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1.  Changes in Body Mass Index Following HAART Initiation among HIV-Infected Women in the Women's Interagency HIV Study 
Examine changes in, and factors associated with changing body mass index (BMI) in women following highly active antiretroviral therapy (HAART) initiation.
1177 HIV-infected Women's Interagency HIV Study participants who contributed 10,754 years of follow-up following HAART initiation were studied. Changes in median BMI up to 15 years following HAART initiation, and the highest and lowest BMI reached following HAART initiation were summarized by pre-HAART BMI category (<18.5 [underweight], 18.5–<25.0 [normal weight], 25.0–<30.0 [overweight], 30.0–<40.0 [obese], and ≥ 40.0 [morbidly obese]). Multivariate mixed effects ordinal logistic regression estimated the degree of association of each exposure of interest with post-HAART BMI.
Before HAART, 39% percent of women had normal BMI, 31% were overweight, 23% were obese, and 5% were morbidly obese. Following HAART initiation, median BMI change (per 5 years) was 0.21 kg/m2 (90% confidence interval [CI]: −1.33, 0.42) for those with normal pre-HAART BMI, 0.39 kg/m2 (90% CI: 0.15,0.66) for overweight, 0.31 kg/m2 (90% CI: −1.18,0.67) for obese, and −0.36kg/m2 for morbidly obese women. After initiating HAART, 40% with normal pre-HAART BMI became overweight at some point; of those overweight, 46% remained overweight and 47% became obese; 71% of obese women remained obese and 27% became morbidly obese. Each year of nucleoside analog reverse transcriptase inhibitor use was associated with a 3% decreased odds of reaching a higher BMI category (OR 0.97, 95% CI: 0.95, 0.99), while each year of protease inhibitor or non-nucleoside analog reverse transcriptase inhibitor use were associated with a 6% (OR 1.06, 95% CI: 1.04, 1.08) and 5%(OR 1.05, 95% CI: 1.01, 1.08) increased odds of having a higher BMI category, respectively.
Although overweight and obesity are highly prevalent in this large cohort of HIV-infected, minority women, HAART use was associated with only a modest increase in BMI over time.
PMCID: PMC4285631  PMID: 25580365
Obesity; Body mass index; HIV; Women; HAART; Women's interagency HIV study
2.  The Association of Self-perception of Body Fat Changes and Quality of Life in the Women’s Interagency HIV Study 
AIDS care  2013;25(12):10.1080/09540121.2013.793265.
Body fat changes are of concern to HIV-seropositive adults on highly active antiretroviral therapy (HAART). Studies examining the association of body fat changes and quality of life (QOL) in the setting of HIV infection have been conducted predominately in men. We examined the relationship of self-perceived body fat change with QOL among 1,671 HAART-using HIV-seropositive women (mean age 40 ± 8 years; 54% African American, 24% reporting ≤ 95% HAART adherence) from the Women’s Interagency HIV Study. Self-perception of any fat loss was associated with lower overall QOL. Report of any peripheral fat loss was strongly associated with nearly all QOL domains (i.e., physical functioning, role functioning, energy/fatigue, social functioning, pain, emotional well-being, health perception, and perceived health index) except cognitive functioning, whereas report of any central fat loss was significantly associated with lower social and cognitive functioning. Report of any central fat gain was associated with lower overall QOL, but only physical functioning, energy/fatigue, and cognitive functioning were significantly affected. A significant association of report of any peripheral fat gain with overall QOL was not observed, however peripheral fat gain was significantly associated with lower physical functioning and pain. We found that any report of fat loss, especially in peripheral body sites is associated with lower QOL, as was any report of central fat gain. Ultimately health providers and patients need to be informed of these associations so as to better support HIV-seropositive women who live with these effects.
PMCID: PMC3769511  PMID: 23656440
body image perception; lipoatrophy; lipohypertrophy; Quality of life; HIV-seropositive women; HAART
3.  Association of HIV Infection, Hepatitis C Virus Infection, and Metabolic Factors With Liver Stiffness Measured by Transient Elastography 
The Journal of Infectious Diseases  2013;208(11):1776-1783.
Background. Few studies have examined the relationship of human immunodeficiency virus (HIV) monoinfection and its associated perturbations with liver fibrosis.
Methods. Using multivariable linear regression, we examined the demographic, behavioral, metabolic and viral factors associated with transient elastography–measured liver stiffness in 314 participants (165 HIV positive/hepatitis C virus [HCV] negative, 78 HIV positive/HCV positive, 14 HIV negative/HCV positive, 57 HIV negative/HCV negative) in the Women's Interagency HIV Study.
Results. Compared with HIV negative/HCV negative women, HIV positive/HCV positive women had higher median liver stiffness values (7.1 vs 4.4 kPa; P < .001); HIV positive/HCV negative and HIV negative/HCV negative women had similar liver stiffness values (both 4.4 kPa; P = .94). HIV/HCV coinfection remained associated with higher liver stiffness values (74% higher; 95% confidence interval [CI], 49–104) even after multivariable adjustment. Among HCV positive women, waist circumference (per 10-cm increase) was associated with 18% (95% CI, 7.5%–30%) higher liver stiffness values after multivariable adjustment; waist circumference showed little association among HIV positive/HCV negative or HIV negative/HCV negative women. Among HIV positive/HCV negative women, history of AIDS (13%; 95% CI, 4% –27%) and HIV RNA (7.3%; 95% CI, 1.59%–13.3%, per 10-fold increase) were associated with greater liver stiffness.
Conclusions. HCV infection but not HIV infection is associated with greater liver stiffness when infected women are compared with those with neither infection. Our finding that waist circumference, a marker of central obesity, is associated with greater liver stiffness in HIV/HCV-coinfected but not HIV-monoinfected or women with neither infection suggests that in the absence of HCV-associated liver injury the adverse effects of obesity are lessened.
PMCID: PMC3814832  PMID: 23901097
HIV; HCV; liver fibrosis; transient elastography; obesity; women
4.  Self-Reported Body Fat Change in HIV-Infected Men Is a Marker of Decline in Physical Health-Related Quality of Life with Aging, Independent of Co-Morbidity 
PLoS ONE  2014;9(12):e114166.
Self-perception of changes in body fat among HIV+ persons is associated with decreased health related quality of life in cross-sectional studies. The longitudinal impact of body fat changes on health related quality of life, while accounting for comorbidity and anatomic location or severity of body fat changes, is unknown.
This was a longitudinal analysis of HIV+ and HIV- Multicenter AIDS Cohort Study (MACS) participants who completed questionnaires assessing self-perceived body fat changes (baseline visit) and a health related quality of life (Short Form-36) at baseline and then ≥5 years later.
Relationships between body fat changes and change in Short Form-36 Physical and Mental Component Summary scores were investigated using mixed-model regression.
We studied 270 HIV+ and 247 HIV- men. At baseline, ≥50% of HIV+ men reported body fat changes; physical component but not mental component summary scores were lower among HIV+ men who reported moderate/severe leg or abdominal fat changes (p<0.05). At follow-up, physical component summary scores were significantly lower among men with face, leg, or abdominal fat changes compared to men without perceived fat changes (p<0.05). No significant changes were seen in mental component scores by fat change location or severity. In the final model, body fat changes at any site or severity were significant predictors of a decline in physical component summary score (p<0.05), independent of demographics or comorbidities. Mental component summary score was not associated with body fat changes, but higher mental component summary score was associated with increasing age and time.
Negative self-perceived body fat changes were associated with decline in physical health related quality of life, independent of comorbidities, and may be a marker of an increased risk for physical function decline with aging.
PMCID: PMC4250188  PMID: 25436612
5.  Alcohol consumption trajectory patterns in adult women with HIV infection 
AIDS and behavior  2013;17(5):1705-1712.
HIV-infected women with excessive alcohol consumption are at risk for adverse health outcomes, but little is known about their long-term drinking trajectories. This analysis included longitudinal data, obtained from 1996–2006, from 2791 women with HIV from the Women’s Interagency HIV Study. Among these women, the proportion in each of five distinct drinking trajectories was: continued heavy drinking (3%), reduction from heavy to non-heavy drinking (4%), increase from non-heavy to heavy drinking (8%), continued non-heavy drinking (36%), and continued non-drinking (49%). Depressive symptoms, other substance use (crack/cocaine, marijuana, and tobacco), co-infection with HCV, and heavy drinking prior to enrollment were associated with trajectories involving future heavy drinking. In conclusion, many women with HIV change their drinking patterns over time. Clinicians and those providing alcohol-related interventions might target those with depression, current use of tobacco or illicit drugs, HCV infection, or a previous history of drinking problems.
PMCID: PMC3534826  PMID: 22836592
Alcohol consumption; women; HIV-infection; trajectories
6.  It Gets Better: Resolution of Internalized Homophobia over Time and Associations with Positive Health Outcomes among MSM 
AIDS and behavior  2013;17(4):1423-1430.
Health disparities research among gay and bisexual men has focused primarily on risk and deficits. However, a focus on resiliencies within this population may greatly benefit health promotion. We describe a pattern of resilience (internalized homophobia (IHP) resolution) over the life-course and its associations with current health outcomes. 1,541 gay and bisexual men from the Multi-Center AIDS Cohort study, an ongoing prospective study of the natural and treated histories of HIV, completed a survey about life-course events thought to be related to health. The majority of men resolved IHP over time independent of demographics. Men who resolved IHP had significantly higher odds of positive health outcomes compared to those who did not. These results provide evidence of resilience among participants that is associated with positive health outcomes. Understanding resiliencies and incorporating them into interventions may help to promote health and well-being among gay and bisexual men.
PMCID: PMC3708613  PMID: 23283578
Gay men’s health; Resilience; Internalized Homophobia; MSM Health Promotion; Syndemics
7.  Cochlear Function among HIV-Seropositive and HIV-Seronegative Men and Women 
Ear and hearing  2014;35(1):10.1097/AUD.0b013e3182a021c8.
There is limited research about cochlear function in adults who are human immunodeficiency virus (HIV) positive (+). The aim of the present study was to collect measures of cochlear function in a large sample of adults with, or at risk for, HIV infection, to evaluate associations between HIV status, HIV treatment, and cochlear function.
Distortion product otoacoustic emissions (DPOAEs) were used to evaluate cochlear function in 506 participants; 329 men, 150 of whom were HIV+, and 177 women, 136 of whom were HIV+. DPOAEs were measured at frequencies 1000, 2000, 3000, 4000, and 6000 Hz. A DPOAE nonresponse (NR) was defined as an absolute DPOAE level less than −15 dB SPL or a difference between the absolute DPOAE level and the background noise level less than 6 dB. The total number of NRs was calculated for each ear. The associations of demographic variables, HIV status, and HIV treatment with number of NRs were evaluated with univariate and multivariate ordinal regression models.
There was a statistically significant increase in the odds of higher numbers of NRs with age, being male, and being non-Black, but not with HIV status. Among HIV+ participants, there were no statistically significant associations of the HIV disease status or treatment variables with higher number of NRs.
The authors found no evidence of impaired cochlear function by HIV disease status or highly active antiretroviral therapy–treated HIV infection in this cross-sectional study.
PMCID: PMC3872496  PMID: 24080949
8.  A 12-year comparison of students’ perspectives on diversity at a Jesuit Medical School 
Medical Education Online  2014;19:10.3402/meo.v19.23401.
Many studies have assessed perspectives of medical students toward institutional diversity, but few of them have attempted to map changes in diversity climate over time.
This study aims to investigate changes in diversity climate at a Jesuit medical institution over a 12-year period.
In 1999, 334 medical students completed an anonymous self-administered online survey, and 12 years later, 406 students completed a comparable survey in 2011. Chi-square tests assessed the differences in percent responses to questions of the two surveys, related to three identities: gender, race, and sexual orientation.
The 1999 versus 2011 samples were 46% versus 49% female, 61% versus 61% Caucasian, and 41% vs. 39% aged 25 years or older. Findings suggested improvements in medical students’ perceptions surrounding equality ‘in general’ across the three identities (p<0.001); ‘in the practice of medicine’ based on gender (p<0.001), race/ethnicity (p=0.60), and sexual orientation (p=0.43); as well as in the medical school curriculum, including course text content, professor’s delivery and student–faculty interaction (p<0.001) across the three identities. There was a statistically significant decrease in experienced or witnessed events related to gender bias (p<0.001) from 1999 to 2011; however, reported events of bias based on race/ethnicity (p=0.69) and sexual orientation (p=0.58) only showed small decreases.
It may be postulated that the improvement in students’ self-perceptions of equality and diversity over the past 12 years may have been influenced by a generational acceptance of cultural diversity and, the inclusion of diversity training courses within the medical curriculum. Diversity training related to race and sexual orientation should be expanded, including a follow-up survey to assess the effectiveness of any intervention.
PMCID: PMC3938797  PMID: 24581334
medical students; diversity; curriculum; equality; survey; identity
9.  Uptake and Predictors of Anal Cancer Screening in Men Who Have Sex with Men 
American journal of public health  2013;103(9):e88-e95.
To understand attitudes about and acceptance of anal Pap screening among men who have sex with men (MSM).
1742 MSM in the Multicenter AIDS Cohort Study (MACS) were offered free anal Pap screening (cytology) and reported history of, attitudes about, and experience with anal Pap screening. Predictors of declining screening were explored with multivariate logistic regression.
A history of ever having anal Pap screening was uncommon among HIV-uninfected MSM, but more common among HIV-infected MSM (10% vs. 39%, p<0.001). Most participants expressed moderate or strong interest in anal Pap screening (86%), no anxiety about screening (66%), and a strong belief in the utility of anal Pap screening (65%). Acceptance of anal Pap screening offered during this study was high (85%) across all four U.S. study sites. Among those screened, most reported it was not a big deal, or not as bad as expected, while 3% reported it was scary. Declining to have anal Pap screening was associated with Black race, anxiety specifically about the screening, and low interest in screening, but not age or HIV status.
This study demonstrated high acceptance of anal Pap screening among both HIV-infected and HIV-uninfected MSM across four U.S. study sites.
PMCID: PMC3740081  PMID: 23865658
10.  Lower Liver-Related Death in African American Women With HIV/HCV Co-Infection Compared to Caucasian and Hispanic Women 
Hepatology (Baltimore, Md.)  2012;56(5):1699-1705.
Among individuals with and without concurrent human immunodeficiency virus (HIV), racial/ethnic differences in the natural history of hepatitis C virus (HCV) have been described. African-Americans have lower spontaneous HCV clearance than Caucasians, yet slower rates of liver fibrosis once chronically infected. It is not clear how these differences in the natural history of hepatitis C affect mortality, in either HIV positive or negative individuals. We conducted a cohort study of HIV/HCV co-infected women followed in the multicenter, NIH-funded Women’s Interagency HIV Study (WIHS) to determine the association of self-reported race/ethnicity with all-cause and liver-related mortality. Survival analyses were performed using Cox proportional hazards models. The eligible cohort (n=794) included 140 Caucasians, 159 Hispanics, and 495 African Americans. There were 438 deaths and 49 liver-related deaths during a median follow-up of 8.9 years and maximum follow-up of 16 years. African American co-infected women had significantly lower liver-related mortality compared to Caucasian (HR 0.41 95% CI 0.19–0.88, p=0.022) and Hispanic co-infected women (HR 0.38 95% CI 0.19–0.76, p=0.006). All-cause mortality was similar between racial/ethnic groups (HRs for all comparisons 0.82–1.03, logrank p=0.8).
African American co-infected women were much less likely to die from liver disease as compared to Caucasians and Hispanics, independent of other causes of death. Future studies are needed to investigate the reasons for this marked racial/ethnic discrepancy in liver-related mortality.
PMCID: PMC3440547  PMID: 22618868
race; ethnicity; viral hepatitis; mortality; gender
11.  Labor force participation and health-related quality of life in HIV-positive men who have sex with men: The Multicenter AIDS Cohort Study 
AIDS and behavior  2012;16(8):2350-2360.
Too many people with HIV have left the job market permanently and those with reduced work capacity have been unable to keep their jobs. There is a need to examine the health effects of labor force participation in people with HIV. This study presents longitudinal data from 1,415 HIV-positive men who have sex with men taking part in the Multicenter AIDS Cohort Study. Generalized Estimating Equations show that employment is associated with better physical and mental health quality of life and suggests that there may be an adaptation process to the experience of unemployment. Post-hoc analyses also suggest that people who are more physically vulnerable may undergo steeper health declines due to job loss than those who are generally healthier. However, this may also be the result of a selection effect whereby poor physical health contributes to unemployment. Policies that promote labor force participation may not only increase employment rates but also improve the health of people living with HIV.
PMCID: PMC3575137  PMID: 22814570
12.  Application of Syndemic Theory to Black Men Who Have Sex with Men in the Multicenter AIDS Cohort Study 
This study analyzed data from a large prospective epidemiologic cohort study among men who have sex with men (MSM), the Multicenter AIDS Cohort Study, to assess syndemic relationships among Black MSM in the cohort (N = 301). We hypothesized that multiple interconnections among psychosocial health conditions would be found among these men, defining syndemic conditions. Constituents of syndemic conditions measured included reported depression symptoms, sexual compulsiveness, substance use, intimate partner violence (IPV), and stress. We found significant evidence of syndemics among these Black men: depression symptoms were independently associated with sexual compulsiveness (odds ratios [OR]: 1.88, 95% CI = 1.1, 3.3) and stress (OR: 2.67, 95% CI = 1.5, 4.7); sexual compulsiveness was independently associated with stress (OR: 2.04, 95% CI = 1.2, 3.5); substance misuse was independently associated with IPV (OR: 2.57, 95% CI = 1.4, 4.8); stress independently was associated with depression symptoms (OR: 2.67, 95% CI = 1.5, 4.7), sexual compulsiveness (OR: 2.04, 95% CI = 1.2, 3.5) and IPV (OR: 2.84, 95% CI = 1.6, 4.9). Moreover, men who reported higher numbers of syndemic constituents (three or more conditions) reportedly engaged in more unprotected anal intercourse compared to men who had two or fewer health conditions (OR: 3.46, 95% CI = 1.4–8.3). Findings support the concept of syndemics in Black MSM and suggest that syndemic theory may help explain complexities that sustain HIV-related sexual transmission behaviors in this group.
PMCID: PMC3535137  PMID: 22383094
HIV; Syndemics; Black men; Sexual risk; Epidemiology
13.  Adversity and Syndemic Production Among Men Participating in the Multicenter AIDS Cohort Study: A Life-Course Approach 
We tested a theory of syndemic production among men who have sex with men (MSM) using data from a large cohort study.
Participants were 1551 men from the Multicenter AIDS Cohort Study enrolled at 4 study sites: Baltimore, Maryland–Washington, DC; Chicago, Illinois; Los Angeles, California; and Pittsburgh, Pennsylvania. Participants who attended semiannual visits from April 1, 2008, to March 31, 2009, completed an additional survey that captured data about events throughout their life course thought to be related to syndemic production.
Using multivariate analysis, we found that the majority of life-course predictor variables (e.g., victimization, internalized homophobia) were significantly associated with both the syndemic condition and the component psychosocial health outcomes (depressive symptoms, stress, stimulant use, sexual compulsivity, intimate partner violence). A nested negative binomial analysis showed that the overall life course significantly explained variability in the syndemic outcomes (χ2 = 247.94; P < .001; df = 22).
We identified life-course events and conditions related to syndemic production that may help to inform innovative interventions that will effectively disentangle interconnecting health problems and promote health among MSM.
PMCID: PMC3518355  PMID: 23153154
14.  Pain, psychological symptoms and prescription drug misuse in HIV: A literature review 
Journal of pain management  2012;5(2):111-118.
Pain is a common problem among persons living with HIV. In this population, pain often co-occurs with psychological symptoms, as well as illicit drug abuse. Recently, the misuse of prescription drugs, including the misuse of opioid medications for pain relief, has emerged as a significant public health problem. The purpose of this article is to review the literature on the associations among pain, illicit drug use, and symptoms of depression and anxiety in the misuse of prescription medications in HIV disease.
Results and Conclusions
Although relatively little attention has centered on the management of pain, psychological symptoms and other distressing, yet treatable symptoms in HIV, the fact that drug abuse behaviors now constitute a primary risk factor for HIV infection requires a shift in focus for clinicians and researchers alike. There is currently little agreement regarding the medical provision of opioids to persons with a history of illicit drug use. Thus, additional research is required to ensure adequate treatment of pain and psychological symptoms in persons living with HIV while minimizing the risk of prescription drug misuse.
PMCID: PMC3697768  PMID: 23826434
prescription drug abuse; opioids; pain medications; pain management; anxiety; depression
15.  Assessing mortality in women with hepatitis C virus and HIV using indirect markers of fibrosis 
AIDS (London, England)  2012;26(5):599-607.
Co-infection with hepatitis C virus (HCV) is a major cause of morbidity and mortality in HIV-infected individuals. However, predictors of mortality are poorly defined and most studies have focused predominantly on co-infection in men. We evaluated whether two indirect markers of hepatic fibrosis, aspartate aminotransferase-to-platelet ratio index (APRI) and FIB-4 scores, were predictive of mortality in a well defined longitudinal cohort of HCV/HIV-co-infected women on HAART.
HCV/HIV-co-infected women on antiretroviral therapy enrolled in Women’s Interagency HIV Study (WIHS), a National Institutes of Health-funded prospective, multicenter, cohort study of women with and at risk for HIV infection were included. Using Cox regression analysis, associations between APRI and FIB-4 with all-cause mortality were assessed.
Four hundred and fifty HCV/HIV-co-infected women, of whom 191 women died, had a median follow-up of 6.6 years and 5739 WIHS visits. Compared with women with low APRI or FIB-4 levels, severe fibrosis was significantly associated with an increased risk of all-cause mortality {APRI: hazard ratio 2.78 [95% confidence interval (CI) 1.87, 4.12]; FIB-4: hazard ratio 2.58 (95% CI 1.68, 3.95)}. Crude death rates per 1000 patient-years increased with increasing liver fibrosis: 34.8 for mild, 51.3 for moderate and 167.9 for severe fibrosis as measured by FIB-4. Importantly, both APRI and FIB-4 increased during the 5 years prior to death for all women: the slope of increase was greater for women dying a liver-related death compared with nonliver-related death.
Both APRI and FIB-4 are independently associated with all-cause mortality in HCV/HIV-co-infected women and may have clinical prognostic utility among women with HIV and HCV.
PMCID: PMC3698040  PMID: 22156972
fibrosis markers; hepatitis C virus; HIV; longitudinal study; mortality
16.  Online Health-Searching Behavior Among HIV-Seropositive and HIV-Seronegative Men Who Have Sex With Men in the Baltimore and Washington, DC Area 
Searching online for health information is common among American adults. However, there have been few studies to investigate the online health-searching behaviors among men who have sex with men (MSM) with human immunodeficiency virus (HIV).
To estimate the prevalence of Internet use among HIV-seropositive MSM and compare their online behaviors with HIV-seronegative men with chronic disease(s).
This study was performed at the Baltimore/Washington, DC site of the Multicenter AIDS Cohort Study (MACS). A total of 200 MACS participants were asked to answer a self-administered questionnaire on a first-come basis during a semiannual study visit (from July to November 2011); 195 (97.5%) participants completed the survey. Multiple logistic regression models were used to investigate the factors influencing their online health-searching behaviors.
The median age of the 195 MSM participants was 57 years, 64.6% were white, 59.0% were employed, and 88.2% had Internet access at home and/or other locations. Of the 95 HIV-seropositive participants, 89.5% currently used highly active antiretroviral therapy (HAART) and 82.1% had Internet access. After adjusting for age and race/ethnicity, the HIV-seropositive participants were less likely to perform online searches for general disease-related information compared to the HIV-seronegative men with chronic disease(s) (OR 0.20, 95% CI 0.06-0.68, P=.01). There were no statistically significant associations with HIV status and searching for new medications/treatments (OR 0.55, 95% CI 0.19-1.55, P=.26) or support/advice from other patients (OR 0.52, 95% CI 0.18-1.53, P=.24). Increasing age by 5 years led to a decrease by 29% in the odds of online health-related searches for general information (OR 0.71, 95% CI 0.52-0.98, P=.03) and 26% for support/advice from other patients (OR 0.74, 95% CI 0.56-0.98, P=.03). A decrease of 25% for new medications/treatments was also seen, but was not statistically significant (OR 0.75, 95% CI 0.57-1.01, P=.06).
This study shows that HIV-seropositive MSM have similar online health-searching behaviors as HIV-seronegative men with chronic disease(s). Independent of HIV status, older MSM are less likely to perform online health-related searches.
PMCID: PMC3650934  PMID: 23644412
Internet; information seeking behavior; HIV infections; chronic disease; patient care
17.  Hepatitis C Viremia Is Associated with Cytomegalovirus IgG Antibody Levels in HIV-Infected Women 
PLoS ONE  2013;8(4):e61973.
Individuals with HIV infection exhibit high cytomegalovirus (CMV) IgG levels, but there are few data regarding the association of hepatitis C virus (HCV) with the immune response against CMV.
Associations of HCV with CMV seropositivity and CMV IgG levels were studied in 635 HIV-infected women, 187 of whom were HCV-seropositive, with adjustment in multivariable models for age, race/ethnicity, and HIV disease characteristics. Eighty one percent of the women reported receipt of highly active antiretroviral therapy (HAART) prior to or at CMV testing.
In adjusted models women with chronic HCV had higher CMV IgG levels than those without HCV RNA (β = 2.86, 95% CI:0.89 – 4.83; P = 0.004). The association of HCV RNA with CMV IgG differed by age (Pinteraction = 0.0007), with a strong association observed among women in the low and middle age tertiles (≤45.3 years of age; β = 6.21, 95% CI:3.30 – 9.11, P<0.0001) but not among women in the high age tertile. CMV IgG levels were not associated with non-invasive measures of liver disease, APRI and FIB-4, or with HCV RNA level and adjustment for Epstein-Barr virus (EBV) IgG levels did not affect the association between HCV and CMV.
CMV IgG levels are higher in HCV/HIV co-infected women than in HIV mono-infected women. Further research on the association of HCV with CMV IgG is indicated because prior studies have found CMV IgG to be associated with morbidity and mortality in the general population and subclinical carotid artery disease in HIV-infected patients.
PMCID: PMC3629158  PMID: 23613990
18.  The Relationship Between Race and HIV-Distal Sensory Polyneuropathy in a Large Cohort of US Women 
Journal of the Neurological Sciences  2011;315(1-2):129-132.
HIV-distal sensory polyneuropathy (HIV-DSPN) is a common complication of HIV infection, yet race as a potential risk factor is not known.
Between April and October 2009, as part of the NIH Women’s Interagency HIV Study (WIHS), 1414 women, 973 of whom were HIV-infected, were clinically evaluated for peripheral neuropathy. Utilizing available clinical, laboratory, and sociodemographic variables, we conducted a cross-sectional analysis of factors associated with HIV-DSPN. Multivariable logistic regression was used to examine factors independently associated with HIV-DSPN.
36% of HIV-infected women met our definition of HIV-DSPN. 41.3% of African Americans, 34.8% of Whites and 24.7% of Hispanics had DSPN. Age, Hepatitis C-co-infection, and diabetes were each significantly associated with HIV-DSPN. After controlling for age, diabetes, Hepatitis C co-infection, alcohol use, current dideoxy-nucleoside reverse transcriptase inhibitor use, current CD4 count, and plasma HIV viral load, HIV-DSPN was significantly associated with ethnicity; the odds ratio was 1.67 (p=0.001) in African-Americans compared to other racial groups.
The prevalence of HIV-DSPN in women was lower than reported in prior studies. The likelihood of HIV-DSPN was higher in African-Americans compared to other racial groups. HIV-DSPN was more common in those co-infected with Hepatitis C, older individuals, and diabetics. Further prospective studies are needed to explore the relationship between gender, race, and HIV-DSPN, and the mechanistic basis for racial differences.
PMCID: PMC3299869  PMID: 22123155
HIV-associated sensory polyneuropathy; African-Americans; race; women; gender; diabetes; Hepatitis C
19.  The Cumulative Effects of Medication Use, Drug Use, and Smoking on Erectile Dysfunction Among Men Who Have Sex With Men 
The Journal of Sexual Medicine  2012;9(4):1106-1113.
Erectile dysfunction (ED) is highly prevalent among Human Immunodeficiency Virus-seropositive (HIV+) men who have sex with men (MSM). There is a need for additional research to determine the correlates of HIV+ and HIV-seronegative (HIV−) MSM, especially regarding non-antiretroviral medication use.
This study examined the prevalence of ED and the socio-demographic, medical conditions, medication use, and substance use correlates of ED among HIV+ and HIV− MSM.
A modified version of the International Index of Erectile Function (IIEF) for MSM was self-administered by participants enrolled in the Multicenter AIDS Cohort Study (MACS), an ongoing prospective study of the natural and treated histories of HIV infection among MSM in the United States. The study sample included 1,340 participants, including 612 HIV+ and 728 HIV− men. Poisson regression with robust error variance was used to estimate prevalence ratios of ED in multivariable models in combined (HIV+/−) and separate analyses.
Main outcome measure
ED was determined by the summed scores of a modified version of the IIEF validated among MSM.
Twenty-one percent of HIV+ MSM and 16% of HIV− MSM reported ED. Being >55 years of age, Black race, cumulative pack-years of smoking, cumulative antihypertensive use, and cumulative antidepressant use had significant positive associations with the prevalence of ED in the total sample. Among HIV+ men, duration of antihypertensive use and antidepressant use were significantly associated with increasing prevalence of ED. Among HIV− men, being >55 years of age, Black race, and cigarette smoking duration were associated with increased prevalence of ED.
Predictors of ED may differ by HIV status.. Although smoking cessation and effective medication management may be important as possible treatment strategies for ED among all MSM, there may be a burden on sexual functioning produced by non-HIV medications for HIV+ men.
PMCID: PMC3319271  PMID: 22321450
20.  Cumulative exposure to stimulants and immune function outcomes among HIV-positive and HIV-negative men in the Multicenter AIDS Cohort Study 
We examined associations between stimulant use (methamphetamine and cocaine) and other substances (nicotine, marijuana, alcohol, inhaled nitrites) with immune function biomarkers among HIV-seropositive (HIV+) men using highly active antiretroviral therapy (ART) and -seronegative (HIV−) men in the Multicenter AIDS Cohort Study (MACS). Among HIV+ men, cumulative adherence to ART (4.07, 95% CI: 3.52, 4.71, per 10 years of adherent HAART use), and recent cohort enrollment (1.38; 95% CI: 1.24, 1.55) were multiplicatively associated with increases in CD4+/CD8+ ratios. Cumulative use of methamphetamine (0.93; 95% CI: 0.88, 0.98, per 10 use years), cocaine (0.93; 95% CI: 0.89, 0.96, per 10 use years), and cumulative medical visits (0.99; 95% CI: 0.98, 0.99, per 10 visit years), each showed small negative associations with CD4+/CD8+ ratios. Among HIV- men, cumulative medical visits (0.996; 95% CI: 0.993, 0.999), cumulative number of male sexual partners (0.999; 95% CI: 0.998, 0.9998, per 10 partner years) and cigarette pack years (1.10; 95% CI: 1.02, 1.18, per 10 pack years) were associated with CD4+/CD8+ ratios over the same period. ART adherence is associated with a positive immune function independent of stimulant use, underscoring the influence of ART on immune health for HIV+ men who engage in stimulant use.
PMCID: PMC3576843  PMID: 22930295
HIV; men; methamphetamine; cocaine; CD4+/CD8+ ratio; antiretroviral therapy; adherence; Multicenter AIDS Cohort Study
21.  The mediating role of pain in substance use and depressive symptoms among Multicenter AIDS Cohort Study (MACS) participants 
Pain  2011;152(12):2757-2764.
Pain in HIV frequently co-occurs with substance use and depression. The complex associations among patient characteristics, pain, depression, and drug use in HIV suggests a role for testing models that can account for relationships simultaneously, control for HIV status and also test for mediation. Using structural equation modeling (SEM), the current study examined associations among pain, sociodemographics, illicit drug use and depressive symptoms in 921 HIV seropositive and 1,019 HIV seronegative men from the Multicenter AIDS Cohort Study (MACS), an ongoing prospective study of the natural history of HIV infection among gay/bisexual men. Longitudinal repeated measures data collected over a 6 year period were analyzed using predictive path models in which sociodemographics, HIV status and CD4+ cell counts predicted pain which in turn predicted depressive symptoms and illicit drug use. The path models did not differ substantially between HIV seropositive and seronegative men. Analyses using the total sample indicated that pain served both as a mediator and as a predictor of more use of cannabis, cocaine and heroin, as well as more depressive symptoms. HIV seropositive status predicted more use of inhaled nitrites. In this cohort, having lower CD4+ cell counts (predicted by HIV status), being African-American, less educated, and older were all associated with more pain which in turn was associated with more illicit drug use and more depressive symptoms. The results underscore the need for adequate pain management, particularly among vulnerable subgroups of HIV seropositive and HIV seronegative men to reduce the risk of drug use and depression.
PMCID: PMC3215839  PMID: 21962911
substance use; depression; HIV; pain; drug use
22.  The relationship between methamphetamine and popper use and risk of HIV seroconversion in the multicenter AIDS cohort study 
The association between methamphetamine use and HIV seroconversion for men who have sex with men (MSM) was examined using longitudinal data from the Multicenter AIDS Cohort Study.
Seronegative (n=4003) men enrolled in 1984–85, 1987–1991 and 2001–2003 were identified. Recent methamphetamine and popper use were determined at either the current or the previous visit. Time to HIV-seroconversion was the outcome of interest. Covariates included race/ethnicity, cohort, study site, educational level, number of sexual partners, number of unprotected insertive anal sexual partners (UIAS), number of unprotected receptive anal sexual partners (URAS), insertive rimming, cocaine use at either the current or last visit, ecstasy use at either the current or last visit, any needle use since last visit, CES-D depression score > 16 since last visit, and alcohol consumption.
After adjusting for covariates, there was an approximately 1.46-fold independent increased relative hazard (HR) of HIV seroconversion for methamphetamine use. The HR associated with popper use was 2.1 [95% CI 1.63, 2.70]. The HR of HIV seroconversion increased with URAS ranging from 1.87 [95% CI 1.40, 2.51] for 1 partner to 9.32 [95% CI 6.20, 13.98] for 5+ partners. The joint HR for methamphetamine and popper use was 3.05 [95% CI 2.12, 4.37]. Most notably, there was a significant joint HR for methamphetamine use and URAS of 2.71 [95% CI 1.81, 4.04] for men with 1 unprotected receptive anal sex partner, which increased in a dose-dependent manner for >1 partners.
Further examination of the synergism of patterns of drug use and sexual risk behaviors on rates of HIV seroconversion will be necessary in order to develop new HIV prevention strategies for drug-using MSM.
PMCID: PMC3486782  PMID: 17325605
Multicenter AIDS cohort study; methamphetamine; HIV seroconversion; MSM
Cytokine  2011;56(2):325-331.
Tuberculosis (TB) is the worldwide leading cause of death among HIV-infected individuals, accounting for more than half of AIDS-related deaths. A high risk of tuberculosis (TB) has been shown in early stages of the HIV disease, even in the presence of normal CD4+ cell counts. Moreover, the factors that determine protective immunity vs. susceptibility to M. tuberculosis cannot be fully explained by simple changes in IFNγ levels or a shift from Th1 to Th2 cytokines. This work investigated the relationship between cytokine expression profiles in peripheral blood mononuclear cells (PBMC) and susceptibility to M. tuberculosis in ten HIV+ women who went on to develop TB. RNA transcripts for IL-4, IL-4δ2, IL-10, IL-12(p35), IL-13, IL-17A, IFNγ and TNFα were measured by real-time quantitative PCR in unstimulated or TB peptide antigen-stimulated PBMCs from ten HIV+ women with positive tuberculin skin tests (TST) and compared with HIV-seropositive and seronegative women without previous TB and negative TST. Stimulated PBMC cultures showed significantly lower expression of IL-12p35 (p=0.004) and IL-10 (p=0.026) in the HIV+TB+ group six to twelve months before onset of TB compared to HIV+TB− women. Unstimulated PBMC from HIV+TB+ women also had lower expression of Th2 cytokines [IL-4 (p=0.056) and IL-13 (p=0.050)] compared to HIV+TB− women. These results suggest that lower IL-12 production by PBMC in response to TB antigens and lower levels of both Th1 and Th2 cytokines by PBMC correlate with future development of TB in HIV-infected women and may be responsible for their increased susceptibility.
PMCID: PMC3466167  PMID: 21880503
Interferon-γ(IFNγ); Interleukin-4 (IL-4); Interleukin-12 (IL-12); Human Immunodeficiency Virus (HIV); Tuberculosis (TB)
24.  Prevalence of Abnormalities in Vestibular Function and Balance among HIV-Seropositive and HIV-Seronegative Women and Men 
PLoS ONE  2012;7(5):e38419.
Most HIV-seropositive subjects in western countries receive highly active antiretroviral therapy (HAART). Although many aspects of their health have been studied, little is known about their vestibular and balance function. The goals of this study were to determine the prevalences of vestibular and balance impairments among HIV-seropositive and comparable seronegative men and women and to determine if those groups differed.
Standard screening tests of vestibular and balance function, including head thrusts, Dix-Hallpike maneuvers, and Romberg balance tests on compliant foam were performed during semiannual study visits of participants who were enrolled in the Baltimore and Washington, D. C. sites of the Multicenter AIDS Cohort Study and the Women's Interagency HIV Study.
No significant differences by HIV status were found on most tests, but HIV-seropositive subjects who were using HAART had a lower frequency of abnormal Dix-Hallpike nystagmus than HIV-seronegative subjects. A significant number of nonclassical Dix-Hallpike responses were found. Age was associated with Romberg scores on foam with eyes closed. Sex was not associated with any of the test scores.
These findings suggest that HAART-treated HIV infection has no harmful association with vestibular function in community-dwelling, ambulatory men and women. The association with age was expected, but the lack of association with sex was unexpected. The presence of nonclassical Dix-Hallpike responses might be consistent with central nervous system lesions.
PMCID: PMC3364989  PMID: 22675462
25.  Changes in Stimulant Drug Use Over Time in the MACS: Evidence for Resilience Against Stimulant Drug Use Among Men Who Have Sex with Men 
AIDS and Behavior  2012;16(1):151-158.
Stimulant drug use is associated with numerous health problems among men who have sex with men (MSM). This paper describes how stimulant drug use changes over a four and one-half year period from 2003 until 2008. Participants were 2,389 men (17,222 person-visits) from The Multicenter AIDS Cohort Study (MACS)—an ongoing, prospective study of HIV infection among MSM. Group-based trajectory analyses of data from these men over the study period yielded a four groups solution: consistent users (9.8%), men whose use increased (5.4%), men whose use declined (6.9%), and abstinent or rarely-using men (77.9%). There were significant differences between groups in terms of demographic, behavioral risk and HIV serostatus. Men who increased or decreased stimulant drug use over time reported congruent changes in sexual risk taking. The fact that sexual risk levels parallel stimulant drug use over time suggests that finding ways to lower rates of stimulant drug use among MSM could be a tool in HIV prevention.
PMCID: PMC3133874  PMID: 21191644
Drug use; Gay men’s health; HIV risk behavior; MSM; Stimulant use

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