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.

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.

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.

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.

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.

A review of opioid prescribing practices and associations with repeat opioid prescriptions in a contemporary outpatient HIV clinic.

OBJECTIVES: Among persons in current HIV outpatient care, data on opioid prescribing are lacking. This study aims to evaluate predictors of repeat opioid prescribing and to characterize outpatient opioid prescribing practices. METHODS: Retrospective cross-sectional study of persons ≥18 years in HIV outpatient care who completed an annual behavioral assessment between June 2008 and June 2009. Persons were grouped by ≤1 and ≥2 opioid prescriptions (no-repeat-opioid and repeat-opioids, respectively). Independent predictors for repeat-opioids were evaluated. Opioid prescribing practices were characterized in a sub-study of persons prescribed any opioid. RESULTS: Overall, 659 persons were included, median age 43 years, 70% men, and 68% African American. Independent predictors of repeat-opioids (88 [13%] persons) included opportunistic illnesses (both current and previous), depression, peripheral neuropathy, and hepatitis C coinfection (P<0.05). In the subgroup, 140 persons received any opioid prescription (96% short-acting, 33% tramadol). Indications for opioid prescribing were obtained in 101 (72%) persons, with 97% for noncancer-related pain symptoms. Therapeutic response was documented on follow-up in 67 (48%) persons, with no subjective relief of symptoms in 63%. Urine drug screens were requested in 6 (4%) persons, and all performed were positive for illicit drugs. CONCLUSIONS: Advanced HIV disease and greater medical and neuropsychiatric comorbidity predict repeat opioid prescribing, and these findings reflect the underlying complexities in managing pain symptoms in this population. We also highlight multiple deficiencies in opioid prescribing practices and nonadherence to guidelines, which are of concern as effective and safe pain management for our HIV-infected population is an optimal goal.

Aging and HIV infection: a comparison between older HIV-infected persons and the general population.

BACKGROUND: As HIV-infected persons age, the relative contribution of HIV infection, combination antiretroviral therapy (cART), and the normal aging process to the frequent comorbidities is unknown. METHODS: We prospectively evaluated comorbidities, cardiovascular risk, cognitive function, and anthropomorphic and laboratory parameters of HIV-infected persons aged 50 years and over in two US urban clinics. Results were compared to controls from the National Health and Nutrition Examination Survey (NHANES) matched 1:1 by age, race, gender, smoking status, and body mass index (BMI). RESULTS: We enrolled 122 HIV-infected persons; median age 55 years, 83% male, 57% Caucasian, 39% current smokers, mean BMI 26 kg/m2, and 92% on cART. Compared to controls, HIV-infected persons had a higher prevalence of hypertension (54% vs 38%), hypertriglyceridemia (51% vs 33%), low bone mineral density (BMD) (39% vs 0%), and lipodystrophy and greater receipt of antihypertensive and lipid-lowering medications (all Ps < .05). Groups were similar in prevalence of coronary heart disease, diabetes mellitus, chronic viral hepatitis, non-AIDS-defining malignancies and Framingham Risk and cognitive function scores. CONCLUSIONS: Older HIV-infected persons have a higher prevalence of hypertension, hypertriglyceridemia, low BMD, and lipodystrophy than matched controls, suggesting that HIV and treatment-related factors exceed "normal" aging in the development of those problems.

Comparisons of sexual behaviors and STD prevalence among older and younger individuals with HIV infection.

Knowledge of an HIV-infected individual's sexual behaviors and routine sexually transmitted diseases (STDs) testing greatly facilitates HIV prevention efforts, but current data in older individuals are lacking. This study was developed to compare sexual behaviors and STD prevalence between older HIV-infected individuals and their younger counterparts. We conducted a cross-sectional cohort study of HIV-infected individuals > or =18 years who completed an annual behavioral assessment. A total of 541 individuals completed the assessment. Analyses were performed to examine differences in sexual behaviors and STD prevalence between age groups: younger (18-35 years) (30%), middle-aged (36-49 years) (46%), and older (> or =50 years) (24%). Older individuals were most likely to be male and Caucasian with longest time since HIV diagnosis, greatest receipt of highly active antiretroviral therapy (HAART), and highest rates of HIV RNA <50 copies/mL (all p<0.001). Reports of recent sexual activity decreased with age, younger (56%) vs. middle-aged (43%) vs. older (27%) (p<0.001). The median number of recent sex partners was one (range 1-25) and 68% overall reported using condoms consistently; these parameters did not differ by age group. STD prevalence was 8% (gonorrhea [9], chlamydia [7], and syphilis [20]) and was highest among younger individuals (younger [11%] vs. middle-aged [7%] vs. older [3%]). Our results demonstrated that with older age, sexual activity declines but inconsistent condom use remains commonly reported. Furthermore, STDs were identified among all age groups. This latter finding reinforces the need for secondary prevention efforts among all individuals living with HIV/AIDS.

Sexual behaviors and results of bacterial sexually transmitted infections testing among frail HIV-infected individuals.

BACKGROUND: The impact of premature frailty in HIV-infected individuals on the prevalence of sexual behaviors and sexually transmitted infections (STIs) is unknown. METHODS: We compared these factors among individuals aged ≥ 18 years, who had prior determination of a frailty phenotype at the Washington University HIV Clinic between June and December 2008. All P values were 2-tailed and considered significant at <.05. RESULTS: Of 445 individuals (71% male, 30% Caucasian, median age 43 years) assessed, the prevalence of frailty was 9%. Reports of recent sexual activity (44%) did not differ by frailty status. Consistent condom use (69% overall) was similar between sexually active frail and nonfrail individuals, and there was no significant difference in STI prevalence between groups (0 vs 32 [9%], P = .08). CONCLUSION: In this relatively young population, frailty did not affect reports of recent sexual activity or consistent condom use and no significant difference in STI prevalence was observed.

HIV and aging: two converging epidemics.

With the aging of the Human immunodeficiency virus (HIV) epidemic, we are now faced with unprecedented and complex challenges, which need to be addressed in order to maximize care of the older HIV-infected population. Older persons have greater comorbidity than their younger counterparts. The compound effects of HIV infection, its treatment and increasing age on the incidence and prevalence of cardiovascular disease, malignancies, cognitive impairment, depression and frailty are of increasing concern.

Adverse effects of tenofovir use in HIV-infected pregnant women and their infants.

BACKGROUND: Data regarding use of tenofovir disoproxil fumarate in HIV-infected pregnant women are limited. OBJECTIVE: To identify adverse effects of tenofovir use during pregnancy in HIV-infected women and their infants. METHODS: In a retrospective case series, the charts of 127 pregnant HIV-infected women who received highly active antiretroviral therapy (HAART) between 2001 and 2005 were reviewed. Those who received tenofovir during pregnancy were selected for this study. Each woman's chart was reviewed for clinical data and adverse events during the pregnancy; each infant's chart was reviewed for growth parameters from birth to 12 months. RESULTS: Fifteen HIV-infected women with limited treatment options were prescribed HAART containing tenofovir during 16 pregnancies. In utero tenofovir exposure was a median of 127 days (range 6-259). Tenofovir was well tolerated by all women throughout pregnancy. There were 15 successful deliveries occurring at a median (range) of 36 weeks (30-40), with a median birth weight of 3255 g (1135-3610). Complications, including 1 spontaneous abortion, occurred in 9 pregnancies and were not attributed to tenofovir. Eleven (73%) women had abnormal laboratory results, including 6 who experienced grade 1 hemoglobin abnormalities; 4 of these women had preexisting anemia. Calculated glomerular filtration rate (calculated by Modification of Diet in Renal Disease equation) remained above 90 mL/min/1.73 m(2) in all women, except one who had a transient decline. Fourteen infants demonstrated normal growth and development for weight and height at birth, as well as during the 12-month follow-up period; no congenital malformations were documented. Mother-to-child transmission of HIV was not observed in this cohort. CONCLUSIONS: Tenofovir was found to be a well-tolerated component of HAART in this small cohort. Longer-term assessment of tenofovir effects on childhood growth and larger prospective studies of tenofovir use in pregnant women are warranted.

Effect of postpartum HIV treatment discontinuation on long-term maternal outcome.

BACKGROUND: Long-term maternal outcomes after postpartum antiretroviral therapy (ART) discontinuation are unknown. METHODS: Retrospective review of pregnancies in HIV-infected women on treatment between 1997 and 2005. Women were grouped by postpartum ART use and followed until new opportunistic infection (OI), death or last clinic visit. RESULTS: Of 172 pregnancies, postpartum ART discontinuation occurred in 123 (71.5%) women and was associated with greater parity, no partner during pregnancy, and no indication for OI prophylaxis or preconception ART in multivariate analysis (P < .05). Median follow-up was 32.5 months after delivery. There were 12 OIs and 2 deaths; 10 OIs and both deaths occurred in women who had discontinued ART. CONCLUSION: Postpartum ART discontinuation is common, especially among those with less advanced HIV disease, but may leave women at increased risk of long term adverse outcomes. This study highlights the need for larger longitudinal studies to determine appropriate recommendations for postpartum ART administration.

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.

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.

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.

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.

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.