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BACKGROUND: The introduction of vaccines during the COVID-19 pandemic provided an opportunity to slow transmission of SARS-CoV-2, but initial uptake of COVID-19 vaccination was slow. We analyzed data from a randomized clinical trial of the mRNA-1273 vaccine (NCT04811664) to describe the patterns of uptake of COVID-19 vaccines among young adults. METHODS: The CoVPN 3006 trial randomized adults ages 18-29 from 44 sites in the United States to receive 1) immediate mRNA-1273 vaccination from the study site, or 2) standard of care, including the option to seek vaccination at any time in the future. Randomization occurred between March and November 2021, and an observational arm of adults who declined vaccination was enrolled beginning June 2021. Among participants in the standard of care (SoC) or Vaccine Declined arms, we estimated demographic, behavioral, and health history correlates of vaccination, and the four-month cumulative incidence of COVID-19 vaccination using inverse probability weighted Kaplan-Meier estimators. RESULTS: Among 728 SoC and 470 Vaccine Declined participants, 79% and 16% received COVID-19 vaccination, respectively. SoC and Vaccine Declined participants were more likely to seek and receive vaccination if they reported COVID-19 preventive behaviors, including wearing masks, physically distancing, and avoiding large gatherings. We identified strong predictors of vaccination in the Vaccine Declined arm, including attending class in person (adjusted risk ratio [aRR]: 0.47, 95% confidence interval [CI] 0.21, 1.03), having a COVID-19 relevant medical condition (aRR: 1.95, 95% CI: 0.89, 4.26), and avoiding large gatherings (aRR: 2.24, 95% CI: 1.18, 4.25), though low vaccination rates in this arm led to imprecise estimates. CONCLUSIONS: Individuals who initially decline vaccination can be convinced to vaccinate, particularly if they are already practicing other forms of COVID-19 prevention. Continued outreach and education from the scientific community can combat low vaccine confidence.
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OBJECTIVE: Biological markers of stress have been associated with HIV progression and pathogenesis but not with HIV incidence. We sought to determine if elevated stress-responsive biomarkers would be associated with incident HIV among adolescent girls and young women (AGYW). DESIGN: We conducted a case-cohort study within the HIV Prevention Trials Network (HPTN) 068 study among 949 AGYW in South Africa. Cases were AGYW who tested HIV-positive during the eight-year follow-up. Unmatched controls were randomly selected from the HIV-negative population at enrollment. METHODS: Dried blood spots from cases and controls were tested from enrollment (2011-2012) for C-reactive protein (CRP), herpes simplex virus type-1 (HSV-1) antibody titers, and cytomegalovirus (CMV) antibody titers. Cox proportional hazards models estimated the association between each biomarker and time to incident HIV. RESULTS: Compared to AGYW with the lowest CRP levels, those with medium and high CRP levels had a higher hazard ratio (HR) of incident HIV (HR: 1.45, 95% CI: 0.95, 2.21; HR: 1.50, 95% CI: 0.98,2.30, respectively), although not statistically significant. The relative hazard of incident HIV was also higher among AGYW who were CMV seropositive vs. seronegative (low antibodies HR: 2.18, 95% CI: 1.2,3.87; medium HR: 2.25, 95% CI: 1.28,3.95; high HR: 1.78, 95% CI: 0.99,3.21). Those with the highest HSV-1 antibody levels experienced an increased hazard of HIV compared to those who were HSV-1 seronegative (HR: 1.58, 95% CI: 1.03,2.44). CONCLUSIONS: Biological stress may increase AGYW's susceptibility to HIV acquisition through changes in immune function, viral infection, and increased biological vulnerability to disease.
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BACKGROUND: Infectious disease-related stigma is a pervasive global issue that impedes disease control efforts by increasing reluctance to seek treatment or engagement in prevention behaviors for fear of ostracism. Despite this, there is limited research on COVID-19 stigma in Africa, specifically rural South Africa, which has faced infectious disease-related stigma throughout the HIV epidemic. METHODS: Population-based surveys were conducted among 1,662 adults living in the Agincourt Health and Socio-Demographic Surveillance System (AHDSS) area in Mpumalanga, South Africa, in August-October 2020 and August-October 2021. Surveys measured anticipated COVID-19-related stigma from low to high levels. Changes in stigma between surveys were compared using Wilcoxon ranked sign tests, and log-binomial models estimated the association between socio-demographic factors and anticipated stigma at both intervals. Qualitative interviews were conducted in 2022 among 31 adults who completed the original surveys, and the data were analyzed thematically to describe anticipated, perceived, and enacted stigma. RESULTS: Anticipated stigma significantly decreased from the first to the second survey (p-value:<0.0001). Stigma was significantly higher among older age groups. In 2020, those less knowledgeable about COVID-19 were 2.24 times as likely to have higher levels of anticipated stigma compared to those who were more knowledgeable (RR:2.24, 95% CI: 1.90,2.64). Fear of being stigmatized influenced willingness to disclose infection. Participants perceived COVID-19 stigma as similar to HIV/AIDS stigma, but concern and fear reduced over time, with differences observed across generations and sexes. For some, fear of death and mistrust of others endorsed enacting stigma toward others. CONCLUSION: While COVID-19 stigma decreased over time in rural South Africa, different forms of stigma persisted and influenced participants' willingness to reveal their COVID-19 infection status. Given South Africa's history with infectious disease-related stigma hindering public health efforts, it is crucial that government bodies prioritize strategies to mitigate stigma in rural communities.
Subject(s)
COVID-19 , Rural Population , Social Stigma , Humans , COVID-19/psychology , COVID-19/epidemiology , South Africa/epidemiology , Female , Male , Adult , Middle Aged , Surveys and Questionnaires , Young Adult , SARS-CoV-2/isolation & purification , AdolescentABSTRACT
OBJECTIVE: The aim of this study was to estimate the longitudinal associations of state-level anti-LGBTQ+ policies and county-level politics with individual HIV prevention outcomes among sexual and gender minoritized (SGM) youth. DESIGN: Keeping it LITE-1 prospectively enrolled 3330 SGM youth and young adults (ages 13-34) at increased risk of HIV throughout the United States from 2017 to 2022. METHODS: Semiannual surveys collected self-reported HIV prevention measures [current preexposure prophylaxis (PrEP) use, weekly PrEP adherence, HIV/STI testing in the past 6âmonths]. Geolocation was linked with state-level LGBTQ+ policy data and county-level election data. Generalized linear models with GEE estimated the single and joint longitudinal associations for two exposures [state-level policy climate (more discriminatory vs. less discriminatory) and county-level political majority (Democratic/swing vs. Republican)] with each outcome. RESULTS: Among participants living in a state with more discriminatory laws, those in a Democratic/swing county had a 6-percentage point increase in PrEP use (95% confidence interval: 0.02, 0.09) compared to those in a Republican county. Those living in a Republican county but a state with less discriminatory laws saw a similar increase (0.05; -0.02,0.11). Residing in both a Democratic/swing county and a state with less discriminatory laws, relative to a Republican county and a state with more discriminatory laws, was associated with a 10-percentage point increase in PrEP use (0.10; 0.06,0.14) and a 5-percentage point increase in HIV/STI testing (0.05; 0.00,0.09). CONCLUSION: More progressive state and local policies were each associated with increased PrEP use, and together, doubled the magnitude of this association. PrEP is underutilized among SGM youth, and anti-LGBTQ+ policies may exacerbate this gap in coverage.
Subject(s)
HIV Infections , Pre-Exposure Prophylaxis , Sexual and Gender Minorities , Humans , Adolescent , HIV Infections/prevention & control , Male , Female , Young Adult , Sexual and Gender Minorities/statistics & numerical data , United States , Adult , Prospective Studies , Longitudinal Studies , Health Policy , Disease Transmission, Infectious/prevention & controlABSTRACT
BACKGROUND: One in four South African women will experience intimate partner violence (IPV) in their lifetime, potentially increasing their biological stress. In South Africa, limited IPV and stress research has utilized multiple timepoints or examined modifying factors. Cash transfers (CTs) are associated with reduced IPV and stress and may be an intervention target. AIMS: We used data-driven methods to identify longitudinal IPV trajectory groups among South African adolescent girls and young women (AGYW), estimate each group's association with stress, and assess modification by a CT. METHODS: A total of 2,183 South African AGYW ages 13 to 24 years from the HIV Prevention Trials Network 068 study were randomized to a CT or control group. Physical IPV was measured five times (2011-2017), and stress was captured once (2018-2019). Stress measures included the Cohen Stress Scale and stress biomarkers (C-reactive protein (CRP), cytomegalovirus (CMV), herpes simplex virus type-1 (HSV-1)). Group-based trajectory modeling identified IPV trajectories; ordinal logistic regression estimated the association between trajectory group and stress. RESULTS: A two-group quadratic trajectory model was identified (higher trajectory group = 26.7% of AGYW; lower trajectory group = 73.3%). In both groups, the probability of IPV increased from ages 13 to 17 years before declining in early adulthood. However, the higher group's probability peaked later and declined gradually. The higher trajectory group was associated with an increased odds of elevated CRP (OR: 1.41, 95% CI [1.11, 1.80]), but not with other stress measures. The CT modified the relationship with CMV: a positive association was observed among the usual care arm (OR: 1.59, 95% CI [1.11, 2.28]) but not the CT arm (OR: 0.85, 95% CI [0.61, 1.19]). CONCLUSIONS: Sustained IPV risk during adolescence was associated with elevated CRP in young adulthood. The relationship between IPV and elevated CMV was attenuated among those receiving a CT, suggesting that CTs could possibly reduce biological stress due to IPV.
Subject(s)
Intimate Partner Violence , Stress, Psychological , Humans , Female , South Africa , Adolescent , Intimate Partner Violence/statistics & numerical data , Young Adult , Stress, Psychological/epidemiology , Longitudinal Studies , Logistic ModelsABSTRACT
PURPOSE: In the United States, youth experience suboptimal HIV pre-exposure prophylaxis (PrEP) adherence. One common idea posits that this is due to their developing decision-making skills. However, quantitative evidence of this assumption is limited. We therefore examined whether individual decision-making factors, such as HIV risk perception and sexual behavior, predicted PrEP adherence in a national trial of young sexual and gender minorities (YSGMs). METHODS: In 2019-2021, the Adolescent Medicine Trials Network for HIV Interventions 142 study enrolled 225 PrEP users (ages 16-24) throughout the country. Regression models estimated the associations between HIV risk perception (using a modified Perceived HIV Risk Scale), sexual behavior (condomless anal sex in ≤ 3 months), and self-reported oral PrEP adherence (≥4 pills in the past week) at the same time point (baseline) and longitudinally (3 months). RESULTS: Baseline risk perception (risk ratio [RR]: 0.92, 95% confidence interval [CI]: 0.82, 1.04) and condomless anal sex (RR: 1.10, 95% CI: 0.97, 1.25) were not associated with PrEP adherence at the same time point and did not predict 3-month adherence (RR: 0.97, 95% CI: 0.85, 1.11; RR: 1.05, 95% CI: 0.93, 1.19, respectively). Baseline risk perception was not associated with condomless anal sex at either time point (baseline RR: 1.16, 95% CI: 0.94, 1.43; 3-month RR: 1.07, 95% CI: 0.90, 1.28). DISCUSSION: In this national trial of YSGM, HIV risk perception and condomless anal sex did not predict PrEP adherence. Targeting individual-level perceptions and behaviors will likely insufficiently address youth's suboptimal PrEP use. Future research should identify YSGM-specific adherence drivers and train providers to recognize such motivations.
Subject(s)
HIV Infections , Medication Adherence , Pre-Exposure Prophylaxis , Sexual Behavior , Sexual and Gender Minorities , Humans , HIV Infections/prevention & control , Male , Adolescent , Female , Sexual and Gender Minorities/psychology , Sexual and Gender Minorities/statistics & numerical data , United States , Young Adult , Medication Adherence/statistics & numerical data , Health Knowledge, Attitudes, Practice , Anti-HIV Agents/therapeutic use , Anti-HIV Agents/administration & dosageABSTRACT
PURPOSE: To evaluate how changes in visual acuity are associated with changes in quality of life (QoL) among patients with non-infectious uveitis taking antimetabolites. METHODS: This secondary analysis of the multicenter First-line Antimetabolites as Steroid-sparing Treatment (FAST) Uveitis Trial involves 216 participants randomized to methotrexate or mycophenolate mofetil. Vision-related (NEI-VFQ and IND-VFQ) and health-related (PCS and MCS SF-36v2) QoL and visual acuity were measured at baseline and 6-month primary endpoint. RESULTS: Visual acuity was significantly associated and correlated with all QoL measures (Spearman correlation coefficients = 0.5, 0.5, 0.3, and 0.4 for NEI-VFQ, IND-VFQ, SF-36v2 MCS and PCS, respectively). All observed changes in QoL met or exceeded the minimal clinically important difference definition on each scale. Treatment group was not significantly associated with any QoL measure. CONCLUSION: By adding insight beyond visual acuity, QoL provides a more comprehensive picture of the patient experience during uveitis treatment.Abbreviations and Acronyms: QoL = quality of life; VR-QoL = vision-related quality of life; HR-QoL = health-related quality of life; FAST = First-line Antimetabolites as Corticosteroid Sparing Treatment; NEI-VFQ = National Eye Institute Visual Functioning Questionnaire; IND-VFQ = Indian Visual Functioning Questionnaire; SF-36v2 = Medical Outcomes Study 36-Item Short Form Survey; PCS = physical component score; MCS = mental component score; 95% CI = 95% confidence interval; MCID = minimal clinically important difference.
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Quality of Life , Uveitis , Humans , Antimetabolites , Health Status , Uveitis/drug therapy , Visual Acuity , Surveys and Questionnaires , Sickness Impact ProfileABSTRACT
ABSTRACTStressful life circumstances (e.g. violence and poverty) have been associated with elevated biomarkers, including C-reactive protein (CRP), cytomegalovirus (CMV), and herpes simplex virus type-1 (HSV-1), among older adults in high-income settings. Yet, it remains unknown whether these relationships exist among younger populations in resource-limited settings. We therefore utilised a cohort of 1,279 adolescent girls and young women (AGYW) from the HIV Prevention Trials Network 068 study in rural South Africa to examine the associations between 6 hypothesized stressors (intimate partner violence (IPV), food insecurity, depression, socioeconomic status (SES), HIV, childhood violence) and 3 biomarkers that were measured using dried blood spots (CRP, CMV, and HSV-1). Ordinal logistic regression estimated the lagged and cross-sectional associations between each stressor and each biomarker. IPV was cross-sectionally associated with elevated CMV (OR = 2.45, 95% CI = 1.05,5.72), while low SES was cross-sectionally associated with reduced CMV (OR = 0.73, 95% CI = 0.58,0.93). AGYW with HIV had elevated biomarkers cross-sectionally (CRP: OR = 1.51, 95% CI = 1.08,2.09; CMV: OR = 1.86, 95% CI = 1.31,2.63; HSV-1: OR = 1.68, 95% CI = 1.17,2.41) and in a lagged analysis. The association between violence and CMV could help explain how violence results in stress and subsequently worse health among AGYW; however, additional research is needed to disentangle the longitudinal nature of IPV and stress.
Subject(s)
Cytomegalovirus Infections , HIV Infections , Intimate Partner Violence , Adolescent , Female , Humans , Aged , Child , Cytomegalovirus , Cross-Sectional Studies , South Africa/epidemiology , Cytomegalovirus Infections/epidemiology , HIV Infections/epidemiologyABSTRACT
BACKGROUND: Adolescent girls and young women (AGYW) living with HIV who have higher stress levels may be at risk of stress-related biological alterations, which could influence HIV progression and adherence to antiretroviral therapy (ART). SETTING: We aimed to estimate associations among stress-responsive biomarkers, ART adherence, and viral suppression in AGYW living with HIV in South Africa. We also hypothesized that psychosocial stressors [eg, depression, food insecurity, low socioeconomic status (SES), and HSV-2] would be associated with higher biomarker levels. METHODS: We used 2018/2019 data from the HIV Prevention Trials Network 068 cohort to assess associations between stress-responsive biomarkers and viral suppression (<1000 copies/mL) and ART adherence measured using dried blood spot cards. Stress-responsive biomarkers included C-reactive protein, herpes simplex virus type 1, and cytomegalovirus infection and reactivation. Associations were estimated using unadjusted log-binomial or ordinal logistic regression models. RESULTS: In 166 AGYW living with HIV, there was no association between stress-responsive biomarkers and viral suppression or ART adherence. However, increased C-reactive protein levels were associated with higher HSV-2 infection [odds ratio (OR) 1.98; 95% confidence interval (CI) 1.11, 3.52], being a government grant recipient (OR 3.21; 95% CI: 1.30, 7.92), lower food insecurity (OR 0.34; 95% CI: 0.13, 0.90), and increased body mass index (OR 1.07; 95% CI: 1.01, 1.14). CONCLUSIONS: High prevalence of psychosocial stressors and persistent herpesviruses in AGYW living with HIV has the potential to lead to poorer health outcomes. More research is needed to untangle relationships between economic stability, chronic disease, and chronic stress.
Subject(s)
HIV Infections , Adolescent , Female , Humans , Biomarkers , C-Reactive Protein , Herpesvirus 2, Human , HIV Infections/complications , HIV Infections/drug therapy , HIV Infections/epidemiology , Medication Adherence , South Africa/epidemiology , Viral Load , Young AdultABSTRACT
OBJECTIVE: Determine the feasibility, acceptability, and preliminary effectiveness of financial incentives to motivate re-engagement in HIV care in Shinyanga, Tanzania. METHODS: Out-of-care people living with HIV (PLHIV) were identified from medical records in four clinics and home-based care providers (HBCs) from April 13, 2018 to March 3, 2020. Shinyanga Region residents, ≥18 years, who were disengaged from care were randomized 1:1 to a financial incentive (â¼$10 USD) or the standard of care (SOC), stratified by site, and followed for 180 days. Primary outcomes were feasibility (located PLHIV who agreed to discuss the study), acceptability (enrollment among eligibles), and re-engagement in care (clinic visit within 90 days). RESULTS: HBCs located 469/1,309 (35.8%) out-of-care PLHIV. Of these, 215 (45.8%) were preliminarily determined to be disengaged from care, 201 (93.5%) agreed to discuss the study, and 157 eligible (100%) enrolled. Within 90 days, 71 (85.5%) PLHIV in the incentive arm re-engaged in care vs. 58 (78.4%) in the SOC (Adjusted Risk Difference [ARD] = 0.08, 95% CI: -0.03, 0.19, p = 0.09). A higher proportion of incentivized PLHIV completed an additional (unincentivized) visit between 90-180 days (79.5% vs. 71.6%, ARD = 0.10, 95% CI: -0.03, 0.24, p = 0.13) and remained in care at 180 days (57.8% vs. 51.4%, ARD = 0.07, 95% CI: -0.09, 0.22, p = 0.40). CONCLUSIONS: Short-term financial incentives are feasible, acceptable, and have the potential to encourage re-engagement in care, warranting further study of this approach.
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HIV Infections , Motivation , Humans , Pilot Projects , HIV Infections/drug therapy , TanzaniaABSTRACT
Background: To date, COVID-19 vaccine coverage in the African region falls far too short of global goals. Increasing vaccination rates requires understanding barriers to vaccination so that effective interventions that sensitively and effectively address barriers to vaccination can be implemented. Methods: To assess COVID-19 vaccination levels and identify major barriers to vaccine uptake we conducted a population-based, cross-sectional survey among 1662 adults 18 and older from August 25 to October 29 2021 in the Agincourt Health and Socio-Demographic Surveillance System (AHDSS) area, Mpumalanga, South Africa. Results: Half of participants reported receiving a COVID-19 vaccine (50.4%) with 41.1% being fully vaccinated and 9.3% being partially vaccinated; 49.6% were unvaccinated. More women than men were vaccinated (55.5% vs 42.8%, P < 0.001), and older age groups were more likely to be vaccinated than younger age groups (P < 0.001). Among the unvaccinated, 69.0% planned to get vaccinated as soon as possible, while 14.7% reported definitely not wanting the vaccine. Major barriers to vaccination included lacking information on eligibility (12.3%) or where to get vaccinated (13.0%), concerns about side effects (12.5%), and inconvenient hours and locations for vaccination (11.0%). Confidence in the safety and efficacy of COVID-19 vaccines was higher among those vaccinated than unvaccinated (75.3% vs 51.2%, 75.8% vs 51.0%, both P < 0.001, respectively). Conclusions: Increasing vaccination in South Africa beyond current levels will require a concerted effort to address concerns around vaccine safety and increase confidence in vaccine efficacy. Clarifying eligibility and ensuring access to vaccines at times and places that are convenient to younger populations, men, and other vulnerable groups is necessary.
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COVID-19 , Vaccines , Adult , Aged , COVID-19/epidemiology , COVID-19/prevention & control , COVID-19 Vaccines , Cross-Sectional Studies , Female , Humans , Male , SARS-CoV-2 , South Africa/epidemiology , Vaccination HesitancyABSTRACT
PURPOSE: Sub-analysis of the FAST Trial comparing change in CD4 (∆CD4) from baseline through 12 months in uveitis patients treated with mycophenolate mofetil (MMF) and methotrexate (MTX). METHODS: Patients were randomly allocated to 1.5 g twice daily MMF or 25 mg weekly MTX. Individuals with CD4 counts at baseline, 6 months (or treatment failure prior), and 12 months (or treatment failure between 6 and 12 months) were included. The association between treatment and ∆CD4 (cells/µL) was analyzed using multivariable linear regression. RESULTS: There was no significant difference in ∆CD4 between MMF and MTX at 6 months (-31.7 cells/µL for MMF compared to MTX; 95% CI: -358.2 to 294.8, P = .85) and 12 months (-78.3 cells/µL for MMF compared to MTX; 95% CI: -468.0 to 311.3; P = .69). CONCLUSION: There was no significant difference in ∆CD4 between MMF and MTX from baseline to 12 months, suggesting that MMF does not confer additional risk of CD4 lymphopenia in uveitic patients.ClinicalTrials.gov Identifier: NCT01829295.
Subject(s)
Mycophenolic Acid , Uveitis , Antimetabolites , CD4 Lymphocyte Count , Humans , Immunosuppressive Agents/therapeutic use , Methotrexate/therapeutic use , Mycophenolic Acid/adverse effects , Mycophenolic Acid/therapeutic use , Steroids , Uveitis/chemically induced , Uveitis/diagnosis , Uveitis/drug therapyABSTRACT
INTRODUCTION: Conditional economic incentives are shown to promote medication adherence across a range of health conditions and settings; however, any long-term harms or benefits from these time-limited interventions remain largely unevaluated. We assessed 2-3 years outcomes from a 6-month incentive programme in Tanzania that originally improved short-term retention in HIV care and medication possession. METHODS: We traced former participants in a 2013-2016 trial, which randomised 800 food-insecure adults starting HIV treatment at three clinics to receive either usual care (control) or up to 6 months of cash or food transfers (~US$11/month) contingent on timely attendance at monthly clinic appointments. The primary intention-to-treat analysis estimated 24-month and 36-month marginal risk differences (RD) between incentive and control groups for retention in care and all-cause mortality, using multiple imputation for a minority of missing outcomes. We also estimated mortality HRs from time-stratified Cox regression. RESULTS: From 3 March 2018 to 19 September 2019, we determined 36-month retention and mortality statuses for 737 (92%) and 700 (88%) participants, respectively. Overall, approximately 660 (83%) participants were in care at 36 months while 43 (5%) had died. There were no differences between groups in retention at 24 months (86.5% intervention vs 84.4% control, RD 2.1, 95% CI -5.2 to 9.3) or 36 months (83.3% vs 77.8%, RD 5.6, -2.7 to 13.8), nor in mortality at either time point. The intervention group had a lower rate of death during the first 18 months (HR 0.27, 95% CI 0.10 to 0.74); mortality was similar thereafter (HR 1.13, 95% CI 0.33 to 3.79). CONCLUSION: These findings confirm that incentives are a safe and effective tool to promote short-term adherence and potentially avert early deaths at the critical time of HIV treatment initiation. Complementary strategies are recommended to sustain lifelong retention in HIV care. TRIAL REGISTRATION NUMBER: NCT01957917.
Subject(s)
HIV Infections , Motivation , Adult , Follow-Up Studies , HIV Infections/drug therapy , Humans , Medication Adherence , TanzaniaABSTRACT
PURPOSE: To evaluate changes in health-related and vision-related quality of life (VRQoL) among patients with noninfectious uveitis who were treated with antimetabolites. DESIGN: Secondary analysis of a randomized controlled trial. PARTICIPANTS: Patients with noninfectious uveitis from India, the United States, Australia, Saudi Arabia, and Mexico. METHODS: From 2013 through 2017, 216 participants were randomized to receive 25 mg weekly oral methotrexate or 1.5 g twice daily oral mycophenolate mofetil. Median changes in quality of life (QoL) were measured using Wilcoxon signed-rank tests, and differences between treatment groups were measured using linear mixed models, adjusting for baseline QoL score, age, gender, and site. Among Indian patients, VRQoL scores from a general scale (the National Eye Institute Visual Function Questionnaire [NEI-VFQ]) and a culturally specific scale (the Indian Visual Function Questionnaire [IND-VFQ]) were compared using Pearson correlation tests. MAIN OUTCOME MEASURES: Vision-related QoL (NEI-VFQ and IND-VFQ) and health-related QoL (HRQoL; physical component score [PCS] and mental component score [MCS] of the Medical Outcomes Study 36-Item Short Form Survey [SF-36v2]) were measured at baseline, the primary end point (6 months or treatment failure before 6 months), and the secondary end point (12 months or treatment failure between 6 and 12 months). RESULTS: Among 193 participants who reached the primary end point, VRQoL increased from baseline by a median of 12.0 points (interquartile range [IQR], 1.0-26.1, NEI-VFQ scale), physical HRQoL increased by a median of 3.6 points (IQR, -1.4 to 14.9, PCS SF-36v2), and mental HRQoL increased by a median of 3.0 points (IQR, -3.7 to 11.9, MCS SF-36v2). These improvements in NEI-VFQ, SF-36v2 PCS, and SF-36v2 MCS scores all were significant (P < 0.01). The linear mixed models showed that QoL did not differ between treatment groups for each QoL assessment (NEI-VFQ, IND-VFQ, PCS SF-36v2, and MCS SF-36v2; P > 0.05 for all). The NEI-VFQ and IND-VFQ scores for Indian participants were correlated highly at baseline and the primary and secondary end points (correlation coefficients, 0.87, 0.80, and 0.90, respectively). CONCLUSIONS: Among patients treated with methotrexate or mycophenolate mofetil for uveitis, VRQoL and HRQoL improved significantly over the course of 1 year and did not differ by treatment allocation. These findings suggest that antimetabolites could improve overall patient well-being and daily functioning.
Subject(s)
Enzyme Inhibitors/therapeutic use , Immunosuppressive Agents/therapeutic use , Methotrexate/therapeutic use , Mycophenolic Acid/therapeutic use , Quality of Life/psychology , Uveitis/drug therapy , Administration, Oral , Adult , Aged , Female , Health , Health Status , Humans , Male , Middle Aged , Prospective Studies , Sickness Impact Profile , Surveys and Questionnaires , Uveitis/psychology , Vision, OcularABSTRACT
BACKGROUND: Juvenile idiopathic arthritis (JIA)-associated uveitis is a chronic paediatric ocular inflammatory condition that can result in visual impairment. Adalimumab, a tumour necrosis factor (TNF)-alpha inhibitor, effectively controls joint and eye inflammation; however, its long-term use may increase the risk of adverse health outcomes and place an undue financial burden on the patient and healthcare system given its high cost. There is great interest for patients to stop adalimumab following remission due to these reasons but there is a lack of information on the ability to maintain control after discontinuing adalimumab. METHODS: The Adalimumab in Juvenile Idiopathic Arthritis-associated Uveitis Trial (ADJUST) is a multicentred, international trial that will randomise 118 participants aged 2 years and older with controlled JIA-associated uveitis to either continue adalimumab or discontinue adalimumab and receive a placebo. The trial will compare the time to uveitis recurrence between the two groups over 12 months. All participants will receive the standard weight-based dose of adalimumab or placebo: 20 mg biweekly (if < 30 kg) or 40 mg biweekly (if ≥ 30 kg). DISCUSSION: This is the first randomised controlled trial to assess the efficacy of discontinuing adalimumab after demonstrating control of JIA-associated uveitis for at least 12 months. The results of ADJUST will provide information on clinical outcomes to guide clinicians in their decision-making regarding discontinuation of adalimumab. TRIAL REGISTRATION: ClinicalTrials.gov NCT03816397. Registered on 25 January 2019. EudraCT 2019-000412-29. Registered on 17 January 2019.