinal nerve fibre layer thickness and contrast sensitivity in HIV-infected individuals in South Africa: a case-control study

BACKGROUND: Antiretroviral treatment (ART) has altered the spectrum of HIV-related eye disease, resulting in a lower prevalence of retinal opportunistic infections (OIs). However, abnormalities in visual function have been reported in HIV-infected individuals despite effective viral suppression and the absence of retinal OIs. These changes may be mediated by an HIV-associated 'neuroretinal disorder', characterized by changes in the retinal nerve fibre layer (RNFL). HIV infection may also be associated with accelerated biological aging. The aim of this study was to investigate the relationships between contrast sensitivity, RNFL thickness, HIV infection and frailty in South African adults. METHODS: Case-control study of 225 HIV-infected individuals without retinal OIs and 203 gender/age-matched HIV-seronegative individuals. Peri-papillary RNFL thickness was determined with spectral domain optical coherence tomography in four quadrants. CS was measured using a Pelli-Robson chart. Frailty was assessed using standard criteria. Multivariable linear and logistic regression were used to assess associations between HIV status and RNFL/CS and frailty. RESULTS: The median age of both groups was similar (41.2 vs. 41.9 years, p = 0.37). 88% of HIV-infected individuals were receiving ART and their median CD4 count was 468 cells/μl. Adjusted CS score was lower in HIV-infected participants compared to HIV-seronegative individuals (1.76 vs. 1.82, p = 0.002). Independent predictors of poor CS in the HIV-infected group were positive frailty status and current HIV viral load >2 log copies/ml. Lower CS score was also associated with thin temporal RNFL in HIV-infected individuals (p = 0.04). Superior quadrant RNFL thickness was greatest in ART-naïve participants relative to the HIV-uninfected group (p-trend = 0.04). Longer ART duration was associated with thinning of inferior and nasal RNFL quadrants (p-trend = 0.03 and 0.04, respectively). CONCLUSIONS: Contrast sensitivity is reduced in HIV-infected individuals and functionally associated with frailty and unsuppressed viraemia. This may reflect structural changes in the RNFL that are evident despite the absence of OIs

Systematic review of prevalence and predictors of frailty in individuals with human immunodeficiency virus

Objectives To describe the prevalence and predictors of frailty in individuals with the human immunodeficiency virus (HIV) using systematic review methodology. Design Review. Setting Community. Participants Older adults with HIV. Measurements Medline, CINAHL, EMBASE, PsychInfo, and PubMed were searched for original observational studies with populations including individuals with HIV in which frailty was assessed using the frailty phenotype or a variant thereof. Studies were examined for frailty prevalence and predictors of the syndrome in those with HIV. Results Thirteen of 322 citations were included for full review. All demonstrated the presence of frailty in individuals with HIV, with prevalence ranging from 5% to 28.6% depending on population studied. HIV was a risk factor for frailty. Predictors of frailty included older age, comorbidities, diagnosis of acquired immunodeficiency syndrome, and low current CD4+ cell count. Conclusion HIV appears to be an independent risk factor for frailty, with frailty occurring in individuals with HIV at rates comparable with older individuals without HIV. Heterogeneity in study populations and frailty assessment measures hamper accurate description of the problem. Future longitudinal work with standardized methodology is needed to describe prevalence accurately and confirm predictors

Safety and Efficacy of Adalimumab in Patients with Noninfectious Uveitis in an Ongoing Open-Label Study: VISUAL III

PURPOSE: To evaluate safety and efficacy of adalimumab in patients with noninfectious intermediate, posterior, or panuveitis. DESIGN: Phase 3, open-label, multicenter clinical trial extension (VISUAL III). PARTICIPANTS: Adults meeting treatment failure (TF) criteria or who completed VISUAL I or II (phase 3, randomized, double-masked, placebo-controlled) without TF. METHODS: Patients received adalimumab 40 mg every other week. Interim follow-up data were described from VISUAL III weeks 0 through 78. MAIN OUTCOME MEASURES: Disease quiescence, steroid-free quiescence, active inflammatory chorioretinal/retinal vascular lesions, anterior chamber cell grade, vitreous haze grade, best-corrected visual acuity (BCVA), and corticosteroid dose. Binary data were reported using nonresponder imputation (NRI), continuous data using last observation carried forward and as-observed analysis, and corticosteroid dose using observed-case analysis. Adverse events (AEs) were reported from first adalimumab dose in VISUAL III through interim cutoff. RESULTS: Of 424 patients enrolled, 371 were included in intent-to-treat analysis. At study entry, 242 of 371 (65%) patients had active uveitis; 60% (145/242, NRI) achieved quiescence at week 78, and 66% (95/143, as-observed) of those were corticosteroid free. At study entry, 129 of 371 (35%) patients had inactive uveitis; 74% (96/129, NRI) achieved quiescence at week 78, and 93% (89/96, as-observed) of those were corticosteroid free. Inflammatory lesions, anterior chamber grade, and vitreous haze grade showed initial improvement followed by decline in patients with active uveitis and remained stable in patients with inactive uveitis. BCVA improved in patients with active uveitis from weeks 0 to 78 (0.27 to 0.14 logMAR; left and right eyes; as-observed) and remained stable in patients with inactive uveitis. Mean corticosteroid dose decreased from 13.6 mg/day (week 0) to 2.6 mg/day (week 78) in patients with active uveitis and remained stable in those with inactive uveitis (1.5-1.2 mg/day). AEs (424 events/100 patient-years) and serious AEs (16.5 events/100 patient-years) were comparable with previous VISUAL trials. CONCLUSIONS: Patients with active uveitis at study entry who received adalimumab therapy were likely to achieve quiescence, improve visual acuity, and reduce their daily uveitis-related systemic corticosteroid use. Most patients with inactive uveitis at study entry sustained quiescence without a systemic corticosteroid dose increase. No new safety signals were identified

Long-Term Safety and Efficacy of Adalimumab in Patients With Noninfectious Intermediate Uveitis, Posterior Uveitis, or Panuveitis

PURPOSE: To evaluate long-term efficacy and safety of extended treatment with adalimumab in patients with noninfectious intermediate, posterior, or panuveitis. DESIGN: Open-label, multicenter, phase 3 extension study (VISUAL III). PARTICIPANTS: Adults who had completed a randomized, placebo-controlled phase 3 parent trial (VISUAL I or II) without treatment failure (inactive uveitis) or discontinued after meeting treatment failure criteria (active uveitis). METHODS: Patients received subcutaneous adalimumab 40 mg every other week. Data were collected for ≤362 weeks. Adverse events (AEs) were recorded until 70 days after the last dose of study drug. MAIN OUTCOME MEASURES: Main outcome measures were long-term safety and quiescence; other efficacy variables included inflammatory lesions, anterior chamber cell and vitreous haze grade, macular edema, visual acuity, and dose of uveitis-related corticosteroids. RESULTS: Of 424 patients enrolled, 67% (283/424) had active uveitis and 33% (141/424) had inactive uveitis at study entry; 60 patients subsequently met exclusion criteria, and 364 patients were included in the intent-to-treat analysis. Efficacy variables were analyzed through week 150 when approximately 50% of patients (214/424) remained in the study. The percentage of patients in quiescence increased from 34% (122/364) at week 0 to 85% (153/180) at week 150. Corticosteroid-free quiescence was achieved by 54% (66/123) and 89% (51/57) of patients with active or inactive uveitis at study entry, respectively, by week 150. Mean daily dose of corticosteroids was reduced from 9.4±17.1 mg/day at week 0 (n=359) to 1.5±3.9 mg/day at week 150 (n=181). The percentage of patients who achieved other efficacy variables increased over time for those with active uveitis at study entry and was maintained for those with inactive uveitis. The most frequently reported treatment-emergent AEs of special interest for adalimumab were infections (n=275; 78.7 events/100 patient-years); AEs and serious AEs occurred at a rate of 396 events/100 patient-years and 15 events/100 patient-years, respectively. CONCLUSIONS: Long-term treatment with adalimumab led to quiescence and reduced corticosteroid use for patients who entered VISUAL III with active uveitis and maintenance of quiescence for those with inactive uveitis. AEs were comparable to those reported in the parent trials and consistent with the known safety profile of adalimumab