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OBJECTIVES: Telemedicine became the primary mode of delivering care during the COVID-19 pandemic. We describe the impact of telemedicine on access to care for people with HIV (PWH) by comparing the proportion of PWH engaged in care prior to and during the COVID-19 pandemic. DESIGN AND METHODS: We conducted an observational analysis of patients enrolled in the Johns Hopkins HIV Clinical Cohort, a single-center cohort of patients at an urban HIV subspecialty clinic affiliated with an academic center. Due to the COVID-19 pandemic, the clinic transitioned from in-person to mostly telemedicine visits. We compared patients receiving care in two time periods. The pre-pandemic period included 2,010 people with ≥1 visit scheduled between September 1(st) 2019 and March 15(th) 2020. The pandemic period included 1,929 people with ≥1 visit scheduled between March 16(th) 2020 and September 30(th) 2020. We determined the proportion of patients completing ≥1 of their scheduled visits during each period. RESULTS: Visit completion increased significantly from 88% pre-pandemic to 91% during the pandemic (p=0.008). Visit completion improved significantly for patients age 20–39 (82% to 92%, p

Background Opioid use is prevalent among people living with human immunodeficiency virus (HIV; PLWH) and adversely affects HIV outcomes. We assessed the effect of buprenorphine (BUP) initiation on subsequent HIV viral loads. Methods We identified PLWH from the Johns Hopkins HIV Clinical Cohort who initiated BUP between 2002 and 2017. Poisson regression with robust variance was used to estimate the prevalence of viral suppression ( Results We identified 279 PLWH who initiated BUP. After BUP initiation, PLWH were more likely to be virally suppressed (prevalence ratio [PR], 1.19; 95% confidence interval [CI], 1.03–1.37). After matching PLWH who initiated BUP to controls and accounting for measured and unmeasured confounders, BUP initiation increased viral suppression for both those on antiretroviral therapy (ART) at baseline (PERR PR, 1.08; 95% CI, 1.00–1.18) and those not on ART at baseline (PR, 1.31; 95% CI, 1.10–1.61). Conclusions Our results indicate that the initiation of BUP results in an increase in the probability of being virally suppressed after accounting for both measured and unmeasured confounders. Persons with opioid use disorder should initiate BUP to not only treat substance use but also to increase viral suppression allowing for treatment as prevention.

This prospective, nonrandomized implementation study evaluated a computerized brief intervention (CBI) for persons with HIV (PWH) and heavy/hazardous alcohol use. CBI was integrated into two HIV primary care clinics. Eligible patients were engaged in care, ≥18 years old, English speaking, endorsed heavy/hazardous alcohol use on the Alcohol Use Disorders Identification Test - C (AUDIT-C). Two 20-minute computerized sessions using cognitive behavioral techniques were delivered by a 3-D avatar on touch screen tablets. Of 816 eligible AUDIT-C scores, 537 (66%) resulted in CBI invitation, 226 (42%) of invited patients enrolled, and 176 (78%) of enrolled patients watched at least one session. CBI enrollment was associated with a significant average reduction of 9.1 drinks/week (95% CI: −14.5, −3.6) 4–12 months post-enrollment. Among those who participated in one or both sessions, average reduction in drinks/week was 11.7 drinks/week (95% CI: −18.8, −4.6). There was corresponding improvement in AUDIT-C scores. Overall patients reported high levels of intervention satisfaction, particularly among older and Black patients. These promising results point to a practical intervention for alcohol reduction in this vulnerable patient population with elevated rates of heavy/hazardous drinking. Future research should examine strategies to increase initial engagement, strengthen intervention effects to increase the number of patients who achieve non-hazardous drinking, and examine the duration of therapeutic effects.

We estimated joint associations between having history of alcohol use disorder (AUD) (based on prior ICD-9/ICD-10 codes) and recent self-reported alcohol use and viral non-suppression (≥ 1 viral load measurement > 20 copies/mL in the same calendar year as alcohol consumption was reported) among patients on ART enrolled in routine care, 2014–2018, in an urban specialty clinic. Among 1690 patients, 26% had an AUD, 21% reported high-risk alcohol use, and 39% had viral non-suppression. Relative to person-years in which people without AUD reported not drinking, prevalence of viral non-suppression was higher in person-years when people with AUD reported drinking at any level; prevalence of viral non-suppression was not significantly higher in person-years when people with AUD reported not drinking or person-years when people without AUD reported drinking at any level. No level of alcohol use may be “safe” for people with a prior AUD with regard to maintaining viral suppression.

BACKGROUND: In time-to-event analyses, there is limited guidance on when persons who are lost to follow-up (LTFU) should be censored. METHODS: We simulated bias in risk estimates for: (1) a composite event of measured (outcome only observable in a patient encounter) and captured events (outcome observable outside a patient encounter); and a (2) measured or (3) captured event in the presence of a competing event of the other type, under three censoring strategies: (i) censor at the last study encounter; (ii) censor when LTFU definition is met; and (iii) a new, hybrid censoring strategy. We demonstrate the real-world impact of this decision by estimating: (1) time to Acquired Immune Deficiency Syndrome diagnosis (AIDS) or death, (2) time to initiation of antiretroviral therapy (ART), and (3) time to death prior to ART initiation among adults engaged in HIV care. RESULTS: For (1) our hybrid censoring strategy was least biased. In our example, 5-year risk of AIDS or death was over-estimated using last-encounter censoring (25%) and under-estimated using LTFU-definition censoring (21%), compared to results from our hybrid approach (24%). Last-encounter censoring was least biased for (2). When estimating 5-year risk of ART initiation, LTFU-definition censoring underestimated risk (80% versus 85% using last-encounter censoring). LTFU-definition censoring was least biased for (3). When estimating 5-year risk of death before ART initiation, last-encounter censoring overestimated risk (5.2% versus 4.7% using LTFU-definition censoring). CONCLUSIONS: The least biased censoring strategy for time-to-event analyses in the presence of LTFU depends on the event and estimand of interest.

High mortality rates among persons with HIV with a history of injection drug use (PWID) are thought to be driven in part by higher rates of external cause-related mortality. We followed 4,796 persons aged 18–70 engaged in continuity HIV care from 2001–2015 until death or administrative censoring. We compared cause-specific (csHR) and subdistribution hazards (sdHR) of death due to external causes among PWID and persons who acquired their HIV infection through other routes (non-IDU). We standardized estimates on age, sex, race, and HIV-related health status. The standardized csHR for external cause-related death was 3.57 (95% CI: 2.39, 5.33), and the sdHR was 3.14 (95% CI: 2.16, 4.55). The majority of external cause-related deaths were overdose-related and standardized sdHR was 4.02 (95% CI: 2.40, 6.72). Absolute rate of suicide was low but the csHR for PWID compared to non-IDU was most elevated for suicide (6.50, 95% CI: 1.51, 28.03). HIV-infected PWID are at a disproportionately increased risk of death due to external causes, particularly overdose and suicide.

Purpose Health plan disenrollment occurs frequently in commercial insurance claims databases. If individuals who disenroll are different from those who remain enrolled, informative censoring may bias descriptive statistics as well as estimates of causal effect. We explored whether patterns of disenrollment varied by patient or health plan characteristics. Methods In a large cohort of commercially insured adults (2007-2013), we examined two primary outcomes: (a) within-year disenrollment between January 1 and December 30, which was considered to occur due to patient disenrollment from the health plan, and (b) end-of-year disenrollment on December 31, which was considered to occur due to either patient disenrollment from the health plan or withdrawal of the entire health plan from the commercial insurance database. In yearly cohorts, we identified factors independently associated with disenrollment by using log-binomial regression models to estimate risk ratios (RR) and 95% confidence intervals (CI). Results Among 2 053 100 unique patient years, the annual proportion of within-year disenrollment remained steady across years (range, 13% to 14%) whereas the annual proportion of end-of-year disenrollment varied widely (range, 8% to 26%). Independent predictors of within-year disenrollment were related to health status, including age, comorbidities, frailty, hospitalization, emergency room visits, use of durable medical equipment, use of preventive care, and use of prescription medications. In contrast, independent predictors of end-of-year disenrollment were related to health plan characteristics including insurance plan type and geographic characteristics. Conclusions Differential risk of disenrollment suggests that analytic approaches to address selection bias should be considered in studies using commercial insurance databases.

OBJECTIVE The aim of this study was to describe the risk of viral nonsuppression across the depression care cascade. DESIGN A clinical cohort study. METHODS We used depressive symptoms (PHQ-8 ≥ 10) self-reported on computer-assisted surveys, clinical diagnoses of depression in the medical record in the prior year and pharmacologic (any prescription for an antidepressant) and psychologic treatments for depression (attendance at at least two mental health visits in the prior year) to classify patients into groups: no history of depression; prior depression diagnosis; current indication for depression treatment (symptoms or clinical diagnosis); and treated depression (stratified by presence of persistent symptoms). We associated position in the depression care cascade with viral nonsuppression (>200 copies/ml) 7 days before to 6 months after the index self-report of depressive symptoms. RESULTS History of depression [adjusted risk difference (aRD) relative to no history = 5.9%, 95% confidence interval (95% CI): 1.5-10.3] and current depression (symptoms or diagnosis) in the absence of treatment (aRD relative to no current depression or depression treatment = 4.8%, 95% CI: 1.8-7.8) were associated with a higher risk of viral nonsuppression than no history of depression. Depression treatment mitigated this association (aRD = -0.4%, 95% CI: -2.5 to 1.7). CONCLUSION The relationship between depression care cascade and viral suppression is complex. Untreated depression and clinically unrecognized depressive symptoms were both related to viral nonsuppression. Treated depression was not associated with viral nonsuppression; however, a high proportion of treated patients still had depressive symptoms. Depression treatment should be titrated if patients' symptoms are not responsive and patients with a history of depression should be monitored for ART adherence.

Background: Although antiretroviral therapy (ART) is known to be protective against HIV-related mortality, the expected magnitude of effect is unclear because existing estimates of the effect of ART may not directly generalize to recently HIV-diagnosed persons.

In response to the threat posed by the coronavirus disease 2019 (COVID-19) pandemic, many universities are encouraging or requiring online instruction. Teaching an epidemiology course online is different in many respects from teaching in person. In this article, we review specific approaches and strategies related to teaching epidemiology online during the pandemic and beyond, including a discussion of options for course format, grading and assessment approaches, pandemic-related contingencies, and the use of technology. Throughout this article we present practical, epidemiology-specific teaching examples. Moreover, we also examine 1) how the lessons learned about the practice of epidemiology during the pandemic can be integrated into the didactic content of epidemiology training programs and 2) whether epidemiologic pedagogy and teaching strategies should change in the long term, beyond the COVID-19 pandemic. The pandemic has served to heighten our awareness of concerns related to student health and safety, as well as issues of accessibility, equity, and inclusion. Our goal is to present a practical overview connecting pandemic-era online teaching with thoughts about the future of epidemiologic instruction.

Learning health systems use data to generate knowledge that informs clinical care, but few studies have evaluated how to leverage patient-reported mental health symptoms and substance use data to make patient-specific predictions. We developed a general Bayesian prediction algorithm that uses self-reported psychiatric symptoms and substance use within a population to predict future symptoms and substance use for individuals in that population. We validated our approach in 2444 participants from two clinical cohorts - the National Network of Depression Centers and the Johns Hopkins HIV Clinical Cohort - by predicting symptoms of depression, anxiety, and mania as well as alcohol, heroin, and cocaine use and comparing our predictions to observed symptoms and substance use. When we dichotomized mental health symptoms as moderate-severe vs. none-mild, individual predictions yielded areas under the ROC curve (AUCs) of 0.84 [95% confidence interval 0.80-0.88] and 0.85 [0.82-0.88] for symptoms of depression in the two cohorts, AUCs of 0.84 [0.79-0.88] and 0.85 [0.82-0.88] for symptoms of anxiety, and an AUC of 0.77 [0.72-0.82] for manic symptoms. Predictions of substance use yielded an AUC of 0.92 [0.88-0.97] for heroin use, 0.90 [0.82-0.97] for cocaine use, and 0.90 [0.88-092] for alcohol misuse. This rigorous, mathematically grounded approach could provide patient-specific predictions at the point of care. It can be applied to other psychiatric symptoms and substance use indicators, and is customizable to specific health systems. Such approaches can realize the potential of a learning health system to transform ever-increasing quantities of data into tangible guidance for patient care.

Background In some time-to-event analyses, it is unclear whether loss to follow up should be treated as a censoring event or competing event. Such ambiguity is particularly common in HIV research that uses routinely collected clinical data to report the timing of key milestones along the HIV care continuum. In this setting, loss to follow up may be viewed as a censoring event, under the assumption that patients who are "lost" from a study clinic immediately enroll in care elsewhere, or a competing event, under the assumption that people "lost" are out of care all together. Methods We illustrate an approach to address this ambiguity when estimating the 2-year risk of antiretroviral treatment initiation among 19,506 people living with HIV who enrolled in the IeDEA Central Africa cohort between 2006 and 2017, along with published estimates from tracing studies in Africa. We also assessed the finite sample properties of the proposed approach using simulation experiments. Results The estimated 2-year risk of treatment initiation was 69% if patients were censored at loss to follow up or 59% if losses to follow up were treated as competing events. Using the proposed approach, we estimated that the 2-year risk of antiretroviral therapy initiation was 62% (95% confidence interval: 61, 62). The proposed approach had little bias and appropriate confidence interval coverage under scenarios examined in the simulation experiments. Conclusions The proposed approach relaxes the assumptions inherent in treating loss to follow up as a censoring or competing event in clinical HIV cohort studies.

PURPOSE: A comparison of stage at cancer diagnosis and cancer treatment rates between people with HIV (PWH) and the general US population is needed to identify any disparities by HIV status. METHODS: We compared 236 PWH in clinical care diagnosed with cancer from 1997 to 2014 to a sample from NCI’s Surveillance, Epidemiology and End Results (SEER) Program, presumed to be HIV negative. We performed G-computation using random forest methods to estimate stage and treatment percent differences (PD) by HIV. We conducted sensitivity analyses among non-AIDS-defining cancers (NADC), by sex and by CD4 ≤ 200 or > 200 cells/mm(3). RESULTS: PWH were less likely to be diagnosed at localized stage (PD = − 16%; 95% CI − 21, − 11) and more likely to be diagnosed at regional stage (PD = 14%; 95% CI 8, 19) than those in SEER. Cancer treatment rates were 13% lower among PWH as compared to SEER (95% CI − 18, − 8). The difference in percent receiving cancer treatment was more pronounced for those with lower CD4 at cancer diagnosis (PD −15%; 95% CI − 27, − 6). Lower treatment rates were observed among NADC, males, and women with CD4 ≤ 200. CONCLUSION: Cancer care for PWH could be improved by diagnosis at earlier stages and increasing rates of cancer treatment.

Background Excess adiposity, which affects 69% of US adults, increases coronary heart disease ( CHD ) risk in an association that manifests below conventional obesity cut points. The population‐level impact on CHD risk that is attainable through modest adiposity reductions in populations is not well characterized. We estimated the effect of hypothetical reductions in both body mass index ( BMI ) and waist circumference ( WC ) on CHD incidence. Methods and Results The study population included 13 610 ARIC (Atherosclerosis Risk in Communities) participants. Our hypothetical reduction in BMI or WC was applied relative to the temporal trend, with no hypothetical reduction among those with BMI >24 or WC >88 cm, respectively. This threshold for hypothetical reduction is near the clinical guidelines for excess adiposity. CHD risk differences compared the hypothetical reduction with no reduction. Sensitivity analysis was conducted to estimate the effect of applying the hypothetical BMI reduction at the established overweight cut point of 25. Cumulative 12‐year CHD incidence with no intervention was 6.3% (95% CI, 5.9–6.8%). Risk differences following the hypothetical BMI and WC reductions were −0.6% (95% CI, −1.0% to −0.1%) and −1.0% (95% CI, −1.4% to −0.5%), respectively. These results were robust for the sensitivity analyses. Consequently, we estimated that this hypothetical reduction of 5% in BMI and WC, respectively, could have prevented 9% and 16%, respectively, of the CHD events occurring in this study population over 12 years, after adjustment for established CHD risk factors. Conclusions Meaningful CHD risk reductions could derive from modest reductions in adiposity attainable through lifestyle modification.

INTRODUCTION: Few studies examine how depression and substance use interact to affect HIV control. METHODS: In 14,380 persons with HIV (PWH), we used logistic regression and generalized estimating equations to evaluate how symptoms of depression interact with alcohol, cocaine, opioid, and methamphetamine use to affect subsequent retention in care, maintaining an active prescription for ART, and consistent virologic suppression. RESULTS: Among PWH with no or mild depressive symptoms, heavy alcohol use had no association with virologic suppression (OR 1.00 [0.95–1.06]); among those with moderate or severe symptoms, it was associated with reduced viral suppression (OR 0.80 [0.74–0.87]). We found no interactions with heavy alcohol use on retention in care or maintaining ART prescription or with other substances for any outcome. DISCUSSION: These results highlight the importance of treating moderate or severe depression in PWH, especially with comorbid heavy alcohol use, and support multifaceted interventions targeting alcohol use and depression.

Background The United States National HIV/AIDS Strategy established goals to reduce disparities in retention in human immunodeficiency virus (HIV) care, antiretroviral therapy (ART) use, and viral suppression. The impact of sex, age, and sexual HIV acquisition risk (ie, heterosexual vs same-sex contact) on the magnitude of HIV-related racial/ethnic disparities is not well understood. Methods We estimated age-stratified racial/ethnic differences in the 5-year restricted mean percentage of person-time spent in care, on ART, and virally suppressed among 19 521 women (21.4%), men who have sex with men (MSM; 59.0%), and men who have sex with women (MSW; 19.6%) entering HIV care in the North American AIDS Cohort Collaboration on Research and Design between 2004 and 2014. Results Among women aged 18-29 years, whites spent 12.0% (95% confidence interval [CI], 1.1%-20.2%), 9.2% (95% CI, .4%-20.4%), and 13.5% (95% CI, 2.7%-22.5%) less person-time in care, on ART, and virally suppressed, respectively, than Hispanics. Black MSM aged ≥50 years spent 6.3% (95% CI, 1.3%-11.7%), 11.0% (95% CI, 4.6%-18.1%), and 9.7% (95% CI, 3.6%-16.8%) less person-time in these stages, respectively, than white MSM ≥50 years of age. Among MSM aged 40-49 years, blacks spent 9.8% (95% CI, 2.4%-16.5%) and 11.9% (95% CI, 3.8%-19.3%) less person-time on ART and virally suppressed, respectively, than whites. Conclusions Racial/ethnic differences in HIV care persist in specific populations defined by sex, age, and sexual HIV acquisition risk. Clinical and public health interventions that jointly target these demographic factors are needed.

Background Alcohol misuse is associated with increased human immunodeficiency virus sexual risk behaviors by women. Drug use, intimate partner violence (IPV), and depressive symptoms frequently co-occur, are well-recognized alcohol misuse comorbidities, and may interact to increase risk behaviors. Using a syndemic framework we examined associations between drug use, IPV, and depressive symptoms and sexual risk behaviors by 400 women with alcohol misuse attending an urban sexually transmitted infections clinic. Methods Participants completed computer-assisted interviews querying drug use, IPV, and depressive symptoms and sexual risk behavior outcomes—unprotected sex under the influence of alcohol, sex for drugs/money, and number of lifetime sexual partners. We used multivariable analysis to estimate prevalence ratios (PR) for independent and joint associations between drug use, IPV, and depressive symptoms and our outcomes. To investigate synergy between risk factors we calculated the relative excess prevalence owing to interaction for all variable combinations. Results In multivariable analysis, drug use, IPV, and depressive symptoms alone and in combination were associated with higher prevalence/count of risk behaviors compared with women with alcohol misuse alone. The greatest prevalence/count occurred when all three were present (unprotected sex under the influence of alcohol [PR, 2.6; 95% confidence interval, 1.3–4.9]), sex for money or drugs [PR, 2.6; 95% confidence interval, 1.7–4.2], and number of lifetime partners [PR, 3.2; 95% confidence interval, 1.9–5.2]). Drug use, IPV, and depressive symptoms did not interact synergistically to increase sexual risk behavior prevalence. Conclusions A higher prevalence of sexual risk behaviors by women with alcohol misuse combined with drug use, IPV, and depressive symptoms supports the need for alcohol interventions addressing these additional comorbidities.

Accurate, routine measurement of recent illicit substance use is challenging. The Johns Hopkins Human Immunodeficiency Virus Clinical Cohort (Baltimore, Maryland) collects 2 imperfect but routine measurements of recent substance use: medical record review and self-interview. We used Bayesian latent class modeling to estimate sensitivity and specificity of each measurement as well as prevalence of substance use among 2,064 patients engaged in care during 2007-2015. Sensitivity of medical record review was higher than sensitivity of self-interview for cocaine and heroin use; posterior estimates ranged from 44% to 76% for cocaine use and from 39% to 67% for heroin use, depending on model assumptions and priors. In contrast, sensitivity of self-interview was higher than sensitivity of medical record review for any alcohol use, hazardous alcohol use, and cigarette smoking. Posterior estimates of sensitivity of self-interview were generally above 80%, 85%, and 87% for each substance, respectively. Specificity was high for all measurements. From one model, we estimated prevalence of substance use in the cohort to be 12.5% for cocaine, 9.3% for heroin, 48.5% for alcohol, 21.4% for hazardous alcohol, and 55.4% for cigarettes. Prevalence estimates from other models were generally comparable. Measurement error of substance use is nontrivial and should be accounted for in subsequent analyses.

Persons with HIV who have entered care but have viral load > 1500 copies/mL may be the source of the majority of new HIV infections in the United States. We followed patients engaged in continuity care in the Johns Hopkins HIV Clinical Cohort between January 2010 and August 2015. We estimated person-time spent with viral load > 1500 copies/mL while in care after antiretroviral therapy (ART) initiation, while in care, and while alive. Person-time was classified according to the most recent viral load measurement. Of 11,283.1 person-years in care on after ART initiation, 11,954.7 person-years in care and 13,990.0 total person-years of follow-up spent alive, 12.5, 14.8%, and between 12.6 and 27.2%, respectively (depending on assumptions about the viral load of persons lost to clinic) were spent with viral load > 1500 copies/mL. Patients with lower baseline CD4 cell count, younger age, black race, history of injection drug use, or baseline hazardous alcohol use spent more time with viral load > 1500 copies/mL after ART initiation.

Highlights • Unhealthy alcohol use is prevalent among women attending STI clinics. • We tested whether CBI or CBI-IVR-TM, reduced alcohol use among women in this setting. • Neither CBI nor CBI-IVR-TM reduced alcohol use more than control. • 2/3 of women had an alcohol use disorder, 65% substance use, 28% depressive symptoms. • CBI is insufficient for alcohol reduction in this high severity, high comorbidity setting., Objective We sought to determine if a computer delivered brief alcohol intervention (CBI) with or without interactive voice response counseling and text messages (CBI-IVR-TM), reduced alcohol use and sexual risk behaviors compared to attention control. Methods We conducted a 3-arm RCT among women (n = 439) recruited from Baltimore City Sexually Transmitted Infection (STI) Clinics. Eligibility included: 1) consumption of >7 drinks per week or 2) ≥2 episodes of heavy episodic drinking or ≥2 episodes of sex under the influence of alcohol in the prior three months. Research assessments conducted at baseline, 3, 6 and 12 months included a 30-day Timeline Followback querying daily alcohol use, drug use, and sexual activity. We used the MINI International Neuropsychiatric Interview-DSM-IV to ascertain drinking severity. Primary alcohol outcomes included: drinking days, heavy drinking days, drinks per drinking day. Secondary sexual risk outcomes included number of sexual partners, days of condomless sex, and days of condomless sex under the influence of drugs and alcohol. Results Median age was 31 (IQR 25–44 years), 88% were African American, 65% reported current recreational drug use, and 26% endorsed depressive symptoms. On the MINI 66% met criteria for alcohol use disorder (49% alcohol dependence, 18% abuse). At follow-up, all three groups reduced drinking days, heavy drinking days, drinks per drinking day and drinks per week with no significant differences between study arms. There was no difference in sexual risk outcomes among the groups. Conclusions Among women attending an urban STI clinic single session CBI with or without IVR and text message boosters was insufficient to reduce unhealthy alcohol use or sexual risk behaviors beyond control. The high severity of alcohol use and the prevalence of mental health symptoms and other substance use comorbidity underscores the importance of developing programs that address not only alcohol use but other determinants of STI risk among women.

While marijuana use is prevalent among persons with HIV (PWH), few studies have examined the relationship between marijuana use and HIV treatment outcomes independent of alcohol and other drug use.We conducted a prospective cohort study to examine the relationships between frequency of marijuana use and antiretroviral therapy (ART) adherence and viral suppression in patients enrolled in the Johns Hopkins HIV Clinical Cohort between September 2013 through November 2015 (N=1377). We categorized marijuana use as no use, none in the last 3months, monthly use or less, weekly/daily. Our outcomes of interest were use of ART, ≥90 ART adherence, and viral suppression (HIV1-RNA200 copies). We conducted multivariable analyses to examine associations between the frequency of marijuana use and our treatment outcomes, using generalized estimating equations to account for repeated measures. Other independent variables of interest included alcohol use, other drug use, and depressive symptoms. Analyses were adjusted for age, race, sex and HIV acquisition risk factor.In multivariable analyses we found no statistically significant association between frequency of marijuana use and our treatment outcomes. Alcohol use, other drug use and depressive symptoms were associated with lower odds of ART adherence and viral suppression.In this sample of PWH in care, frequency of marijuana use independent of other substance use does not appear to be associated with negative HIV treatment outcomes. Our results indicate that unlike alcohol, other substances and depression, marijuana use may not be a barrier to the effective treatment of HIV.

Depression affects up to 30% of human immunodeficiency virus (HIV)-infected individuals. We estimated joint effects of antiretroviral therapy (ART) initiation and depressive symptoms on time to death using a joint marginal structural model and data from a cohort of HIV-infected women from the Women's Interagency HIV Study (conducted in the United States) from 1998–2011. Among 848 women contributing 6,721 years of follow-up, 194 participants died during follow-up, resulting in a crude mortality rate of 2.9 per 100 women-years. Cumulative mortality curves indicated greatest mortality for women who reported depressive symptoms and had not initiated ART. The hazard ratio for depressive symptoms was 3.38 (95% confidence interval (CI): 2.15, 5.33) and for ART was 0.47 (95% CI: 0.31, 0.70). Using a reference category of women without depressive symptoms who had initiated ART, the hazard ratio for women with depressive symptoms who had initiated ART was 3.60 (95% CI: 2.02, 6.43). For women without depressive symptoms who had not started ART, the hazard ratio was 2.36 (95% CI: 1.16, 4.81). Among women reporting depressive symptoms who had not started ART, the hazard ratio was 7.47 (95% CI: 3.91, 14.3). We found a protective effect of ART initiation on mortality, as well as a harmful effect of depressive symptoms, in a cohort of HIV-infected women.

Background:Epidemiologic studies that aim to estimate a causal effect of an exposure on a particular event of interest may be complicated by the existence of competing events that preclude the occurrence of the primary event. Recently, many articles have been published in the epidemiologic literatur

Background Black and Latina transgender women (TW) experience a disparate burden of HIV and related comorbidities, including poor mental health and cardiovascular disease (CVD) risks. Pervasive multilevel stigma and discrimination operate as psychosocial stressors for TW living with HIV and shape health disparities for this population. Gender-affirming hormone therapy (GAHT) is commonly used by TW to facilitate alignment of the body with gender identity; in the context of stigma, GAHT may both improve mental health and increase CVD risks. Objective This study aims to quantify the longitudinal relationship between stigma and chronic stress among black and Latina TW living with HIV. Secondary objectives include identifying pathways linking chronic stress to HIV comorbidities and exploring chronic stress as a mediator in the pathway linking stigma and GAHT to CVD comorbidities. Methods This US-based mixed methods longitudinal study will enroll a prospective cohort of 200 black and Latina TW living with HIV, collecting quantitative survey data, qualitative interviews, and biomarkers of chronic stress. Interviewer-administered surveys will include validated psychosocial measures of self-reported stigma and discrimination, perceived stress, CVD risk factors, mental health, access to gender-affirming care, coping, and social support. Medical record abstraction will collect data on GAHT use, CD4 count, HIV viral load, antiretroviral therapy, treatment, and comorbid conditions. Clinical measures will include physiological biomarkers as well as salivary and blood-based biomarkers of chronic stress. Survey data will be collected every 6 months (baseline, and 6, 12, 18, and 24 months), and biospecimens will be collected at baseline and at 12 and 24 months. A purposive subsample (stratified by use of GAHT and presence of depressive symptoms) of 20 to 30 TW living with HIV will be invited to participate in in-depth interviews at 6 and 18 months to explore experiences of intersectional stigma, chronic stress, and the role of GAHT in their lives. Results This study was funded by the National Institute on Minority Health and Health Disparities in December 2018. The study community advisory board and scientific advisors provided critical input on study design. Recruitment began in October 2019 (n=29 participants as of submission) and data collection will continue through 2022, with publication of baseline results anticipated summer 2021. Conclusions This study will focus on black and Latina TW living with HIV, an understudied health disparities population, advance both stigma and intersectionality research, and move chronic stress physiology research toward a more nuanced understanding of sex and gender. The comprehensive methodology will support the exploration of the role of exogenous estrogen in the pathways between stress and HIV comorbidities, elucidating the role of GAHT in the stress-health relationship. Finally, this study will provide longitudinal evidence of the impact of stigma-related chronic stress on the lives of black and Latina TW living with HIV integrating qualitative and quantitative data with psychosocial, clinical, and biological measures. International Registered Report Identifier (IRRID) DERR1-10.2196/17076

A total of 236 people with HIV (PWH) with cancer diagnosed between 1997 and 2014 in the Johns Hopkins HIV Clinical Cohort (JHHCC) were compared with a sample from NCI's Surveillance, Epidemiology, and End Results (SEER) Program, presumed to be HIV negative. Using G-computation with random survival forest methods, we estimated 5-year restricted mean survival time (RMST) differences by HIV status. Sensitivity analyses were performed among non-AIDS defining cancers, males, females, and stratifying PWH by CD4 ≤ 200 or >200 cells/mm(3) at cancer diagnosis. PWH with CD4 ≤ 200 cells/mm(3) had decreased survival compared with those in SEER (−7 months; 95% CI = −13 to −2). Women with HIV and CD4 ≤ 200 cells/mm(3) at cancer diagnosis had lower survival than SEER women (−10 months; 95% CI = −18 to −2). In the total population, there was no significant difference in 5-year RMST; however, women with HIV and low CD4 had higher mortality despite accounting for stage at diagnosis and first course of cancer treatment.

The prevalence of tobacco smoking among people with HIV (PWH) ranges from 40% to 70%. Additionally, tobacco smoking is higher among low-income individuals, yet few studies have examined tobacco smoking in low socioeconomic status PWH. Using data from a cohort of PWH receiving care in an urban HIV clinic, we characterized factors associated with current and former smoking and with initiation/re-initiation and cessation of tobacco use. Among a study sample of 1,607 PWH, the prevalence of current smoking was 46.6% among men and 46.0% among women. Current smoking in men and women was associated with Medicaid insurance status, substance use, and panic symptoms. In women, but not men, hazardous alcohol use decreased the likelihood of quitting smoking and increased the risk of initiation/re-initiation. Smoking interventions for low-income, urban PWH may need to be tailored to address mental health and substance use comorbidities.

Among people with HIV, alcohol use is associated with increased prevalence of sexual transmission behaviors. We examined associations between alcohol use in the prior year and sexual behaviors approximately six months later among 1857 women, 6752 men who have sex with men (MSM) and 2685 men who have sex with women (MSW). Any alcohol use was associated with increased risk of unsafe vaginal sex among women; anal sex and =>2 anal sex partners among MSM; and anal sex, =>2 anal or vaginal sex partners, and unsafe vaginal sex among MSW. In particular, among women >7 alcoholic drinks/week and among MSW =>5 alcoholic drinks/drinking day increased the likelihood of certain subsequent sexual behaviors. For all groups, especially women, the risk of sex under the influence of drugs/alcohol markedly increased with increases in quantity and frequency of alcohol consumption. These different patterns of drinking and sexual behaviors indicate the importance of tailored counseling messages to women, MSM and MSW.

Ancillary service needs likely influence time to diagnosis and presentation for HIV care. The effect of both met and unmet needs on late presentation to HIV care is not well understood. We used baseline data from 348 people with HIV (PWH) with no prior HIV care who enrolled in iENGAGE (a randomized controlled trial (RCT) of an intervention to support retention in care) at one of four HIV clinics in the US. A standardized baseline questionnaire collected information on ancillary service needs, and whether each need was presently unmet. We examined covariates known to be associated with disease stage at presentation to care and their association with needs. We subsequently assessed the relationship of needs with CD4 accounting for those other covariates by estimating prevalence ratios (PR) using inverse probability weights. Most patients enrolling in the RCT were male (79%) and the majority were Black (62%); median age was 34 years. Prevalence of any reported individual need was 69%. One-third of the sample had a baseline CD4 cell count

Describe all-cause mortality associated with history of injection drug use (IDU) after a validated diagnosis of four noncommunicable disease (NCD) diagnoses: end-stage liver disease (ESLD); end-stage renal disease (ESRD); cancer; or myocardial infarction (MI) or stroke.We followed four cohorts of persons in continuity HIV care in the Johns Hopkins HIV Clinic with a validated diagnosis of ESLD (n = 67), ESRD (n = 187), cancer (n = 424), and MI or stroke (n = 213) from 1996 through approximately 2014.Crude and adjusted Cox proportional hazards models to estimate hazard ratios for death after a validated diagnosis of one of four NCD diagnoses associated with history of IDU as an HIV acquisition risk factor.History of IDU was not associated with death after ESRD (adjusted hazard ratio 0.98, 95% confidence interval (CI) 0.57-1.68). Associations between history of IDU and death after ESLD and MI or stroke were weak, imprecise and not statistically significant (hazard ratio 1.17, 95% CI 0.63-2.19; hazard ratio 1.21, 95% CI 0.80-1.83). History of IDU was not associated with death after cancer in the first 6 months, but subsequently, the adjusted hazard ratio was 2.03 (95% CI 1.26-3.27).Persons with a history of injection drug use and non-IDU had strikingly similar risk and hazard of mortality after several major NCD diagnoses. Mortality after cancer diagnosis in this cohort was higher for persons with a history of IDU than those without; this may be because of being diagnosed with a different mix of specific sites and stages of cancers.

Compared to HIV-infected persons who do not inject drugs (non-IDU), persons who inject drugs (PWID) experience disparities in linking to medical care, initiating antiretroviral therapy (ART) and achieving viral suppression. There has been little attention to changes in these disparities over time. We estimated the proportion of PWID and non-IDU retained in care, on ART, and virally suppressed each year from 2001–2012 in the Johns Hopkins HIV Clinical Cohort (JHHCC). We defined active clinic patients as those who had ≥1 clinical visit, CD4 cell count, or viral load between July 1 of the prior year, and June 30 of the analysis year. Within a calendar year, retention was defined as ≥2 clinical visits or HIV-related laboratory measurements >90 days; ART use was defined as ≥1 ART prescription active ≥30 days; and viral suppression was defined as ≥1 HIV viral load

Risk is an important parameter to describe the occurrence of health outcomes over time. However, many outcomes of interest in healthcare settings, such as disease incidence, treatment initiation, and cause-specific mortality, may be precluded from occurring by other events, often referred to as competing events. Here, we review straightforward approaches to estimate risk in the presence of competing events. We illustrate the application of these methods using timely examples in pharmacoepidemiologic research and compare results to those obtained using analytic simplifications commonly used to handle competing events. These examples demonstrate how the analytic methods used to account for competing events affect the interpretation of results from pharmacoepidemiologic studies.

Traditional epidemiologic approaches allow us to compare counterfactual outcomes under 2 exposure distributions, usually 100% exposed and 100% unexposed. However, to estimate the population health effect of a proposed intervention, one may wish to compare factual outcomes under the observed exposure distribution to counterfactual outcomes under the exposure distribution produced by an intervention. Here, we used inverse probability weights to compare the 5-year mortality risk under observed antiretroviral therapy treatment plans to the 5-year mortality risk that would had been observed under an intervention in which all patients initiated therapy immediately upon entry into care among patients positive for human immunodeficiency virus in the US Centers for AIDS Research Network of Integrated Clinical Systems multisite cohort study between 1998 and 2013. Therapy-naïve patients (n = 14,700) were followed from entry into care until death, loss to follow-up, or censoring at 5 years or on December 31, 2013. The 5-year cumulative incidence of mortality was 11.65% under observed treatment plans and 10.10% under the intervention, yielding a risk difference of -1.57% (95% confidence interval: -3.08, -0.06). Comparing outcomes under the intervention with outcomes under observed treatment plans provides meaningful information about the potential consequences of new US guidelines to treat all patients with human immunodeficiency virus regardless of CD4 cell count under actual clinical conditions.

Author(s): Gosiker, Bennett J; Lesko, Catherine R; Rich, Ashleigh J; Crane, Heidi M; Kitahata, Mari M; Reisner, Sari L; Mayer, Kenneth H; Fredericksen, Rob J; Chander, Geetanjali; Mathews, William C; Poteat, Tonia C | Abstract: BackgroundTransgender women (TW) are disproportionately affected by both HIV and cardiovascular disease (CVD).ObjectivesWe aim to quantify prevalence of elevated predicted CVD risk for TW compared to cisgender women (CW) and cisgender men (CM) in HIV care and describe the impact of multiple operationalizations of CVD risk score calculations for TW.DesignWe conducted a cross-sectional analysis of patients engaged in HIV care between October 2014 and February 2018.SettingThe Centers for AIDS Research Network of Integrated Clinical Systems, a collaboration of 8 HIV clinical sites in the United States contributed data for this analysis.Patients221 TW, 2983 CW, and 13467 CM.MeasurementsThe measure of interest is prevalence of elevated 10-year cardiovascular disease risk based on ACC/AHA Pooled Cohort Risk Assessment equations (PCE) and the Framingham Risk Score (FRS), calculated for TW by: birth-assigned sex (male); history of exogenous sex hormone use (female/male); and current gender (female).ResultsUsing birth-assigned sex, the adjusted prevalence ratio (aPR) was 2.52 (95% CI: 1.08,5.86) and 2.58 (95% CI: 1.71,3.89) comparing TW to CW, by PCE and FRS, respectively. It was 1.25 (95% CI: 0.54,2.87) and 1.25 (95% CI: 0.84,1.86) comparing TW to CM, by PCE and FRS, respectively. If TW were classified according to current gender versus birth-assigned sex, their predicted CVD risk scores were lower.LimitationsPCE and FRS have not been validated in TW with HIV. Few adjudicated CVD events in the data set precluded analyses based on clinical outcomes.ConclusionsAfter adjustment for demographics and history of HIV care, prevalence of elevated CVD risk in TW was similar to CM and equal to or higher than in CW, depending operationalization of the sex variable. Future studies with CVD outcomes are needed to help clinicians accurately estimate CVD risk among TW with HIV.

Importance Immunologic decline associated with cancer treatment in people with HIV is not well characterized. Quantifying excess mortality associated with cancer treatment–related immunosuppression may help inform cancer treatment guidelines for persons with HIV. Objective To estimate the association between cancer treatment and CD4 count and HIV RNA level in persons with HIV and between posttreatment CD4 count and HIV RNA trajectories and all-cause mortality. Design, Setting, and Participants This observational cohort study included 196 adults with HIV who had an incident first cancer and available cancer treatment data while in the care of The Johns Hopkins HIV Clinic from January 1, 1997, through March 1, 2016. The study hypothesized that chemotherapy and/or radiotherapy in people with HIV would increase HIV RNA levels owing to treatment tolerability issues and would be associated with a larger initial decline in CD4 count and slower CD4 recovery compared with surgery or other treatment. An additional hypothesis was that these CD4 count declines would be associated with higher mortality independent of baseline CD4 count, antiretroviral therapy use, and risk due to the underlying cancer. Data were analyzed from December 1, 2017, through April 1, 2018. Exposures Initial cancer treatment category (chemotherapy and/or radiotherapy vs surgery or other treatment). Main Outcomes and Measures Post–cancer treatment longitudinal CD4 count, longitudinal HIV RNA level, and all-cause mortality. Results Among the 196 participants (135 [68.9%] male; median age, 50 [interquartile range, 43-55] years), chemotherapy and/or radiotherapy decreased initial CD4 count by 203 cells/μL (95% CI, 92-306 cells/μL) among those with a baseline CD4 count of greater than 500 cells/μL. The decline for those with a baseline CD4 count of no greater than 350 cells/μL was 45 cells/μL (interaction estimate, 158 cells/μL; 95% CI, 31-276 cells/μL). Chemotherapy and/or radiotherapy had no detrimental association with HIV RNA levels. After initial cancer treatment, every 100 cells/μL decrease in CD4 count resulted in a 27% increase in mortality (hazard ratio, 1.27; 95% CI, 1.08-1.53), adjusting for HIV RNA level. No significant increase in mortality was associated with a unit increase in log10HIV RNA after adjusting for CD4 count (hazard ratio, 1.24; 95% CI, 0.94-1.65). Conclusions and Relevance In this study, chemotherapy and/or radiotherapy was associated with significantly reduced initial CD4 count in adults with HIV compared with surgery or other treatment. Lower CD4 count after cancer treatment was associated with an increased hazard of mortality. Further research is necessary on the immunosuppressive effects of cancer treatment in adults with HIV and whether health care professionals must consider the balance of cancer treatment efficacy against the potential cost of further immunosuppression. Monitoring of immune status may also be helpful given the decrease in CD4 count after treatment and the already immunocompromised state of patients with HIV.

Among persons with human immunodeficiency virus (HIV) infection, illegal drug use and hazardous alcohol use are hypothesized to be strong risk factors for failure to achieve or maintain a suppressed HIV viral load, but accurate quantification of this association is difficult because of challenges involved in measuring substance use as part of routine clinical care. We estimated the associations of recent cocaine use, opioid/heroin use, and hazardous alcohol use with unsuppressed viral load among 1,554 persons receiving care at the John G. Bartlett Specialty Practice (Baltimore, Maryland) between 2013 and 2017. We accounted for measurement error in substance use using Bayesian models and prior estimates of the sensitivity and specificity of 2 imperfect measures of substance use derived from a previous analysis in this cohort. The prevalence difference for unsuppressed viral load associated with recent cocaine use was 11.3% (95% credible interval (CrI): 6.4, 17.0); that associated with recent opioid/heroin use was 13.2% (95% CrI: 6.6, 20.7); and that associated with recent hazardous alcohol use was 8.5% (95% CrI: 3.2, 14.4). Failure to account for measurement error resulted in clinically meaningful underestimates of the prevalence difference. Time-varying substance use is prevalent and difficult to measure in routine care; here we demonstrate a method that improves the utility of imperfect data by accounting for measurement error.

Background Restricted mean survival time (RMST) is an underutilized estimand in time-to-event analyses. Herein, we highlight its strengths by comparing time to (1) all-cause mortality and (2) initiation of antiretroviral therapy (ART) for HIV-infected persons who inject drugs (PWID) and persons who do not inject drugs. Methods RMST to death was determined by integrating the Kaplan-Meier survival curve to 5 years of follow-up. To account for the competing risks of death and loss-to-clinic when estimating time to ART, we calculated RMST to ART initiation by estimating the area between the survival curve for ART initiation and the cumulative incidence curve for death or loss-to-clinic. We standardized all curves using inverse probability of exposure weights. Results We followed 3044 HIV-positive, ART-naive persons from enrollment into the Johns Hopkins HIV Clinical Cohort from 1996 to 2014. PWID had a − 0.19 year (95% confidence interval (CI): − 0.29, − 0.10) difference in survival over 5 years of follow-up compared to persons who did not inject drugs. There was no difference between the two groups in time not on ART while alive and in clinic (RMST difference = 0.08, 95% CI: -0.10, 0.36). Conclusions PWID have similar expected time to ART initiation after properly accounting for their greater risk of death and loss-to-clinic. Electronic supplementary material The online version of this article (10.1186/s12874-018-0484-z) contains supplementary material, which is available to authorized users.

The HIV care continuum is a critical framework for situational awareness of the HIV epidemic; yet challenges to accurate enumeration of continuum components hamper continuum estimation in practice. We describe local surveillance-based estimation of the HIV continuum in the United States, reviewing common practices as recommended by the Centers for Disease Control and Prevention. Furthermore, we review some challenges and biases likely to threaten existing continuum estimates. Current estimates rely heavily on the use of CD4 cell count and HIV viral load laboratory results reported to surveillance programs as a proxy for receipt of HIV-related outpatient care. As such, continuum estimates are susceptible to bias because of incomplete laboratory reporting and imperfect sensitivity and specificity of laboratory tests as a proxy for routine HIV care. Migration of HIV-infected persons between jurisdictions also threatens the validity of continuum estimates. Data triangulation may improve but not fully alleviate biases.

The objective of this randomized trial was to compare breastfeeding among women who received a levonorgestrel-releasing intrauterine system within 6–48 h (early) or 4–6 weeks (standard) after an uncomplicated vaginal birth. Analysis groups of 86 women in each arm were needed to demonstrate a 20% difference in any breastfeeding. Thirty-five women were randomized to the early ( N =17) and standard ( N =18) arms. The combination of unsuccessful placement (2/17; 12%), expulsions (7/17; 41%) and removals (3/17; 18%) reached 71% (12/17) in the early arm, so the study was stopped. In our small study cohort, levonorgestrel-releasing intrauterine system insertion between 6 and 48h after vaginal birth was associated with a high rate of expulsion or removal soon after insertion.

The HIV care continuum has gained significant traction as a useful framework among both public health practitioners and academic researchers. The continuum estimates the proportion of HIV-infected persons who are HIV diagnosed, linked to and retained in care, initiated on antiretroviral therapy, and virally suppressed. Public health practitioners are increasingly being called upon (and required) to estimate and improve the HIV care continuum in their jurisdiction (e.g., state, dependent area, and metropolitan statistical area). Public health estimates of the HIV care continuum typically rely on CD4 counts and viral loads reported to HIV surveillance. In this issue of Sexually Transmitted Diseases, Toren et al. use surveillance data to show that the time between HIV diagnosis and viral suppression for persons diagnosed as having HIV in Seattle & King County decreased dramatically from 2007 to 2013. We welcome the contribution by Toren et al. as a valuable and timely contribution to the literature on the effects of rapidly changing treatment paradigms on improvements in the HIV care continuum. Being population-based, public health surveillance data offer a unique opportunity to obtain unbiased estimates of the HIV care continuum. Estimation of the HIV care continuum is inherently limited in clinical cohorts. Namely, clinical cohorts represent a nonrandom subset of all HIV-diagnosed persons who (1) ever entered care and (2) remained in care at the clinic where the cohort is based. Because surveillance data are population-based, the recent work by Toren et al. has the advantage of being able to include all persons diagnosed as having HIV in Seattle & King County, including persons who never enter care and never achieve viral suppression. The inclusion of persons diagnosed as having HIV avoids bias inherent in clinic-based analyses: (1) of absolute time toviral suppression if personswho never enter care and thus never suppress are excluded from the risk set, (2) of characteristics associated with prompt viral suppression if HIV-infected persons who enter care differ from those who do not enter care, and (3) of changing time to viral suppression over calendar time if the characteristics of HIV-infected persons who entered care varied over time. Most clinics do not have the resources for extensive patient tracing if patients fail to return for follow-up. Patients may leave a clinic because they move out of the area, switch clinical providers within the same area, or fall out of clinical care; this information is not generally recorded. In one clinical cohort, loss to clinic was substantial (5-year risk, 46%), yet mortality among persons lost to clinic was similar to mortality among persons retained in care, suggesting that some of those who were lost to clinic likely entered care elsewhere and loss to clinic may overestimate loss to care. Because public health surveillance data are not clinic based, they (hypothetically) capture laboratory measures for HIV-infected patients, regardless of the provider who ordered the laboratories, and therefore follow patients if they change clinics within the same area. (Rules for laboratory reporting and levels of compliance with reporting rules vary across jurisdictions.) However, public health surveillance data still cannot typically distinguish between persons who move out of jurisdiction and persons who are lost to care. Seattle & King County is one of very few public health agencies that have gathered additional information to distinguish out-migration from loss to care so that emigrants can be censored. Indeed, Seattle & King County is also one of a minority of public health jurisdictions that have been collecting laboratory surveillance data consistently enough to be able to estimate changes in time to viral suppression. Name-based reporting of HIV diagnoses was not implemented in all 50 states until 2008, a full year after follow-up in the analysis by Toren et al. began. From 2011 to 2013, of 50 states and 6 dependent areas, only 19, 18, and 28 jurisdictions (respectively) had laboratory data that were estimated to be at least 95% complete. These observations serve to illustrate both how quickly HIV

BACKGROUND: The inflammatory effects of injection drug use may result in an impaired immune response to antiretroviral therapy (ART). We examined CD4 response to first ART regimen among individuals in routine HIV care, stratified by injection drug use-related HIV acquisition. SETTING: Cohort study including patients who initiated ART between 2000–2015 in the Johns Hopkins HIV Clinic. METHODS: We followed individuals from ART initiation until death, loss to follow-up, loss of viral load suppression (350). RESULTS: Of 1,244 patients initiating ART, 30.4% were IDU. Absolute CD4 cell difference at the 50(th) percentile comparing IDU to non-IDU was −25 cells (95% CI: −63, 35), −66 cells (95% CI: −141, 16), and −91 cells (95% CI: −190, −5) at 2, 4, and 6 years after ART initiation, respectively. Results were similar (non-IDU with slightly higher CD4 count, but not statistically significant differences) at other percentiles and stratified by baseline CD4. CONCLUSIONS: CD4 recovery following ART initiation was similar for IDU and non-IDU, conditional on consistent viral load suppression.

Purpose Among HIV-infected persons, antiretroviral therapy (ART) and depression are strongly associated with mortality. We estimated reductions in 5-year mortality in Women's Interagency HIV Study participants under plausible hypothetical increases in ART initiation and reductions in depression (CES-D score≥16). Methods We followed 885 ART-naive Women's Interagency HIV Study participants for 5 years from their first study visit after April 1998 to death or censoring. We used the parametric extended g-formula to estimate cumulative mortality under the natural course (NC) and alternative exposure distributions. Results Baseline prevalence of depression was 52% and 62% initiated ART by 5 years. Compared with mortality under NC (13.2%), immediate ART and elimination of 36% or 67% of depressive episodes were associated with risk differences (RDs) of −5.2% (95% CI: −7.7%, −2.6%) and −5.7 (95% CI: −8.7, −2.7). Compared with immediate ART and NC for depression, additionally eliminating 67% of the depressive episodes was associated with RD = −1.6 (95% CI: −3.9, 0.8). Compared with 5-year mortality under NC for ART and elimination of 67% of depression, also initiating ART immediately was associated with RD = -2.6 (95% CI: -5.0, -0.3). Conclusions Increasing ART initiation and reducing depression were associated with moderate reductions in 5-year mortality among HIV-infected women.

Excess adiposity, which affects 30% of the world’s population, is associated with risk of coronary heart disease (CHD), yet the potential reductions in CHD burden attainable through shifts in the population distributions of adiposity are unclear. Risk of CHD conveyed by excess adiposity is mostly mediated by the associated metabolic dysregulation, with manifestations such as hypertension and diabetes. Considering these metabolic pathways, we estimated the effect of hypothetical population reductions in general adiposity [body mass index (BMI)] or visceral adiposity [indexed by waist circumference (WC)], each consistent with lifestyle modification, on the risk of incident CHD in a US-based biracial population. The study population included 13,610 ARIC study participants aged 45-64 years, after excluding those with CHD (667) or chronic conditions associated with weight change (969) at baseline. Our hypothetical intervention reduced general adiposity (BMI) or waist circumference (WC) by 5% relative to the temporal trend observed under no intervention; the intervention was applied only among those with BMI > 24 kg/m2 (or WC>88 cm). For example, an individual who increased from a BMI of 25.2 to 27 over the study period under no intervention would increase from 24 to 25.7 following the intervention. Incident CHD was ascertained from 1987 to 2001. CHD risk differences were estimated comparing the intervention to no intervention. Over the follow-up time, 736 (BMI analysis) and 712 (WC analysis) incident CHD events occurred. For the BMI analysis, the median BMI (kg/m2) at the end of follow-up was 28.2 under no intervention and 25.6 under the hypothetical intervention. The cumulative 12-year incidence of CHD and 95% CI under no intervention was 6.3% (5.9, 6. 8%) and the risk difference following the hypothetical BMI change was -0.6% (-1.0, -0.1%). For the WC analysis, the median WC (cm) at the end of follow-up was 100.6 under no intervention and 98.3 under the hypothetical intervention. The cumulative 12-year incidence of CHD and 95% CI was 6.2% (5.8, 6. 7%) under no intervention and the risk difference following the hypothetical WC change was -1.0% (-1.4, -0.5%). Hence, 9% and 16% of CHD events occurring in this study population over 12 years could have been prevented by an annual 5% shift in BMI and WC, respectively. We estimated that meaningful reductions in CHD risk could result from modest reductions in adiposity that are consistent with what might be observed under public health efforts aimed at lifestyle modification. CHD risk reduction was larger under a hypothetical WC reduction compared to a BMI reduction, consistent with metabolic dysregulation associated with visceral adiposity. Public health messages and clinical recommendations that promote modification in WC, perhaps with reference to clothing size, would offer more concrete targets than similar messages for composite measures such as BMI.

To examine the association between perceived stress and subsequent alcohol use in women living with HIV.Women (n=338) receiving HIV care between April 2006 and July 2010 who enrolled in either a brief intervention for hazardous drinking or a cohort of non-hazardous drinkers completed a 90-day drinking and drug use history, and completed stress, depression and anxiety measures at 0, 6, and 12 months. We examined the association between perceived stress at months 0 or 6 and measures of quantity and frequency of alcohol use in months 3-6 and 9-12, respectively.The association between perceived stress and subsequent alcohol use depended on whether women were heavy or moderate drinkers at index visit. Among women reporting ≥7 drinks/week at index visit, high levels of perceived stress were associated with subsequent increased alcohol intake. However, among women reporting0 but7 drinks/week at index visit, high levels of perceived stress were associated with a subsequent reduction in drinking.Baseline drinking status moderates the relationship between perceived stress and subsequent alcohol use. Perceived stress is an important therapeutic target in women who are heavy drinkers.

Background. The clinical status of human immunodeficiency virus (HIV)–positive persons at the time of presentation to medical care has important individual- and population-level implications. Methods. We synthesized the literature on clinical status of adults newly presenting to care for HIV infection in developed countries to generate an estimate of the time trend for CD4 cell count at the initiation of HIV care. We systematically searched PubMed for studies published between January 2000 and November 2011 to identify those that reported CD4 cell count for patients newly presenting to HIV care according to standardized inclusion criteria. We abstracted the mean or median CD4 cell count or reconstructed the mean CD4 cell count from the presented data describing the number or proportion of patients in CD4 cell count categories. We estimated the change in CD4 cell count over time by modeling it as a weighted linear function of calendar year. Results. Based on a meta-regression of 197 point estimates encompassing CD4 cell count measurements from 169 007 patients in 44 studies, mean CD4 cell count at presentation increased minimally by 1.5 cells/μL per year (95% CI, −6.1 to 5.5 cells/μL per year), from 307 cells/μL in 1992 to 336 cells/μL in 2011. Conclusions. In developed countries, patients’ CD4 cell counts at first presentation to medical care have not increased meaningfully over the past 20 years. New and innovative strategies are imperative to identify persons earlier in the course of their infection and link them promptly with medical care.

Pulmonary disease remains a primary source of morbidity and mortality in persons living with HIV (PLWH), although the advent of potent combination antiretroviral therapy has resulted in a shift from predominantly infectious to noninfectious pulmonary complications. PLWH are at high risk for COPD, pulmonary hypertension, and lung cancer even in the era of combination antiretroviral therapy. The underlying mechanisms of this are incompletely understood, but recent research in both human and animal models suggests that oxidative stress, expression of matrix metalloproteinases, and genetic instability may result in lung damage, which predisposes PLWH to these conditions. Some of the factors that drive these processes include tobacco and other substance use, direct HIV infection and expression of specific HIV proteins, inflammation, and shifts in the microbiome toward pathogenic and opportunistic organisms. Further studies are needed to understand the relative importance of these factors to the development of lung disease in PLWH.

Heavy alcohol use has adverse effects in women with HIV. We examined the association between changes in alcohol use (measured with Timeline Followback) and changes in antiretroviral therapy adherence (medication possession ratio) and viral suppression (HIV RNA), measured over 6-month intervals. Among women who were (1) non-adherent or not virologically suppressed and (2) infrequent binge drinkers or non-heavy drinkers at baseline, increasing drinking was significantly associated with lower odds of subsequently improving adherence or viral suppression (OR of becoming adherent of 0.90 in infrequent binge drinkers; OR of becoming suppressed of 0.81 and 0.75 in infrequent binge drinkers and non-heavy drinkers, respectively). Our findings suggest that for these women, increasing drinking may be a barrier to achieving viral suppression. Addressing this barrier by integrating proactive alcohol counseling strategies into routine HIV care may be key to improving viral suppression rates among women retained in HIV care.

Objective Incidence of HIV-associated non-AIDS (HANA) related comorbidities is increasing in HIV-infected individuals. Our objective was to estimate the risk of HANA comorbidity associated with history of injection drug use (IDU) correctly accounting for higher death rates among people who inject drugs (PWID). Design We followed HIV-infected persons aged 25-59 years who enrolled in the Johns Hopkins HIV Clinical Cohort between 1995 and May 2014, from enrollment until HANA comorbidity diagnosis, death, age 60, or administrative censoring. Methods We compared cumulative incidence ('risk'), by age, of validated diagnoses of HANA comorbidities among HIV-infected PWID and non-IDU; specifically, we considered end-stage renal disease (ESRD), end-stage liver disease (ESLD), myocardial infarction, stroke, and non-AIDS-defining cancer. We used competing risk methods appropriate to account for death, standardized to the marginal distribution of baseline covariates, and adjusted for potential differential loss-to-clinic. Results Of 5490 patients included in this analysis, 37% reported IDU as an HIV transmission risk. By age 55 years, PWID had higher risk of ESLD [risk difference = 6.8, 95% confidence interval (CI): -1.9, 15.5] and ESRD (risk difference = 11.1, 95% CI: 1.2, 21.0) than did non-IDU. Risk of myocardial infarction and stroke were similar among PWID and non-IDU. Risk of non-AIDS-defining cancer was lower among PWID than among non-IDU (risk difference at 55 years: -4.9, 95% CI: -11.2, 1.3). Conclusion Not all HANA comorbidities occur with higher incidence in PWID compared with non-IDU. However, higher incidence of ESRD and ESLD among PWIDs highlights the importance of recognition and management of markers of these comorbidities in early stages among PWID.

OBJECTIVES We present a novel, patient-centric, longitudinal summary of patient progress through the HIV care continuum. Using this new approach, we compare person-time spent alive, in care, on antiretroviral therapy (ART), and virally suppressed among people who inject drugs (PWID) and those who do not (non-IDU). DESIGN Prospective clinical observational cohort study. METHODS We followed ART-naive patients with detectable HIV viral loads who enrolled in the Johns Hopkins HIV Clinical Cohort from enrollment until the occurrence of several care continuum-related milestones, including ART initiation and viral suppression, and until several care continuum-related failures, including loss to clinic and death. We added and subtracted cumulative incidence curves to estimate the proportion of the cohort in each of seven continuum stages across the 10 years following enrollment in clinical care. RESULTS PWID composed 32% of the study sample (n = 1443). Over 10 years following enrollment in care, PWID and non-IDU spent only 23 and 37%, respectively, of person-time in care, on ART, and virally suppressed. PWID lost 8.9 more months of life compared with non-IDU and spent an additional 5.0 months on ART but not virally suppressed, and an additional 5.5 months in care but not on ART. There were not meaningful improvements in the 5-year restricted mean person-time differences comparing PWID to non-IDU across enrollment cohorts (2000-2003, 2004-2007, 2008-2014). CONCLUSION Efforts to increase viral suppression among PWID should focus on increasing ART initiation and improving adherence to therapy.

Background Although antiretroviral therapy (ART) is known to be protective against HIV-related mortality, the expected magnitude of effect is unclear because existing estimates of the effect of ART may not directly generalize to recently HIV-diagnosed persons. Methods In this study, we estimated 5-year mortality risks for immediate versus no ART initiation among patients (n = 12,547) in the Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) using the complement of adjusted Kaplan-Meier survival functions. We subsequently standardized estimates to persons diagnosed with HIV in the USA between 2009 and 2011, who were enumerated using national surveillance data. Results The 5-year mortality, had all patients in the CNICS immediately initiated ART, was 10.6% [95% confidence interval (CI): 9.3%, 11.9%] compared with 28.3% (95% CI: 19.1%, 37.5%) had ART initiation been delayed at least 5 years. The 5-year mortality risk difference due to ART among patients in the CNICS was -17.7% (95% CI: -27.0%, -8.4%). Based on methods for generalizing an estimate from a study sample to a different target population, the expected risk difference due to ART initiation among recently HIV-diagnosed persons in the USA was -19.1% (95% CI: -30.5%, -7.8%). Conclusions Immediate ART initiation substantially lowers mortality among persons in the CNICS and this benefit is expected to be similar among persons recently diagnosed with HIV in the USA. We demonstrate a method by which concerns about generalizability can be addressed and evaluated quantitatively.

The impact of pharmacist-assisted management (PAM) of pharmacotherapy for patients with human immunodeficiency virus (HIV) infection was investigated.A retrospective cohort analysis was conducted to evaluate antiretroviral therapy (ART) outcomes in treatment-naive patients initiated on ART at an HIV clinic. Eligible patients enrolled in the clinic during the period 1999-2013 were classified into two groups: those referred to a clinic-based HIV pharmacist for initiation of ART (the PAM group) and those managed by a primary care provider (the control group). The primary study objective was the median time to viral suppression; secondary objectives included the durability of response to the first ART regimen. Relative hazards for the events of interest were estimated using a marginal structural Cox proportional hazards model and Kaplan-Meier curves, with inverse probability weights used to control for selection and confounding bias.Patients referred for PAM services (n = 819) typically had higher baseline viral loads and lower CD4+ cell counts than those in the control group (n = 436). The likelihood of viral suppression during the first two years after ART initiation was significantly higher in the PAM group versus the control group (hazard ratio, 1.37; 95% confidence interval, 1.18-1.59; p0.0001). The median durability of the first ART regimen was 100 months in the PAM group versus 44 months in the control group (p0.05).In treatment-naive patients, suppression of HIV viral load occurred earlier when pharmacists assisted with initiating ART than when ART was initiated without that assistance.