Direct and Indirect Effects of Heavy Alcohol Use on Clinical Outcomes in a Longitudinal Study of HIV Patients on ART.

In a cohort of patients receiving care for HIV, we examined longitudinally the impact of past 30-day frequency of heavy drinking (consuming 5+ drinks on one occasion) on HIV-related (detectable viral load and CD4+ T cell count) and non-HIV-related (hemoglobin and biomarkers of kidney function and liver fibrosis) clinical outcomes and the extent to which these effects were due to reduced antiretroviral therapy (ART) adherence. Data came from the Study to Understand the Natural History of HIV/AIDS in the Era of Effective Therapy. Between March 2004 and June 2006, 533 individuals receiving ART were recruited and followed every 6 months for six years. Using longitudinal mediation analysis, we estimated natural direct effects (NDE) of heavy drinking frequency (never, 1-3 times, or 4+ times in the past 30 days) on clinical outcomes and natural indirect effects (NIE) mediated via ART adherence. A one-level increase in heavy drinking frequency had a significant negative NDE on CD4+ T-cell counts (-10.61 cells/mm3; 95 % CI [-17.10, -4.12]) and a significant NIE through reduced ART adherence of -0.72 cells/mm3 (95 % CI [-1.28, -0.15]), as well as a significant NIE on risk of detectable viral load (risk ratio = 1.03; 95 % CI [1.00, 1.05]). Heavy drinking had a significant detrimental NIE on a combined index of 5-year mortality risk and detrimental NDE and total effect on a biomarker of liver fibrosis. Heavy drinking has deleterious effects on multiple clinical outcomes in people living with HIV, some of which are mediated through reduced ART adherence.

The Relationship of Social Support and Neighborhood Perceptions among Individuals with HIV.

Social support has been noted to improve health outcomes for individuals with HIV. Understanding how neighborhoods contribute to feelings of social support is beneficial to create environments where populations with HIV can be supported. This study assessed the relationship between neighborhood perceptions and social support with HIV management. A total of 201 individuals were recruited; individuals with HIV, 18 years or older, who were eligible to participate in the 2-hour interview. Psychiatric diagnostic interviews were conducted alongside assessments of social support and neighborhood perceptions; biomedical markers were abstracted from medical records. Correlations and linear regression analyses were performed to assess relationships between social support and neighborhood perceptions with HIV management biomarkers. The majority of the sample was male (68.8%) and African American (72.3%), with a mean age of 43.1 years. Overall, 78% were receiving combination antiretroviral therapy (cART) prescriptions, with 69% being virally suppressed. Fear of neighborhood activities was independently associated with receiving current cART. Reports of social support and neighborhood perceptions were highly correlated. Findings suggest that supportive home environments likely would improve perceptions of social support.

Duration of Influenza Virus Shedding Among HIV-Infected Adults in the cART Era, 2010-2011.

The duration of influenza virus shedding in HIV-infected adults is unknown and could affect quarantine and treatment recommendations. Participants were monitored for influenza-like illness (ILI), defined as fever and cough or sore throat, using weekly telephone audio computer-assisted self-interviews. Those with ILI were further evaluated at three HIV specialty clinics. For those with influenza, we collected nasopharyngeal washes every 3 days after the date of confirmed influenza infection for 21-28 days; specimens underwent reverse transcriptase - polymerase chain reaction (RT-PCR) and viral culture. Duration of influenza virus shedding was the interval from the date of onset (day 0) of ILI to the date of last culture-positive specimen. Characteristics were compared between patients with and without influenza using Fisher's exact test. We used the Wilcoxon rank-sum test to examine factors that may have affected influenza virus shedding. From October 2010 to April 2011, we enrolled 961 participants in syndromic surveillance and diagnosed 20 patients with influenza whose characteristics were as follows: median age 48 years (interquartile range [IQR]: 43-53), 60% male, 50% non-Hispanic black, 95% had been prescribed combination highly active antiretroviral therapy (cART), 85% were virologically suppressed (HIV RNA <400 copies/ml), median CD4 cell count 317 cells/mm3 (IQR: 190-544), and median follow-up time 21 days (IQR: 19-22). Compared with persons without influenza, persons with influenza were more likely to be older, use injection drugs, and have a lower median CD4 cell count and were less likely to have had an influenza vaccination in the past 12 months. Median durations of shedding, PCR detection, and ILI symptoms were 3 (IQR: 0-5), 10 (IQR: 6-15), and 14 days (IQR: 12-26), respectively. Median days of shedding were similar among patients with and without any prior influenza vaccination (0 vs. 4, p = .448), HIV viral suppression (2 vs. 6, p = .053), and oseltamivir use (5 vs. 0, p = .083). HIV-infected persons on cART in our study shed influenza virus for a similar duration as that reported for HIV-uninfected persons.

High Prevalence of Low Bone Mineral Density and Substantial Bone Loss over 4 Years Among HIV-Infected Persons in the Era of Modern Antiretroviral Therapy.

HIV-infected persons are living longer on combination antiretroviral therapy (cART) but experiencing more comorbidities including low bone mineral density (BMD). Using data from the Study to Understand the Natural History of HIV and AIDS in the Era of Effective Therapy (SUN Study), we determined the prevalence of low BMD (T-score below one standard deviation of the reference mean) and compared it with matched controls from the National Health and Nutrition Examination Survey (NHANES). We also assessed 4-year longitudinal BMD changes among participants virologically suppressed on cART. Of 653 participants included in this analysis (77% male, 29% black, median age 41 years, median CD4(+) cell count 464 cells/mm(3), 89% with HIV RNA <400 copies/ml), 51% and 10% had baseline osteopenia and osteoporosis, respectively. Low BMD at the femoral neck was significantly more prevalent than for the NHANES controls (47% versus 29%, p<0.001). Lower body mass index, nonwhite race, longer tenofovir exposure, older age, being unemployed or retired, and lower apolipoprotein E were independently associated with baseline osteoporosis. Among 170 participants virologically suppressed on cART and with longitudinal BMD data, 31% experienced substantial bone loss (≥5% BMD decline from baseline) over 4 years. Female sex, current smoking, and longer stavudine use were more common among participants who had substantial bone loss, although these variables failed to reach statistical significance. Low BMD was highly prevalent among HIV-infected persons. One-third of participants experienced substantial bone loss despite cART, suggesting the need for monitoring and potential clinical interventions.

Psychiatric Diagnoses among an HIV-Infected Outpatient Clinic Population.

As individuals with HIV infection are living longer, the management of psychiatric disorders has increasingly been incorporated into comprehensive care. Individuals were recruited from an outpatient HIV clinic to assess the prevalence and related associations of current psychiatric disorders and biomarkers. Of the 201 participants who completed the interviews, the median age was 43.5 years, and the majority was male and African American. Most were receiving HIV therapy and 78% of those had achieved virologic suppression. Prevalent psychiatric diagnoses included major depressive disorder, generalized anxiety, and agoraphobia. Alcohol and cocaine/crack abuse and dependence were common substance use disorders. Current receipt of HIV therapy was less common among those diagnosed with generalized anxiety disorder. Agoraphobia was the only disorder associated with unsuppressed viral load. Psychiatric and substance use disorders are highly prevalent among an urban HIV clinic population, although we identified few associations between psychiatric diagnoses and HIV diseases status.

Elevated Soluble CD14 and Lower D-Dimer Are Associated With Cigarette Smoking and Heavy Episodic Alcohol Use in Persons Living With HIV.

BACKGROUND: Persons living with HIV are at increased risk for cardiovascular disease in part because of persistent inflammation and coagulation activation. METHODS: We examined whether smoking and heavy episodic alcohol use (defined as 5 or more drinks on one occasion) were associated with greater monocyte activation (soluble CD14) and coagulation (D-dimer) in participants in the Study to Understand the Natural History of HIV and AIDS in the Era of Effective Therapy (the "SUN" Study), a prospective observational cohort. RESULTS: Using regression analysis (n = 689), current smoking compared with nonsmoking was associated with significantly elevated soluble CD14 (B = 135.57, 95% confidence interval: 84.95 to 186.19, P < 0.001), whereas heavy alcohol use compared with nonheavy use was associated with significantly lower D-dimer levels (B = -0.059, 95% confidence interval: -0.102 to -0.016, P = 0.007). CONCLUSIONS: Smoking cessation should be encouraged by HIV care providers to improve mortality outcomes from all causes of death, particularly cardiovascular disease.

Short communication: The Veterans Aging Cohort Study Index is an effective tool to assess baseline frailty status in a contemporary cohort of HIV-infected persons.

The Veterans Aging Cohort Study (VACS) Index has previously been used to identify frail HIV-infected persons. However, data demonstrating the independent association between the VACS Index and baseline frailty status is lacking. Furthermore, the ability of the VACS Index to also reflect transitions in frailty status over time is unknown. We used data from the Study to Understand the Natural History of HIV and AIDS in the Era of Effective Therapy (SUN Study) to determine independent association of baseline frailty status with the VACS Index. We also evaluated VACS Index changes with frailty status transitions over time. We included 303 participants (median age 48 years, 76% men, 57% non-Hispanic white, 91% with plasma HIV RNA <400 copies/ml, and median CD4(+) cell count 595 cells/ml) with baseline and follow-up frailty assessments and used the Fried's criteria to define frailty status. There were 184 (61%) nonfrail, 112 (37%) prefrail, and seven (2%) frail participants at baseline. Prefrail/frail participants had significantly higher median VACS Index scores compared with nonfrail participants (18 versus 10, p<0.001). In multivariable analysis, prefrailty/frailty was independently associated with a higher VACS Index score (odds ratio 1.025, p=0.019). After a median follow-up of 12 months, participants who remained prefrail/frail compared to those who remained nonfrail continued to have higher median VACS Index scores. The VACS Index score did not significantly change with transitions in frailty status over time. Our study highlights the potential utility of the VACS Index in frailty assessment within the clinical setting.

Parks as a tool for HIV management.

Access to parks improves overall health outcomes in the general population. Given that HIV infection has become a chronic disease to manage, among populations engaged in medical care, parks may be promoted as physical activity opportunities in order to manage chronic comorbid conditions. We conducted a cross-sectional examination of the relationships between sociodemographic and biomedical characteristics to park proximity among 635 individuals receiving outpatient HIV care. The data collected included HIV-related biomarkers, depression, and diagnoses of other chronic diseases. The total acres of parks an individual is exposed within one-quarter mile from their home were assessed. The cohort included 635 individuals (67% men, 73% black, and 21% white, mean age 42 years). Unemployment was negatively associated with park availability. Park proximity was not associated with depression or HIV biomarkers. As yet, little effort has been committed to promoting park usage as a low-cost, sustainable method to addressing comorbidities among individuals with HIV.

Persistent HIV-related stigma among an outpatient US clinic population.

Despite advancements in the public's understanding of HIV infection, felt stigma towards individuals living with HIV persists. Stigma has been associated with adverse health outcomes, including poor adherence to care, and increased participation in HIV transmission risk behaviours. We evaluated the level of felt stigma and its relationship to other psychosocial and medical factors among a sample of 201 individuals with HIV engaged in care. The overall mean stigma score, as measured by the Reece Stigma Scale, was 21.7 (SD 8.7). In univariate analysis, felt stigma scores were higher among women, African Americans, younger participants, and individuals with less education. Higher felt stigma scores were also found among individuals who reported having fair to poor overall health, moderate to severe symptoms of depression and anxiety, and those with a current diagnosis of alcohol dependence, generalised anxiety disorder, agoraphobia, pain disorder, and current smokers. Higher felt stigma scores were independently associated with individuals with anxiety symptoms. These analyses highlight that stigma persists among individuals with HIV and may play an important role in HIV care. The relationship between psychiatric disorders and psychosocial factors highlights an opportunity to develop interventions that will address these common comorbidities and reduce stigma.

Monocyte-activation phenotypes are associated with biomarkers of inflammation and coagulation in chronic HIV infection.

BACKGROUND: Soluble biomarkers of inflammation predict non-AIDS related morbidity and mortality among human immunodeficiency virus (HIV)-infected persons. Exploring associations between plasma biomarkers and cellular phenotypes may identify sources of excess inflammation. METHODS: Plasma biomarkers (interleukin 6 [IL-6] level, D-dimer level, high-sensitivity C-reactive protein [hsCRP] level, soluble CD14 [sCD14] level, and soluble CD163 [sCD163] level) were measured from cryopreserved samples from the Study to Understand the Natural History of HIV/AIDS in the Era of Effective Therapy (SUN Study). We performed immunophenotyping of peripheral blood mononuclear cells for markers of T-cell and monocyte activation, maturation, and migration. We evaluated associations between cellular phenotypes and soluble biomarkers by Spearman rank correlation and multivariate linear regression. RESULTS: Participants' (n = 670) median age was 41 years, 88% were prescribed antiretroviral therapy, 72% had a plasma HIV RNA load of <400 copies/mL, and the median CD4(+) T-lymphocyte count was 471 cells/µL. After adjustment, CD14(++)CD16(+) monocytes were associated with higher levels of IL-6, hsCRP, and sCD163; associations with IL-6 and hsCRP persisted in persons with suppressed HIV replication. While CCR5(+) monocytes positively associated with D-dimer levels, CCR2(+) monocytes were inversely associated with hsCRP levels. CONCLUSIONS: Plasma inflammatory biomarkers that predict morbidity and mortality were strongly associated with monocyte activation and migration, modestly associated with T-cell maturation, and not associated with CD8(+) T-cell activation phenotypes. These findings suggest that strategies to control monocyte activation warrant further investigation.

Improving cervical cancer screening rates in an urban HIV clinic.

Human immunodeficiency virus (HIV)-infected women are at increased risk of invasive cervical cancer; however, screening rates remain low. The objectives of this study were to analyze a quality improvement intervention to increase cervical cancer screening rates in an urban academic HIV clinic and to identify factors associated with inadequate screening. Barriers to screening were identified by a multidisciplinary quality improvement committee at the Washington University Infectious Diseases clinic. Several strategies were developed to address these barriers. The years pre- and post-implementation were analyzed to examine the clinical impact of the intervention. A total of 422 women were seen in both the pre-implementation and post-implementation periods. In the pre-implementation period, 222 women (53%) underwent cervical cancer screening in the form of Papanicolaou (Pap) testing. In the post-implementation period, 318 women (75.3%) underwent cervical cancer screening (p < 0.01). Factors associated with lack of screening included fewer visits attended (pre: 4.2 ± 1.5; post: 3.4 ± 1.4; p < 0.01). A multidisciplinary quality improvement intervention was successful in overcoming barriers and increasing cervical cancer screening rates in an urban academic HIV clinic.

Depression severity is associated with increased risk behaviors and decreased CD4 cell counts.

Depression is a common comorbidity among HIV-infected individuals. We studied the relationship between depressive symptoms, risk behaviors (risky-sexual behavior, tobacco, alcohol, and illicit drug use) and HIV outcomes. This cross-sectional study conducted in 2009 at the Washington University HIV Clinic included screening for depression with patient health questionnaire, survey of sexual behavior, illicit drug, alcohol, and tobacco use within 30 days. Sociodemographics, plasma HIV RNA levels, CD4 cell counts, and sexually transmitted disease test results were obtained from medical records. Multivariate logistic and linear regression models were used to assess the association between depressive symptoms severity and risk behaviors, HIV outcomes and combination antiretroviral therapy (cART) adherence. A total of 624 persons completed the assessment of whom 432 (69%) were male and 426 (68%) African-American. The median CD4 cell count was 410 cells/mm(3) and 479 persons (77%) were on cART of whom 112 (23%) had HIV RNA level > 400 copies/mL. Overall, 96 (15%) had symptoms of major depressive disorder. Depressive symptom severity was associated with increased likelihood of high-risk drinking (odds ratio [OR], 2.4; 95% confidence interval [CI], 1.1-5.1), current tobacco use (OR, 1.8; 95% CI, 1.1-2.9), illicit drug use (OR, 1.7; 95% CI, 1.0-2.8), and risky-sexual behavior (OR, 1.5; 95% CI, 0.8-2.7). Suboptimal cART adherence (visual analog scale < 95%) was also associated with depressive symptoms severity (p < 0.05). After adjustment for age, sex, race, receipt of cART, and cART adherence, depressive symptoms severity was independently associated with lower CD4 cell count (p < 0.05) but not with higher HIV RNA level (p = 0.39). Depression adversely affects HIV-infected individuals, requiring greater effort at utilizing multidisciplinary interventions.

Immunologic predictors of coronary artery calcium progression in a contemporary HIV cohort.

BACKGROUND: Identifying immunologic mechanisms that contribute to premature cardiovascular disease (CVD) among HIV-positive patients will inform prevention strategies. METHODS: Coronary artery calcium (CAC) progression was studied in an HIV cohort. Immunophenotypes were measured on baseline cryopreserved peripheral blood mononuclear cells using multicolor flow cytometry. Logistic regression identified predictors of CAC progression after adjusting for traditional and HIV-related risk factors. RESULTS: Baseline characteristics for the analysis cohort (n=436) were median age 42 years, median CD4 cell count 481 cells/µl, and 78% receiving antiretroviral therapy. Higher frequencies of CD16 monocytes were associated with greater likelihood of CAC progression, after adjusting for traditional and HIV risk factors [odds ratio per doubling was 1.66 for CD14/CD16 (P=0.02), 1.36 for CD14/CD16 (P=0.06), and 1.69 for CD14/CD16 (P=0.01)]. Associations for CD16 monocytes persisted when restricted to participants with viral suppression. We found no significant associations for CAC progression with other cellular phenotypes, including T-cell activation and senescence markers. CONCLUSION: Circulating CD16 monocytes, potentially reflecting a more pro-atherogenic subpopulation, independently predicted greater CAC progression among HIV-infected persons at low risk for AIDS. In contrast to T-cell abnormalities classically associated with AIDS-related disease progression, these data highlight the potential role of monocyte activation in HIV-related CVD risk.

Identifying risk factors for HIV-associated neurocognitive disorders using the international HIV dementia scale.

HIV-associated neurocognitive disorders (HAND) persist despite great advancements in combination antiretroviral therapy (cART). The gold standard for diagnosing cognitive impairment consists of a time-consuming neuropsychological battery of tests given by a trained neuropsychologist, however in the outpatient HIV clinic this is not feasible. The International HIV Dementia Scale (IHDS) was developed to help identify individuals with cognitive impairment in the outpatient setting. The IHDS is moderately sensitive for detecting more symptomatic forms of HAND but sensitivity has been shown to be poor in mild impairment. The IHDS has not been evaluated in developed countries in large cohort populations. We conducted a prospective cross-sectional study of only HIV+ individuals in an urban clinic and evaluated the prevalence of HAND and associated risk factors for cognitive impairment using the IHDS. A total of 507 HIV+ individuals participated in the study of which the majority were male (65 %) and African American (68 %); and 41 % had cognitive impairment. On multivariate analysis, African American race (p = 2.21), older age (p = 1.03), high school education or less (p = 2.03) and depression (p = 1.05) were associated with cognitive impairment. The high prevalence of HAND in this group suggests that more severe forms of HAND persist despite cART. Identified risk factors were non-HIV-related and suggest that environmental and sociodemographic factors have a significant impact on cognitive functioning and should be given more attention. The IHDS should be further evaluated in large cohort HIV+ and HIV- populations in the United States, as there remains a significant need to identify an effective brief screening tool for cognitive impairment.

HIV-infected adolescent, young adult and pregnant smokers: important targets for effective tobacco control programs.

Tobacco use is inextricably linked to a number of health risks both in the general and HIV-infected populations. There is, however, a dearth of research on effective tobacco control programs among people living with HIV, and especially among adolescents, young adults and pregnant women, groups with heightened or increased vulnerability secondary to tobacco use. Adolescents and young adults constitute a growing population of persons living with HIV infection. Early and continued tobacco use in this population living with a disease characterized by premature onset multimorbidity and chronic inflammation is of concern. Additionally, there is an increased acuity for tobacco control among HIV-infected pregnant women to reduce pregnancy morbidity and improve fetal outcome. This review will provide an important summary of current knowledge of tobacco use among HIV-infected adolescents, young adults and pregnant women. The effects of tobacco use in these specific populations will be presented and the current state of tobacco control within these populations, assessed.

Efavirenz outperforms boosted atazanavir among treatment-naive HIV-1-infected persons in routine clinical care.

BACKGROUND: Effectiveness of antiretroviral therapy (ART) in a routine clinical care may result different from the clinical trials. We assessed the virologic outcomes in treatment-naive persons who received either efavirenz (EFV) or atazanavir/ritonavir (ATV/r) with a backbone of tenofovir/emtricitabine (TDF/FTC) as their combination ART (cART). METHODS: This was a retrospective cohort study conducted at the Washington University HIV Outpatient Clinic from January 2004 to June 2009. Predictors of virologic suppression (HIV RNA level <400 copies/mL) by week 48 were assessed by multivariate Cox proportional hazards regression models. RESULTS: Of 324 persons, 221(68%) received EFV and 103 (32%) received ATV/r. Persons on EFV had 1.4-fold increased likelihood of virologic suppression (95% confidence interval, 1.0-1.8) when compared to ATV/r after adjustment with primary drug resistance, pre-cART opportunistic infection, HIV RNA levels, and timing to start cART. CONCLUSIONS: In routine clinical care settings, EFV had higher likelihood of achieving virologic suppression than ATV/r with backbone of TDF/FTC.

Sadness in the SUN: using computerized screening to analyze correlates of depression and adherence in HIV-infected adults in the United States.

We used a standardized screening tool to examine frequency of depression and its relation to antiretroviral medication adherence among HIV-infected persons on highly active antiretroviral therapy (HAART) in the Study to Understand the Natural History of HIV/AIDS in the Era of Effective Therapy (SUN Study). This is a prospective observational cohort of 700 HIV-infected patients enrolled between March 2004 and June 2006 in four U.S. cities, who completed a confidential audio computer-assisted self-interview [ACASI] with behavioral risk and health-related questions at baseline and 6-month follow-up visits, including the nine-question PRIME-MD depression screener and a validated 3-day antiretroviral adherence question. Among 539 eligible participants receiving HAART, 14% had depression at baseline (22% women, 12% men). In multivariable analysis using generalized estimating equations (GEE) to account for repeated measurements through 24 months of follow-up, persons who reported depression on a given ACASI were twice as likely to report nonadherence to antiretrovirals on the same ACASI (Odds ratio [OR] 2.02, 95% CI: 1.15, 3.57] for mild/moderate depression versus none); such persons were also less likely to have HIV viral load<400 copies/mL. Self-administered computerized standardized screening tools can identify at-risk individuals with depression who may benefit from interventions to improve antiretroviral adherence.

Paragonimus kellicotti flukes in Missouri, USA.

Paragonimiasis is an infection caused by lung flukes of the genus Paragonimus. In Asia, P. westermani infections are relatively common because of dietary practices. However, in North America, cases of paragonimiasis, which are caused by P. kellicotti flukes, are rare. Only 7 autochthonous cases of paragonimiasis were reported during 1968-2008. In 2009, we reported 3 new case-patients with paragonimiasis who had been seen at our medical center over an 18-month period. Six additional case-patients were identified in St. Louis, Missouri, USA, and treated at Washington University-affiliated health centers in 2009-2010. We report detailed descriptions of these case-patients, which includes unusual clinical manifestations. We also describe public health interventions that were undertaken to inform the general public and physicians about the disease and its mode of transmission.

Screening anxiety in the HIV clinic.

Individuals with HIV experience fluctuating levels of distress throughout the course of their infection. This cross-sectional study was conducted to examine the prevalence of and associations between anxiety symptoms, sociodemographic, and biomedical markers among individuals presenting for care. A total of 635 individuals were screened, the majority of whom was male and African American. Younger individuals, African Americans, individuals with less education, and those who were unemployed were more likely to express more severe anxiety symptoms. Individuals who were not currently receiving antiretroviral therapy (ART) were 1.61 times more likely to experience higher anxiety symptoms. Among individuals receiving ART, higher levels of anxiety were associated with less adherence, higher viral loads and lower CD4 cell counts. Current smokers were 1.66 times more likely to have higher rates of anxiety. When controlling for these significant factors, younger, unemployed, and less educated individuals were more likely to express more severe anxiety symptoms. These findings highlight the importance of screening and management of anxiety as an integral component of HIV care.