Elizabeth T. Golub

Crack cocaine, disease progression, and mortality in a multicenter cohort of HIV-1 positive women.

Background:Longitudinal associations between patterns of crack cocaine use and progression of HIV-1 disease are poorly understood, especially among women. This study explores relationships between crack use and HIV-1 disease outcomes in a multicenter cohort of infected women. Methods:Subjects were 1686 HIV-seropositive women enrolled at six US research centers in the Womens Interagency HIV Study. Approximately 80% were non-white and 29% used crack during the study period. Cox survival and random regression analysis examined biannual observations made April 1996 through September 2004. Outcome measures included death due to AIDS-related causes, CD4 cell count, HIV-1 RNA level, and newly acquired AIDS-defining illnesses. Results:Persistent crack users were over three times as likely as non-users to die from AIDS-related causes, controlling for use of HAART self-reported at 95% or higher adherence, problem drinking, age, race, income, education, illness duration, study site, and baseline virologic and immunologic indicators. Persistent crack users and intermittent users in active and abstinent phases showed greater CD4 cell loss and higher HIV-1 RNA levels controlling for the same covariates. Persistent and intermittent crack users were more likely than non-users to develop new AIDS-defining illnesses controlling for identical confounds. These results persisted when controlling for heroin use, tobacco smoking, depressive symptoms, hepatitis C virus coinfection, and injection drug use. Conclusion:Use of crack cocaine independently predicts AIDS-related mortality, immunologic and virologic markers of HIV-1 disease progression, and development of AIDS-defining illnesses among women.

A peer-education intervention to reduce injection risk behaviors for Hiv and hepatitis C virus infection in young injection drug users

Objectives:To evaluate whether a behavioral intervention, which taught peer education skills, could reduce injection and sexual risk behaviors associated with primary HIV and hepatitis C virus infection (HCV) among young injection drug users (IDU). Design:We conducted a randomized controlled trial involving HIV and HCV antibody-negative IDU, aged 15–30 years, recruited in five United States cities. A six-session, small-group, cognitive behavioral, skills-building intervention in which participants were taught peer education skills (n = 431) was compared with a time-equivalent attention control (n = 423). Baseline visits included interviews for sociodemographic, psychosocial, and behavioral factors during the previous 3 months; HIV and HCV antibody testing; and pre/posttest counselling. Procedures were repeated 3 and 6 months postintervention. Results:The intervention produced a 29% greater decline in overall injection risk 6 months postintervention relative to the control [proportional odds ratio 0.71; 95% confidence limit (CL) 0.52, 0.97], and a 76% decrease compared with baseline. Decreases were also observed for sexual risk behaviors, but they did not differ by trial arm. Overall HCV infection incidence (18.4/100 person-years) did not differ significantly across trial arms (relative risk 1.15; 95% CL 0.72, 1.82). No HIV seroconversions were observed. Conclusion:Interventions providing information, enhancing risk-reduction skills, and motivating behavior change through peer education training can reduce injection risk behaviors, although risk elimination might be necessary to prevent HCV transmission.

Factors Associated with Interest in Initiating Treatment for Hepatitis C Virus (HCV) Infection among Young HCV-Infected Injection Drug Users

OBJECTIVE We sought to identify factors associated with interest in receiving therapy for hepatitis C virus (HCV) infection among HCV-infected injection drug users (IDUs) in 3 United States cities. METHODS IDUs aged 18-35 years who were HCV-infected and seronegative for human immunodeficiency virus underwent surveys on behaviors, experience, and interest in treatment for HCV infection and readiness to quit drug use. RESULTS Among treatment-naive IDUs (n=216), 81.5% were interested in treatment for HCV infection, but only 27.3% had seen a health-care provider since receiving a diagnosis of HCV infection. Interest in treatment for HCV infection was greater among IDUs with a high perceived threat of progressive liver disease, those with a usual source of care, those without evidence of alcohol dependence, and those with higher readiness scores for quitting drug use. Interest in treatment for HCV infection was 7-fold higher among IDUs who were told by their health-care provider that they were at risk for cirrhosis or liver cancer. CONCLUSIONS Improving provider-patient communication and integrating treatments for substance abuse and HCV may increase the proportion of IDUs who initiate treatment for HCV infection.

Screening for depressive symptoms among HCV-infected injection drug users: Examination of the utility of the CES-D and the Beck Depression Inventory

The prevalence of depression is high among injection drug users (IDUs) and among those infected with the hepatitis C virus (HCV). Moreover, one of the drugs used in the standard treatment for HCV infection (interferon) has been known to exacerbate, underlying psychiatric disorders such as depression and has been associated with the development of major, depressive disorder among HCV-infected patients. For these reasons, the most recent National Institutes of Health consensus statement on the management of HCV infection recommends the identification and treatment of depression prior to the start of HCV treatment. This study aimed to examine the extent of current moderate/severe depressive symptoms in a cohort of HCV-infected IDUs as measured by two screening tools, the Center for Epidemiologic Studies Depression Scale (CES-D) and the Beck Depression Inventory (BDI). Subjects were participants in a multisite behavioral intervention trial among HCV-seropositive, human immunodeficiency virus-negative IDUs aged 18–35 years; the trial was designed to prevent secondary transmission of HCV and to enhance uptake of HCV treatment. Baseline data on demographics, risk behaviors, depression, alcohol use, and health care utilization were measured via audio computer-assisted self-interview. A factor analysis was conducted on each scale to examine the clustering of items used in each to measure depressive symptoms. Baseline depressive symptoms, as measured via the CES-D and the BDI, were also compared using Pearson’s correlation coefficient. Of 193 HCV-infected individuals enrolled to date, 75,6% were male, and 65.3% were white. Median age was 25.8 years. Factor analyses revealed that these scales measured depression differently; a distinct somatic component was present in the BDI, but not the CES-D. Using cutoff scores of 23 for the CES-D and 19 for the BDI, 44.0% and 41.5% of the participants were identified as having moderate/severe depressive symptoms, respectively. Over half (56.0%) were identified as having depressive symptoms

Variations in Serum Mullerian Inhibiting Substance Between White, Black and Hispanic Women

OBJECTIVE To compare serum müllerian inhibiting substance (MIS) levels between white, black, and Hispanic women to determine whether ovarian aging occurs at a different time course for women of different racial groups. DESIGN Longitudinal study of serum MIS levels in women of different race and ethnicity over two different time points. SETTING Womens Interagency HIV Study, a multicenter prospective cohort study. PATIENT(S) Serum samples obtained from 809 participants (122 white, 462 black, and 225 Hispanic women). INTERVENTION(S) Comparison of serum MIS between women of different race and ethnicity at two time points (median age 37.5 years and 43.3 years). MAIN OUTCOME MEASURE(S) Variation in MIS by race and ethnicity over time, controlling for age, body mass index, HIV status, and smoking. RESULT(S) Compared with white women, average MIS values were lower among black (25.2% lower) and Hispanic (24.6% lower) women, adjusting for age, body mass index, smoking, and HIV status. CONCLUSION(S) There is an independent effect of race and ethnicity on the age-related decline in MIS over time.

The effect of HIV infection and HAART on inflammatory biomarkers in a population-based cohort of women.

Objective:HIV causes inflammation that can be at least partially corrected by HAART. To determine the qualitative and quantitative nature of cytokine perturbation, we compared cytokine patterns in three HIV clinical groups, including HAART responders (HAART), untreated HIV noncontrollers, and HIV-uninfected (NEG). Methods:Multiplex assays were used to measure 32 cytokines in a cross-sectional study of participants in the Womens Interagency HIV Study. Participants from three groups were included: HAART (n = 17), noncontrollers (n = 14), and HIV NEG (n = 17). Results:Several cytokines and chemokines showed significant differences between noncontrollers and NEG participants, including elevated interferon gamma-induced 10 (IP-10) and tumor necrosis factor-&agr; (TNF-&agr;) and decreased interleukin-12(p40) [IL-12(p40)], IL-15, and fibroblast growth factor-2 (FGF-2) in noncontroller participants. Biomarker levels among HAART women more closely resembled the NEG, with the exception of TNF-&agr; and FGF-2. Secondary analyses of the combined HAART and noncontroller groups revealed that IP-10 showed a strong, positive correlation with viral load and negative correlation with CD4+ T-cell counts. The growth factors vascular endothelial growth factor, epidermal growth factor, and FGF-2 all showed a positive correlation with increased CD4+ T-cell counts. Conclusion:Untreated, progressive HIV infection was associated with decreased serum levels of cytokines important in T-cell homeostasis (IL-15) and T-cell phenotype determination (IL-12), and increased levels of innate inflammatory mediators such as IP-10 and TNF-&agr;. HAART was associated with cytokine profiles that more closely resembled those of HIV-uninfected women. The distinctive pattern of cytokine levels in the three study groups may provide insights into HIV pathogenesis, and responses to therapy.

Vitamin D deficiency in HIV-infected and HIV-uninfected women in the United States

Background:Vitamin D deficiency is of increasing concern in HIV-infected persons because of its reported association with a number of negative health outcomes that are common in HIV. We undertook this study to determine the prevalence and predictors of vitamin D deficiency among a nationally representative cohort of middle-aged, ethnically diverse, HIV-infected and HIV-uninfected women enrolled in the Womens Interagency HIV Study (WIHS). Methods:Vitamin D testing was performed by Quest Diagnostics on frozen sera using the liquid chromatography/mass spectroscopy method. Vitamin D deficiency was defined as 25(OH)D ≤20 ng/mL. Comparisons of continuous and categorical characteristics among HIV-infected and HIV-uninfected women were made by Wilcoxon tests and Pearson χ2 tests, respectively. Results:One thousand seven hundred seventy-eight women (1268 HIV positive) were studied. Sixty-three percent had vitamin D deficiency (60% HIV positive vs. 72% HIV negative; P < 0.001). Multivariable predictors of vitamin D deficiency were being African American (adjusted odds ratio 3.02), Hispanic (adjusted odds ratio 1.40), body mass index (adjusted odds ratio 1.43), age (adjusted odds ratio 0.84), HIV positive (adjusted odds ratio 0.76), glomerular filtration rate <90·mL−1·min−1 (adjusted odds ratio 0.94), and WIHS sites Los Angeles (adjusted odds ratio 0.66) and Chicago (adjusted odds ratio 0.63). In the HIV-positive women, multivariate predictors were undetectable HIV RNA (adjusted odds ratio 0.69), CD4 50-200 cells per cubic millimeter (adjusted odds ratio 1.60), CD4 <50 cells per cubic millimeter (adjusted odds ratio 1.94), and recent protease inhibitor use (adjusted odds ratio 0.67). Conclusions:In this study of more than 1700 women in the United States, most women with or without HIV infection had low vitamin D levels and African American women had the highest rates of vitamin D deficiency. An understanding of the role that vitamin D deficiency plays in non-AIDS-related morbidities is planned for investigation in WIHS.

Short-term bone loss in HIV-infected premenopausal women.

Background:Low bone mineral density (BMD) has been reported in HIV+ women, but less is known about the longitudinal evolution of BMD and fracture incidence. Methods:In 100 HIV+ and 68 HIV− premenopausal women in the Womens Interagency HIV Study, BMD was measured by dual energy x-ray absorptiometry at the femoral neck (FN) and lumbar spine (LS) at index visit and after a median of 2.5 years. Results:In HIV+ women, BMD at index visit was normal but 5% lower at the LS and FN than in HIV− women. Annual percent decrease in BMD did not differ between HIV+ and HIV− women at the LS (−0.8% ± 0.2% vs −0.4% ± 0.2%, P = 0.20) or FN (−0.8% ± 0.3% vs −0.6% ± 0.3%, P = 0.56) and remained similar after adjustment for age, weight, and BMD at index visit. Among HIV+ women, bone loss was associated with vitamin D deficiency and opiate use but not with use or class of antiretrovirals. Incidence of self-reported fracture was 0.74 per 100 person-years in HIV+ women and similar in HIV− women. Conclusions:In premenopausal HIV+ women, index BMD was lower than comparable HIV− women; however, rates of bone loss at the LS and FN were similar over 2.5 years of observation, irrespective of antiretroviral therapy.

Fracture incidence in HIV-infected women: results from the Women's Interagency HIV Study

Background:The clinical importance of the association of HIV infection and antiretroviral therapy (ART) with low bone mineral density (BMD) in premenopausal women is uncertain because BMD stabilizes on established ART and fracture data are limited. Methods:We measured time to first new fracture at any site with median follow-up of 5.4 years in 2391 (1728 HIV-infected, 663 HIV-uninfected) participants in the Womens Interagency HIV Study (WIHS). Self-report of fracture was recorded at semiannual visits. Proportional hazard models assessed predictors of incident fracture. Results:At baseline, HIV-infected women were older (40 ± 9 vs. 36 ± 10 years, P < 0.0001), more likely to report postmenopausal status and be hepatitis C virus-infected, and weighed less than HIV-uninfected women. Among HIV-infected women, mean CD4+ cell count was 482 cells/μl; 66% were taking ART. Unadjusted incidence of fracture did not differ between HIV-infected and uninfected women (1.8 vs. 1.4/100 person-years, respectively, P = 0.18). In multivariate models, white (vs. African-American) race, hepatitis C virus infection, and higher serum creatinine, but not HIV serostatus, were statistically significant predictors of incident fracture. Among HIV-infected women, older age, white race, current cigarette use, and history of AIDS-defining illness were associated with incidence of new fracture. Conclusion:Among predominantly premenopausal women, there was little difference in fracture incidence rates by HIV status, rather traditional risk factors were important predictors. Further research is necessary to characterize fracture risk in HIV-infected women during and after the menopausal transition.

Association of Race, Substance Abuse, and Health Insurance Coverage With Use of Highly Active Antiretroviral Therapy Among HIV-Infected Women, 2005

OBJECTIVES We examined racial/ethnic disparities in highly active antiretroviral therapy (HAART) use and whether differences are moderated by substance use or insurance status, using data from the Womens Interagency HIV Study (WIHS). METHODS Logistic regression examined HAART use in a longitudinal cohort of women for whom HAART was clinically indicated in 2005 (N = 1354). RESULTS Approximately 3 of every 10 eligible women reported not taking HAART. African American and Hispanic women were less likely than were White women to use HAART. After we adjusted for potential confounders, the higher likelihood of not using HAART persisted for African American but not for Hispanic women. Uninsured and privately insured women, regardless of race/ethnicity, were less likely than were Medicaid enrollees to use HAART. Although alcohol use was related to HAART nonuse, illicit drug use was not. CONCLUSIONS These findings suggest that expanding and improving insurance coverage should increase access to antiretroviral therapy across racial/ethnic groups, but it is not likely to eliminate the disparity in use of HAART between African American and White women with HIV/AIDS.