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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

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 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.

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.

Author(s): Drummond, M Bradley; Huang, Laurence; Diaz, Philip T; Kirk, Gregory D; Kleerup, Eric C; Morris, Alison; Rom, William; Weiden, Michael D; Zhao, Enxu; Thompson, Bruce; Crothers, Kristina | Abstract: ObjectiveHIV-infected individuals are susceptible to development of chronic lung diseases, but little is known regarding the prevalence and risk factors associated with different spirometric abnormalities in this population. We sought to determine the prevalence, risk factors and performance characteristics of risk factors for spirometric abnormalities among HIV-infected individuals.DesignCross-sectional cohort study.MethodsWe analyzed cross-sectional US data from the NHLBI-funded Lung-HIV consortium - a multicenter observational study of heterogeneous groups of HIV-infected participants in diverse geographic sites. Logistic regression analysis was performed to determine factors statistically significantly associated with spirometry patterns.ResultsA total of 908 HIV-infected individuals were included. The median age of the cohort was 50 years, 78% were men and 68% current smokers. An abnormal spirometry pattern was present in 37% of the cohort: 27% had obstructed and 10% had restricted spirometry patterns. Overall, age, smoking status and intensity, history of Pneumocystis infection, asthma diagnosis and presence of respiratory symptoms were independently associated with an abnormal spirometry pattern. Regardless of the presence of respiratory symptoms, five HIV-infected participants would need to be screened with spirometry to diagnose two individuals with any abnormal spirometry pattern.ConclusionsNearly 40% of a diverse US cohort of HIV-infected individuals had an abnormal spirometry pattern. Specific characteristics including age, smoking status, respiratory infection history and respiratory symptoms can identify those at risk for abnormal spirometry. The high prevalence of abnormal spirometry and the poor predictive capability of respiratory symptoms to identify abnormal spirometry should prompt clinicians to consider screening spirometry in HIV-infected populations.

Objective To incorporate preexposure prophylaxis and other biomedical or intensive behavioral interventions into the care of injection drug users (IDUs), health care providers need validated, rapid, risk screening tools for identifying persons at highest risk of incident HIV infection. Methods To develop and validate a brief screening tool for assessing the risk of contracting HIV (ARCH), we included behavioral and HIV test data from 1904 initially HIV-uninfected men and women enrolled and followed in the AIDS Linked to the Intravenous Experience prospective cohort study between 1988 and 2008. Using logistic regression analyses with generalized estimating equations, we identified significant predictors of incident HIV infection, then rescaled and summed their regression coefficients to create a risk score. Results The final logistic regression model included age, engagement in a methadone maintenance program, and a composite injection risk score obtained by counting the number of the following 5 behaviors reported during the past 6 months: injection of heroin, injection of cocaine, sharing a cooker, sharing needles, or visiting a shooting gallery. The area under the receiver operating characteristic curve was 0.720; possible scores on the index ranged from 0 to 100 and a score 46 or greater had a sensitivity of 86.2% and a specificity of 42.5%, appropriate for a screening tool. Discussion We developed an easy to administer 7-question screening tool with a cutoff that is predictive of incident HIV infection in a large prospective cohort of IDUs in Baltimore. The ARCH-IDUs screening tool can be used to prioritize persons who are injecting illicit drugs for consideration of preexposure prophylaxis and other intensive HIV prevention efforts.

BACKGROUND HIV and hepatitis C virus (HCV) infections may increase interleukin-6 (IL-6) and C-reactive protein (CRP). However, relationships between inflammatory biomarkers, chronic viral infections, clinical factors, and behavioral factors remain poorly understood. METHODS Using linear regression, we modeled cross-sectional associations between loge IL-6 or loge CRP levels and HCV, HIV, injection drug use, and comorbidity among 1191 injection drug users. RESULTS Mean age was 47 years, 46.0% reported currently injecting drugs, 59.0% were HCV monoinfected, and 27% were HCV/HIV coinfected. In multivariable models, higher loge IL-6 was associated with HCV monoinfection [β = 0.191, 95% confidence interval (CI): 0.043 to 0.339] and HCV/HIV coinfection (β = 0.394, 95% CI: 0.214 to 0.574). In contrast, HCV monoinfection (β = -0.523, 95% CI: -0.275 to -0.789) and HCV/HIV coinfection (β = -0.554 95% CI: -0.260 to -0.847) were associated with lower CRP. Lower CRP with HCV infection was independent of liver fibrosis severity, synthetic function, or liver injury markers; CRP decreased with higher HCV RNA. Increased injection intensity was associated with higher IL-6 (P = 0.003) and CRP (P < 0.001); increasing comorbidity (P < 0.001) and older age (P = 0.028) were associated with higher IL-6; older age was associated with higher CRP among HCV-uninfected participants (P = 0.021). CONCLUSION HIV and HCV infections contribute to chronic inflammation; however, reduced CRP possibly occurs through HCV-mediated mechanisms. Findings highlight potentially modifiable contributors to inflammation.

The advancement of anti-retroviral therapy (ART) has led to improved survival and longer life expectancy for persons living with human immunodeficiency virus (HIV) infection.[1-3] Subsequently there is increased recognition of development of age-associated chronic diseases (e.g., cardiovascular, metabolic, renal, neurological) and non-AIDS-defining malignancies occurring in these individuals.[4-8] Emerging data suggests an increased prevalence of chronic lung disease in HIV-infected individuals, the spectrum of which includes both chronic airflow obstruction and restrictive lung disease.[9-12] HIV-infection has been shown to increase the diagnosis of self-reported and administratively diagnosed COPD.[13, 14] We have previously shown that the odds of airflow obstruction were increased >3-fold among HIV-infected individuals with the highest plasma viral load independent of smoking compared to epidemiologically similar HIV-negative individuals.[15] Respiratory infections, increased in HIV-infected individuals, are associated with restrictive lung disease.[12] Beyond these cross-sectional reports, few studies have evaluated longitudinal lung function decline among HIV-infected persons.[12, 16] Because earlier studies were prior to widespread ART availability and recent studies were limited by small numbers of persons, short duration of follow-up, and lack of HIV-negative comparator groups, the independent effect of HIV disease markers on lung function decline remains unanswered. The AIDS Linked to the Intravenous Experience (ALIVE) study is a longitudinal cohort of persons with a history of injecting drugs with or at-risk for HIV infection followed in Baltimore, Maryland since 1988.[17] The ALIVE study collects behavioral, clinical, and laboratory data at regular six-month intervals and recently instituted serial spirometric measures into the data collection protocol. With nearly ubiquitous cigarette smoking and substantial prevalence of respiratory symptoms and obstructive lung disease (OLD),[18-20] ALIVE represents an appropriate population to examine the effect of HIV infection on changes in lung function. In the current study, we use longitudinal data from ALIVE to determine the independent association of HIV infection on lung function decline over almost three years of observations. We hypothesized that HIV infection, particularly more advanced HIV disease, would be associated with accelerated lung function decline. Some of these results have been previously presented at the 19th Conference on Retroviruses and Opportunistic Infections and published in abstract form.[21]

Objective HIV infection and low CD4+ T-cell count are associated with an increased risk of persistent oncogenic HPV infection – the major risk factor for cervical cancer. Few reported prospective cohort studies have characterized the incidence of invasive cervical cancer (ICC) in HIV-infected women.

With the advent of effective antiretroviral therapy (ART), the spectrum of disease experienced by those with HIV infection has changed. Viral suppression is common1 and incident AIDS defining events are rare.2 Yet, those with HIV infection continue to experience excess mortality 3;4 which is incompletely described by age, CD4 count, and HIV-1 RNA alone.5 Despite ART, chronic HIV infection appears to exacerbate generic pathophysiologic processes associated with aging which increase physiologic vulnerability relative to demographically similar uninfected individuals.6–8 Consistent with current treatment guidelines9, HIV providers routinely monitor general indicators of organ system injury including hemoglobin, platelets, aspartate and alanine transaminase (AST and ALT), creatinine, and viral hepatitis C infection (HCV) but have no index with which to integrate these data into an overall estimate of disease burden or mortality risk. Such a comprehensive measure would be useful as a means of more effectively motivating behavior change in the clinical setting10, improved risk stratification in the analysis of observational data11 and more effective randomized trials12. For example, indices such as the Framingham Risk Index has enhanced research and care in cardiovascular disease13 and several geriatric risk indices are enhancing research and care for those aging without HIV infection.14 While the cumulative evidence supporting the accuracy and generalizability of the VACS Index exceeds that for any prior HIV risk index, the VACS Index builds upon important prior research.15–22 Most prior indices emphasized AIDS defining conditions, CD4 cell count, and HIV-1 RNA. Some recognized the importance of age and anemia16;20. However much has changed since these indices were developed and validated. Specifically, the increasing role of multi-organ system injury (reflected by FIB 4, eGFR, and hemoglobin) and of hepatitis C infection (HCV), and the decreasing role of AIDS Defining Illnesses, CD4 count, and HIV-1 RNA. By including FIB-4, HCV, eGFR, hemoglobin and age, and placing less weighting upon CD4 count and HIV-1 RNA, the VACS Index better reflects more of the major common pathways of physiologic injury among those on antiretroviral therapy. As a result, the Veterans Aging Cohort Study Index (VACS Index) discriminates risk of mortality more effectively than an index restricted to CD4 count, HIV-1 RNA and age (Restricted Index).23 24 Importantly, the discrimination of the VACS Index rivals that of indices in clinical use including the Framingham Index13 and those recommended for use among geriatric patients.14 Nevertheless, prognostic indices developed in one sample (those within the Veterans Affairs Healthcare System (VA)) may not generalize to a new sample or important subgroups.25 Further, indices effective at one particular point in clinical care (ART initiation) may not generalize beyond treatment initation.25 We use data from the North American AIDS Cohort Collaboration (NA-ACCORD) to test the generalizability of the VACS Index outside the VA and at differing intervals of exposure to ART. We then combine data from NA-ACCORD and VA to translate index scores to an estimated absolute risk of mortality and compare predicted to observed mortality by cohort and subgroups defined by sex, age, race, and HIV-1 RNA titer.

ObjectiveTo evaluate whether HAART is associated with subsequent sexual and drug-related risk behavior compensation among injection drug users (IDUs).DesignA community-based cohort study of 362 HIV-infected IDUs initiating HAART in Baltimore, Maryland.MethodsHAART use and risk behavior was assessed at 8316 biannual study visits (median 23). Using logistic regression with generalized estimating equations (GEE), we examined the effect of HAART initiation on changes in risk behavior while adjusting for sociodemographics, alcohol use, CD4 cell count, year of initiation and consistency of HAART use.ResultsAt HAART initiation, participants were a median of 44.4 years old, 71.3% men and 95.3% African-American. In multivariable analysis, HAART initiation was associated with a 75% reduction in the likelihood of unprotected sex [adjusted odds ratio (aOR) 0.25; 95% confidence interval (CI), 0.19-0.32] despite no change in overall sexual activity (aOR 0.95; 0.80-1.12). Odds of any injecting decreased by 38% (aOR 0.62; 0.51-0.75) after HAART initiation. Among the subset of persistent injectors, needle-sharing increased nearly two-fold (aOR 1.99; 1.57-2.52). Behavioral changes were sustained for more than 5 years after HAART initiation and did not differ by consistency of HAART use. Reporting specific high-risk behaviors in the year prior to initiation was a robust predictor of engaging in those behaviors subsequent to HAART.ConclusionOverall, substantial declines in sexual risk-taking and active injecting argue against significant behavioral compensation among IDUs following HAART initiation. These data also provide evidence to support identifying persons with risky pre-HAART behavior for targeted behavioral intervention.

Proteinuria occurs commonly among HIV-infected and uninfected injection drug users (IDUs) and is associated with increased mortality risk. Vitamin D deficiency, highly prevalent among IDUs and potentially modifiable, may contribute to proteinuria. To determine whether vitamin D is associated with proteinuria in this population, we conducted a cross-sectional study in the AIDS Linked to the IntraVenous Experience (ALIVE) Study.25(OH)-vitamin D levels were measured in 268 HIV-infected and 614 HIV-uninfected participants. The association between vitamin D deficiency (10 ng/ml) and urinary protein excretion was evaluated by linear regression. The odds of persistent proteinuria (urine protein-to-creatinine ratio200 mg/g on two occasions) associated with vitamin D deficiency was examined using logistic regression.One-third of participants were vitamin D-deficient. Vitamin D deficiency was independently associated with higher urinary protein excretion (P 0.05) among HIV-infected and diabetic IDUs (P-interaction 0.05 for all). Persistent proteinuria occurred in 18% of participants. Vitamin D deficiency was associated with greater than six-fold odds of persistent proteinuria among diabetic IDUs [odds ratio (OR) 6.29, 95% confidence interval (CI) 1.54, 25.69] independent of sociodemographic characteristics, comorbid conditions, body mass index, and impaired kidney function [estimated glomerular filtration rate (eGFR)60 ml/min per 1.73 m(2)]; no association, however, was observed among nondiabetic IDUs (OR 1.06, 95% CI 0.64, 1.76) (P-interaction0.05).Vitamin D deficiency was associated with higher urinary protein excretion among those with HIV infection and diabetes. Vitamin D deficiency was independently associated with persistent proteinuria among diabetic IDUs, although not in nondiabetic persons. Whether vitamin D repletion ameliorates proteinuria in these patients requires further study.

Background and objectives: Proteinuria is a major determinant of chronic kidney disease. We aimed to characterize the prevalence and correlates of proteinuria in a cohort of HIV-infected and uninfected injection drug users. Design, setting, participants, & measurements: A cross-sectional analysis was performed among 902 injection drug users (273 HIV-infected) in the AIDS Linked to the Intravenous Experience cohort. The primary outcome was proteinuria defined as having a urine protein/creatinine concentration ratio >200 mg/g. Poisson regression with robust variance was used to determine prevalence ratios. Results: Overall, 24.8% of participants had proteinuria; the prevalence was 2.9 times higher among HIV-infected participants (45%) compared with HIV-uninfected participants (16%). In addition, age, health insurance, employment status, hepatitis B and C serostatus, diabetes, and high BP were associated with proteinuria. Neither antiretroviral therapy nor features of illicit drug use history were associated with proteinuria. In multivariate analysis, HIV infection, unemployment, increased age, diabetes, hepatitis C infection, and high BP were significantly associated with a higher prevalence of proteinuria. Conclusions: In an aging, predominantly African-American cohort of injection drug users, we found a striking burden of proteinuria that was strongly associated with HIV status. In addition to being a pathway to ESRD, proteinuria is a potent risk factor for cardiovascular morbidity and mortality. Evaluation of aggressive screening and disease-modification strategies in this high-risk population is warranted.

Among individuals infected with the human immunodeficiency virus (HIV), biomarkers that predict mortality are also used to determine the time when antiretroviral therapy is initiated. No studies have evaluated the impact of the frequency of marker measurements for either their predictive value of mortality or how they may influence inference of the effect of therapy initiation in analyses from observational data.We identified 244 persons who were contemporaneously enrolled in both the AIDS Link to the IntraVenous Experience (an interval cohort) and the Johns Hopkins HIV Clinical Cohort between 1995 and 2004. Data from each study were used separately in 2 ways. We applied time-dependent proportional hazards models to examine the predictive associations between markers and mortality, and marginal structural models to examine the causal inference of therapy on mortality. Biomarkers were used to derive the inverse probability weights.The timing frequencies of marker measurements in the interval cohort (CD4 interquartile range = 175-194 days) were less heterogeneous than in the clinical cohort (interquartile range = 38-121 days). Despite this, the results were concordant for CD4 (R = 0.537 [95% confidence interval = 0.345-0.707] and (R = 0.488 [0.297-0.666], respectively). Similar concordance was found for the HIV-1 RNA and hemoglobin analyses. When evaluating the causal effect of highly active antiretroviral therapy (HAART), the relative hazards were 0.34 for the interval cohort study (95% CI = 0.15-0.77) and 0.27 for the clinical cohort study (0.11-0.66).Utilizing a unique co-enrollment of patients in 2 different types of cohort studies, we find empirical evidence that inferences drawn from these different structures are similar.

We characterized patterns of highly active antiretroviral therapy (HAART) use and predictors of nonstructured treatment interruptions (NTIs) among injection drug users (IDUs) in Baltimore, MD.Three hundred thirty-five IDUs who initiated HAART from 1996 to 2006 were studied. NTIs were defined as any subsequent 6-month interval where HAART was not reported. Predictors of the first NTI and subsequent restart of HAART were examined using Cox regression.Two hundred sixty (78%) reportedor =1 NTI. Of 215 withor =1 follow-up visit after the NTI, 44 (20%) never restarted HAART, 62 (29%) restarted and remained on HAART, and 109 (51%) reported multiple NTIs. NTIs were less likely among those who initiated HAART in later calendar years and had a recent outpatient visit and more likely among women, persons with detectable HIV RNA at the prior visit, and those who reported injecting daily. Among those with NTIs, interuptions occurred earlier in persons who were younger, who did not have a prior AIDS diagnosis, and who were actively injecting; NTIs lasted longer in persons who had higher HIV RNA levels, in persons who were incarcerated, and in persons drinking alcohol. A recent outpatient visit and not actively injecting were associated with restarting HAART.NTIs were common in this population and occurred most frequently in the setting of active drug use and disruption of health care. Effective linkages between primary care for HIV and substance abuse treatment may improve HAART outcomes in this population.

Introduction: Between 1990 and 1998, tuberculin skin tests (TST) and isoniazid preventive therapy (IPT) were provided to injection drug users participating in the AIDS Linked to the Intravenous Experiences cohort. Methods: A registry match was conducted with the AIDS Linked to the Intravenous Experiences cohort database and the Maryland State Department of Health and Mental Hygiene tuberculosis registry. Results: Of 2010 participants, 1753 (74%) had a TST placed and read; 536 (31%) were positive. TST positivity was 16% in HIV positives; 39% in HIV negatives (P < 0.01). Overall, 299 (56%) TST reactors started IPT; 165 (55%) completed 6 months. Three tuberculosis (TB) cases were diagnosed among HIV negatives (incidence rate = 0.16/1000 person-years); 19 among HIV positives (1.94/1000 person-years; incidence rate ratio 12.3 (3.61-64.70). Within the entire cohort, TB rates were 0.81 per 1000 person-years for those not receiving IPT, 0.48 per 1000 person-years for those receiving any IPT, 0.29 per 1000 person-years for those completing at least 30 days, and 0 per 1000 person-years for completers. Ten cases of TB occurred in HIV-infected individuals with negative TSTs. Discussion: IPT was associated with protection against TB, but uptake was modest. Although it is likely that TB incidence would have increased, especially in HIV-positive subjects, if the IPT program had not occurred, more significant declines in TB incidence in this population will require improved methods for ensuring uptake and completion of IPT and preventing disease in TST-negative individuals.

Mutations in NPHS2, the gene that encodes podocin, are well-established causes of both familial and sporadic steroid-resistant focal segmental glomerulosclerosis (FSGS) in the pediatric population, but have not been well-characterized in late-onset disease. To investigate the role of NPHS2 polymorphisms in sporadic cases of late-onset FSGS, we studied 377 biopsy-confirmed FSGS cases and 919 controls. We identified 18 single nucleotide polymorphisms (SNPs) by resequencing a subgroup of cases and controls, and subsequently genotyped African-American and European-American cases and controls for five missense SNPs, three SNPs within introns, and four SNPs in the 3' untranslated region. No homozygotes or compound heterozygotes were observed for any missense mutation. R138Q carriers were more frequent among FSGS cases relative to controls (OR = 4.9, P = 0.06), but heterozygosity for the other four missense mutations was equally distributed among FSGS cases and controls. Finally, a common haplotype of noncoding SNPs carried by 20% of African-Americans, but not observed in European-Americans, was strongly associated with a 50% reduction in risk for sporadic FSGS (OR = 0.5, P = 0.001). These results indicate that genetic variation or mutation of NPHS2 may play a role in late-onset sporadic FSGS.

Background: Iron deficiency is common among female injection drug users, but it is unclear whether iron supplementation can reduce anemia and improve iron status without increasing plasma hepatitis C virus (HCV) or HIV RNA levels. Methods: We conducted a phase 3, double-blind, randomized, controlled clinical trial of daily micronutrients with 18 mg of iron (iron group) versus micronutrients without iron (control group) for 12 months among hepatitis C-positive female injection drug users in Baltimore, Maryland. The main outcome measures were hemoglobin, markers of iron status, plasma HCV RNA, plasma HIV RNA, and liver enzymes at 6 and 12 months of follow-up. Results: Four hundred fifty-eight women (320 HIV-negative and 138 HIV-positive) enrolled in the trial. There were no significant differences in the proportion of women with anemia, ferritin

Although most hepatitis C virus (HCV) infections are acquired by injection drug use, prospective data on the progression of liver fibrosis are sparse. Baseline liver biopsies were obtained (1996-1998) on a random sample of 210 out of 1667 HCV-positive injection drug users (IDUs). Subjects were followed biannually, with a second biopsy offered to those eligible. Paired biopsies were scored 0 to 6 (modified Ishak score), significant fibrosis was defined as score 3 or greater, and progression of fibrosis was defined as an increase 2 or more units or clinical evidence of end-stage liver disease. Predictive values of blood markers [FibroSURE, aspartate aminotransferase-to-platelet-ratio index (APRI) and alanine aminotransferase (ALT)] were assessed for detection of contemporaneous and future liver fibrosis. Among 119 prospectively followed IDUs, 96% were African American; 97% HCV genotype 1a/b; 27% HIV-infected, and median age was 42 years. Most (90.7%) did not have significant liver fibrosis at first biopsy. Although predictive value for detecting insignificant fibrosis at first biopsy was greater than 95% for FibroSURE, APRI, and ALT, specificities were 88.9%, 72.7%, and 72.7%, respectively. After 4.2 years median follow-up, 21% had progression of fibrosis, which was significantly associated with serum level of HCV RNA and ALT. No serological test had predictive value greater than 40% for contemporaneous or future significant fibrosis. Even initial biopsy result had only a 30.4% value for predicting future significant fibrosis. In conclusion, significant liver fibrosis and progression were detected in some, but not most, IDUs in this cohort. In this setting with low fibrosis prevalence, FibroSURE, ALT, and APRI tests predict insignificant fibrosis; however, further work is needed to find noninvasive markers of significant liver fibrosis.