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Background The impact of adopting a race-free estimated glomerular filtration rate (eGFR) creatinine (eGFRcr) equation on racial differences in chronic kidney disease (CKD) progression among people with human immunodeficiency virus (PWH) is unknown. Methods We defined eGFR stages using the original race-adjusted Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) eGFRcr equation and the new race-free CKD-EPI eGFRcr equation. We then estimated 5-year probabilities of transitioning from baseline kidney function to more advanced eGFR stages and examined the association of race (black vs white) with rates of CKD progression using Markov models. Results With the race-adjusted eGFRcr equation, black participants (n = 31 298) had a lower risk of progressing from eGFR stage 1 to 2 (hazard ratio [HR], 0.77; 95% confidence interval [CI], .73–.82), an equal risk of progressing from stage 2 to 3 (1.00; .92–.07) and a 3-fold risk of progressing from stage 3 to 4 or 5 (3.06; 2.60–3.62), compared with white participants (n = 27 542). When we used the race-free eGFRcr equation, 16% of black participants were reclassified into a more severe eGFR stage at baseline. The reclassified black individuals had a higher prevalence of CKD risk factors than black PWH who were not reclassified. With the race-free eGFRcr equation, black participants had a higher risk of disease progression across all eGFR stages than white participants. Conclusions The original eGFRcr equation systematically masked a subgroup of black PWH who are at high-risk of CKD progression. The new race-free eGFRcr equation unmasks these individuals and may allow for earlier detection and management of CKD.

We created a brief version of The Index, a validated patient-reported measure that has potential to quickly identify patients at risk for poor retention. We analyzed Index scores from 2406 patients from 2016 to 2017 in a national cohort of patients in human immunodeficiency virus (HIV) care. Index scores predicted poor retention 12 months after administered.

BackgroundRacial inequities exist in retention in human immunodeficiency virus (HIV) care and multilevel analyses are needed to contextualize and address these differences. Leveraging data from a multisite clinical cohort of people with HIV (PWH), we assessed the relationships between patient race and residential characteristics with missed HIV care visits.MethodsMedical record and patient-reported outcome (PRO; including mental health and substance-use measures) data were drawn from 7 participating Center for AIDS Research Network of Integrated Clinical Systems (CNICS) sites including N = 20 807 PWH from January 2010 through December 2015. Generalized estimating equations were used to account for nesting within individuals and within census tracts in multivariable models assessing the relationship between race and missed HIV care visits, controlling for individual demographic and health characteristics and census tract characteristics.ResultsBlack PWH resided in more disadvantaged census tracts, on average. Black PWH residing in census tracts with higher proportion of Black residents were more likely to miss an HIV care visit. Non-Black PWH were less likely to miss a visit regardless of where they lived. These relationships were attenuated when PRO data were included.ConclusionsResidential racial segregation and disadvantage may create inequities between Black PWH and non-Black PWH in retention in HIV care. Multilevel approaches are needed to retain PWH in HIV care, accounting for community, healthcare setting, and individual needs and resources.

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

Background Retention in care (RIC) leads to reduced HIV transmission and mortality. Few studies have investigated clinic services and RIC among people living with HIV (PLWH) in the United States. We conducted a multisite retrospective cohort study to identify clinic services associated with RIC from 2010–2016 in the United States. Methods PLWH with ≥1 HIV primary care visit from 2010–2016 at 7 sites in the Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) were included. Clinic-level factors evaluated via site survey included patients per provider/trainee, navigation, RIC posters/brochures, laboratory test timing, flexible scheduling, appointment reminder methods, and stigma support services. RIC was defined as ≥2 encounters per year, ≥90 days apart, observed until death, administrative censoring (31 December 2016), or loss to follow-up (censoring at first 12-month interval without a visit with no future visits). Poisson regression with robust error variance, clustered by site adjusting for calendar year, age, sex, race/ethnicity, and HIV transmission risk factor, estimated risk ratios (RRs) and 95% confidence intervals (CIs) for RIC. Results Among 21 046 PLWH contributing 103 348 person-years, 67% of person-years were retained. Availability of text appointment reminders (RR, 1.13; 95% CI, 1.03–1.24) and stigma support services (RR, 1.11; 95% CI, 1.04–1.19) were associated with better RIC. Disparities persisted for age, sex, and race. Conclusions Availability of text appointment reminders and stigma support services was associated with higher rates of RIC, indicating that these may be feasible and effective approaches for improving RIC.

Background Substance use is common among people living with human immunodeficiency virus (PLWH) and a barrier to achieving viral suppression. Among PLWH who report illicit drug use, we evaluated associations between HIV viral load (VL) and reduced use of illicit opioids, methamphetamine/crystal, cocaine/crack, and marijuana, regardless of whether or not abstinence was achieved. Methods This was a longitudinal cohort study of PLWH from 7 HIV clinics or 4 clinical studies. We used joint longitudinal and survival models to examine the impact of decreasing drug use and of abstinence for each drug on viral suppression. We repeated analyses using linear mixed models to examine associations between change in frequency of drug use and VL. Results The number of PLWH who were using each drug at baseline ranged from n = 568 (illicit opioids) to n = 4272 (marijuana). Abstinence was associated with higher odds of viral suppression (odds ratio [OR], 1.4–2.2) and lower relative VL (ranging from 21% to 42% by drug) for all 4 drug categories. Reducing frequency of illicit opioid or methamphetamine/crystal use without abstinence was associated with VL suppression (OR, 2.2, 1.6, respectively). Reducing frequency of illicit opioid or methamphetamine/crystal use without abstinence was associated with lower relative VL (47%, 38%, respectively). Conclusions Abstinence was associated with viral suppression. In addition, reducing use of illicit opioids or methamphetamine/crystal, even without abstinence, was also associated with viral suppression. Our findings highlight the impact of reducing substance use, even when abstinence is not achieved, and the potential benefits of medications, behavioral interventions, and harm-reduction interventions.

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

Background The effect of depressive symptoms on progression through the human immunodeficiency virus (HIV) treatment cascade is poorly characterized. Methods We included participants from the Centers for AIDS Research Network of Integrated Clinic Systems cohort who were antiretroviral therapy (ART) naive, had at least 1 viral load and HIV appointment measure after ART initiation, and a depressive symptom measure within 6 months of ART initiation. Recent depressive symptoms were measured using the Patient Health Questionnaire-9 (PHQ-9) and categorized using a validated cut point (PHQ-9 ≥10). We followed participants from ART initiation through the first of the following events: loss to follow-up (>12 months with no HIV appointment), death, administrative censoring (2011-2014), or 5 years of follow-up. We used log binomial models with generalized estimating equations to estimate associations between recent depressive symptoms and having a detectable viral load (≥75 copies/mL) or missing an HIV visit over time. Results We included 1057 HIV-infected adults who contributed 2424 person-years. At ART initiation, 30% of participants reported depressive symptoms. In multivariable analysis, recent depressive symptoms increased the risk of having a detectable viral load (risk ratio [RR], 1.28; 95% confidence interval [CI], 1.07, 1.53) over time. The association between depressive symptoms and missing an HIV visit (RR, 1.20; 95% CI, 1.05, 1.36) moved to the null after adjustment for preexisting mental health conditions (RR, 1.00; 95% CI, 0.85, 1.18). Conclusions Recent depressive symptoms are a risk factor for unsuppressed viral load, while preexisting mental health conditions may influence HIV appointment adherence.

BACKGROUND: Age-associated conditions are increasingly common among persons living with human immunodeficiency virus (HIV) (PLWH). A longitudinal investigation of their accrual is needed given their implications on clinical care complexity. We examined trends in the co-occurrence of age-associated conditions among PLWH receiving clinical care, and differences in their prevalence by demographic subgroup. METHODS: This cohort study was nested within the North American AIDS Cohort Collaboration on Research and Design. Participants from HIV outpatient clinics were antiretroviral therapy–exposed PLWH receiving clinical care (ie, ≥1 CD4 count) in the United States during 2000–2009. Multimorbidity was irreversible, defined as having ≥2: hypertension, diabetes mellitus, chronic kidney disease, hypercholesterolemia, end-stage liver disease, or non–AIDS-related cancer. Adjusted prevalence ratios (aPR) and 95% confidence intervals (CIs) comparing demographic subgroups were obtained by Poisson regression with robust error variance, using generalized estimating equations for repeated measures. RESULTS: Among 22969 adults, 79% were male, 36% were black, and the median baseline age was 40 years (interquartile range, 34–46 years). Between 2000 and 2009, multimorbidity prevalence increased from 8.2% to 22.4% (P(trend) < .001). Adjusting for age, this trend was still significant (P < .001). There was no difference by sex, but blacks were less likely than whites to have multimorbidity (aPR, 0.87; 95% CI, .77–.99). Multimorbidity was the highest among heterosexuals, relative to men who have sex with men (aPR, 1.16; 95% CI, 1.01–1.34). Hypertension and hypercholesterolemia most commonly co-occurred. CONCLUSIONS: Multimorbidity prevalence has increased among PLWH. Comorbidity prevention and multisubspecialty management of increasingly complex healthcare needs will be vital to ensuring that they receive needed care.

Background. The long-term effectiveness of human immunodeficiency virus (HIV) treatments containing integrase inhibitors is unknown. Methods. We use observational data from the Centers for AIDS Research Network of Integrated Clinical Systems and the Centers for Disease Control and Prevention to estimate 4-year risk of AIDS and all-cause mortality among 415 patients starting a raltegravir regimen compared to 2646 starting an efavirenz regimen (both regimens include emtricitabine and tenofovir disoproxil fumarate). We account for confounding and selection bias as well as generalizability by standardization for measured variables, and present both observational intent-to-treat and per-protocol estimates. Results. At treatment initiation, 12% of patients were female, 36% black, 13% Hispanic; median age was 37 years, CD4 count 321 cells/µL, and viral load 4.5 log10 copies/mL. Two hundred thirty-five patients incurred an AIDS-defining illness or died, and 741 patients left follow-up. After accounting for measured differences, the 4-year risk was similar among those starting both regimens (ie, intent-to treat hazard ratio [HR], 0.96 [95% confidence interval {CI}, .63-1.45]; risk difference, -0.9 [95% CI, -4.5 to 2.7]), as well as among those remaining on regimens (ie, per-protocol HR, 0.95 [95% CI, .59-1.54]; risk difference, -0.5 [95% CI, -3.8 to 2.9]). Conclusions. Raltegravir and efavirenz-based initial antiretroviral therapy have similar 4-year clinical effects. Vigilance regarding longer-term comparative effectiveness of HIV regimens using observational data is needed because large-scale experimental data are not forthcoming.

Background Rates of early syphilis in US women are steadily increasing but predictors of infection in this group are not clearly defined. Methods This retrospective analysis focused on women enrolled in the US CFAR Network of Integrated Clinical Systems cohort between January 2005 and December 2016 with syphilis testing performed. The primary outcome of incident syphilis infection was defined serologically as a newly positive test with positive confirmatory testing after a negative test or a 2-dilution increase in RPR titer. Infection rates were calculated for each woman-year in care with testing. Predictors of syphilis were sought among socio-demographics, clinical information, and self-reported behaviors. Multivariable logistic regression models were created and a subgroup analysis assessed predictors in women of reproductive age. Results The annual rate of incident syphilis among 4416 women engaged in HIV care and tested during the 12-year study period was 760 per 100,000 person-years. Independent predictors of infection were injection drug use (IDU) as a risk factor for HIV acquisition (aOR 2.2, CI 1.3-3.9), hepatitis C infection (aOR 1.9, CI 1.1-3.4), black race (aOR 2.2, CI 1.3-3.7 compared to white race) and more recent entry to care (since 2005 compared to 1994-2004). Predictors were similar in women age 18-49. Conclusions Syphilis infection is common among US women in HIV care. Syphilis screening and prevention efforts should focus on women reporting drug use and with hepatitis C co-infection. Future studies should identify specific behaviors that mediate syphilis acquisition risk in women who use drugs.

BACKGROUND Before implementation of the Patient Protection and Affordable Care Act (ACA) in 2014, 100 000 persons living with human immunodeficiency virus (HIV) (PLWH) lacked healthcare coverage and relied on a safety net of Ryan White HIV/AIDS Program support, local charities, or uncompensated care (RWHAP/Uncomp) to cover visits to HIV providers. We compared HIV provider coverage before (2011-2013) versus after (first half of 2014) ACA implementation among a total of 28 374 PLWH followed up in 4 sites in Medicaid expansion states (California, Oregon, and Maryland), 4 in a state (New York) that expanded Medicaid in 2001, and 2 in nonexpansion states (Texas and Florida). METHODS Multivariate multinomial logistic models were used to assess changes in RWHAP/Uncomp, Medicaid, and private insurance coverage, using Medicare as a referent. RESULTS In expansion state sites, RWHAP/Uncomp coverage decreased (unadjusted, 28% before and 13% after ACA; adjusted relative risk ratio [ARRR], 0.44; 95% confidence interval [CI], .40-.48). Medicaid coverage increased (23% and 38%; ARRR, 1.82; 95% CI, 1.70-1.94), and private coverage was unchanged (21% and 19%; 0.96; .89-1.03). In New York sites, both RWHAP/Uncomp (20% and 19%) and Medicaid (50% and 50%) coverage were unchanged, while private coverage decreased (13% and 12%; ARRR, 0.86; 95% CI, .80-.92). In nonexpansion state sites, RWHAP/Uncomp (57% and 52%) and Medicaid (18% and 18%) coverage were unchanged, while private coverage increased (4% and 7%; ARRR, 1.79; 95% CI, 1.62-1.99). CONCLUSIONS In expansion state sites, half of PLWH relying on RWHAP/Uncomp coverage shifted to Medicaid, while in New York and nonexpansion state sites, reliance on RWHAP/Uncomp remained constant. In the first half of 2014, the ACA did not eliminate the need for RWHAP safety net provider visit coverage.

BACKGROUND The goal of targeted antiretroviral therapy initiation is to minimize disease progression among patients with human immunodeficiency virus while minimizing the therapeutic burden on these patients. We examine whether the effect of delaying therapy initiation from 500 cells/mm(3) to 350 or 200 cells/mm(3) is modified by age at entry into care. METHODS We used the parametric g-formula to compare 10-year mortality under 3 CD4 cell count thresholds for therapy initiation among 3532 patients who entered care at 1 of 8 sites in the United States between 1998 and 2013. Results are reported separately for patients 18 to 34, 35 to 44, and 45 to 65 years of age at study entry. RESULTS In the observed data, 10-year mortality was 13% (165 deaths). Mortality increased from 11% under therapy initiation at 500 cells/mm(3) to 12% at 350 cells/mm(3) (risk difference [RD]: 0.87; 95% confidence interval [CI]: .56, 2.17) and to 14% at 200 cells/mm(3) (RD: 2.71; 95% CI: 1.79, 5.38). The effect of delaying therapy became greater with age: RDs comparing the 350-cells/mm(3) threshold with the 500-cells/mm(3) threshold ranged from -0.03 (95% CI: -0.15, 1.76) for patients 18 to 34 years of age to 0.99 (95% CI: -.27, 1.98) for patients 35 to 44 and to 2.30 (95% CI: 1.29, 5.42) for patients 45 to 65. CONCLUSIONS Delaying therapy increased 10-year mortality in the full cohort. Subgroup analysis highlights that patients entering care at older ages may be more vulnerable to the consequences of delayed ART initiation than younger patients.

Background. Using a dynamic visual display, we examine the changes in human immunodeficiency virus type 1 (HIV-1) plasma viral load and CD4 cell count for 5 years after antiretroviral therapy initiation in a large cohort of patients with HIV. Methods. Patients at a Centers for AIDS Research Network of Integrated Clinical Systems site who initiated combination antiretroviral therapy between 1 January 2000 and 31 December 2012 were followed for 5 years for HIV-1 plasma viral load, CD4 cell count, and mortality. The joint distribution of CD4 cell count and viral load over time was depicted in an animated display using a bivariate kernel smoother. Results. Within days of therapy initiation, many patients had a suppressed viral load and their median CD4 cell count had increased. However, the median CD4 cell count remained below normal levels throughout follow-up period and the proportion of patients with high viral load occasionally increased, even years after therapy initiation. Conclusions. The dramatic changes in viral load and CD4 cell count after therapy initiation highlight the overwhelming effectiveness of antiretroviral therapy in the modern era. However, this work also emphasizes the need for pharmaceutical or behavioral interventions to prevent virologic failure and to stimulate complete recovery of normal CD4 cell count.

Background. Our objective was to determine the impact of combination antiretroviral therapy (cART) and the degree of immunosuppression on biologic false-positive (BFP) rapid plasma reagin (RPR) tests among persons infected with human immunodeficiency virus (HIV). Methods. This was a nested retrospective study of HIV-infected patients enrolled in the Johns Hopkins HIV Clinical Cohort. BFP RPR was defined as a reactive RPR and a nonreactive fluorescent treponemal antibodyabsorption (FTA-ABS) test. Patients with BFP tests were compared to 2 control groups: HIV-infected patients (1) with active syphilis (reactive RPR and FTA-ABS) and (2) without current syphilis (nonreactive RPR). A persistent BFP test was defined by having at least 2 visits with consistent BFP at all visits. Results. Of 711 patients with HIV, 96 (13.5%) had BFP tests and 342 (48.1%) had syphilis. Twenty-two of 96 (23%) had persistent BFP tests. cART use was associated with decreased odds of BFP tests compared to having syphilis (adjusted odds ratio [AOR], 0.31; 95% CI, .15–.63) and those with nonreactive RPR (AOR, 0.42; 95% CI, .22–.81). cART use was also associated with decreased odds of BFP persistence (AOR, 0.07; 95% CI, .01–.33). Neither CD4 count nor HIV RNA was significantly associated with BFP test results. Lower RPR titers, younger age, and injection drug use were associated with increased odds of BFP. Conclusions. The use of cART appears to decrease the odds of BFP RPR tests. This finding suggests that nontreponemal titer fluctuations in persons with HIV may reflect the influence of factors unrelated to syphilis disease activity.

Background. Retention in care for human immunodeficiency virus (HIV)–infected patients is a National HIV/AIDS Strategy priority. We hypothesized that retention could be improved with coordinated messages to encourage patients' clinic attendance. We report here the results of the first phase of the Centers for Disease Control and Prevention/Health Resources and Services Administration Retention in Care project. Methods. Six HIV-specialty clinics participated in a cross-sectionally sampled pretest-posttest evaluation of brochures, posters, and messages that conveyed the importance of regular clinic attendance. 10 018 patients in 2008–2009 (preintervention period) and 11 039 patients in 2009–2010 (intervention period) were followed up for clinic attendance. Outcome variables were the percentage of patients who kept 2 consecutive primary care visits and the mean proportion of all primary care visits kept. Stratification variables were: new, reengaging, and active patients, HIV RNA viral load, CD4 cell count, age, sex, race or ethnicity, risk group, number of scheduled visits, and clinic site. Data were analyzed by multivariable log-binomial and linear models using generalized estimation equation methods. Results. Clinic attendance for primary care was significantly higher in the intervention versus preintervention year. Overall relative improvement was 7.0% for keeping 2 consecutive visits and 3.0% for the mean proportion of all visits kept (P

Inpatient medication errors and adverse drug events are common, costly, and may lead to significant patient injury and death [1–9]. Persons living with human immunodeficiency virus (HIV) (PLWH) are at increased risk of medication errors given their complex medication regimens, multiple comorbid conditions, and interactions with inpatient providers who lack experience with antiretroviral therapy (ART) [10–12]. ART medication errors may have serious long-term consequences, including the development of drug resistance, treatment failure, or death [13]. Prior research suggests that ART medication errors are on the rise. In 1998, ART medication errors were detected in 12% of admissions, but by 2004–2007, the error rate had increased to 21%–26% of admissions [12, 14–16]. Since these studies were conducted, significant advances in ART and health information technology have occurred. Efavirenz, ritonavir-boosted atazanavir, ritonavir-boosted darunavir, and raltegravir are highly effective at decreasing HIV viral replication and have favorable side effect profiles and simple dosing schedules; thus, in combination with tenofovir and emtricitabine, these drugs are preferentially recommended for treatment naive patients by the Department of Health and Human Services Panel on Antiretroviral Guidelines for Adults and Adolescents [17]. Moreover, an increasing number of hospitals are using computerized provider order entry (CPOE) and clinical support tools, which have been touted as mechanisms for decreasing medication errors and improving patient safety [2, 18, 19]. However, recent data indicate that these technologies may facilitate certain types of medication errors [20–23]. The effect of improvements in HIV therapy and introduction of new technologies on ART medication errors is yet to be determined. As such, the goal of this analysis was to provide a current estimate of antiretroviral prescribing errors in the hospital setting, to evaluate the duration of ART medication errors, and to identify patient and hospital risk factors for these errors.

We have previously showed that as antiretroviral therapy has improved over time since 1995-1996, the likelihood of achieving virologic suppression has also improved. Antiretroviral therapy and antiretroviral therapy guidelines have continued to evolve, and we wished to determine the trend in human immunodeficiency virus (HIV-1) RNA levels over time in HIV-infected persons receiving care in our large urban HIV clinical practice in Baltimore, Maryland.The HIV-1 RNA level was assessed each year from 1996 through 2010 at the date closest to 1 July for all patients in care and followed up in the Johns Hopkins HIV Clinical Cohort. The clinic population's median HIV-1 RNA level and stratified threshold levels were plotted. The demographic characteristics of the population were also assessed over time.From 1996 (shortly after highly active antiretroviral therapy [HAART] was introduced) to 2010, the median HIV-1 RNA level decreased from 10,400 to200 copies/mL. The proportion of patients with an HIV-1 RNA level500 copies/mL decreased from 75% to only 16% during this same period. The population itself became older, had a higher proportion of women, and a lower proportion of patients with injection drug use as a transmission risk, but it was geographically stable. There was an increase in HAART use over time.Our results demonstrate the remarkable impact of increased use of and improved management with HAART in this urban HIV-infected population.

The epidemiology of human immunodeficiency virus (HIV) infection in the United States has changed significantly over the past 30 years. HIV/acquired immune deficiency syndrome (HIV/AIDS) is currently a disease of greater demographic diversity, affecting all ages, sexes, and races, and involving multiple transmission risk behaviors. At least 50,000 new HIV infections will continue to be added each year; however, one-fifth of persons with new infections may not know they are infected, and a substantial proportion of those who know they are infected are not engaged in HIV care. Barriers to early engagement in care may be specific to a demographic group. In this paper, the current epidemiology of HIV/AIDS in the United States is reviewed in order to understand the challenges, successes, and best practices for removing the barriers to effective diagnosis and receipt of HIV care within specific demographic groups.

Background. Most persons with human immunodeficiency virus (HIV) infection in the United States present to care with advanced disease, and many patients discontinue therapy prematurely. We sought to evaluate sex and racial/ethnic disparities in life-years lost as a result of risk behavior, late presentation, and early discontinuation of HIV care, and we compared these survival losses for HIV-infected persons with losses attributable to high-risk behavior and HIV disease itself. Methods. With use of a state-transition model of HIV disease, we simulated cohorts of HIV-infected persons and compared them with uninfected individuals who had similar demographic characteristics. We estimated non‐ HIV-related mortality with use of risk-adjusted standardized mortality ratios, as well as years of life lost because of late presentation and early discontinuation of antiretroviral therapy (ART) for HIV infection. Data from the national HIV Research Network, stratified by sex and race/ethnicity, were used for estimating CD4 + cell counts at ART initiation. Results. For HIV-uninfected persons in the United States who have risk profiles similar to those of individuals with HIV infection, the projected life expectancy, starting at 33 years of age, was 34.58 years, compared with 42.91 years for the general US population. Those with HIV infection lost an additional 11.92 years of life if they received HIV care concordant with guidelines; late treatment initiation resulted in 2.60 additional years of life lost, whereas premature ART discontinuation led to 0.70 more years of life lost. Losses from late initiation and early discontinuation were greatest for Hispanic individuals (3.90 years). Conclusions. The high-risk profile of HIV-infected persons, HIV infection itself, as well as late initiation and early discontinuation of care, all lead to substantial decreases in life expectancy. Survival disparities resulting from late initiation and early discontinuation of therapy are most pronounced for Hispanic HIV-infected men and women. Interventions focused on risk behaviors, as well as on earlier linkage to and better retention in care, will lead to improved survival for HIV-infected persons in the United States.

Background.African Americans with human immunodeficiency virus type 1 (HIV-1) infection and kidney disease are at increased risk of end-stage renal disease requiring renal replacement therapy (RRT), particularly in urban areas with high rates of poverty and injection drug use. It is unknown how the widespread use of highly active antiretroviral therapy (HAART) has affected survival during RRT in this vulnerable population.Methods.African American patients infected with HIV-1 who required RRT were identified from 2 cohorts that included 4509 Africans Americans infected with HIV-1 who were recruited during the period 1988–2004 in Baltimore, Maryland. Survival after initiation of RRT was compared for those who initiated treatment in the pre-HAART and the HAART eras using Kaplan-Meier curves. Cox proportional hazards regression analysis was used to adjust for potential confounders.Results.RRT was initiated in 162 patients (3.6%) during 10.6 years of follow-up (119 during the HAART era). Compared with patients who started RRT in the pre-HAART era, those in the HAART era were older (P < .001) and more likely to have CD4 cell counts of ⩽200 cells/mm 3 (P = .01). A total of 126 patients (78%) died during follow-up; among those who initiated RRT during the HAART era, 87 deaths occurred (73%). Median survival time in the pre-HAART era was 22.4 months (95% confidence interval [CI], 9.3–30.7); during the HAART era, it was 19.9 months (95% CI, 14.7–26.5; P = .94). In the multiple Cox regression model, factors independently associated with increased mortality included age (hazard ratio [HR], 1.30; 95% CI, 1.06–1.60; P = .01), lower serum albumin level (HR, 0.72; 95% CI, 0.57–0.91; P < .007), lower CD4 cell count (HR, 0.90; 95% CI, 0.82–0.99; P < .03), and the lack of HAART (HR, 0.52; 95% CI, 0.33–0.82; P = .005).Conclusions.Older age, lower serum albumin level, lower CD4 cell count, and the lack of HAART are independent predictors of poor survival among African Americans infected with HIV-1 undergoing RRT in a resource-limited urban area. RRT survival was similar in the pre-HAART and HAART eras, likely reflecting inadequate HIV treatment in this population.

Background. Directly administered antiretroviral therapy (DAART) in methadone clinics has the potential to improve treatment outcomes for human immunodeficiency virus (HIV)—infected injection drug users (IDUs).Methods. DAART was provided at 3 urban methadone clinics. Eighty-two participants who were initiating or reinitiating highly active antiretroviral therapy (HAART) received supervised doses of therapy at the clinic on the mornings on which they received methadone. Treatment outcomes in the DAART group were compared with outcomes in 3 groups of concurrent comparison patients, who were drawn from the Johns Hopkins HIV Cohort. The concurrent comparison patients were taking HAART on a self-administered basis. The 3 groups of concurrent comparison patients were as follows: patients with a history of IDU who were receiving methadone at the time HAART was used (the IDU-methadone group; 75 patients), patients with a history of IDU who were not receiving methadone at the time that HAART was used (the IDU-nonmethadone group; 244 patients), and patients with no history of IDU (the non-IDU group; 490 patients).Results. At 12 months, 56% of DAART participants achieved an HIV type 1 RNA level

Background. Technical limitations in the sensitivity of commercial genotyping methods may prevent clinicians from determining whether drug-resistant human immunodeficiency virus type 1 (HIV-1) is present in patients with low-level viremia. We performed ultrasensitive HIV-1 genotyping for patients with persistent plasma virus loads of 50-400 copies/mL to better define the prevalence of drug resistance and the most common resistance mutations during persistently detectable low-level viremia. Methods. Genotyping of HIV-1 was performed with an ultrasensitive clonal genotyping method. Results. We studied 21 patients who had persistent, detectable, low-level viremia for a median of 11 months. Nine (43%) of 21 patients had HIV-1 isolates with significant resistance mutations. The most common mutations were M184V, K65R, and M41L/T215Y. Conclusions. The finding that clinically significant resistance mutations were present in some but not all patients with persistent viremia (range, 50-400 copies/mL) highlights the need to improve the sensitivity of current clinical assays for detection of drug resistance.

Methadone-maintenance treatment clinics are strategically appealing sites for provision of directly administered antiretroviral therapy (DAART) to human immunodeficiency virus type 1 (HIV-1)-infected injection drug users (IDUs). We initiated an ongoing DAART protocol at a university-associated methadone clinic in April 2001, which continues to enroll participants. Participants ingested antiretroviral medications under direct supervision on days they attended the clinic; evening doses and doses on "methadone take-home days" were self-administered. Comparison IDUs receiving either standard care or treatment-adherence support were randomly selected from the population of the HIV-1 clinic where DAART participants received their primary care for HIV-1 infection, with frequency matching by sex, prior antiretroviral exposure, and receipt of methadone therapy. In an intention-to-treat analysis, 79% of DAART participants achieved HIV-1 RNA levels of

Although human immunodeficiency virus-infected people aged > or =50 years have a blunted CD4 cell recovery when receiving highly active antiretroviral therapy (HAART), there are few data on mortality. Mortality rates were studied for 253 individuals aged > or =50 years and a younger group of 535 people in a retrospective cohort; for untreated persons in each age group, the proportions surviving at 3 years were 83% and 70% (P

Anemia, a common hematologic complication in human immunodeficiency virus (HIV)-infected patients, can be caused by mechanisms including infections, neoplasms, or drug treatment. Studies have consistently found anemia to be associated with reduced survival, even when potentially confounding factors were controlled for. Importantly, recovery from anemia has been shown to reduce this risk to approximately the same level as seen among patients never having had anemia. Although anemia traditionally has been treated with blood transfusions, recent studies have shown recombinant human erythropoietin (r-HuEPO) to be effective in elevating hematocrit values and reducing transfusion requirements in HIV-infected patients who have endogenous erythropoietin levels of < or = 500 IU/L. Therapy with r-HuEPO has been shown to be safe and well tolerated. In a recent study, moreover, receipt of erythropoietin was associated with a decreased risk of death, whereas transfusion was associated with an increased risk. If these results are confirmed, the link between r-HuEPO and decreased risk of death in HIV-infected patients with anemia will be further strengthened.

Medicaid is rapidly moving toward managed care throughout the United States and will have a major impact on care programs for those infected with human immunodeficiency virus (HIV). The experience at the Johns Hopkins HIV Care Service is an example of the transition from fee-for-service to managed care. The Maryland Medicaid program, which has required enrollment of all Medicaid recipients since June 1997, uses an adjusted payment rate and separately funds protease inhibitors. Elements that made the transition to a managed care organization possible included the early development of a comprehensive network of services and a database showing that historical Medicaid payments were low compared with the statewide experience. Our Medicaid managed care program promotes unlimited access to specialists, rejects the "gatekeeper" concept for any service, and includes an open formulary. Nevertheless, it is uncertain that the services now provided can be sustained with anticipated reductions in payments that seem inevitable with Medicaid policies here and nationally.

Clinical predictions alone are insufficiently accurate to identify patients with specific types of bloodstream infection; laboratory assays might improve such predictions. Therefore, we performed a prospective cohort study of 356 episodes of sepsis syndrome and did Limulus amebocyte lysate (LAL) assays for endotoxin. The main outcome measures were bacteremia and infection due to gram-negative organisms; other types of infection were secondary outcomes. Assays were defined as positive if the result was > or = 0.4 enzyme-linked immunosorbent assay units per milliliter. There were positive assays in 119 (33%) of 356 episodes. Assay positivity correlated with the presence of fungal bloodstream infection (P < .003) but correlated negatively with the presence of gram-negative organisms in the bloodstream (P = .04). A trend toward higher rates of mortality in the LAL assay-positive episodes was no longer present after adjusting for severity. Thus, results of LAL assay did not correlate with the presence of bacteremia due to gram-negative organisms or with mortality after adjusting for severity but did correlate with the presence of fungal bloodstream infection.

A cross-sectional study was conducted to assess the prevalence and microbiology of oral infection due to fluconazole-resistant Candida in patients with AIDS. Oral swab specimens for fungal cultures were obtained from 100 consecutive outpatients with CD4 lymphocyte counts of200/mm3. At least one fungal organism demonstrating in vitro resistance to fluconazole (minimum inhibitory concentration,or = 8 micrograms/mL) was isolated from 26 (41%) of 64 patients for whom cultures were positive. When fluconazole-resistant C. albicans was isolated, in vitro resistance correlated with clinical thrush. None of 10 patients from whom only non-albicans species of Candida were isolated had active thrush. The patients from whom fluconazole-resistant Candida albicans was isolated had lower CD4 cell counts (median, 9/mm3), a greater number of treated episodes of thrush (median, 4.5), and a greater median duration of prior fluconazole treatment (231 days) than did patients from whom fluconazole-susceptible C. albicans was isolated (median CD4 cell count, 58/mm3 [P = .004]; median number of treated episodes of thrush, 2.0 [P = .001]; and median duration of prior fluconazole treatment, 10 days [P = .01]; respectively). In a multivariate analysis, the number of episodes and duration of fluconazole therapy were independent predictors of resistance.

To determine the incidence and clinical manifestations of herpes zoster in a hospital-based clinic for adults infected with human immunodeficiency virus (HIV), we reviewed the records of all patients for whom zoster was diagnosed at or after their first clinic visit. Fifty-two episodes of zoster occurred in 45 patients during 1,614 person-years of follow-up (incidence, 3.2 episodes per 100 person-years). The following major complications of zoster occurred in 12 patients (27%): ocular complications (5), neurological complications (4), and chronic atypical skin lesions (5). Six patients each had postherpetic neuralgia and bacterial superinfection, which were the common minor complications of zoster. Multivariate analysis revealed that only a low CD4 cell count (< or = 200/mm3) was predictive of a major complication of zoster (OR, 13.2; 95% CI, 1.52-114; P = .019). Thus, complications of herpes zoster are common in patients with HIV infection, especially those with advanced immunosuppression.

To The Editor—We thank Holtzman and Gallagher for their interest in our work [1]. Consistent with our study, which identified antiretroviral (ARV) medication errors in 29% of admissions during the first hospital day [2], they report an error rate of 26% among hospitalized human immunodeficiency virus (HIV)–infected patients prescribed ARV medications at Temple University Hospital in Philadelphia, PA [1]. We would like to clarify a misunderstanding by Holtzman and Gallagher of our study methods. As we stated in the methods section of our paper, our study was a retrospective review of ARV medication errors, and not an evaluation of a pharmacist intervention [2]. Two clinical pharmacists retrospectively reviewed medical orders to identify ARV medication errors for study purposes, and were not present in real time to identify and correct medication errors. At Johns Hopkins Hospital, the HIV/AIDS service has a specialized clinical pharmacist who reviews all medications administered on the prior day. However, our study included not only patients admitted to the HIV/AIDS service, but also those admitted to medicine, surgery, obstetrics and gynecology, neurology, and psychiatry. These other services do not routinely include pharmacists on the rounding team. Since we did not specifically evaluate a clinical pharmacist intervention on medication orders, we offered clinical pharmacy review of medication orders as a possible reason for the decline in errors on the second day of hospitalization for two reasons: (1) prior studies have demonstrated the efficacy of clinical pharmacists in decreasing ARV medication errors [3], and (2) 64% of our study patients were admitted to the HIV/AIDS service, which has a dedicated HIV clinical pharmacist. Other interventions, both educational and technological, may also be important to correcting ARV medication errors that occur early in hospitalization.

Vancomycin-resistant Enterococcus (VRE) is a major nosocomial pathogen. We collected clinical and laboratory data on 93 hospitalized adults with VRE bacteremia and 101 adults with vancomycin-susceptible enterococcal (VSE) bacteremia. Risk factors for VRE bacteremia included central venous catheterization, hyperalimentation, and prolonged hospitalization prior to the initial blood culture. VRE-infected patients were less likely to have undergone recent surgery or have polymicrobial bacteremia, suggesting a pathogenesis distinct from traditional VSE bacteremia. Prior exposure to metronidazole was the only significant pharmacologic risk factor for VRE bacteremia. Animal studies suggest metronidazole potentiates enterococcal overgrowth in the gastrointestinal tract and translocation into the bloodstream. An increasing APACHE II score was the major risk factor for death in a multivariate analysis, with VRE status being of only borderline significance.