The anxiety care continuum and its association with viral suppression among persons with HIV.

OBJECTIVE: It is unclear how often anxiety is diagnosed and treated and whether anxiety treatment is associated with improved viral suppression in persons with HIV. In this study, we characterized the anxiety care continuum and its association with viral suppression in a large urban HIV clinic in the United States. DESIGN: Observational cohort study. METHODS: We described the anxiety care continuum by combining data on self-reported anxiety symptoms, engagement in mental health care, clinical diagnoses and prescriptions from 1,967 persons receiving HIV care and treatment in Baltimore, Maryland, from 2014-23. We examined cross-sectional associations with viral suppression. All analyses were stratified by sex and race/ethnicity; a secondary analysis adjusted for age, years in care, and depressive symptoms. RESULTS: Nearly 1 in 5 patients reported mild-severe symptoms of anxiety but were not currently receiving mental health care or pharmacologic treatment for anxiety; 6% of patients reported anxiety symptoms but were receiving treatment, and 7% had been treated for anxiety that was currently in remission. The prevalence of viral suppression ranged from 87-89% across the anxiety care continuum except among patients with untreated moderate-severe anxiety, only 81% of whom were virally suppressed (95% CI: 80, 83). In adjusted models, untreated moderate-severe anxiety remained associated with viral non-suppression across demographic groups. CONCLUSION: We observed a robust association between untreated anxiety and viral non-suppression in a large urban cohort of persons with HIV. Screening for anxiety may identify patients with unmet mental health care needs who face barriers to maintaining viral suppression.

Spatio-temporal patterns of excess mortality from non-COVID causes of death in the United States, march-December 2020.

Objectives To estimate the burden of excess mortality from 17 underlying causes of death between March-December 2020 in the United States, and to compare trends in excess deaths from non-COVID causes vs. from COVID-19. Methods Using time series models, we estimated monthly counts of all-cause and cause-specific excess deaths. We stratified by geographic region and compared temporal trends in excess deaths from non-COVID causes to trends in deaths attributed to COVID-19. Results Of approximately 500,000 excess deaths, 70% were attributed to COVID-19. We observed increases in several underlying causes of death, ranging from a 3% increase in kidney disease deaths to a 24% increase in homicides, as well as decreases in deaths from cancer (-0.3%), influenza and pneumonia (-2%), chronic lower respiratory disease (-3%), and suicide (-7%). Trends in excess deaths from cardiovascular disease, diabetes, and Alzheimer's disease closely mirrored trends in deaths from COVID-19. Trends in excess liver disease, homicide, suicide, and motor vehicle accident deaths were negatively correlated with trends in deaths from COVID-19. There was wide regional variation in excess death rates for some causes of death, including a disproportionate increase in homicide and motor vehicle accident deaths in the Great Lakes, and a sustained reduction in cancer deaths in the Mideast and New England. Conclusions Increases in cardiovascular disease, diabetes, and Alzheimer's disease deaths from March-December 2020 likely reflect healthcare system disruptions or acute complications of COVID-19. Excess deaths from homicide and liver disease are more likely to reflect social and economic effects of the emerging pandemic, or other separate causes.

Association between switching to integrase strand transfer inhibitors and incident diabetes in people with HIV.

OBJECTIVE: Integrase strand transfer inhibitors (INSTI) are associated with weight gain in people with HIV (PWH), but their impact on diabetes is unclear. We evaluated the association between switching from nonnucleoside reverse-transcriptase inhibitors (NNRTI) or protease inhibitors (PI) to INSTI and incident diabetes. DESIGN: Longitudinal cohort study. METHODS: We included PWH aged ≥18 years from the Johns Hopkins HIV Clinical Cohort (2007-2023) without history of diabetes who had used NNRTI or PI for ≥180 days. We followed participants up to 10 years from HIV primary care visits where they switched to INSTI or continued NNRTI or PI. We estimated the hazard of incident diabetes associated with switching to INSTI using weighted Cox regression with robust variance estimator. RESULTS: We included 2075 PWH who attended 22 116 visits where they continued NNRTI or PI and 631 visits where they switched to INSTI. Switching to INSTI was associated with a weighted hazard ratio (wHR) of 1.11 [95% confidence interval (CI), 0.77-1.59] for incident diabetes. The association if no weight gain occurred during the first two years was not qualitatively different (wHR 1.22; 95% CI, 0.82-1.80). In a posthoc analysis, switching to INSTI conferred a significant wHR of 1.79 (95% CI, 1.13-2.84) for diabetes within the first two years but not after. CONCLUSIONS: Switching from NNRTI or PI to INSTI did not significantly increase overall diabetes incidence in PWH, although there may be elevated risk in the first two years. These findings can inform considerations when switching to INSTI-based regimens.

Incidence of non-AIDS defining comorbidities among young adults with perinatally acquired HIV in North America.

OBJECTIVE: The aim of this study is to describe the incidence of diabetes mellitus type 2 (T2DM), hypercholesterolemia, hypertriglyceridemia, hypertension, and chronic kidney disease (CKD) from 2000 to 2019 among North American adults with perinatally acquired HIV (PHIV) aged 18-30 years. DESIGN: Description of outcomes based on electronic health records for a cohort of 375 young adults with PHIV enrolled in routine HIV care at clinics contributing data to the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD). METHODS: We estimated overall, sex, and race-stratified cumulative incidences using Turnbull estimation, and incidence rates using quasi-Poisson regression. T2DM was defined as glycosylated hemoglobin more than 6.5% or based on clinical diagnosis and medication use. Hypercholesterolemia was based on medication use or total cholesterol at least 200 mg/dl. Hypertriglyceridemia was based on medication use or fasting triglyceride at least 150 mg/dl or nonfasting at least 200 mg/dl. Hypertension was based on clinical diagnosis. CKD was defined as estimated glomerular filtration rates less than 90 ml/mi|1.73 m 2 for at least 3 months. RESULTS: Cumulative incidence by age 30 and incidence rates from age 18 to 30 (per 100 person-years) were T2DM: 19%, 2.9; hypercholesterolemia: 40%, 4.6; hypertriglyceridemia: 50%, 5.6; hypertension: 22%, 2.0; and CKD: 25%, 3.3. Non-Black women had the highest incidence of hypercholesterolemia and hypertriglyceridemia, Black adults had the highest hypertension incidence, and Black men had the highest CKD incidence. CONCLUSION: There was a high incidence of five chronic comorbidities among people with PHIV. Earlier screening at younger ages might be considered for this unique population to strengthen prevention strategies and initiate treatment in a timely way.

Association of Alcohol Use with COVID-19 Infection and Hospitalization Among People Living with HIV in the United States, 2020.

Alcohol use was associated with elevated COVID-19 risk in the general population. People with HIV (PWH) have high prevalences of alcohol use. To evaluate the effect of alcohol use on COVID-19 risks among PWH, we estimated the risk of COVID-19 diagnosis and COVID-19-related hospitalization among PWH in routine care at 8 HIV primary care centers that contributed data to the Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) cohort according to their alcohol use just prior to the COVID-19 pandemic. The CNICS data repository includes demographic characteristics, clinical diagnoses, and laboratory test results from electronic medical records and other sources. Alcohol use, substance use, and mental health symptoms were self-reported on tablet-based standardized surveys. Alcohol use was categorized according to standard, sex-specific Alcohol Use Disorder Identification Test-Consumption instrument cut-offs. We followed 5,496 PWH (79% male, 48% Black race, median age = 53 years) from March 1, 2020 to December 31, 2020. Relative to PWH with no baseline alcohol use, the adjusted hazard ratio (aHR) of COVID-19 diagnosis was 1.09 (95% confidence interval [CI]: 0.78, 1.51) for lower-risk drinking and 1.19 (95%CI: 0.81, 1.73) for unhealthy drinking. The aHR of COVID-19-related hospitalization was 0.82 (95%CI: 0.33, 1.99) for lower-risk drinking and 1.25 (95%CI: 0.50, 3.09) for unhealthy drinking. Results were not modified by recent cocaine or non-prescribed opioid use, depressive symptoms, or diagnoses of alcohol use disorder. The study suggested a slightly increased, but not statistically significant risk of COVID-19 diagnosis and hospitalization associated with unhealthy alcohol use.

The association of changes in depression severity after the onset of the COVID-19 pandemic and viral nonsuppression among people with HIV.

OBJECTIVE: This study sought to characterize changes in depressive symptom severity during the COVID-19 pandemic and the association of these changes with HIV viral nonsuppression among people with HIV (PWH). DESIGN: A clinical cohort study. METHODS: We included PWH in the Johns Hopkins HIV Clinical Cohort who completed the Patient Health Questionnaire 8 (PHQ-8) prepandemic (1 March 2018 to 28 February 2020) and during the COVID-era (1 September 2020 to 28 February 2022). PWH were classified according to depression severity categories prepandemic and during the COVID-era as: consistently depressed (prepandemic PHQ-8 >4 and no change in severity category); consistently nondepressed (prepandemic PHQ-8 ≤4 and no change in severity category); worsened (changed to a higher severity category) and; improved (change to a lower severity category). The association between changes in depressive symptom severity and viral nonsuppression (HIV RNA >200 copies/ml on the earliest viral load measured 7 days before to 12 months after the COVID-era PHQ-8 survey) was assessed using multivariable logistic regression. RESULTS: Of 793 PWH, mean age was 56 (SD 10) years, 60% were male individuals and 88% were Black. After the onset of the pandemic, 60% were consistently nondepressed, 9% were consistently depressed, 15% worsened and 16% improved. PWH who worsened had 2.47 times the odds of viral nonsuppression (95% CI: 1.09-5.55) compared with the nondepressed group. Associations among other groups were not statistically significant. CONCLUSION: Worsening depression during the COVID-era was associated with HIV viral nonsuppression. Strategies to monitor and address depression among PWH may contribute to reduced risk of viral nonsuppression.

Hepatitis C Treatment in People With HIV: Potential to Eliminate Disease and Disparity.

Access to direct acting antivirals (DAAs) may be associated with reductions in hepatitis C virus (HCV) viremia prevalence among people with human immunodeficiency virus (PWH). Among 3755 PWH, estimated HCV viremia prevalence decreased by 94.0% from 36% (95% confidence interval [CI], 27%-46%) in 2009 (pre-DAA era) to 2% (95% CI, 0%-4%) in 2021 (DAA era). Male sex, black race, and older age were associated with HCV viremia in 2009 but not in 2021. Injection drug use remained associated with HCV viremia in 2009 and 2021. Targeted interventions are needed to meet the HCV care needs of PWH who use drugs.

Investigating the impact of suboptimal prescription of preoperative antiplatelets and statins on race and ethnicity-related disparities in major limb amputation.

BACKGROUND: Non-Hispanic Black and Hispanic patients with symptomatic PAD may receive different treatments than White patients with symptomatic PAD. The delivery of guideline-directed medical treatment may be a modifiable upstream driver of race and ethnicity-related disparities in outcomes such as limb amputation. The purpose of our study was to investigate the prescription of preoperative antiplatelets and statins in producing disparities in the risk of amputation following revascularization for symptomatic peripheral artery disease (PAD). METHODS: We used data from the Vascular Quality Initiative, a vascular procedure-based registry in the United States (2011-2018). We estimated the probability of preoperative antiplatelet and statin prescriptions and 1-year incidence of amputation. We then estimated the amputation risk difference between race/ethnicity groups that could be eliminated under a hypothetical intervention. RESULTS: Across 100,579 revascularizations, the 1-year amputation risk was 2.5% (2.4%, 2.6%) in White patients, 5.3% (4.9%, 5.6%) in Black patients, and 5.3% (4.7%, 5.9%) in Hispanic patients. Black (57.5%) and Hispanic patients (58.7%) were only slightly less likely than White patients (60.9%) to receive antiplatelet and statin therapy. However, the effect of antiplatelets and statins was greater in Black and Hispanic patients such that, had all patients received these medications, the estimated risk difference comparing Black to White patients would have reduced by 8.9% (-2.9%, 21.9%) and the risk difference comparing Hispanic to White patients would have been reduced by 17.6% (-0.7%, 38.6%). CONCLUSION: Even though guideline-directed care appeared evenly distributed by race/ethnicity, increasing access to such care may decrease health care disparities in major limb amputation.

Effects of Race and Gender Classifications on Atherosclerotic Cardiovascular Disease Risk Estimates for Clinical Decision-Making in a Cohort of Black Transgender Women.

Introduction: Despite their dynamic, socially constructed, and imprecise nature, both race and gender are included in common risk calculators used for clinical decision-making about statin therapy for atherosclerotic cardiovascular disease (ASCVD) prevention. Methods and Materials: We assessed the effect of manipulating six different race-gender categories on ASCVD risk scores among 90 Black transgender women. Results: Risk scores varied by operationalization of race and gender and affected the proportion for whom statins were recommended. Discussion: Race and gender are social constructs underpinning racialized and gendered health inequities. Their rote use in ASCVD risk calculators may reinforce and perpetuate existing inequities.

Cardiovascular Disease Risk Estimation for Transgender and Gender-Diverse Patients: Cross-Sectional Analysis of Baseline Data From the LITE Plus Cohort Study.

Introduction: Approximately 2% of the U.S. population identifies as transgender, and transgender people experience disproportionate rates of cardiovascular disease mortality. However, widely used cardiovascular disease risk estimators have not been validated in this population. This study sought to determine the impact on statin therapy recommendations using 3 different approaches to operationalizing sex in the American Health Association/American College of Cardiology Pooled Cohort Equation Risk Estimator. Methods: This is a cross-sectional analysis of baseline clinical data from LITE Plus, a prospective cohort study of Black and/or Latina transgender women with HIV. Data were collected from October 2020 to June 2022 and used to calculate Pooled Cohort Equation scores. Results: The 102 participants had a mean age of 43 years. A total of 88% were Black, and 18% were Latina. A total of 79% were taking gender-affirming hormones. The average Pooled Cohort Equation risk score was 6% when sex assigned at birth was used and statins would be recommended for the 31% with Pooled Cohort Equation >7.5%. The average risk score was 4%, and 18% met the criteria for statin initiation when current gender was used; the mean risk score was 5%, and 22% met the criteria for statin initiation when current hormone therapy was used. Conclusions: Average Pooled Cohort Equation risk scores vary substantially depending on the approach to operationalizing the sex variable, suggesting that widely used cardiovascular risk estimators may be unreliable predictors of cardiovascular disease risk in transgender populations. Collection of sex, gender, and hormone use in longitudinal studies of cardiovascular health is needed to address this important limitation of current risk estimators.

Implementing a peer-supported, integrated strategy for substance use disorder care in an outpatient infectious disease clinic is associated with improved patient outcomes.

BACKGROUND: Substance use disorder (SUD) and infectious disease (ID) care integration may lead to improvements in SUD and ID outcomes. We assessed implementation of integrating peer-supported SUD care in an outpatient ID setting. METHODS: In this implementation study, we describe REcovery in Specialty care Through medication and OutREach (RESTORE), a low-threshold SUD program implemented in a Baltimore outpatient ID clinic. Key program components were clinician training and support in SUD care, prescription of SUD treatment medications, and peer-based psychosocial support provided by peer recovery specialists. We assessed clinician adoption of RESTORE and compared patient outcomes from baseline to 6 months. RESULTS: Between January 2019 and January 2022, the number of ID clinicians (N=61) who prescribed buprenorphine increased eightfold from 3 (5%) to 24 (39%). Of 258 ID patients referred to RESTORE, 182 (71%) engaged, 137 consented to study participation. Mean age in the study sample was 52.1 (SD=10.4), 63% were male, 84% were Black/African-American. Among 127 (93%) who completed 6-month follow-up, fewer participants reported illicit/non-prescribed opioid use in the past 30 days at follow-up (32%) compared to baseline (52%; p<0.001). Similar reductions were noted for cocaine use (47% to 34%; p=0.006), emergency department visits (23% to 9%; p=0.002), and inpatient hospitalizations (15% to 7%; p=0.025). CONCLUSION: SUD care integration into an outpatient ID care setting using a peer-supported implementation strategy was adopted by clinicians and improved clinical outcomes for patients. This strategy is a promising approach to treating people with infectious diseases and SUD.

Impact of subgroup-specific heterogeneities and dynamic changes in mortality rates on forecasted population size, deaths, and age distribution of persons receiving antiretroviral treatment in the United States: a computer simulation study.

PURPOSE: Model-based forecasts of population size, deaths, and age distribution of people with HIV (PWH) are helpful for public health and clinical services planning but are influenced by subgroup-specific heterogeneities and changes in mortality rates. METHODS: Using an agent-based simulation of PWH in the United States, we examined the impact of distinct approaches to parametrizing mortality rates on forecasted epidemiology of PWH on antiretroviral treatment (ART). We first estimated mortality rates among (1) all PWH, (2) sex-specific, (3) sex-and-race/ethnicity-specific, and (4) sex-race/ethnicity-and-HIV-acquisition-risk-specific subgroups. We then assessed each scenario by (1) allowing unrestricted reductions in age-specific mortality rates over time and (2) restricting the mortality rates among PWH to subgroup-specific mortality thresholds from the general population. RESULTS: Among the eight scenarios examined, those lacking subgroup-specific heterogeneities and those allowing unrestricted reductions in future mortality rates forecasted the lowest number of deaths among all PWH and 9 of the 15 subgroups through 2030. The forecasted overall number and age distribution of people with a history of injection drug use were sensitive to inclusion of subgroup-specific mortality rates. CONCLUSIONS: Our results underscore the potential risk of underestimating future deaths by models lacking subgroup-specific heterogeneities in mortality rates, and those allowing unrestricted reductions in future mortality rates.

Measuring time in buprenorphine treatment stages among people with HIV and opioid use disorder by retention definition and its association with cocaine and hazardous alcohol use.

BACKGROUND: We use a novel, longitudinal approach to describe average time spent in opioid use disorder (OUD) cascade of care stages for people with HIV (PWH) and with OUD, incorporating four definitions of treatment retention. Using this approach, we describe the impact of cocaine or hazardous alcohol use on time spent retained on buprenorphine. METHODS: We followed PWH with OUD enrolled in the Johns Hopkins HIV Clinical Cohort from their first buprenorphine treatment episode between 2013 and 2020. We estimated 4-year restricted mean time spent on buprenorphine below buprenorphine retention threshold, on buprenorphine above retention threshold, off buprenorphine and in HIV care, loss to follow-up, and death. Retention definitions were based on retention threshold (180 vs 90 days) and allowable treatment gap (7 vs 30 days). Differences in 2-year restricted mean time spent retained on buprenorphine were estimated for patients with and without cocaine or hazardous alcohol use. RESULTS: The study sample (N = 179) was 63% male, 82% non-Hispanic Black, and mean age was 53 (SD 8) years. Patients spent on average 13.9 months (95% CI 11.4, 16.4) on buprenorphine over 4 years. There were differences in time spent retained on buprenorphine based on the retention definition, ranging from 6.5 months (95% CI 4.6, 8.5) to 9.6 months (95% CI 7.4, 11.8). Patients with cocaine use spent fewer months retained on buprenorphine. There were no differences for patients with hazardous alcohol use. CONCLUSIONS: PWH with OUD spend relatively little time receiving buprenorphine in their HIV primary care clinic. Concurrent cocaine use at buprenorphine initiation negatively impact time on buprenorphine.

The temporal relationship of alcohol use and subsequent self-reported health status among people with HIV.

Background: Alcohol use among people with HIV is associated with worse HIV treatment outcomes. Its impact on self-reported health status is unclear. Setting: Longitudinal cohort of people with HIV engaged in care across 7 clinics participating in the Centers for AIDS Research Network of Integrated Care Systems between January 2011 and June 2014. Methods: A total of 5046 participants were studied. A quantile regression model estimated the association of alcohol use levels with subsequent self-reported health status score, accounting for multiple covariates including depressive symptoms. Women, men who have sex with women, and men who have sex with men were analyzed separately. Results: Prevalence of heavy alcohol use was 21%, 31%, and 37% among women, men who have sex with women, and men who have sex with men, respectively. Women with heavy alcohol use had a subsequently decreased median self-reported health status score compared to women with no or moderate alcohol use (odds ratio [OR]: 0.76; 95% confidence interval [CI]: 0.58-0.99); this association was not explained by the presence of depressive symptoms. There was no observed association of alcohol use level on subsequent self-reported health status among men who have sex with women. Men who have sex with men reporting no alcohol use had a subsequently decreased median self-reported health status compared to moderate alcohol use (OR: 0.88; 95% CI: 0.80-0.97). Conclusion: Heavy alcohol use is associated with worsened self-reported health status at subsequent visits among women with HIV and not men with HIV.

Alcohol use and the longitudinal HIV care continuum for people with HIV who enrolled in care between 2011 and 2019.

PURPOSE: We described the impact of alcohol use on longitudinal engagement in HIV care including loss to follow-up, durability of viral suppression, and death. METHODS: We followed a cohort of 1781 people with HIV from enrolled in care at one of seven US clinics, 2011-2019 through 102 months. We used a multistate, time-varying Markov process and restricted mean time to summarize engagement in HIV care over follow-up according to baseline self-reported alcohol use (none, moderate, or unhealthy). RESULTS: Our sample (86% male, 54% White) had median age of 35 years. Over 102 months, people with no, moderate, and unhealthy alcohol use averaged 62.3, 61.1, and 59.5 months virally suppressed, respectively. People who reported unhealthy or moderate alcohol use spent 5.1 (95% confidence intervals (CI): 0.8, 9.3) and 7.6 (95%CI: 3.1, 11.7) more months lost to care than nondrinkers. Compared to no use, unhealthy alcohol use was associated with 3.4 (95%CI: -5.6, -1.6) fewer months in care, not virally suppressed. There were no statistically significant differences after adjustment for demographic and clinical characteristics. CONCLUSIONS: Moderate or unhealthy drinking at enrollment in HIV care was associated with poor retention in care. Alcohol use was not associated with time spent virally suppressed.

Joint effects of substance use disorders and recent substance use on HIV viral non-suppression among people engaged in HIV care in an urban clinic, 2014-2019.

AIMS: To estimate the joint effects of substance use disorder (SUD) and recent substance use on human immunodeficiency virus (HIV) non-suppression. DESIGN: Retrospective clinical cohort study with repeated observations within individuals. SETTING: Baltimore, Maryland, United States. PARTICIPANTS: 1881 patients contributed 10 794 observations. MEASUREMENTS: The primary independent variable was the combination of history of SUD and recent substance use. History of SUD was defined as any prior International Classification of Diseases 9/10 code for cocaine or opioid disorder. Recent substance use was defined as the self-report of cocaine or non-prescribed opioid use on the National Institute of Drug Abuse-modified Alcohol, Smoking and Substance Involvement Screening Test or clinician-documented cocaine or opioid use abstracted from the medical record. The outcome was viral non-suppression, defined as HIV RNA >200 copies/mL on the first viral load measurement within 1 year subsequent to each observation of substance use. We adjusted for birth sex, Black race, age, HIV acquisition risk factors, years in care and CD4 cell count. In secondary analyses, we also adjusted for depressive, anxiety and panic symptoms, cannabis use and cannabis use disorder. FINDINGS: On their first observation, 31% of patients had a history of an SUD and 18% had recent substance use. Relative to no history of SUD and no recent substance use, the 1-year fully adjusted risk difference (RD) for viral non-suppression associated with cocaine and opioid use disorder and recent substance use was 7.7% (95% CI = 5.3%-10.0%), the RD was 5.5% (95% CI = 1.2%-9.7%) for history of cocaine use disorder without recent substance use, and the RD was 4.6% (95% CI = 2.7%-6.5%) for recent substance use without a SUD. CONCLUSIONS: Substance use and substance use disorders appear to be highly prevalent among, and independently associated with, viral non-suppression among people with HIV.

When Does Differential Outcome Misclassification Matter for Estimating Prevalence?

BACKGROUND: When accounting for misclassification, investigators make assumptions about whether misclassification is "differential" or "nondifferential." Most guidance on differential misclassification considers settings where outcome misclassification varies across levels of exposure, or vice versa. Here, we examine when covariate-differential misclassification must be considered when estimating overall outcome prevalence. METHODS: We generated datasets with outcome misclassification under five data generating mechanisms. In each, we estimated prevalence using estimators that (a) ignored misclassification, (b) assumed misclassification was nondifferential, and (c) allowed misclassification to vary across levels of a covariate. We compared bias and precision in estimated prevalence in the study sample and an external target population using different sources of validation data to account for misclassification. We illustrated use of each approach to estimate HIV prevalence using self-reported HIV status among people in East Africa cross-border areas. RESULTS: The estimator that allowed misclassification to vary across levels of the covariate produced results with little bias for both populations in all scenarios but had higher variability when the validation study contained sparse strata. Estimators that assumed nondifferential misclassification produced results with little bias when the covariate distribution in the validation data matched the covariate distribution in the target population; otherwise estimates assuming nondifferential misclassification were biased. CONCLUSIONS: If validation data are a simple random sample from the target population, assuming nondifferential outcome misclassification will yield prevalence estimates with little bias regardless of whether misclassification varies across covariates. Otherwise, obtaining valid prevalence estimates requires incorporating covariates into the estimators used to account for misclassification.