Causal Effects of Stochastic PrEP Interventions on HIV Incidence Among Men Who Have Sex With Men.

Antiretroviral preexposure prophylaxis (PrEP) is highly effective in preventing human immunodeficiency virus (HIV) infection, but uptake has been limited and inequitable. Although interventions to increase PrEP uptake are being evaluated in clinical trials among men who have sex with men (MSM), those trials cannot evaluate effects on HIV incidence. Estimates from observational studies of the causal effects of PrEP-uptake interventions on HIV incidence can inform decisions about intervention scale-up. We used longitudinal electronic health record data from HIV-negative MSM accessing care at Fenway Health, a community health center in Boston, Massachusetts, from January 2012 through February 2018, with 2 years of follow-up. We considered stochastic interventions that increased the chance of initiating PrEP in several high-priority subgroups. We estimated the effects of these interventions on population-level HIV incidence using a novel inverse-probability weighted estimator of the generalized g-formula, adjusting for baseline and time-varying confounders. Our results suggest that even modest increases in PrEP initiation in high-priority subgroups of MSM could meaningfully reduce HIV incidence in the overall population of MSM. Interventions tailored to Black and Latino MSM should be prioritized to maximize equity and impact.

Socioeconomic Status and CD4 Count Among People with HIV Who Inject Drugs in St. Petersburg, Russia.

Lack of access to resources is a "fundamental cause" of poor HIV outcomes across the care cascade globally and may have the greatest impact on groups with co-existing marginalized identities. In a sample of people living with HIV (PWH) who inject drugs and were not on antiretroviral therapy (ART), we explored associations between access to resources and HIV severity. Fundamental Cause Theory (FCT) sees socioeconomic status/access to resources as a root cause of disease and emphasizes that individuals with limited resources have fewer means to mitigate health risks and implement protective behaviors, which ultimately generates disparities in health outcomes. Guided by the FCT, we hypothesized that resource depletion (primary aim) and lower income (secondary aim) were associated with increased HIV severity. Using baseline data from the Linking Infectious and Narcology Care (LINC-II) trial of ART-naive PWH who inject drugs in St. Petersburg, Russia (n = 225), we examined the association between "past year resource runout" (yes vs. no) and "low-income (< 300 USD a month)" and the outcome HIV severity (CD4 count, continuous). We fit two separate linear regression models adjusted for gender, age, time since HIV diagnosis, and prior ART use. Participants had a mean age of 37.5 years and were 60% male. Two thirds (66%) reported resource depletion, and 30% had income below 300 USD a month. Average CD4 count was 416 cells/mm3 (SD 285). No significant association was identified between either resource depletion or low-income and HIV severity (adjusted mean difference in CD4 count for resource depletion: - 4.16, 95% CI - 82.93, 74.62; adjusted mean difference in CD4 count for low-income: 68.13, 95% CI - 15.78, 152.04). Below-average income and running out of resources were common among PWH who inject drugs and are not on ART in St. Petersburg, Russia. Resource depletion and low-income were not significantly associated with HIV disease severity as captured by CD4 count. The nuanced relationship between socioeconomic status and HIV severity among people with HIV who inject drugs and not on ART merits further examination in a larger sample.

HIV, substance use, and intersectional stigma: Associations with mental health among persons living with HIV who inject drugs in Russia.

HIV stigma is associated with negative physical and mental health outcomes. Intersectional stigma among persons living with HIV (PLHIV) results from interrelated, synergistic impacts of experiencing multiple stigma forms. Its relation with mental health outcomes is still an emerging area of study in this key population. This study aimed to evaluate associations of intersectional stigma, defined as endorsing high levels of HIV and substance use stigmas, with depressive and anxiety symptoms in a cohort of 111 PLHIV who inject drugs in St. Petersburg, Russia. Over a third of participants (37%) reported experiencing intersectional stigma (i.e., both stigma scores above the median). In adjusted analysis, lower Patient Health Questionnaire depression scale (PHQ-9) scores (beta (ß=-4.31, 95% CI: -7.11 - -1.51, p = 0.003) and Generalized Anxiety Disorders Scale (GAD-7) scores (ß=-3.64, 95% CI: -5.57 - -1.71, p < 0.001) were associated with having low scores for both HIV and substance use stigmas. Lower PHQ-9 scores (ß=-3.46, 95% CI: -5.72 - -1.19, p = 0.003) and GAD-7 scores (ß=-3.06, 95% CI: -4.62 - -1.50, p < 0.001) were also associated with high stigma on either HIV or substance use stigma scales. Controlling for demographics, depressive symptoms approximately linearly increased from both forms of stigma low to experiencing either form of stigma high to experiencing intersectional stigma, while levels of anxiety symptoms were comparable among participants with both types of stigma low and one stigma high. Participants who experienced intersectional stigma reported the greatest severity of both depressive and anxiety symptoms, as compared to individuals who endorsed low stigma scores (i.e., low stigma on both HIV and substance use stigma scales) or high scores of only one form of stigma. This suggests that intersectional stigma in this population of PLHIV who inject drugs in Russia is linked with worsened mental health outcomes, exceeding the effects of experiencing one form of stigma alone. Interventions to help people cope with intersectional stigma need to consider affective symptoms and tailor coping strategies to address impacts of multiple forms of mental health distress.

Correlates of Intersectional HIV and Substance Use Stigma Affecting People with HIV and Substance Use in St. Petersburg, Russia.

People with HIV (PWH) who inject drugs often experience coexisting HIV- and substance use-related stigma manifestations. We assessed correlates of HIV stigma (Berger HIV stigma scale), substance use stigma (Substance Abuse Self-stigma scale) and intersectional HIV and substance use stigma in a cohort of PWH with a lifetime history of drug use in St. Petersburg, Russia. Intersectional stigma was defined as having a score greater than the median for both forms of stigma. Of the 208 participants, 56 (27%) had intersectional stigma. Depressive symptoms and alcohol dependence were significantly associated with a higher HIV and substance stigma score, but not with intersectional stigma. Individual and community interventions to reduce the impact of HIV stigma and substance use stigma affecting PWH who inject drugs should consider assessing and addressing mental health and unhealthy substance use. Further work with longitudinal data is needed to understand mechanisms leading to intersectional stigma.

RESUMEN: Las personas infectadas por el VIH que se inyectan drogas a menudo experimentan manifestaciones de estigma relacionadas con el uso de sustancias y el propio VIH. En este estudio evaluamos los correlatos de estigma asociado al VIH (escala de estigma asociado al VIH de Berger), el estigma asociado al uso de sustancias ("Substance Abuse Self-stigma Scale") y el estigma interseccional del VIH y el uso de sustancias en una cohorte de personas infectadas por el VIH con antecedente de uso de drogas en San Petersburgo, Rusia. El estigma interseccional se definió como una puntuación superior a la mediana para ambas formas de estigma. De los 208 participantes, 56 (27%) tenían estigma interseccional. Los síntomas depresivos y la dependencia del alcohol se asociaron significativamente con una puntuación más alta de estigma relacionado con el VIH y las sustancias, pero no con el estigma interseccional. Las intervenciones individuales y comunitarias para reducir el impacto del estigma asociado al VIH y al uso de sustancias que afectan a las personas con VIH que se inyectan drogas deben tener en cuenta la salud mental y el uso nocivo de sustancias. Se necesitan estudios con datos longitudinales para comprender mejor los mecanismos que conducen al estigma interseccional.

Effects of a COVID-19 Public Health Lockdown on Drinking and Health Behavior Among Persons with HIV and with Unhealthy Alcohol use in Uganda.

To better understand the impact of Uganda's initial COVID-19 lockdown on alcohol use, we conducted a cross-sectional survey (August 2020-September 2021) among persons with HIV (PWH) with unhealthy alcohol use (but not receiving an alcohol intervention), enrolled in a trial of incentives to reduce alcohol use and improve isoniazid preventive therapy. We examined associations between bar-based drinking and decreased alcohol use, and decreased alcohol use and health outcomes (antiretroviral therapy [ART] access, ART adherence, missed clinic visits, psychological stress and intimate partner violence), during lockdown. Of 178 adults surveyed whose data was analyzed, (67% male, median age: 40), 82% reported bar-based drinking at trial enrollment; 76% reported decreased alcohol use during lockdown. In a multivariate analysis, bar-based drinking was not associated with greater decreases in alcohol use during lockdown compared to non-bar-based drinking (OR = 0.81, 95% CI: 0.31-2.11), adjusting for age and sex. There was a significant association between decreased alcohol use and increased stress during lockdown (adjusted ß = 2.09, 95% CI: 1.07-3.11, P < 0.010), but not other health outcomes.

Post-traumatic stress disorder and risky opioid use among persons living with HIV and chronic pain.

Persons with HIV (PWH) experience chronic pain and Post-Traumatic Stress Disorder (PTSD) at higher rates than the general population, and more often receive opioid medications to treat chronic pain. A known association exists between PTSD and substance use disorders, but less is known about the relationship between PTSD and risky opioid use among PWH taking prescribed opioid medications. In this observational study of PWH on long-term opioid medications for pain we examined associations between PTSD symptom severity based on the Post Traumatic Stress Disorder Checklist for DSM-5 (PCL-5, response range 0-80) and the following outcomes: 1) risk for opioid misuse (COMM score ≥13); 2) risky alcohol use (AUDIT score ≥8); 3) concurrent benzodiazepine prescription; and 4) morphine equivalent dose. Among 166 patients, 38 (23%) had a PCL-5 score over 38, indicating high PTSD symptom burden. Higher PCL-5 score (per 10 point difference) was associated with increased odds of opioid misuse (aOR 1.55; 95%CI: 1.31-1.83) and risky drinking (aOR: 1.28;1.07-1.52). No significant association was observed between PCL-5 score and benzodiazepine prescriptions or morphine equivalent dose. These findings suggest that when addressing alcohol and opioid use in PWH on long term opioid therapy, attention to PTSD symptoms is especially important given the higher risk for risky alcohol and opioid use among patients with this common comorbid condition.

Understanding Early Pandemic Severe Acute Respiratory Syndrome Coronavirus 2 Transmission in a Medical Center by Incorporating Public Sequencing Databases to Mitigate Bias.

BACKGROUND: Throughout the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, healthcare workers (HCWs) have faced risk of infection from within the workplace via patients and staff as well as from the outside community, complicating our ability to resolve transmission chains in order to inform hospital infection control policy. Here we show how the incorporation of sequences from public genomic databases aided genomic surveillance early in the pandemic when circulating viral diversity was limited. METHODS: We sequenced a subset of discarded, diagnostic SARS-CoV-2 isolates between March and May 2020 from Boston Medical Center HCWs and combined this data set with publicly available sequences from the surrounding community deposited in GISAID with the goal of inferring specific transmission routes. RESULTS: Contextualizing our data with publicly available sequences reveals that 73% (95% confidence interval, 63%-84%) of coronavirus disease 2019 cases in HCWs are likely novel introductions rather than nosocomial spread. CONCLUSIONS: We argue that introductions of SARS-CoV-2 into the hospital environment are frequent and that expanding public genomic surveillance can better aid infection control when determining routes of transmission.

Projected Long-Term Impact of the Coronavirus Disease 2019 (COVID-19) Pandemic on Hepatitis C Outcomes in the United States: A Modeling Study.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic disrupted access to and uptake of hepatitis C virus (HCV) care services in the United States. It is unknown how substantially the pandemic will impact long-term HCV-related outcomes. METHODS: We used a microsimulation to estimate the 10-year impact of COVID-19 disruptions in healthcare delivery on HCV outcomes including identified infections, linkage to care, treatment initiation and completion, cirrhosis, and liver-related death. We modeled hypothetical scenarios consisting of an 18-month pandemic-related disruption in HCV care starting in March 2020 followed by varying returns to pre-pandemic rates of screening, linkage, and treatment through March 2030 and compared them to a counterfactual scenario in which there was no COVID-19 pandemic or disruptions in care. We also performed alternate scenario analyses in which the pandemic disruption lasted for 12 and 24 months. RESULTS: Compared to the "no pandemic" scenario, in the scenario in which there is no return to pre-pandemic levels of HCV care delivery, we estimate 1060 fewer identified cases, 21 additional cases of cirrhosis, and 16 additional liver-related deaths per 100 000 people. Only 3% of identified cases initiate treatment and <1% achieve sustained virologic response (SVR). Compared to "no pandemic," the best-case scenario in which an 18-month care disruption is followed by a return to pre-pandemic levels, we estimated a smaller proportion of infections identified and achieving SVR. CONCLUSIONS: A recommitment to the HCV epidemic in the United States that involves additional resources coupled with aggressive efforts to screen, link, and treat people with HCV is needed to overcome the COVID-19-related disruptions.

Joint Models for Estimating Determinants of Cognitive Decline in the Presence of Survival Bias.

BACKGROUND: Identifying determinants of cognitive decline is crucial for developing strategies to prevent Alzheimer's disease and related dementias. However, determinants of cognitive decline remain elusive, with inconsistent results across studies. One reason could be differential survival. Cognitive decline and many exposures of interest are associated with mortality making survival a collider. Not accounting for informative attrition can result in survival bias. Generalized estimating equations (GEE) and linear mixed-effects model (LME) are commonly used to estimate effects of exposures on cognitive decline, but both assume mortality is not informative. Joint models combine LME with Cox proportional hazards models to simultaneously estimate cognitive decline and the hazard of mortality. METHODS: Using simulations, we compared estimates of the effect of a binary exposure on rate of cognitive decline from GEE, weighted GEE using inverse-probability-of-attrition weights, and LME to joint models under several causal structures of survival bias. RESULTS: We found that joint models with correctly specified relationship between survival and cognition performed best, producing unbiased estimates and appropriate coverage. Even those with misspecified relationship between survival and cognition showed advantage under causal structures consistent with survival bias. We also compared these models in estimating the effect of education on cognitive decline after dementia diagnosis using Framingham Heart Study data. Estimates of the effect of education on cognitive decline from joint models were slightly attenuated with similar precision compared with LME. CONCLUSIONS: In our study, joint models were more robust than LME, GEE, and weighted GEE models when evaluating determinants of cognitive decline.

Functional Impairment and Cognitive Symptoms Among People with HIV Infection on Chronic Opioid Therapy for Pain: The Impact of Gabapentin and Other Sedating Medications.

Gabapentin is associated with dizziness, falls, and somnolence yet commonly prescribed to people with HIV (PWH) treated with chronic opioid therapy (COT). Physical function and cognition are understudied when prescribed together. Among PWH on COT, we evaluated whether co-prescribed gabapentin is associated with (a) functional impairment; (b) trouble thinking clearly; and (c) difficulty controlling drowsiness using logistic regression models adjusted for prescribed opioid dose, other (non-gabapentin) sedating medication, substance use disorder, and mental/physical health indicators in a cross-sectional study. Among 166 participants, 40% were prescribed gabapentin, 41% reported functional impairment, 41% trouble thinking clearly, and 38% difficulty controlling drowsiness. Gabapentin co-prescribed with COT was significantly associated with trouble thinking clearly but not with functional impairment or difficulty controlling drowsiness. Clinicians should be cognizant of potential problems with thinking clearly when co-prescribing gabapentin and opioid medication.

Concordance Between Point-of-Care Urine Ethyl Glucuronide Alcohol Tests and Self-Reported Alcohol Use in Persons with HIV in Uganda.

Screening and assessing alcohol use accurately to maximize positive treatment outcomes remain problematic in regions with high rates of alcohol use and HIV and TB infections. In this study, we examined the concordance between self-reported measures of alcohol use and point-of-care (POC) urine ethyl glucuronide (uEtG) test results among persons with HIV (PWH) in Uganda who reported drinking in the prior 3 months. For analyses, we used the screening data of a trial designed to examine the use of incentives to reduce alcohol consumption and increase medication adherence to examine the concordance between POC uEtG (300 ng/mL cutoff) and six measures of self-reported alcohol use. Of the 2136 participants who completed the alcohol screening, 1080 (50.6%) tested positive in the POC uEtG test, and 1756 (82.2%) self-reported using alcohol during the prior 72 h. Seventy-two percent of those who reported drinking during the prior 24 h had a uEtG positive test, with lower proportions testing uEtG positive when drinking occurred 24-48 h (64.7%) or 48-72 h (28.6%) prior to sample collection. In multivariate models, recency of drinking, number of drinks at last alcohol use, and Alcohol Use Disorders Identification Test - Consumption (AUDIT-C) score were associated with uEtG positivity. The highest area under the curve (AUC) for a uEtG positive test was for recency of drinking. Overall, we concluded that several measures of drinking were associated with POC uEtG positivity, with recency of drinking, particularly drinking within the past 24 h, being the strongest predictor of uEtG positivity.

Predicting counterfactual risks under hypothetical treatment strategies: an application to HIV.

The accuracy of a prediction algorithm depends on contextual factors that may vary across deployment settings. To address this inherent limitation of prediction, we propose an approach to counterfactual prediction based on the g-formula to predict risk across populations that differ in their distribution of treatment strategies. We apply this to predict 5-year risk of mortality among persons receiving care for HIV in the U.S. Veterans Health Administration under different hypothetical treatment strategies. First, we implement a conventional approach to develop a prediction algorithm in the observed data and show how the algorithm may fail when transported to new populations with different treatment strategies. Second, we generate counterfactual data under different treatment strategies and use it to assess the robustness of the original algorithm's performance to these differences and to develop counterfactual prediction algorithms. We discuss how estimating counterfactual risks under a particular treatment strategy is more challenging than conventional prediction as it requires the same data, methods, and unverifiable assumptions as causal inference. However, this may be required when the alternative assumption of constant treatment patterns across deployment settings is unlikely to hold and new data is not yet available to retrain the algorithm.

Unhealthy alcohol use and intimate partner violence among men and women living with HIV in Uganda.

BACKGROUND: Intimate partner violence (IPV) and alcohol use are interrelated public health issues. Heavy and frequent alcohol use increase the risk of IPV, but the relationship between alcohol use and IPV (including recent and lifetime IPV victimization and perpetration) has not been well described among persons living with HIV (PWH) in sub-Saharan Africa. METHODS: We used baseline data from the Drinker's Intervention to Prevent Tuberculosis study. All participants were PWH co-infected with tuberculosis and had an Alcohol Use Disorders Identification Test - Consumption (AUDIT-C) positive score (hazardous drinking) and positive urine ethyl glucuronide test, indicating recent drinking. High-risk drinking was defined as AUDIT-C > 6 and/or alcohol biomarker phosphatidylethanol (PEth) ≥ 200 ng/mL. We measured IPV using the Conflict Tactics Scale. We estimated the association between alcohol use level and recent (prior six months) IPV victimization (recent perpetration was too low to study) using multivariable logistic regression models adjusted for gender, age, assets, education, spouse HIV status, religiosity, depressive symptoms, and social desirability. We additionally estimated the interaction of alcohol use and gender on IPV victimization and the association between alcohol use and lifetime victimization and perpetration. RESULTS: One-third of the 408 participants were women. Recent IPV victimization was reported by 18.9% of women and 9.4% of men; perpetration was reported by 3.1% and 3.6% of women and men. One-fifth (21.6%) of those reporting recent IPV victimization also reported perpetration. In multivariable models, alcohol use level was not significantly associated with recent IPV victimization (p = 0.115), nor was the interaction between alcohol use and gender (p = 0.696). Women had 2.34 times greater odds of recent IPV victimization than men (p = 0.016). Increasing age was significantly associated with decreased odds of recent IPV victimization (p = 0.004). CONCLUSION: Prevalence of IPV victimization was comparable to estimates from a recent national survey, while perpetration among men was lower than expected. Alcohol use level was not associated with IPV victimization. It is possible that alcohol use in this sample was too high to detect differences in IPV. Our results suggest that women and younger PWH are priority populations for IPV prevention.

Risk for Non-AIDS-Defining and AIDS-Defining Cancer of Early Versus Delayed Initiation of Antiretroviral Therapy : A Multinational Prospective Cohort Study.

BACKGROUND: Immediate initiation of antiretroviral therapy (ART) regardless of CD4 cell count reduces risk for AIDS and non-AIDS-related events in asymptomatic, HIV-positive persons and is the standard of care. However, most HIV-positive persons initiate ART when their CD4 count decreases below 500 × 109 cells/L. Consequences of delayed ART on risk for non-AIDS-defining and AIDS-defining cancer, one of the most common reasons for death in HIV, are unclear. OBJECTIVE: To estimate the long-term risk difference for cancer with the immediate ART strategy. DESIGN: Multinational prospective cohort study. SETTING: The D:A:D (Data collection on Adverse events of anti-HIV Drugs) study, which included HIV-positive persons from Europe, Australia, and the United States. PARTICIPANTS: 8318 HIV-positive persons with at least 1 measurement each of CD4 cell count and viral load while ART-naive (study period, 2006 to 2016). MEASUREMENTS: The parametric g-formula was used, with adjustment for baseline and time-dependent confounders (CD4 cell count and viral load), to assess the 10-year risk for non-AIDS-defining and AIDS-defining cancer of immediate versus deferred (at CD4 counts <350 and <500 × 109 cells/L) ART initiation strategies. RESULTS: During 64 021 person-years of follow-up, 231 cases of non-AIDS-defining cancer and 272 of AIDS-defining cancer occurred among HIV-positive persons with a median age of 36 years (interquartile range, 29 to 43 years). With immediate ART, the 10-year risk for non-AIDS-defining cancer was 2.97% (95% CI, 2.37% to 3.50%) and that for AIDS-defining cancer was 2.50% (CI, 2.37% to 3.38%). Compared with immediate ART initiation, the 10-year absolute risk differences when deferring ART to CD4 counts less than 500 × 109 cells/L and less than 350 × 109 cells/L were 0.12 percentage point (CI, -0.01 to 0.26 percentage point) and 0.29 percentage point (CI, -0.03 to 0.73 percentage point), respectively, for non-AIDS-defining cancer and 0.32 percentage point (CI, 0.21 to 0.44 percentage point) and 1.00 percentage point (CI, 0.67 to 1.44 percentage points), respectively, for AIDS-defining cancer. LIMITATION: Potential residual confounding due to observational study design. CONCLUSION: In this young cohort, effects of immediate ART on 10-year risk for cancer were small, and further supportive data are needed for non-AIDS-defining cancer. PRIMARY FUNDING SOURCE: Highly Active Antiretroviral Therapy Oversight Committee.

Higher Levels of Alcohol Use Are Associated With Latent Tuberculosis Infection in Adults Living With Human Immunodeficiency Virus.

We assessed associations between hazardous alcohol use and latent tuberculosis infection (LTBI) among adults living with human immunodeficiency virus (HIV) in Uganda. We compared tuberculin skin test positivity across medium, high, and very-high alcohol use levels, classified by AUDIT-C scores. In multivariable analysis, very high use was associated with LTBI (adjusted odds ratio 1.61, 95% confidence interval: 1.03-2.50).

Predictors of pain-related functional impairment among people living with HIV on long-term opioid therapy.

People living with HIV (PLWH) have high levels of functional impairment due to pain, also called pain interference. Long-term opioid therapy (LTOT) is commonly prescribed for chronic pain among PLWH. We sought to better understand the predictors of pain interference, measured with the Brief Pain Inventory Interference subscale (BPI-I), among PLWH with chronic pain on LTOT. Using a prospective cohort of PLWH on LTOT we developed a model to identify predictors of increased pain interference over 1 year of follow up. Participants (n = 166) were 34% female, 72% African American with a median age of 55 years, and 40% had severe pain interference (BPI-I ≥ 7). In multivariable models, substance use disorder, depressive symptoms, PTSD symptoms, financial instability, and higher opioid doses were associated with increased pain interference. Measures of behavioral health and socioeconomic status had the most consistent association with pain interference. In contrast, the biomedical aspects of chronic pain and LTOT - comorbidities, duration of pain - were not predictive of pain interference. PLWH with chronic pain on LTOT with lower socioeconomic status and behavioral health symptoms have higher risk of pain interference. Addressing the social determinants of health and providing access to behavioral health services could improve patients' pain-related functional status.

Post-traumatic stress disorder among persons with HIV who engage in heavy alcohol consumption in southwestern Uganda.

BACKGROUND: We aimed to describe the prevalence of PTSD symptoms and its associated factors in persons living with HIV (PLWH) in Uganda who engage in heavy alcohol use. METHODS: We analyzed baseline data from the Drinkers Intervention to Prevent Tuberculosis study which enrolls PLWH with latent tuberculosis who engage in heavy alcohol consumption. Using the primary care Post Traumatic Stress Disorder (PTSD) screening scale from the DSM-5 (PC-PTSD-5), probable PTSD was defined as reporting ≥3 of 5 assessed symptoms. We conducted the Alcohol Use Disorders Identification Test-Consumption and assessed demographics, smoking, symptoms of depression, and spirituality/religiosity. RESULTS: Of 421 participants enrolled from 2018 through 2020, the majority (68.2%) were male, median age was 40 years (interquartile range [IQR]: 32-47), and median AUDIT-C score was 6 [IQR: 4-8]. Half (50.1%) of the participants reported ever experiencing a traumatic event, and 20.7% reported ≥3 symptoms of PTSD. The most commonly reported PTSD symptoms in the past 1 month in the entire sample were avoidance (28.3%), nightmares (27.3%), and being constantly on guard (21.6%). In multivariable logistic regression analyses, level of alcohol use was not associated with probable PTSD (adjusted odds ratio [AOR] for each AUDIT-C point: (1.02; 95% CI: 0.92-1.14; p = 0.69); however, lifetime smoking (AOR 1.89; 95% CI: 1.10-3.24) and reporting symptoms of depression (AOR 1.89; 95% CI: 1.04-3.44) were independently associated with probable PTSD. CONCLUSIONS AND RECOMMENDATIONS: A history of traumatic events and probable PTSD were frequently reported among persons who engage in heavy drinking, living with HIV in Uganda. Level of alcohol use was not associated with probable PTSD in this sample of PLWH with heavy alcohol use, however other behavioral and mental health factors were associated with probable PTSD. These data highlight the high prevalence of PTSD in this group, and the need for screening and interventions for PTSD and mental health problems.

Effect Estimates in Randomized Trials and Observational Studies: Comparing Apples With Apples.

Effect estimates from randomized trials and observational studies might not be directly comparable because of differences in study design, other than randomization, and in data analysis. We propose a 3-step procedure to facilitate meaningful comparisons of effect estimates from randomized trials and observational studies: 1) harmonization of the study protocols (eligibility criteria, treatment strategies, outcome, start and end of follow-up, causal contrast) so that the studies target the same causal effect, 2) harmonization of the data analysis to estimate the causal effect, and 3) sensitivity analyses to investigate the impact of discrepancies that could not be accounted for in the harmonization process. To illustrate our approach, we compared estimates of the effect of immediate with deferred initiation of antiretroviral therapy in individuals positive for the human immunodeficiency virus from the Strategic Timing of Antiretroviral Therapy (START) randomized trial and the observational HIV-CAUSAL Collaboration.

Effects of connectivity and watercourse distance on temporal coherence patterns in a tropical reservoir.

Temporal coherence exists when environmental variables measured at different spatial locations vary synchronously over time. This is an important property to be analyzed because levels of coherence may indicate the role of regional and local processes in determining population and ecosystem dynamics. Also, studies on temporal coherence may guide the optimal allocation of sampling effort. We analyzed a dataset from a monitoring program undertaken at a tropical reservoir (Peixe Angical Reservoir, State of Tocantins, Brazil) to test three predictions. First, coherence should be a common pattern in the reservoir considering that sampling sites were distributed in a single water body and over a small spatial extent. Second, coherence was expected to decline with increasing watercourse distance and to increase with hydrological connectivity. Third, abiotic variables should exhibit higher coherence than biological variables. Twenty limnological variables were monitored at 14 sites and for 31 months. We found significant levels of coherence for all variables, supporting our first prediction. Watercourse distances, hydrological connectivity, or both were significant predictors of coherence for 17 environmental variables. In all these cases, the signs of the coefficients were in the direction predicted. Interestingly, for some environmental variables (color, turbidity, alkalinity, and total phosphorus), hydrological connectivity was even more important in predicting coherence than watercourse distance. The view that abiotic variables should exhibit higher coherence than biological variables was supported. Our analyses revealed that precipitation was an important factor inducing coherence of a key set of environmental variables, highlighting the role of regional processes in ecosystem dynamics.