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Background Understanding the sources of HIV transmission provides a basis for prioritizing HIV prevention resources in specific geographic regions and populations. This study estimated the number, proportion, and rate of HIV transmissions attributable to individuals along the HIV care continuum, within different HIV transmission risk groups in six US cities. Methods We used a dynamic, compartmental HIV transmission model that draws on racial/ethnic- and risk-behavior-specific linkage to HIV care and use of HIV prevention services from local, state and national surveillance sources. We estimated the rate and number of HIV transmissions attributable to individuals in the stage of acute undiagnosed HIV, non-acute undiagnosed HIV, HIV diagnosed but antiretroviral therapy (ART) naive, off ART, and on ART, stratified by HIV transmission group for the 2019 calendar year. Results Individuals with undiagnosed non-acute HIV infection accounted for the highest proportion of total transmissions in every city, ranging from 36.8% [26.7%-44.9%] in New York City to 64.9% [47.0%-71.6%] in Baltimore. Individuals who had discontinued ART contributed to the second highest percentage of total infections in four of six cities. Individuals with acute HIV had the highest transmission rate per 100 person years, ranging from 76.4 [58.9-135.9] in Miami to 160.2 [85.7-302.8] in Baltimore. Conclusion These findings underline the importance of both early diagnosis and improved ART retention for ending the HIV epidemic in the US. Differences in the sources of transmission across cities indicate that localized priority-setting to effectively address diverse microepidemics at different stages of epidemic control is necessary.

Background: HIV is associated with accelerated decline in lung function and increased risk for chronic obstructive pulmonary disease (COPD). Recently, there has been growing attention toward the impairment in the diffusing capacity of the lungs for carbon monoxide (DLCO), a marker of pulmonary gas exchange, observed among persons living with HIV. Although increased emphysema can contribute to the DLCO impairment observed, other factors may drive this association. Methods: Using cross-sectional data from the Study of HIV in the Etiology of Lung Disease, we studied the association between HIV and DLCO independent of emphysema. We also analyzed the joint influence of HIV and COPD on DLCO impairment. An analysis was conducted among 339 participants (229 with HIV) with lung function and chest CT imaging data. Multivariable regression models were generated with percent predicted DLCO and odds of DLCO impairment as outcomes. Results: After adjusting for confounders, including emphysema severity, HIV was associated with lower DLCO (β −4.02%; P = 0.020) and higher odds of DLCO impairment (odds ratio 1.93; P = 0.017). Even among those without COPD, HIV was independently associated with lower DLCO (β −3.89%; P = 0.049). Compared with HIV-uninfected participants without COPD, those with both HIV and COPD experienced the greatest impairment in DLCO (β −14.81; P < 0.001). Conclusions: HIV is associated with impaired pulmonary gas exchange independent of emphysema severity. Our data also suggest a potentially additive influence between HIV and COPD on DLCO impairment. Further studies should investigate the other factors, including pulmonary vascular disease, which may contribute to DLCO impairment among persons living with HIV.

BACKGROUND: People with HIV (PWH) have a higher hospitalization rate than the general population. The Veterans Aging Cohort Study (VACS) Index at study entry well predicts hospitalization in PWH, but it is unknown if the time-updated parameter improves hospitalization prediction. We assessed the association of parameterizations of the VACS Index 2.0 with the 5-year risk of hospitalization. SETTING: PWH ≥ 30 years old with at least 12 months of antiretroviral therapy (ART) use, and contributing hospitalization data from 2000 to 2016 in North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) were included. Three parameterizations of the VACS Index 2.0 were assessed and categorized by quartile: 1) “baseline” measurement at study entry, 2) time-updated measurements, and 3) cumulative scores calculated using the trapezoidal rule. METHODS: Discrete-time proportional hazard models estimated the crude and adjusted associations (and 95% confidence intervals [CI]) of the VACS Index parameterizations and all-cause hospitalizations. The Akaike information criterion (AIC) assessed the model fit with each of the VACS Index parameters. RESULTS: Among 7,289 patients, 1,537 were hospitalized. Time-updated VACS Index fitted hospitalization best with a more distinct dose-response relationship (score

Background Evidence of whether people living with HIV are at elevated risk of adverse COVID-19 outcomes is inconclusive. We aimed to investigate this association using the population-based National COVID Cohort Collaborative (N3C) data in the USA. Methods We included all adult (aged ≥18 years) COVID-19 cases with any health-care encounter from 54 clinical sites in the USA, with data being deposited into the N3C. The outcomes were COVID-19 disease severity, hospitalisation, and mortality. Encounters in the same health-care system beginning on or after January 1, 2018, were also included to provide information about pre-existing health conditions (eg, comorbidities). Logistic regression models were employed to estimate the association of HIV infection and HIV markers (CD4 cell count, viral load) with hospitalisation, mortality, and clinical severity of COVID-19 (multinomial). The models were initially adjusted for demographic characteristics, then subsequently adjusted for smoking, obesity, and a broad range of comorbidities. Interaction terms were added to assess moderation effects by demographic characteristics. Findings In the harmonised N3C data release set from Jan 1, 2020, to May 8, 2021, there were 1 436 622 adult COVID-19 cases, of these, 13 170 individuals had HIV infection. A total of 26 130 COVID-19 related deaths occurred, with 445 among people with HIV. After adjusting for all the covariates, people with HIV had higher odds of COVID-19 death (adjusted odds ratio 1·29, 95% CI 1·16–1·44) and hospitalisation (1·20, 1·15–1·26), but lower odds of mild or moderate COVID-19 (0·61, 0·59–0·64) than people without HIV. Interaction terms revealed that the elevated odds were higher among older age groups, male, Black, African American, Hispanic, or Latinx adults. A lower CD4 cell count (

Background and aims Over the past decades, people who inject drugs (PWID) have been impacted by the development of combination antiretroviral therapy (cART) to combat HIV/AIDS, the prescription opioid crisis, and increased use of lethal synthetic opioids. We measured how these dynamics have impacted mortality among PWID in an urban U.S. city. Design Prospective cohort study using data from the AIDS Linked to the Intravenous Experience (ALIVE) SETTING: Baltimore, Maryland, USA from 1988-2018. Participants 5,506 adult PWIDs (median age at baseline 37 years). Measurements Mortality was identified by linkage to National Death Index-Plus (NDI-Plus) and categorized into HIV/infectious disease (HIV/ID) deaths, overdose and violence-related (drug-related) deaths, and chronic-disease deaths. Person-time at risk accrued from baseline, and ended at the earliest of death or study period. All-cause and cause-specific mortality were calculated annually. Fine and Gray method was used to estimate the sub-distribution hazards of cause-specific deaths accounting for competing risks. Findings Among 5,506 participants with 84,011 person-years of follow-up, 43.9% were deceased by 2018. Among all deaths, 30.5% were HIV/ID-deaths, 24.4% drug-related deaths, and 33.3% chronic-disease deaths. Age-standardized all-cause mortality increased from 23 to 45 per 1000-person-years from 1988-1996, declined from 1996 through 2012, then trended upward through 2018. HIV/ID-deaths peaked in 1996 coincident with the availability of cART, then continuously declined. Chronic-disease deaths increased continuously as the cohort aged. Drug-related deaths declined until 2011, but increased over 4-fold by 2018. HIV/HCV infection and active injecting were independently associated with HIV/ID and drug-related deaths. Female and Black participants had higher risk of dying from HIV/ID deaths and a lower risk of dying from drug-related deaths than male and non-Black participants. Conclusions Deaths in Baltimore, Maryland, USA attributable to HIV/ID appear to have declined following the widespread use of combination antiretroviral therapy. Increases in the rates of drug-related deaths in Baltimore were observed prior to and continue in conjunction with national mortality rates associated with the opiate crisis.

OBJECTIVE People with HIV (PWH) experience increased prevalence of obstructive lung disease (OLD), regardless of greater observed smoking behaviors. We investigated whether the effect of incident OLD on mortality differed by HIV and HIV viral suppression among persons who inject drugs (PWID) and report smoking history. DESIGN ALIVE is a longitudinal, observational cohort study of HIV-positive and seronegative PWID. This analysis included participants who had at least one spirometry measure to assess OLD between 2007 and 2016, excluding those who never smoked (5%, n = 62) or had baseline OLD (17%, n = 269). METHODS Incident OLD occurred when the first prebronchodilator forced expiratory volume in one second (FEV1)/forced vital capacity (FVC) less than 0.70 during follow-up. The effect of incident OLD on all-cause mortality was estimated in PWH and seronegative participants using inverse-probability-of-treatment-weighted marginal structural models controlling for baseline (age, race, sex, calendar year, smoking pack-years) and time-varying (smoking intensity, viral suppression, and calendar time) confounders. RESULTS Among 1204 participants, 269 (22.3%) and 157 (13.0%) experienced incident OLD and death, respectively, over a median of five person-years of follow-up. There was no effect of OLD on mortality among seronegative participants [hazard ratio = 0.84, 95% confidence interval (CI): 0.47-1.48]; however, PWH diagnosed with OLD experienced an increased mortality risk (hazard ratio = 1.71, 95% CI: 1.04-2.80) during follow-up. HIV viral suppression did not confound or modify the effect of OLD on mortality among PWH. CONCLUSION There was an apparent effect of OLD on all-cause mortality irrespective of viral suppression among PWH but not among seronegative persons, after accounting for baseline and time-varying confounders. These results highlight the need for enhanced screening and management of OLD among PWH.

Background: The AGE hIV cohort study is a prospective cohort study evaluating the occurrence of age-related comorbidities in people living with and without HIV. We previously reported a lower forced vital capacity (FVC) in HIV-positive compared with HIV-negative participants in those without heavy smoking exposure at time of enrolment in the AGE hIV cohort study. In this study we evaluate longitudinal changes in spirometry indices in the same AGE hIV cohort accounting for smoking behaviour and other risk factors. Methods: We obtained pre-bronchodilator spirometry measurements in AGE hIV cohort participants during biennial visits over a median of 5·9 years (IQR 5·7–6·0). Adjusted declines in forced expiratory volume in 1 s (FEV 1), FVC, and FEV 1/FVC ratio were modelled using linear mixed-effects models and compared by HIV status and smoking status. To evaluate whether changes in spirometry measurements could be driven by increased levels of chronic inflammation, we assessed associations between rates of FEV 1 and FVC decline and CD4 and CD8 T-cell counts, and plasma concentrations of C-reactive protein (CRP), interleukin 6, soluble CD14, soluble CD163, and intestinal fatty-acid-binding protein in separate models. The study is registered at ClinicalTrials.gov, NCT01466582. Findings: 500 HIV-positive and 481 HIV-negative participants were included with spirometry data from Oct 29, 2010, to Aug 14, 2018. HIV-positive participants were virally suppressed (

Aims The extent to which human immunodeficiency viral (HIV) infection is independently associated with myocardial disease in the era of combination antiretroviral therapy (cART) remains understudied. We assessed differences in cardiovascular magnetic resonance imaging (CMR) metrics among people living with HIV (PLWH) and without HIV (PWOH). Methods and results Among 436 participants (aged 54.7 ± 6.0 years, 29% women) from three cohorts, we acquired CMR cines, late gadolinium enhancement (LGE), and T1 mapping. Multivariable linear regressions were used to evaluate associations between HIV serostatus and CMR metrics. Baseline characteristics were similar by HIV serostatus; 63% were PLWH of whom 88% received cART and 73% were virally suppressed. Median left ventricular ejection fraction was normal and similar by HIV serostatus (73%, PWOH vs. 72%, PLWH, P = 0.43) as were right ventricular function, biventricular volumes, and masses. LGE prevalence was similar (32%, PWOH vs. 36%, PLWH, P = 0.46) with low scar extents (4.1, PWOH vs. 4.9 g, PLWH, P = 0.51) and few ischaemic scars (3%, PWOH vs. 4%, PLWH, P = 0.70). Extracellular volume fraction (ECV) was higher among PLWH (29.2 ± 4.1% vs. 28.3 ± 3.7%, P = 0.04) as was indexed maximum left atrial (LA) volume (LAVI, 29.7 ± 10.3 vs. 27.8 ± 8.7 mL/m2, P = 0.05). After multivariate adjustment, ECV was 0.84% higher among PLWH (P = 0.05) and LAVI was 2.45 mL/m2 larger (P = 0.01). HIV seropositivity and higher ECV contributed to higher LAVI (P Conclusion HIV seropositivity was independently associated with greater diffuse non-ischaemic fibrosis and larger LA volume but no other differences in CMR metrics.

The latent reservoir for human immunodeficiency virus type 1 (HIV-1) in CD4+ T cells is a major barrier to cure. HIV-1–infected persons who inject drugs (PWID) often struggle to maintain suppression of viremia and experience nonstructured treatment interruptions (NTIs). The effects of injecting drugs or NTIs on the reservoir are unclear. Using the intact proviral DNA assay, we found no apparent effect of heroin or cocaine use on reservoir size. However, we found significantly larger reservoirs in those with frequent NTIs or a shorter interval from last detectable HIV RNA measurement. These results have important implications for inclusion of PWID in HIV-1 cure studies.

Background Chronic respiratory disease represents an important comorbidity for persons living with HIV (PLWH). HIV itself is associated with greater impairment in lung function. We aimed to determine the association between declining lung function and both quality of life (QOL) and health care utilization for PLWH. Methods Using longitudinal data from the Study of HIV Infection in the Etiology of Lung Disease 2009-2017, we studied the association between changes in lung function and both QOL and acute care events (emergency department visit or hospitalization). The Medical Outcomes Studies-HIV Questionnaire provided QOL domains. Multivariable regression models were performed with generalized estimating equations accounting for 1499 participants, 485 with HIV, contributing 10,825 spirometry visits. Results Among PLWH, decreased FEV1 was associated with worse physical health for those with higher viral load [β: -1.66, 95% confidence interval (CI): -3.11 to -0.39] compared to those with viral suppression (β: -0.58, 95% CI: -1.06 to -0.162), even in those without airflow obstruction. Lower FEV1 was also associated with increased odds of both emergency department (odds ratio: 1.21, 95% CI: 1.09 to 1.34) and inpatient (odds ratio: 1.26, 95% CI: 1.12 to 1.42) hospitalizations for PLWH. Lung function was not associated with increased odds of acute care events for HIV-uninfected participants. Conclusions FEV1 declines represent an independent predictor of QOL and acute care events among PLWH. Although the generalizability of these results may be limited, because of the high-risk population included, findings suggest that care for PLWH should involve monitoring FEV1 over time, especially in those with poor virologic control, with emphasis on the development and implementation of interventions to mitigate lung function decline.

Background Current mitigation strategies for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) rely on the population-wide adoption of nonpharmaceutical interventions (NPIs). Monitoring the adoption of NPIs and their associations with SARS-CoV-2 infection history can provide key information for public health. Methods We sampled 1030 individuals in Maryland from 17–28 June 2020 to capture sociodemographically and geographically resolved information about NPI adoption and access to SARS-CoV-2 testing, and examine associations with self-reported SARS-CoV-2 positivity. Results Overall, 92% reported traveling for essential services and 66% visited friends/family. Use of public transport was reported by 18%. In total, 68% reported strict social distancing indoors and 53% reported strict masking indoors; indoor social distancing was significantly associated with age, and race/ethnicity and income were associated with masking. Overall, 55 participants (5.3%) self-reported ever testing positive for SARS-CoV-2, with strong dose-response relationships between several forms of movement frequency and SARS-CoV-2 positivity. In a multivariable analysis, a history of SARS-CoV-2 infection was negatively associated with strict social distancing (adjusted odds ratio [aOR] for outdoor social distancing, 0.10; 95% confidence interval, .03–.33). Only public transport use (aOR for >7 times vs never, 4.3) and visiting a place of worship (aOR for ≥3 times vs never, 16.0) remained significantly associated with SARS-CoV-2 infection after adjusting for strict social distancing and demographics. Conclusions These results support public health messaging that strict social distancing during most activities can reduce SARS-CoV-2 transmission. Additional considerations are needed for indoor activities with large numbers of persons (places of worship and public transportation), where even NPIs may not be possible or sufficient.

Objective Frailty is a critical aging-related syndrome marked by diminished physiologic reserve and heightened vulnerability to stress, predictive of major adverse clinical outcomes in HIV-infected and uninfected adults. Frailty is a dynamic state, yet little data exist on predictors and consequences of frailty transitions. Design/methods Frailty was assessed semiannually among HIV-infected and uninfected persons with prior injection drug use using the five Fried phenotype domains. An inflammatory index score was constructed from IL-6 and soluble TNF-α receptor-1 data. Markov transition models assessed determinants of frailty transitions. Cox proportional hazards models estimated mortality risk. Results Among 1353 AIDS Linked to the IntraVenous Experience participants with 9559 frailty transition assessments, 33% were HIV-infected. Younger age, higher education, employment, reduced comorbidity, HIV virologic suppression, elevated CD4 nadir (>500 cells/μl) and absence of a prior AIDS diagnosis were significantly associated with both reduced frailty progression and greater frailty recovery. Each SD decrease in inflammatory index score was associated with decreased frailty progression [odds ratio 0.78; 95% confidence interval (CI), 0.65, 0.92] and increased frailty recovery (odds ratio 1.29; 95% CI, 1.08, 1.53). Being frail at one of two consecutive visits was associated with increased mortality, compared with maintenance of a nonfrail state. Being frail at both of two consecutive visits demonstrated the highest mortality risk (hazard ratio 3.23; 95% CI, 2.1, 4.96). Conclusion Sustained, and to a lesser degree, intermittent frail states are associated with increased mortality. HIV virologic suppression with earlier antiretroviral therapy, reduced comorbidity, and reduced inflammation may prevent frailty progression and promote frailty recovery, consequently improving survival for persons aging with HIV and persons with prior injection drug use.

Background Whereas safe, curative treatments for hepatitis C virus (HCV) have been available since 2015, there are still 58 million infected persons worldwide, and global elimination may require new paradigms. We sought to understand the acceptability of approaches to long-acting HCV treatment. Methods A cross-sectional, 43-question survey was administered to 1457 individuals with or at risk of HCV at 28 sites in 9 countries to assess comparative interest in a variety of long-acting strategies in comparison with oral pills. Results Among HCV-positive participants, 37.7% most preferred an injection, 5.6% an implant, and 6% a gastric residence device, as compared with 50.8% who stated they would most prefer taking 1–3 pills per day. When compared directly to taking pills, differences were observed in the relative preference for an injection based on age (P Conclusions These data point to high acceptability of long-acting treatments, which for a substantial minority might even be preferred to pills for the treatment of HCV infection. Long-acting treatments for HCV infection might contribute to global efforts to eliminate hepatitis C.

People who inject drugs (PWID) face disparities in human immunodeficiency virus (HIV) treatment outcomes and may be less likely to achieve durable viral suppression. We characterized transitions into and out of viral suppression from 1997 to 2017 in a long-standing community-based cohort study of PWID, the AIDS Link to Intravenous Experience (ALIVE) Study, analyzing HIV-positive participants who had made a study visit in or after 1997. We defined the probabilities of transitioning between 4 states: 1) suppressed, 2) detectable, 3) lost to follow-up, and 4) deceased. We used multinomial logistic regression analysis to examine factors associated with transition probabilities, with a focus on transitions from suppression to other states. Among 1,061 participants, the median age was 44 years, 32% were female, 93% were African-American, 59% had recently injected drugs, and 28% were virologically suppressed at baseline. Significant improvements in durable viral suppression were observed over time; however, death rates remained relatively stable. In adjusted analysis, injection drug use and homelessness were associated with increased virological rebound in earlier time periods, while only age and race were associated with virological rebound in 2012–2017. Opioid use was associated with an increased risk of death following suppression in 2012–2017. Despite significant improvements in durable viral suppression, subgroups of PWID may need additional efforts to maintain viral suppression and prevent premature mortality.

Background Alcohol use in people who inject drugs (PWID) with hepatitis C virus (HCV) infection accelerates liver disease progression. This paper describes the prevalence and associated correlates of alcohol use among HCV antibody positive PWID. Methods In a large cohort of HCV antibody positive PWID (N = 1623) followed from 2005 to 2013, we characterized alcohol use using the AUDIT-C. We used multivariable logistic regression with generalized estimated equations to examine socio-demographic, clinical, and substance use correlates of alcohol use. Results At their initial visit, 41% reported no, 21% reported moderate, and 38% reported heavy alcohol use. The odds of moderate and heavy alcohol use increased with greater intensity of substance use represented by a composite summary variable which ranged from 0 to 3 substances (street-acquired prescription drugs, non-injection cocaine/heroin, and injection drugs) used. Compared to those who used no drugs, those who used 3 substances had 3.71 odds (95% CI: 3.07–4.48) of moderate alcohol use and 3.65 odds (95% CI: 3.20–4.16) of heavy alcohol use. Conclusions The prevalence of moderate/heavy alcohol use is high among HCV antibody positive PWID and occurs frequently in combination with other drug use. This may contribute to progressive liver fibrosis thus limiting the gains achieved from HCV cure. Public health interventions need to address the overlapping epidemics of HCV, alcohol use, and other substance use in this population.

Increasing overdose mortality and new HIV outbreaks in the U.S. highlight the need to identify risk behavior profiles among people who inject drugs (PWID). We characterized latent classes of drug use among a community-based sample of 671 PWID in Baltimore during 2017 and evaluated associations of these classes with sharing syringes, obtaining syringes from pharmacies or syringe services programs (SSPs), and nonfatal overdose in the past 6 months. We identified three classes of current drug use: infrequent use (76% of participants), prescription drug use (12%), and heroin and/or cocaine injection (12%). PWID in the heroin and/or cocaine injection and prescription drug use classes had higher odds of both overdose and sharing syringes (relative to infrequent use). PWID in the prescription drug use class were 64% less likely to obtain syringes through SSPs/pharmacies relative to heroin and/or cocaine injection. Harm reduction programs need to engage people who obtain prescription drugs illicitly.

Hepatocellular carcinoma (HCC) incidence is high in The Gambia, and hepatitis B virus (HBV) infection is the main cause. People coinfected with HBV and hepatitis D virus (HDV) have an even greater risk of HCC and cirrhosis. Using a new HDV quantitative microarray antibody capture (Q-MAC) assay, we evaluated the association between HDV infection and HCC or cirrhosis among participants in The Gambia Liver Cancer Study. In this case-control study, cases had HCC (n = 312) or cirrhosis (n = 119). Controls (n = 470) had no clinical evidence of liver disease and normal serum alpha-foetoprotein. Participants were previously tested for hepatitis B surface antigen (HBsAg); we tested HBsAg+ specimens by HDV Q-MAC, western blot and RNA assays. We evaluated separate cut-offs of the Q-MAC assay for predicting anti-HDV and RNA positivity. Q-MAC correctly identified 29/29 subjects who were western blot-positive (sensitivity = 100%, specificity = 99.4%) and 16/17 who were RNA-positive (sensitivity = 94.1%, specificity = 100%). Compared to controls, cases more often had HBV monoinfection (HBsAg+/HDV RNA-; 54.1% vs 17.0%; odds ratio [OR] = 6.28; P < 0.001) or HBV-HDV coinfection (HBsAg+/HDV RNA+; 3.9% vs 0%; P < 0.001). Risk estimates (for HCC or cirrhosis) based on HDV antibody status and adjusted for covariates (demographics, alcohol, smoking, body mass index, anti-HCV and aflatoxin B1 exposure) yielded consistent results for both HBV monoinfection (adjusted OR = 8.29; 95% confidence interval = 5.74-11.98) and HBV-HDV coinfection (adjusted OR = 30.66; 95% confidence interval = 6.97-134.95). In this Gambian population, HDV Q-MAC had high sensitivity and specificity for both anti-HDV and HDV RNA. HDV infection contributed to the high risk of HCC in The Gambia.

BackgroundIndividuals with immune dysfunction, including people with HIV (PWH) or solid organ transplant recipients (SOT), might have worse outcomes from COVID-19. We compared odds of COVID-19 outcomes between patients with and without immune dysfunction.MethodsWe evaluated data from the National COVID-19 Cohort Collaborative (N3C), a multicenter retrospective cohort of electronic medical record (EMR) data from across the United States, on. 1,446,913 adult patients with laboratory-confirmed SARS-CoV-2 infection. HIV, SOT, comorbidity, and HIV markers were identified from EMR data prior to SARS-CoV-2 infection. COVID-19 disease severity within 45 days of SARS-CoV-2 infection was classified into 5 categories: asymptomatic/mild disease with outpatient care; mild disease with emergency department (ED) visit; moderate disease requiring hospitalization; severe disease requiring ventilation or extracorporeal membrane oxygenation (ECMO); and death. We used multivariable, multinomial logistic regression models to compare odds of COVID-19 outcomes between patients with and without immune dysfunction.FindingsCompared to patients without immune dysfunction, PWH and SOT had a greater likelihood of having ED visits (adjusted odds ratio [aOR]: 1.28, 95% confidence interval [CI] 1.27-1.29; aOR: 2.61, CI: 2.58-2.65, respectively), requiring ventilation or ECMO (aOR: 1.43, CI: 1.43-1.43; aOR: 4.82, CI: 4.78-4.86, respectively), and death (aOR: 1.20, CI: 1.19-1.20; aOR: 3.38, CI: 3.35-3.41, respectively). Associations were independent of sociodemographic and comorbidity burden. Compared to PWH with CD4>500 cells/mm3, PWH with CD43 were independently at 4.4-, 5.4-, and 7.6-times higher odds for hospitalization, requiring ventilation, and death, respectively. Increased COVID-19 severity was associated with higher levels of HIV viremia.InterpretationIndividuals with immune dysfunction have greater risk for severe COVID-19 outcomes. More advanced HIV disease (greater immunosuppression and HIV viremia) was associated with higher odds of severe COVID-19 outcomes. Appropriate prevention and treatment strategies should be investigated to reduce the higher morbidity and mortality associated with COVID-19 among PWH and SOT.

Background The updated Veterans Aging Cohort Study (VACS) Index 2.0 combines general and human immunodeficiency virus (HIV)–specific biomarkers to generate a continuous score that accurately discriminates risk of mortality in diverse cohorts of persons with HIV (PWH), but a score alone is difficult to interpret. Using data from the North American AIDS Cohort Collaboration (NA-ACCORD), we translate VACS Index 2.0 scores into validated probability estimates of mortality. Methods Because complete mortality ascertainment is essential for accurate calibration, we restricted analyses to cohorts with mortality from the National Death Index or equivalent sources. VACS Index 2.0 components were ascertained from October 1999 to April 2018. Mortality was observed up to March 2019. Calibration curves compared predicted (estimated by fitting a gamma model to the score) to observed mortality overall and within subgroups: cohort (VACS/NA-ACCORD subset), sex, age 500 copies/mL, CD4 count Results Among 37230 PWH in VACS and 8061 PWH in the NA-ACCORD subset, median age was 53 and 44 years; 3% and 19% were women; and 48% and 39% were black. Discrimination in NA-ACCORD (C-statistic = 0.842 [95% confidence interval {CI}, .830–.854]) was better than in VACS (C-statistic = 0.813 [95% CI, .809–.817]). Predicted and observed mortality largely overlapped in VACS and the NA-ACCORD subset, overall and within subgroups. Conclusions Based on this validation, VACS Index 2.0 can reliably estimate probability of all-cause mortality, at various follow-up times, among PWH in North America.

Background Sub-Saharan Africa continues with very low hepatitis B (HBV) birth dose vaccination coverage. To guide policy on HBV vaccine for newborns, we explored perceptions, barriers and preferences of pregnant women regarding HBV and the HBV birth dose vaccination Methods We conducted eight focus groups discussions (FGDs) among 70 pregnant women, stratified by rural-urban residence, age and education level, using a structured focus group discussion guide to explore birth dose awareness, perceptions, barriers and preferences. Data were transcribed, coded and analysed using framework analysis. Results Perceptions related to HBV and liver cancer causes and prevention were diverse; most FGD participants did not perceive illnesses as distinctly different. Older women-groups, both urban and rural, had never heard about HBV, but were aware of liver cancer, viewing the disease as fatal. No FGD participants were aware of HBV birth dose. Concerns included vaccine safety, its availability to women who deliver outside the health system and mistrust in health-care worker (HCWs) when handling newborns. Rural-dwelling groups perceived absence of HBV services, while FGDs with young participants believed vaccine side-effects hampered birth dose planning. Most women-groups preferred (i) oral to injectable vaccines; (ii) receiving birth dose education during antenatal, to media-based education; (iii) that newborns receive the birth dose immediately after delivery in the mother's presence. Conclusion Although the birth dose is acceptable among pregnant women, planners need to continuously engage them as key stakeholders during planning to address concerns, in order to raise confidence, maximize uptake and strengthen HBV eradication efforts.

Background There is limited data on the health and social consequences of the COVID-19 pandemic among people who inject drugs (PWID). Methods We conducted a rapid telephone survey from April-June 2020 among participants of the community-based AIDS Linked to the IntraVenous Experience (ALIVE) cohort study in Baltimore, Maryland. This interviewer-administered survey collected information on COVID-19 knowledge, symptoms, testing, diagnosis, and prevention behaviors, recent substance use, housing conditions, interruptions to healthcare, access to harm reduction and drug treatment, mental health, and social support. Results Of 443 current and former PWID who participated in the survey, 36 % were female, 85 % were Black, 33 % were living with HIV and 50 % reported any substance use in the prior six months. COVID-19 awareness was high, but knowledge of symptoms and routes of transmission were lower. PWID reporting recent substance use were less likely to always socially distance (63 % vs. 74 % among those without recent use, p = 0.02), and Black PWID were more likely than non-Black to socially distance (73 % vs. 48 %, p < 0.0001) and use when alone (68 % vs.35 %, p < 0.01). Only 6% reported difficulty accessing healthcare, yet only 48 % of those on opioid-agonist treatment had a four-week supply available. While 34 % reported increased depressive symptoms, participants reported high levels of social support. Conclusions This rapid assessment highlighted that PWID currently using drugs may be less able to practice social distancing and increased SARS-CoV-2 transmission may occur. Ongoing monitoring of substance use and mental health, as well as overdose prevention is necessary as the pandemic and public health responses continue.

BACKGROUND: Chronic hepatitis B (HBV) is the predominant cause of hepatocellular carcinoma (HCC) worldwide. Although HBV coinfection is common in HIV, the determinants of HCC in HIV/HBV coinfection are poorly characterized. We examined the predictors of HCC in a multi-cohort study of HIV/HBV-coinfected individuals. METHODS & RESULTS: We included HIV/HBV-coinfected persons within 22 cohorts of the North American AIDS Cohort Collaboration on Research and Design (1995–2016). First occurrence of HCC was verified by medical record review and/or cancer registry. We used multivariable Cox regression to determine adjusted hazard (aHRs [95% confidence intervals]) of factors assessed at cohort entry (age, sex, race, body mass index), ever during observation (heavy alcohol use, hepatitis C), or time-updated (HIV RNA, CD4+ percentage, diabetes mellitus, HBV DNA). Among 8,354 HIV/HBV-coinfected individuals (median age, 43 years; 93% male; 52.4% non-white), 115 HCC cases were diagnosed over 65,392 person-years (incidence rate, 1.8 [95% CI, 1.5–2.1] events/1,000 person-years). Risk factors for HCC included age 40–49 years (aHR, 1.97 [1.22–3.17]), age ≥50 years (aHR, 2.55 [1.49–4.35]), hepatitis C coinfection (aHR, 1.61 [1.07–2.40]), and heavy alcohol use (aHR, 1.52 [1.04–2.23]), while time-updated HIV RNA >500 copies/mL (aHR, 0.90 [0.56–1.43]) and time-updated CD4+ percentage 200 IU/mL (aHR, 2.22 [1.42–3.47]) and was higher with each 1.0 log(10) IU/mL increase in time-updated HBV DNA (aHR, 1.18 [1.05–1.34]). HBV suppression with HBV-active antiretroviral therapy (ART) for ≥1 year significantly reduced HCC risk (aHR, 0.42 [0.24–0.73]). CONCLUSION: HIV/HBV-coinfected individuals on ART with detectable HBV viremia remain at risk for HCC. To gain maximal benefit from ART for HCC prevention, sustained HBV suppression is necessary.

Background: Individuals with immune dysfunction, including people with HIV (PWH) or solid organ transplant recipients (SOT), might have worse outcomes from COVID-19. We compared odds of COVID-19 outcomes between patients with and without immune dysfunction. Methods: We evaluated data from the National COVID-19 Cohort Collaborative (N3C), a multicenter retrospective cohort of electronic medical record (EMR) data from across the United States, on. 1,446,913 adult patients with laboratory-confirmed SARS-CoV-2 infection. HIV, SOT, comorbidity, and HIV markers were identified from EMR data prior to SARS-CoV-2 infection. COVID-19 disease severity within 45 days of SARS-CoV-2 infection was classified into 5 categories: asymptomatic/mild disease with outpatient care; mild disease with emergency department (ED) visit; moderate disease requiring hospitalization; severe disease requiring ventilation or extracorporeal membrane oxygenation (ECMO); and death. We used multivariable, multinomial logistic regression models to compare odds of COVID-19 outcomes between patients with and without immune dysfunction. Findings: Compared to patients without immune dysfunction, PWH and SOT had a greater likelihood of having ED visits (adjusted odds ratio [aOR]: 1.28, 95% confidence interval [CI] 1.27-1.29; aOR: 2.61, CI: 2.58-2.65, respectively), requiring ventilation or ECMO (aOR: 1.43, CI: 1.43-1.43; aOR: 4.82, CI: 4.78-4.86, respectively), and death (aOR: 1.20, CI: 1.19-1.20; aOR: 3.38, CI: 3.35-3.41, respectively). Associations were independent of sociodemographic and comorbidity burden. Compared to PWH with CD4>500 cells/mm 3 , PWH with CD4

Supplemental Digital Content is Available in the Text., Background: We previously demonstrated a higher prevalence of frailty among AGEhIV-cohort participants with HIV (PWH) than among age- and lifestyle-comparable HIV-negative participants. Furthermore, frailty was associated with the development of comorbidities and mortality. As frailty may be a dynamic state, we evaluated the frequency of transitions between frailty states, and explored which factors were associated with transition toward frailty in this cohort. Methods: The study enrolled 598 PWH and 550 HIV-negative participants aged ≥45 years. Of those, 497 and 479 participants, respectively, participated in ≥2 consecutive biennial study-visits between October 2010 and October 2016, contributing 918 and 915 visit-pairs, respectively. We describe the frequency, direction, and risk factors of frailty transitions. Logistic regression models with generalized estimating equations were used to evaluate determinants for transition to frailty, including HIV-status, socio-demographic, behavioral, HIV-related factors, and various inflammatory and related biomarkers. Results: Transitioning between frailty states in any direction occurred in 36% of a total of 1833 visit-pairs. The odds of nonfrail participants transitioning toward frailty were significantly higher for PWH, occurring in 35 PWH (7.3%) and 25 (5.2%) HIV-negative nonfrail participants, respectively (odd ratioHIV 2.19, 95% confidence interval 1.28 to 3.75). The increased risk among PWH was attenuated when sequentially adjusting for waist–hip ratio, number of pre-existent comorbidities, and the presence of depressive symptoms. Conclusion: PWH are at increased risk of transitioning to frailty, and thereby at increased risk of adverse health outcomes. Whether optimizing the management of obesity, comorbidity, or depressive symptoms may modify the risk of becoming frail requires further investigation.

ObjectiveTo characterize the SARS-CoV-2 testing cascade and associated barriers in three US states.MethodsWe recruited participants from Florida, Illinois, and Maryland (∼1000/state) for an online survey September 16 – October 15, 2020. The survey covered demographics, COVID-19 symptoms, and experiences around SARS-CoV-2 PCR testing in the prior 2 weeks. Logistic regression was used to analyze associations with outcomes of interest.ResultsOverall, 316 (10%) of 3,058 respondents wanted/needed a test in the two weeks prior to the survey. Of these, 166 (53%) were able to get tested and 156 (94%) received results; 53% waited ≥ 8 days to get results from when they wanted/needed a test. There were no significant differences by state. Among those wanting/needing a test, getting tested was significantly less common among men (aOR: 0.46) and those reporting black race (aOR: 0.53) and more common in those reporting recent travel (aOR: 3.35).ConclusionsThere is an urgent need for a national communication strategy on who should get tested and where one can get tested. Additionally, measures need to be taken to improve access and reduce turn-around-time.

Background The availability of effective, oral direct acting antivirals (DAAs) for hepatitis C virus (HCV) treatment has put elimination of HCV as a public health challenge within reach. However, little is known about the characteristics of transmission networks of people who inject drugs (PWID). Methods Sequencing of a segment of the HCV genome was performed on samples collected from a community-based cohort of PWID between August 2005 and December 2016. Phylogenetic trees were inferred, and clusters were identified (70% bootstrap threshold; 0.04 maximum genetic distance threshold). We describe sex, race, age difference, and HIV infection status of potential transmission partners. Logistic regression was used to assess factors associated with being in an HCV cluster. Results Of 508 HCV genotype 1 viremic PWID, 8% (n = 41) were grouped into 20 clusters, consisting of 19 pairs and 1 triad. In adjusted analyses, female sex (odds ratio [OR] 2.3 [95% confidence interval (CI) 1.2–4.5]) and HIV infection (OR 5.7 [CI 2.7–11.9]) remained independently associated with being in an HCV infection cluster. Conclusions Molecular epidemiological analysis reveals that, in this cohort of PWID in Baltimore, HIV infection and female sex were associated with HCV clustering. Combination HCV prevention interventions targeting HIV infected PWID and addressing HCV infection prevention needs of women have potential to advance HCV elimination efforts.

Background Limited prior data suggest that preexisting liver disease is associated with adverse outcomes among patients with coronavirus disease 2019 (COVID-19). Fibrosis-4 (FIB-4) is a noninvasive index of readily available laboratory measurements that represents hepatic fibrosis. We evaluated the association between FIB-4 at the early stage of infection and COVID-19 outcomes. Methods FIB-4 was evaluated at admission in a cohort of 267 patients admitted with early-stage COVID-19 confirmed through reverse-transcription polymerase chain reaction assay. Hazard of ventilator use and of high-flow oxygen was estimated using Cox regression models controlled for covariates. Risks of progression to severe disease and of death/prolonged hospitalization were estimated using multivariable logistic regression models. Results Forty-one (15%) patients progressed to severe disease, 36 (14%) required high-flow oxygen support, 10 (4%) required mechanical ventilator support, and 1 died. FIB-4 between 1.45 and 3.25 was associated with a greater than 5-fold (95% confidence interval [CI], 1.2–28) increased hazard of high-flow oxygen use, a greater than 4-fold (95% CI, 1.5–14.6) increased odds of progression to severe disease, and an over 3-fold (95% CI, 1.4–7.7) increased odds of death or prolonged hospitalization. FIB-4 >3.25 was associated with a greater than 12-fold (95% CI, 2.3–68. 7) increased hazard of high-flow oxygen use and an over 11-fold (95% CI, 3.1–45) increased risk of progression to severe disease. All associations were independent of sex, number of comorbidities, and inflammatory markers (D-dimer, C-reactive protein). Conclusions FIB-4 at the early-stage of COVID-19 had an independent and dose-dependent association with adverse outcomes during hospitalization. FIB-4 provided significant prognostic value for estimating adverse outcomes among COVID-19 patients.

Background Liver fibrosis is common among HIV-infected patients. Risk factors vary by location. Understanding this variation may inform prevention strategies. We compared the prevalence and correlates of liver fibrosis among HIV-infected patients attending care clinics in Uganda. Methods This was a cross-sectional study involving 2030 HIV-infected patients attending care clinics in urban and rural Uganda. Liver fibrosis was defined as liver stiffness measurement (LSM) >7.1 KPa. Proportions and correlates of liver fibrosis were assessed and compared using logistic regression stratified by gender and site. Results Prevalence of liver fibrosis was higher among participants in the rural clinic (15% vs 11%; P = .017). History of tobacco use (urban P = .022; rural P = .035) and serologic evidence of hepatitis C infection (HCV; urban P = .028; rural P = .03) was associated with liver fibrosis in all men. Elevated liver transaminases (urban P = .002; rural P = .028) and increasing age (urban P = .008; rural P = .052) were risk factors among all women. Tobacco use among women was only a risk factor in those attending the rural clinic (P = .003), and detectable HIV viral load (P = .002) for men in the urban clinic. Conclusions Liver fibrosis is prevalent among HIV-infected persons in Uganda. HIV viral suppression and avoiding tobacco may be strategies to prevent liver fibrosis and cancer risk.

Liver fibrosis may be assessed noninvasively with transient electrography (TE). Data on the performance of TE for detecting liver fibrosis in sub-Saharan Africa are limited. We evaluated the diagnostic accuracy of TE by performing liver biopsies on persons with liver fibrosis indicated by TE. We enrolled HIV-infected and HIV-uninfected participants with TE scores consistent with at least minimal disease (liver stiffness measurement [LSM]≥7.1 kPa). Biopsies were performed and staged using the Ishak scoring system. A concordant result was defined using accepted thresholds for significant fibrosis by TE (LSM ≥ 9.3 kPa) and liver biopsy (Ishak score ≥ 2). We used modified Poisson regression methods to quantify the univariate and adjusted prevalence risk ratios (PRR) of the association between covariates and the concordance status of TE and liver biopsy in defining the presence of liver fibrosis. Of 131 participants with valid liver biopsy and TE data, only 5 participants (3.8%) had Ishak score ≥ 2 of whom 4 had LSM ≥ 9.3 kPa (sensitivity = 80%); of the 126 (96.2%) with Ishak score < 2, 76 had LSM < 9.3 kPa (specificity = 61%). In multivariable analysis, discordance was associated with female gender (adjPRR = 1.80, 95%CI 1.1-2.9; P = .019), herbal medicine use (adjPRR 1.64, 95% CI = 1.0-2.5; P = .022), exposure to lake or river water (adjPRR 2.05, 95% CI = 1.1-3.7; P = .016), and current smoking (adjPRR 1.72, 95%CI 1.0-2.9; P = .045). These data suggest that TE among rural Ugandans has low specificity for detection of histologically confirmed liver fibrosis. Caution should be exercised when using this tool to confirm significant liver fibrosis.

Background Frailty is associated with mortality and morbidity in the general geriatric population, but less is known about its impact among the aging but generally younger population with human immunodeficiency virus (HIV). Methods The impact of frailty on all-cause mortality during 6 years of follow-up and incident comorbidity during 4 years of follow-up was assessed among 598 HIV-positive and 550 comparable HIV-negative participants aged ≥ 45 years of the AGEhIV Cohort Study. Frailty encompasses 5 domains; weight loss, low physical activity, exhaustion, decreased grip strength, and slow gait speed. Presence of ≥ 3 denotes frailty, 1–2 prefrailty, and 0 robust. Multivariable Cox and logistic regression models were used to assess the independent relationships of frailty with both outcomes, adjusting for HIV infection and traditional risk factors. Results At baseline, 7.5% (n = 86) of participants were frail. During follow-up, 38 participants died. Mortality rate was significantly higher among frail participants: 25.7/1000 person-years of follow-up (PYFU) (95% confidence interval [CI], 14.2–46.4) compared with prefrail (7.2/1000 PYFU [95% CI, 4.7–11.2]) and robust (2.3/1000 PYFU [95% CI, 1.1–4.9]). In fully adjusted analyses, frailty remained strongly associated with death (hazard ratio, 4.6 [95% CI, 1.7–12.5]) and incident comorbidity (odds ratio, 1.9 [95% CI, 1.1–3.1]). No interactions were observed between frailty and HIV status in all analyses. Conclusions Frailty is a strong predictor of both mortality and incident comorbidity independent from other risk factors. Clinical Trials Registration NCT01466582.

BackgroundCurrent mitigation strategies for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) rely on population-wide adoption of non-pharmaceutical interventions (NPIs). Collecting demographically and geographically resolved data on NPIs and their association with SARS-CoV-2 infection history can provide critical information related to reopening geographies.MethodsWe sampled 1,030 individuals in Maryland from June 17 – June 28, 2020 to capture socio-demographically and geographically resolved information about NPI adoption, access to SARS-CoV-2 testing, and examine associations with self-reported SARS-CoV-2 positivity.ResultsMedian age of the sample was 43 years and 45% were men; Whites and Blacks/African Americans represented 60% and 23%, respectively. Overall, 96% of the sample reported traveling outside their home for non-employment related services: most commonly cited reasons were essential services (92%) and visiting friends/family (66%). Use of public transport was reported by 18% of respondents. 68% reported always social distancing indoors and 53% always wearing masks indoors; indoor social distancing was significantly less common among younger vs. older individuals, and race/ethnicity and income were significantly associated with mask use (pConclusionsUsing a rapid cost-efficient approach, we highlight the role of movement and social distancing on SARS-CoV-2 transmission risk. Continued monitoring of NPI uptake, access to testing, and the subsequent impact on SARS-CoV-2 transmission will be critical for pandemic control and decisions about reopening geographies.Key PointsWhat we didWe utilized an online survey approach to sample residents of Maryland consistent with the distributions of age, gender, race/ethnicity, and income in the state.We asked questions about places (and the frequency) visited for essential and nonessential services in the prior 2 weeks, practice of non-pharmaceutical interventions (NPIs) while visiting various places, and access to SARS-CoV-2 testing.We characterized how movement and adoption of NPIs differed by key demographics (age, race, gender, income) and how these were associated with self-reported SARS-CoV-2 positivity.What we found96% of the sample reported traveling for either essential or non-essential services in the prior 2 weeks; 82% reported traveling for non-essential services.The adoption of NPIs varied by age, race/ethnicity, and income.Self-reported SARS-CoV-2 positivity was highest among Latinos followed by Blacks/African Americans and then Whites.The more frequently a person traveled/visited places for non-essential services, the more likely they were to report ever having tested positive for SARS-CoV-2.The strict practice of social distancing was associated with a lower likelihood of ever having tested positive for SARS-CoV-2; moreover, strict social distancing attenuated the association between most forms of movement and SARS CoV-2 positivityUsing public transport and attending places of worship remained associated with a higher likelihood of having tested positive for SARS-CoV-2 even when practicing social distancing.About 70% of people who wanted a SARS-CoV-2 test were able to get a test but there were delays of a week or more from wanting a test to getting a result among the majority of the sample.What it meansThe more people move the more likely they are to test positive for SARS-CoV-2; if you must travel, practice social distancing as it reduces the likelihood of testing positive.Avoid public transport to the extent possible.Strategies to reduce time from wanting a test to getting a result are critical to enhance early case detection and isolation to curb transmission.

Author(s): Bourgi, Kassem; Jenkins, Cathy A; Rebeiro, Peter F; Palella, Frank; Moore, Richard D; Altoff, Keri N; Gill, John; Rabkin, Charles S; Gange, Stephen J; Horberg, Michael A; Margolick, Joseph; Li, Jun; Wong, Cherise; Willig, Amanda; Lima, Viviane D; Crane, Heidi; Thorne, Jennifer; Silverberg, Michael; Kirk, Gregory; Mathews, William C; Sterling, Timothy R; Lake, Jordan; Koethe, John R; North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) | Abstract: IntroductionWeight gain following antiretroviral therapy (ART) initiation is common, potentially predisposing some persons with HIV (PWH) to cardio-metabolic disease. We assessed relationships between ART drug class and weight change among treatment-naive PWH initiating ART in the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD).MethodsAdult, treatment-naive PWH in NA-ACCORD initiating integrase strand transfer inhibitor (INSTI), protease inhibitor (PI) or non-nucleoside reverse-transcriptase inhibitor (NNRTI)-based ART on/after 1 January 2007 were followed through 31 December 2016. Multivariate linear mixed effects models estimated weight up to five years after ART initiation, adjusting for age, sex, race, cohort site, HIV acquisition mode, treatment year, and baseline weight, plasma HIV-1 RNA level and CD4+ cell count. Due to shorter follow-up for PWH receiving newer INSTI drugs, weights for specific INSTIs were estimated at two years. Secondary analyses using logistic regression and all covariates from primary analyses assessed factors associated with g10% weight gain at two and five years.ResultsAmong 22,972 participants, 87% were male, and 41% were white. 49% started NNRTI-, 31% started PI- and 20% started INSTI-based regimens (1624 raltegravir (RAL), 2085 elvitegravir (EVG) and 929 dolutegravir (DTG)). PWH starting INSTI-based regimens had mean estimated five-year weight change of +5.9kg, compared to +3.7kg for NNRTI and +5.5kg for PI. Among PWH starting INSTI drugs, mean estimated two-year weight change was +7.2kg for DTG, +5.8kg for RAL and +4.1kg for EVG. Women, persons with lower baseline CD4+ cell counts, and those initiating INSTI-based regimens had higher odds of g10% body weight increase at two years (adjusted odds ration=n1.37, 95% confidence interval: 1.20 to 1.56 vs. NNRTI).ConclusionsPWH initiating INSTI-based regimens gained, on average, more weight compared to NNRTI-based regimens. This phenomenon may reflect heterogeneous effects of ART agents on body weight regulation that require further exploration.

Background Prescription drug misuse and its consequences (e.g., overdose) are a major public health concern. While national focus has been on opioids, misuse of sedatives/tranquilizers also occurs. Here we describe the use, correlates, and sources of prescription drugs in a community-based cohort of people who inject drugs (PWID). Methods We included participants of the AIDS Linked to the IntraVenous Experience (ALIVE) study in follow-up in 2014. We defined prescription drug use as use of opioids or sedatives/tranquilizers considering both medical “prescribed by a doctor” and non-medical sources “obtained from the street/friend/relative.” Correlates were evaluated separately for opioids and sedatives/tranquilizers using logistic regression and included socioeconomic factors, health conditions, substance use, and health care access. Results 823 predominantly African-American (90.6%) and male (66.3%) ALIVE participants with a median age of 55 were included. Prevalence of prescription opioid and sedative/tranquilizer use was 25.3% and 16.3% respectively. While the majority (70%) obtained prescription drugs exclusively through medical sources, the 30% who reported any non-medical source were also more likely to use other substances by injection and non-injection routes. PWID reporting prescription drug use (from medical and non-medical sources) were significantly more likely to report other substance use, mental health disorder, and recent contact with health care providers or detoxification facilities. Conclusions Prescription drug use was highly prevalent among PWID. While it is difficult to distinguish medically indicated from non-medical use, high levels of prescription drug use in conjunction with other drugs and alcohol heightens the risk for drug overdose and other adverse consequences.

Exosomes are nanovesicles released from most cell types including immune cells. Prior studies suggest exosomes play a role in HIV pathogenesis, but little is known about exosome cargo in relation to immune responses and oxidative stress. Here, we characterize plasma exosomes in HIV patients and their relationship to immunological and oxidative stress markers. Plasma exosome fractions were isolated from HIV-positive subjects on ART with suppressed viral load and HIV-negative controls. Exosomes were characterized by electron microscopy, nanoparticle tracking, immunoblotting, and LC-MS/MS proteomics. Plasma exosomes were increased in HIV-positive subjects compared to controls, and correlated with increased oxidative stress markers (cystine, oxidized cys-gly) and decreased PUFA (DHA, EPA, DPA). Untargeted proteomics detected markers of exosomes (CD9, CD63, CD81), immune activation (CD14, CRP, HLA-A, HLA-B), oxidative stress (CAT, PRDX1, PRDX2, TXN), and Notch4 in plasma exosomes. Exosomal Notch4 was increased in HIV-positive subjects versus controls and correlated with immune activation markers. Treatment of THP-1 monocytic cells with patient-derived exosomes induced expression of genes related to interferon responses and immune activation. These results suggest that exosomes in ART-treated HIV patients carry proteins related to immune activation and oxidative stress, have immunomodulatory effects on myeloid cells, and may have pro-inflammatory and redox effects during pathogenesis.

Objective The objective of this study was to examine trends in fatal and nonfatal overdose in a community-based sample of current and former people who inject drugs (PWID). Methods Data from 4826 current and former PWID from the AIDS Linked to the IntraVenous Experience (ALIVE) observational cohort study in Baltimore, Maryland, were used to characterize fatal and nonfatal overdose rates from 1998 to 2019. Poisson regression was used to examine factors associated with nonfatal overdose and differences by race among 1052 PWID between 2014 and 2019. Results Fatal overdose rates reached a high of 13 per 1000 person-years in 2018. Among 1052 current and former PWID, of whom 75% were Black and one-third were female, the nonfatal overdose rate of 529 per 1000 person-years in 2019 was 8 times higher than 2014 (incidence rate ratio [IRR]=7.76, 95% CI: 3.35, 18.0). The annual adjusted increase in nonfatal overdose rate was 53% among Black PWID (IRR=1.53, 95% CI: 1.34, 1.75), compared to 14% among White PWID (IRR=1.14, 95% CI: 0.88, 1.46). Urban residence, opioid use, depressive symptoms, and hepatitis C infection were positively associated with nonfatal overdose among Black PWID. Recent injection drug use and tranquilizer use was associated with increased overdose among Black and White PWID. Conclusions Rates of fatal and nonfatal overdose were high and increased from 2014 to 2019 among current and former PWID, with the most dramatic increases in nonfatal overdose observed among Black PWID. These findings highlight the urgent need for additional resources to reduce the differential harms associated with opioids by race.

Although the introduction of antiretroviral therapy has rendered HIV a chronic illness, inconsistent engagement in HIV care by key populations limits its public health impact. Poor engagement in care is especially prevalent among vulnerable populations with mental health and substance use disorders. Beyond structural and health system considerations, psychosocial factors may present challenges to sustained engagement. We conducted a qualitative study using in-depth interviews with 31 primarily African American, urban-based individuals, many with past or current drug use and mental disorders, living with HIV. Participants identified several psychosocial barriers that detract from their motivation to attend appointments and take medication. These included mental distress or detachment over a lack of purpose in life; denial about the need to be engaged in care; insufficient trust in the efficacy of care or the health system; deaths of loved ones leading to bereavement or loss of social support; and engagement in specific avoidance behaviors like drugs and alcohol. The study findings suggest that more comprehensive HIV care, which integrates mental health and substance abuse services in order to enhance meaning and address coping and grief, may be important. Considering these services in addition to improving the logistical components of care such as cues/reminders, accessibility, and patient-provider communication may improve intervention packages.

Background Despite the availability of curative treatment for hepatitis C virus (HCV) infection, because of cost, treatment is often denied until liver fibrosis has progressed to at least moderate fibrosis and, in some cases, cirrhosis. That practice is justified on assumptions that there are no medical consequences to having moderate disease and that disease stage transitions can be anticipated. Methods We performed transient elastography on 964 people chronically infected with HCV with a history of injection drug use living in Baltimore, Maryland. Liver stiffness was evaluated semiannually from 2006 to 2014 using validated cutoffs for moderate fibrosis (8.0-12.3 kPa) and severe fibrosis/cirrhosis (>12.3 kPa). Results Among 964 persons, 62%, 23% and 15% had baseline measurements suggestive of no/mild fibrosis, moderate fibrosis, and severe fibrosis/cirrhosis, respectively. All-cause and nonaccidental mortality were elevated in persons with moderate fibrosis (adjusted hazard ratio [aHR], 1.42 [95% confidence interval {CI}, .96-2.11]; aHR, 1.66 [95% CI, 1.06-2.59], respectively) after adjustment for sociodemographics, substance use, and human immunodeficiency virus status. Despite the increased risk of mortality among those with moderate fibrosis, no combination of demographic, behavioral, and clinical factors, nor changes in stiffness measurements themselves could predict the transition from mild to moderate fibrosis with sufficiently high diagnostic accuracy (C-statistic = 0.72 for best-performing model). Conclusions Delaying treatment for anyone chronically infected with HCV regardless of fibrosis stage may be detrimental given the increased risk of mortality even for those with moderate disease and the inability to predict the transition from mild to moderate disease.

Background People living with human immunodeficiency virus (HIV; PLWH) have a markedly elevated anal cancer risk, largely due to loss of immunoregulatory control of oncogenic human papillomavirus infection. To better understand anal cancer development and prevention, we determined whether recent, past, cumulative, or nadir/peak CD4+ T-cell count (CD4) and/or HIV-1 RNA level (HIV RNA) best predict anal cancer risk. Methods We studied 102 777 PLWH during 1996–2014 from 21 cohorts participating in the North American AIDS Cohort Collaboration on Research and Design. Using demographics-adjusted, cohort-stratified Cox models, we assessed associations between anal cancer risk and various time-updated CD4 and HIV RNA measures, including cumulative and nadir/peak measures during prespecified moving time windows. We compared models using the Akaike information criterion. Results Cumulative and nadir/peak CD4 or HIV RNA measures from approximately 8.5 to 4.5 years in the past were generally better predictors for anal cancer risk than their corresponding more recent measures. However, the best model included CD4 nadir (ie, the lowest CD4) from approximately 8.5 years to 6 months in the past (hazard ratio [HR] for Conclusions Our results are consistent with anal cancer promotion by severe, prolonged HIV-induced immunosuppression. Nadir and cumulative CD4 may represent useful markers for identifying PLWH at higher anal cancer risk.

With most countries in sub-Saharan Africa (SSA) lagging behind schedule to implement a comprehensive viral hepatitis elimination strategy, several barriers to accurate information and hepatitis B virus (HBV) services still exist, that are unique to different regions. In an obstetric population of a high HBV burden SSA setting without antenatal HBV services, we systematically evaluated perceptions and prevention behavioral intentions in relation to HBV and liver cancer.Eligible consenting pregnant women were recruited from public health care facilities in the central and northern regions of Uganda, between October 2016 and December 2017. Standardized procedures and instruments based on the health belief model and theory of planned behavior were used to collect data on socio-demographic characteristics, HBV perceptions and behavioral intentions. Descriptive analysis using Chi-square tests was done to obtain distribution of respondents by levels of perceived risk of HBV and liver cancer for themselves, their child under 5 years and their spouse. Modified Poisson regression analyses were used to evaluate relationships between perception variables and different behavioral outcomes (intention to screen, vaccinate and treat HBV).Perceived risk (PRR = 0.95(0.90-1.00), p = 0.055) was inversely associated with intention to screen for HBV. Conversely, perceived self-efficacy showed a consistent association with intention to screen for HBV (PRR = 1.18(1.10-1.23) p = 0.005), to vaccinate (PRR = 1.20(1.05-1.36) p = 0.006) and to seek treatment for HBV (PRR = 1.40(1.18-1.67) p 0.001). Women from the north, compared to the central region (PRR = 1.76 (1.13-2.72) p = 0.012), and those who self-identified as Catholic (PRR = 1.85 (0.99-3.56) p = 0.056), and as Protestant, (PRR = 2.22 (1.22-4.04) p = 0.002), were more likely to have higher perceived self-efficacy, compared to Muslims. Age and education were not related to perceived self-efficacy.Women in both regions hold incorrect perceptions of HBV and liver cancer risk, with women from the central reporting higher perceived risk than those from the north. High perceived self-efficacy influenced intention to participate in HBV prevention. Programs and policies geared towards enhancing HBV prevention in this sub-population may consider socio-cultural factors observed to influence prevention behaviors. These findings may guide HBV interventions aimed at improving capacity to seek HBV prevention services, thereby promoting HBV micro-elimination in this sub-population.

BackgroundWith most countries in sub-Saharan Africa (SSA) lagging behind schedule to implement a comprehensive viral hepatitis elimination strategy, several barriers to accurate information and hepatitis B virus (HBV) services still exist, that are unique to different regions. In an obstetric population of a high HBV burden SSA setting without antenatal HBV services, we systematically evaluated perceptions and prevention behavioral intentions in relation to HBV and liver cancer.MethodsEligible consenting pregnant women were recruited from public health care facilities in the central and northern regions of Uganda, between October 2016 and December 2017. Standardized procedures and instruments based on the health belief model and theory of planned behavior were used to collect data on socio-demographic characteristics, HBV perceptions and behavioral intentions. Descriptive analysis using Chi-square tests was done to obtain distribution of respondents by levels of perceived risk of HBV and liver cancer for themselves, their child under 5 years and their spouse. Modified Poisson regression analyses were used to evaluate relationships between perception variables and different behavioral outcomes (intention to screen, vaccinate and treat HBV).ResultsPerceived risk (PRR = 0.95(0.90–1.00),p = 0.055) was inversely associated with intention to screen for HBV. Conversely, perceived self-efficacy showed a consistent association with intention to screen for HBV (PRR = 1.18(1.10–1.23)p = 0.005), to vaccinate (PRR = 1.20(1.05–1.36)p = 0.006) and to seek treatment for HBV (PRR = 1.40(1.18–1.67)p p = 0.012), and those who self-identified as Catholic (PRR = 1.85 (0.99–3.56)p = 0.056), and as Protestant, (PRR = 2.22 (1.22–4.04)p = 0.002), were more likely to have higher perceived self-efficacy, compared to Muslims. Age and education were not related to perceived self-efficacy.ConclusionWomen in both regions hold incorrect perceptions of HBV and liver cancer risk, with women from the central reporting higher perceived risk than those from the north. High perceived self-efficacy influenced intention to participate in HBV prevention. Programs and policies geared towards enhancing HBV prevention in this sub-population may consider socio-cultural factors observed to influence prevention behaviors. These findings may guide HBV interventions aimed at improving capacity to seek HBV prevention services, thereby promoting HBV micro-elimination in this sub-population.

Hepatitis B virus (HBV) infection is a leading cause of end-stage liver disease (ESLD) and hepatocellular carcinoma (HCC) in HIV. Factors contributing to the high rates of liver complications among HIV/HBV-coinfected individuals remain unknown.North American AIDS Cohort Collaboration on Research and Design.We performed a retrospective cohort study among HIV/HBV-coinfected patients in 10 US and Canadian cohorts of the North American AIDS Cohort Collaboration on Research and Design that validated ESLD (ascites, spontaneous bacterial peritonitis, variceal hemorrhage, and/or hepatic encephalopathy) and HCC diagnoses from 1996 to 2010. Multivariable Cox regression was used to examine adjusted hazard ratios [aHRs with 95% confidence interval (CIs)] of liver complications (first occurrence of ESLD or HCC) associated with hypothesized determinants and with increasing durations of HIV suppression (≤500 copies/mL).Among 3573 HIV/HBV patients with 13,790 person-years of follow-up, 111 liver complications occurred (incidence rate = 8.0 [95% CI: 6.6 to 9.7] events/1000 person-years). Rates of liver complication were increased with non-black/non-Hispanic race [aHR = 1.76 (1.13-2.74)], diabetes mellitus [aHR = 2.07 (1.20-3.57)], lower time-updated CD4 cell count [200 cells/mm: aHR = 2.59 (1.36-4.91); 201-499 cells/mm: aHR = 1.75 (1.01-3.06) versus ≥500 cells/mm], heavy alcohol use [aHR = 1.58 (1.04-2.39)], and higher FIB-4 at start of follow-up [3.25: aHR = 9.79 (5.73-16.74); 1.45-3.25: aHR = 3.20 (1.87-5.47) versus FIB-41.45]. HIV suppression for ≥6 months was associated with lower liver complication rates compared with those with unsuppressed HIV [aHR = 0.56 (0.35-0.91)].Non-black/non-Hispanic race, diabetes, lower CD4 cell count, heavy alcohol use, and advanced liver fibrosis were determinants of liver complications among HIV/HBV patients. Sustained HIV suppression should be a focus for HIV/HBV-coinfected patients to reduce the risks of ESLD/HCC.

Background Bacterial infection is a major cause of morbidity and mortality for persons who inject drugs (PWID). Injection cessation may help abrogate such infections, but maintaining complete cessation is challenging. Limited data exists on the role of reduced injection intensity on invasive bacterial infection risk. We sought to evaluate decreased risk for bacterial infections following cessation and substantive reduction in the injection intensity. Methods Participants were persons in the AIDS Linked to the Intravenous Experience (ALIVE) cohort with initial high-frequency injection drug use (> 1 daily). Pooled logistic regression with generalized estimating equations was used to estimate risk for invasive bacterial infection (pneumonia, endocarditis, or sepsis) among participants achieving complete injection cessation or reduced injection intensity relative to those with sustained high-frequency use. Results Of 2247 study participants with 12,469 paired study visits, complete injection cessation was achieved at 13.5% and reduced injection intensity at 25.5% of study visits. Adjusting for sociodemographics and HIV status, injection cessation was associated with a 54% reduction of bacterial infection at 3 months (odds ratio [OR] 0.46, 95% CI 0.25–0.84) and a 46% reduction at 6 months (OR 0.54, 95% CI 0.36–0.81). Reduced injection intensity was associated with a 36% reduction of infection at 3 months (OR 0.64, 95% CI 0.43–0.96) and a 26% reduction at 6 months (OR 0.74, 95% CI 0.56–0.98). Conclusions Both complete cessation and reduced injection frequency demonstrate substantial benefit in reducing invasive bacterial infection risk among PWID. With high rates of relapse into injection use, targeting sustained reductions in drug use intensity may be a key harm reduction modality for improving clinical outcomes in this population. Electronic supplementary material The online version of this article (10.1186/s12954-019-0312-8) contains supplementary material, which is available to authorized users.

Introduction Overdose is a leading cause of death in the United States, especially among people who inject drugs (PWID). Improving naloxone access and carrying among PWID may offset recent increases in overdose mortality associated with the influx of synthetic opioids in the drug market. This study characterized prevalence and correlates of several naloxone outcomes among PWID. Methods During 2018, a survey to assess experience with naloxone was administered to 915 participants in the AIDS Linked to the IntraVenous Experience (ALIVE) study, an ongoing community-based observational cohort of people who currently inject or formerly injected drugs in Baltimore, Maryland. We examined the associations of naloxone outcomes (training, supply, use, and regular possession) with socio-demographic, substance use and healthcare utilization factors among PWID in order to characterize gaps in naloxone implementation among this high-risk population. Results Median age was 56 years, 34% were female, 85% were African American, and 31% recently injected. In the past six months, 46% (n = 421) reported receiving training in overdose prevention, 38% (n = 346) had received a supply of naloxone, 9% (n = 85) had administered naloxone, and 9% (n = 82) reported usually carrying a supply of naloxone. Recent non-fatal overdose was not associated with any naloxone outcomes in adjusted analysis. Active opioid use (aOR = 2.10, 95% CI: 1.03, 4.28) and recent treatment of alcohol or substance use disorder (aOR = 2.01, 95% CI: 1.13, 3.56) were associated with regularly carrying naloxone. Conclusion Further work is needed to encourage PWID to carry and effectively use naloxone to decrease rates of fatal opioid overdose. While accessing treatment for substance use disorder was positively associated with carrying naloxone, EMS response to 911 calls for overdose, the emergency department, and syringe services programs may be settings in which naloxone access and carrying could be encouraged among PWID.

Introduction Mental health care may mitigate negative consequences related to substance use and bolster engagement in care for drug dependence. Despite the increased risk of depression among people who inject drugs (PWID), the longitudinal relationship of depression symptoms with depression and drug treatment utilization in this population remains uncharacterized. Methods Data on depressive symptoms and depression treatment from current and former PWID in the ALIVE (AIDS Linked to the IntraVenous Experience) community-based cohort who had ≥3 study visits from July 2005 to June 2016 were included. We used logistic regression analysis with generalized estimating equations to examine factors associated with depression treatment in the 12 months following reported major depressive symptoms (CES-D ≥ 23) in the absence of treatment. We further examined the association between depression, depression treatment, and subsequent engagement in drug treatment among those with active substance use or alcohol dependence. Results Of the 1544 participants, 34% were female, the median age was 51 years, and 91% were African-American. PWID reported major depressive symptoms at 22% of study visits. In adjusted analysis, acute emergency care, suicidal ideation, and recent alcohol or drug treatment were positively associated with initiating depression treatment. Depression was positively associated with subsequent treatment for substance dependence among those actively using (aOR = 1.30, 95% CI: 1.10–1.53). Conclusions PWID experience a high burden of depressive symptoms with significant unmet need of treatment for depression. Our findings suggest that mental health providers should bolster connections to chronic disease and alcohol and drug treatment providers.

BACKGROUND: Low mitochondrial DNA (mtDNA) copy number (CN) is a predictor of adverse aging outcomes, and its status may be altered in human immunodeficiency virus (HIV)–infected persons. This study evaluated the cross-sectional and longitudinal change of mtDNA CN by HIV markers. METHODS: mtDNA CN was measured in the ALIVE (AIDS Linked to the Intravenous Experience) cohort of persons with a history of injecting drugs. Multivariable linear regression models controlling for demographic characteristics, behavior, and hepatitis C virus (HCV) seropositivity assessed the relationship of mtDNA CN to HIV markers (CD4(+) T-cell counts, viral load, antiretroviral therapy [ART] use). Linear mixed models tested the association between HIV markers and age-related mtDNA CN trajectories. RESULTS: Among 741 individuals at baseline, 436 (59%) were infected with HIV. HIV-infected individuals who had lower CD4(+) T-cell counts (P = .01), had higher viral loads (P < .01), and were not receiving ART (P < .01) had significantly lower mtDNA CNs than uninfected persons; there was no difference between participants who were uninfected and HIV-infected individuals who had well-controlled HIV levels. In longitudinal follow-up of 507 participants, from age 50 years onward, mtDNA CN declined significantly faster among HIV-infected individuals than among HIV-uninfected persons (−0.03 units of change/year vs 0.006 units of change/year; P = .04), even among infected individuals with well-controlled HIV. CONCLUSION: Before 50 years of age, mtDNA CN is similar between HIV-infected individuals with well-controlled HIV and uninfected persons, but from age 50 onward, mtDNA CN declines significantly faster among all infected individuals than among HIV-uninfected persons.

BackgroundResearch is needed to better understand relations between immunosuppression and HIV viraemia and risk for non-Hodgkin lymphoma, a common cancer in people living with HIV. We aimed to identify key CD4 count and HIV RNA (viral load) predictors of risk for non-Hodgkin lymphoma, overall and by subtype.MethodsWe studied people living with HIV during 1996-2014 from 21 Canadian and US cohorts participating in the North American AIDS Cohort Collaboration on Research and Design. To determine key independent predictors of risk for non-Hodgkin lymphoma, we assessed associations with time-updated recent, past, cumulative, and nadir or peak measures of CD4 count and viral load, using demographics-adjusted, cohort-stratified Cox models, and we compared models using Akaike's information criterion.FindingsOf 102 131 people living with HIV during the study period, 712 people developed non-Hodgkin lymphoma. The key independent predictors of risk for overall non-Hodgkin lymphoma were recent CD4 count (ie, lagged by 6 months

Background & aimsSpontaneous clearance of hepatitis C virus (HCV) occurs in approximately 30% of infected persons and less often in populations of African ancestry. Variants in major histocompatibility complex (MHC) and in interferon lambda genes are associated with spontaneous HCV clearance, but there have been few studies of these variants in persons of African ancestry. We performed a dense multi-ancestry genome-wide association study of spontaneous clearance of HCV, focusing on individuals of African ancestry.MethodsWe performed genotype analyses of 4423 people from 3 ancestry groups: 2201 persons of African ancestry (445 with HCV clearance and 1756 with HCV persistence), 1739 persons of European ancestry (701 with HCV clearance and 1036 with HCV persistence), and 486 multi-ancestry Hispanic persons (173 with HCV clearance and 313 with HCV persistence). Samples were genotyped using Illumina (San Diego, CA) arrays and statistically imputed to the 1000 Genomes Project. For each ancestry group, the association of single-nucleotide polymorphisms with HCV clearance was tested by log-additive analysis, and then a meta-analysis was performed.ResultsIn the meta-analysis, significant associations with HCV clearance were confirmed at the interferon lambda gene locus IFNL4-IFNL3 (19q13.2) (P= 5.99× 10-50) and the MHC locus 6p21.32 (P= 1.15× 10-21). We also associated HCV clearance with polymorphisms in the G-protein-coupled receptor 158 gene (GPR158) at 10p12.1 (P= 1.80× 10-07). These 3 loci had independent, additive effects of HCV clearance, and account for 6.8% and 5.9% of the variance of HCV clearance in persons of European and African ancestry, respectively. Persons of African or European ancestry carrying all 6 variants were 24-fold and 11-fold, respectively, more likely to clear HCV infection compared with individuals carrying none or 1 of the clearance-associated variants.ConclusionsIn a meta-analysis of data from 3 studies, we found variants in MHC genes, IFNL4-IFNL3, and GPR158 to increase odds of HCV clearance in patients of European and African ancestry. These findings could increase our understanding of immune response to and clearance of HCV infection.

Background: Adults with HIV have an increased burden of non-AIDS-defining cancers, myocardial infarction, end-stage liver disease, and end-stage renal disease. The objective of this study was to estimate the population attributable fractions (PAFs) of preventable or modifiable HIV-related and traditional risk factors for non-AIDS-defining cancers, myocardial infarction, end-stage liver disease, and end-stage renal disease outcomes. Methods: We included participants receiving care in academic and community-based outpatient HIV clinical cohorts in the USA and Canada from Jan 1, 2000, to Dec 31, 2014, who contributed to the North American AIDS Cohort Collaboration on Research and Design and who had validated non-AIDS-defining cancers, myocardial infarction, end-stage liver disease, or end-stage renal disease outcomes. Traditional risk factors were tobacco smoking, hypertension, elevated total cholesterol, type 2 diabetes, renal impairment (stage 4 chronic kidney disease), and hepatitis C virus and hepatitis B virus infections. HIV-related risk factors were low CD4 count (400 copies per mL), and history of a clinical AIDS diagnosis. PAFs and 95% CIs were estimated to quantify the proportion of outcomes that could be avoided if the risk factor was prevented. Findings: In each of the study populations for the four outcomes (1405 of 61 500 had non-AIDS-defining cancer, 347 of 29 515 had myocardial infarctions, 387 of 35 044 had end-stage liver disease events, and 255 of 35 620 had end-stage renal disease events), about 17% were older than 50 years at study entry, about 50% were non-white, and about 80% were men. Preventing smoking would avoid 24% (95% CI 13–35) of these cancers and 37% (7–66) of the myocardial infarctions. Preventing elevated total cholesterol and hypertension would avoid the greatest proportion of myocardial infarctions: 44% (30–58) for cholesterol and 42% (28–56) for hypertension. For liver disease, the PAF was greatest for hepatitis C infection (33%; 95% CI 17–48). For renal disease, the PAF was greatest for hypertension (39%; 26–51) followed by elevated total cholesterol (22%; 13–31), detectable HIV RNA (19; 9–31), and low CD4 cell count (13%; 4–21). Interpretation: The substantial proportion of non-AIDS-defining cancers, myocardial infarction, end-stage liver disease, and end-stage renal disease outcomes that could be prevented with interventions on traditional risk factors elevates the importance of screening for these risk factors, improving the effectiveness of prevention (or modification) of these risk factors, and creating sustainable care models to implement such interventions during the decades of life of adults living with HIV who are receiving care. Funding: National Institutes of Health, US Centers for Disease Control and Prevention, the US Agency for Healthcare Research and Quality, the US Health Resources and Services Administration, the Canadian Institutes of Health Research, the Ontario Ministry of Health and Long Term Care, and the Government of Alberta.