Retinal toxicity in a multinational inception cohort of patients with systemic lupus on hydroxychloroquine.

OBJECTIVE: To evaluate hydroxychloroquine (HCQ)-related retinal toxicity in the Systemic Lupus International Collaborating Clinics (SLICC) inception cohort. METHODS: Data were collected at annual study visits between 1999 and 2019. We followed patients with incident SLE from first visit on HCQ (time zero) up to time of retinal toxicity (outcome), death, loss-to-follow-up or end of study. Potential retinal toxicity was identified from SLICC Damage Index scores; cases were confirmed with chart review. Using cumulative HCQ duration as the time axis, we constructed univariate Cox regression models to assess if covariates (ie, HCQ daily dose/kg, sex, race/ethnicity, age at SLE onset, education, body mass index, renal damage, chloroquine use) were associated with HCQ-related retinal toxicity. RESULTS: We studied 1460 patients (89% female, 52% white). Retinal toxicity was confirmed in 11 patients (incidence 1.0 per 1000 person-years, 0.8% overall). Average cumulative time on HCQ in those with retinal toxicity was 7.4 (SD 3.2) years; the first case was detected 4 years after HCQ initiation. Risk of retinal toxicity was numerically higher in older patients at SLE diagnosis (univariate HR 1.05, 95% CI 1.01 to 1.09). CONCLUSIONS: This is the first assessment of HCQ and retinal disease in incident SLE. We did not see any cases of retinopathy within the first 4 years of HCQ. Cumulative HCQ may be associated with increased risk. Ophthalmology monitoring (and formal assessment of cases of potential toxicity, by a retinal specialist) remains important, especially in patients on HCQ for 10+ years, those needing higher doses and those of older age at SLE diagnosis.

Predictors of Unsuccessful Hydroxychloroquine Tapering and Discontinuation: Can We Personalize Decision-Making in Systemic Lupus Erythematosus Treatment?

OBJECTIVE: Hydroxychloroquine (HCQ) is a key systemic lupus erythematosus (SLE) drug, making concerns of drug shortages grave. Our objective was to evaluate factors associated with poor outcomes after HCQ taper or discontinuation in SLE. METHODS: We studied 5 Canadian SLE cohorts between 1999 and 2019, following patients from the date of HCQ tapering (cohort 1) or discontinuation (cohort 2). A composite outcome was defined as any of the following: a need for therapy augmentation, an increase (of at least 4 points) in the Systemic Lupus Erythematosus Disease Activity Index 2000 score, or hospitalization for SLE. In each cohort, multivariable Cox regression was used to identify demographic and clinical factors associated with time to the earliest of these events. A third cohort continuing to receive HCQ was also studied, to assess whether the same factors influenced the outcome even when the HCQ dose was unchanged. RESULTS: The poor outcome rate, per 100 person-years, was 35.7 (95% confidence interval [95% CI] 31.6-40.3) in the HCQ taper cohort (n = 398), 29.0 (95% CI 25.5-33.0) in the discontinuation cohort (n = 395), and 16.1 (95% CI 13.2-19.6) in the maintenance cohort (n = 395). In patients tapering HCQ, baseline prednisone use was independently associated with greater risk of poor outcomes. In the discontinuation cohort, the risk of poor outcomes was greater for Black patients and those diagnosed with SLE at age ≤25 years. Among those maintaining HCQ, baseline immunosuppressive use and First Nations ethnicity were associated with poor outcomes. CONCLUSION: We identified demographic and clinical factors associated with poor outcomes after HCQ taper/discontinuation. This information is critical in the current setting of potential shortages, but over the long term, such information could inform personalized therapies.

Flares after hydroxychloroquine reduction or discontinuation: results from the Systemic Lupus International Collaborating Clinics (SLICC) inception cohort.

OBJECTIVES: To evaluate systemic lupus erythematosus (SLE) flares following hydroxychloroquine (HCQ) reduction or discontinuation versus HCQ maintenance. METHODS: We analysed prospective data from the Systemic Lupus International Collaborating Clinics (SLICC) cohort, enrolled from 33 sites within 15 months of SLE diagnosis and followed annually (1999-2019). We evaluated person-time contributed while on the initial HCQ dose ('maintenance'), comparing this with person-time contributed after a first dose reduction, and after a first HCQ discontinuation. We estimated time to first flare, defined as either subsequent need for therapy augmentation, increase of ≥4 points in the SLE Disease Activity Index-2000, or hospitalisation for SLE. We estimated adjusted HRs (aHRs) with 95% CIs associated with reducing/discontinuing HCQ (vs maintenance). We also conducted separate multivariable hazard regressions in each HCQ subcohort to identify factors associated with flare. RESULTS: We studied 1460 (90% female) patients initiating HCQ. aHRs for first SLE flare were 1.20 (95% CI 1.04 to 1.38) and 1.56 (95% CI 1.31 to 1.86) for the HCQ reduction and discontinuation groups, respectively, versus HCQ maintenance. Patients with low educational level were at particular risk of flaring after HCQ discontinuation (aHR 1.43, 95% CI 1.09 to 1.87). Prednisone use at time-zero was associated with over 1.5-fold increase in flare risk in all HCQ subcohorts. CONCLUSIONS: SLE flare risk was higher after HCQ taper/discontinuation versus HCQ maintenance. Decisions to maintain, reduce or stop HCQ may affect specific subgroups differently, including those on prednisone and/or with low education. Further study of special groups (eg, seniors) may be helpful.

Translation and validation in Brazilian Portuguese of the reactions to homosexuality scale.

Internalized homonegativity results from the acceptance of negative attitudes about one's same-sex orientation, which has negative consequences for the health of gay, bisexual and other men who have sex with men (GBM). We translated the 7-item Reactions to Homosexuality Scale (RHS) to Brazilian Portuguese and assessed its factor structure, validity and reliability. The first step included the translation, back-translation, evaluation, peer review, and pre-testing of the scale. Then, we piloted the scale in two convenience samples of adult Brazilians recruited online during October 2019 and February to March 2020 through advertisements on Grindr and Hornet, respectively. The largest sample was randomly split into two groups for exploratory factor analysis (EFA) then confirmatory factor analysis (CFA). Criterion and construct validity were assessed via correlations between scale scores and study variables. A total of 5573 GBM (sample 1: 218; sample 2: 5355) completed the RHS. EFA (N = 2652) yielded two eigenvalues greater than one (Factor 1: 3.5 and Factor 2: 1.1). A one-factor solution provided the most interpretable model based on examination of scree plot and item factor loadings (χ2(14) = 1373.1, p < 0.001; CFI = 0.89; TLI = 0.84; RMSEA = 0.19; SRMS = 0.09). Though one-factor CFA showed moderate fit, freeing errors terms to covary, based on item content and interpretation, significantly improved model fit (χ2(12) = 309.1, p < .001; CFI = 0.97; TLI = 0.96; RMSEA = 0.09; SRMR = 0.02). As hypothesized, men who did not self-identify as gay (mean score 17.9 compared to those self-identifying as gay: 11.8) and men who reported no sex with men in the past 6 months (mean score 12.6 compared to those who reported sex with men: 10.6) scored higher reflecting higher internalized homonegativity. The RHS was effectively translated and validated in Brazilian Portuguese and can be used to evaluate the role of internalized homonegativity on GBM's health, as well as its impact on the uptake of HIV prevention technologies.

Cross-cultural adaptation of the Perceived Risk of HIV Scale in Brazilian Portuguese.

BACKGROUND: Valid and reliable instruments are needed to measure the multiple dimensions of perceived risk. The Perceived Risk of HIV Scale is an 8-item measure that assesses how people think and feel about their risk of infection. We set out to perform a cross-cultural adaptation of the scale to Brazilian Portuguese among key populations (gay, bisexual and other men who have sex with men and transgender/non-binary) and other populations (cisgender heterosexual men and cisgender women). METHODS: Methodological study with cross-sectional design conducted online during October/2019 (key populations [sample 1] and other populations) and February-March/2020 (key populations not on pre-exposure prophylaxis [sample 2]). Cross-cultural adaptation of the Perceived Risk of HIV Scale followed Beaton et al. 2000 guidelines and included confirmatory factor analysis, differential item functioning (DIF) using the Multiple-Indicator Multiple-Cause model, and concurrent validity to verify if younger individuals, those ever testing for HIV, and engaging in high-risk behaviors had higher scores on the scale. RESULTS: 4342 participants from key populations (sample 1 = 235; sample 2 = 4107) and 155 participants from other populations completed the measure. We confirmed the single-factor structure of the original measure (fit indices for sample 1 plus other populations: CFI = 0.98, TLI = 0.98, RMSEA = 0.07; sample 2 plus other populations: CFI = 0.97, TLI = 0.95, RMSEA = 0.09). For the comparisons between key populations and other populations, three items (item 2: "I worry about getting infected with HIV", item 4: "I am sure I will not get infected with HIV", and item 8: "Getting HIV is something I have") exhibited statistically significant DIF. Items 2 and 8 were endorsed at higher levels by key populations and item 4 by other populations. However, the effect of DIF on overall scores was negligible (0.10 and 0.02 standard deviations for the models with other populations plus sample 1 and 2, respectively). Those ever testing for HIV scored higher than those who never tested (p < .001); among key populations, those engaging in high-risk behaviors scored higher than those reporting low-risk. CONCLUSION: The Perceived Risk of HIV Scale can be used among key populations and other populations from Brazil.

High-Risk Sexual Behavior, Binge Drinking and Use of Stimulants are Key Experiences on the Pathway to High Perceived HIV Risk Among Men Who Have Sex with Men in Brazil.

In Brazil, pre-exposure prophylaxis (PrEP) is currently available for gay, bisexual, and other men who have sex with men. As PrEP use depends on an individual's perceived risk, we explored pathways by which potentially modifiable behaviors lead to high perceived HIV risk. Using online surveys (N = 16,667), we conducted a path analysis on the basis of ordered sequences of multivariate logistic regressions. High perceived HIV risk was low (26.3%) compared to condomless receptive anal sex (41.4%). While younger age increased the odds of binge drinking and of condomless receptive anal sex, it was associated with decreased odds of high perceived HIV risk. In contrast, use of stimulants increased the odds of condomless receptive anal sex and of high perceived HIV risk. Our results suggest that binge drinking and use of stimulants are key points in different pathways to high-risk sexual behavior and may lead to different perceptions of HIV risk.

RESUMEN: En Brasil, la profilaxis previa a la exposición (PrEP) está disponible actualmente para hombres homosexuales, bisexuales y otros hombres que tienen sexo con hombres. Como el uso de PrEP depende del riesgo percibido de una persona, exploramos vías por las cuales los comportamientos potencialmente modificables conducen a un alto riesgo percibido de VIH. Utilizando datos de encuestas en línea (N = 16.667), realizamos un análisis de ruta sobre la base de secuencias ordenadas de regresiones logísticas multivariadas. El alto riesgo percibido de VIH fue bajo (26,3%) en comparación con el sexo anal receptivo sin condón (41,4%). La edad más joven aumentó las probabilidades de consumo de alcohol en exceso y del sexo anal receptivo sin condón, todavía se asoció con una menor probabilidad de alta percepción de riesgo sobre VIH. Sin embargo, el uso de estimulantes aumentó las probabilidades de tener sexo anal receptivo sin condón y de un alto riesgo percibido de VIH. Nuestros resultados sugieren que el consumo excesivo de alcohol y el uso de estimulantes son puntos clave en diferentes vías de conductas sexuales de alto riesgo y pueden llevar a diferentes percepciones del riesgo de VIH.

Translation and validation of the Short HIV Stigma scale in Brazilian Portuguese.

BACKGROUND: HIV-related stigma, or the degree to which people living with HIV endorse negative stereotypes associated with HIV, is associated with poor continuum of care outcomes. We translated the 12-item Short HIV Stigma scale and evaluated its psychometric properties in a Brazilian context with regard to construct validity and reliability. METHODS: The first step included translation, back-translation, evaluation, peer review, and pre-testing of the Short HIV Sigma scale developed by Reinius et al. (Health Qual Life Outcomes 15(1):115, 2017). The second step involved piloting the scale in three convenience samples of adults recruited online through advertisements on different platforms: Grindr (October/2019) and Hornet (February-March/2020), geospatial network apps for sexual encounters for gay, bisexuals and other men who have sex with men, and social media apps (Facebook and WhatsApp, October/2019). The psychometric evaluation included confirmatory factor analysis, differential item functioning using the Multiple-Indicator Multiple-Cause model, and correlations between subscale scores and antiretroviral treatment use and adherence. Reliability was assessed using Cronbach's alpha, and ordinal alpha and omega from the polychoric correlation matrix. RESULTS: In total, 114, 164, and 1824 participants completed the measure items through Grindr, social media, and Hornet, respectively. We confirmed a 4-factor structure with factors for personalized stigma (3 items), disclosure concerns (3 items), concerns with public attitudes (3 items), and negative self-image (3 items). Small differential item functioning with respect to sample was found for one item ("I feel guilty because I have HIV"), which did not substantively influence estimates of latent factor scores. Grindr and Hornet's participants scored significantly higher than social media participants on all factors except personalized stigma. Higher subscale scores correlated with antiretroviral treatment use among participants from Hornet and with lower treatment adherence in participants from Grindr and Hornet. Reliability as measured by Cronbach's alpha, ordinal alpha and omega were 0.83, 0.88 and 0.93 for the entire scale. DISCUSSION: The Brazilian Portuguese version of the Short HIV Stigma scale had satisfactory psychometric properties with present results suggesting that scores from different samples may be compared without concern that measurement differences substantively influence results though further studies with greater representation of women and heterosexual men are warranted.

Medication nonadherence, multitablet regimens, and food insecurity are key experiences in the pathway to incomplete HIV suppression.

OBJECTIVE: To identify potential pathways by which a variety of factors act to lead to unsuppressed viral load. DESIGN: A prospective cohort of HIV-HCV co-infected adults receiving care from 18 HIV clinics across Canada was followed every 6 months between November 2012 and October 2015. Participants with at least two visits while receiving combined antiretroviral treatment (cART) were included. METHODS: A path analysis was conducted on the basis of ordered sequences of multivariate logistic regressions using generalized estimating equations. The first regression model used incomplete viral suppression (viral load >50 copies/ml) as the outcome of interest and all other variables (i.e. nonadherence, food insecurity, treatment attributes, and other sociodemographic, behavioural, and clinical factors) as potential predictors. Any variable determined to be a statistically significant predictor of incomplete viral suppression was then used as the next outcome of interest in the subsequent regression, until all predictors of each selected outcome were purely explanatory variables. RESULTS: A total of 566 participants had at least two visits. Drivers of incomplete viral suppression included injection drug use, age 45 years or less, living alone, poor health status, longer duration of HIV infection and baseline CD4 cell count less than 200 cells/µl. Nonadherence, food insecurity, and the use of multitablet regimens mediated the effects of these factors on incomplete viral suppression. CONCLUSION: Our results suggest that nonadherence, multitablet regimens, and food insecurity are key points in the pathway to incomplete HIV suppression. These are potentially amenable intervention targets that would not be revealed using traditional regression analyses.