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1.  Gender-related risk factors improve mortality predictive ability of VACS Index among HIV-infected women 
Adding gender-related modifiable characteristics or behaviors to the Veterans Aging Cohort Study (VACS) Index might improve the accuracy of predicting mortality among HIV-infected women on treatment. We evaluated the VACS Index in women with HIV, determined whether additional variables would improve mortality prediction, and quantified the potential for improved survival associated with reduction in these additional risk factors.
The VACS Index (based on age, CD4 count, HIV-1 RNA, hemoglobin, AST, ALT, platelets, creatinine and Hepatitis C status) was validated in HIV-infected women in the Women’s Interagency HIV Study (WIHS) who initiated antiretroviral therapy (ART) between January 1996 and December 2007. Models were constructed adding race, depression, abuse, smoking, substance use, transactional sex, and comorbidities to determine whether predictability improved. Population attributable fractions were calculated.
The VACS Index accurately predicted 5-year mortality in 1057 WIHS women with 1 year on HAART with c-index 0.83 (95% CI 0.79–0.87). In multivariate analysis, the VACS Index score (adjusted hazard ratio [aHR] for 5-point increment 1.30; 95% CI 1.25–1.35), depressive symptoms (aHR 1.73; 95% CI 1.17–2.56) and history of transactional sex (aHR 1.93; 95% CI 1.33–1.82) were independent statistically significant predictors of mortality.
Including depression and transactional sex significantly improved the performance of the VACS Index in predicting mortality among HIV-infected women. Providing treatment for depression and addressing economic and psychosocial instability in HIV infected women would improve health and perhaps point to a broader public health approach to reducing HIV mortality.
PMCID: PMC4644433  PMID: 26284531
HIV; Women; Mortality; Depression; Transactional Sex
AIDS (London, England)  2015;29(10):1183-1193.
To determine the lung cancer incidence and survival time among HIV-infected and uninfected women and men.
Two longitudinal studies of HIV infection in the United States.
Data from 2,549 women in the Women’s Interagency HIV Study (WIHS) and 4,274 men in the Multicenter AIDS Cohort Study (MACS), all with a history of cigarette smoking, were analyzed. Lung cancer incidence rates and incidence rate ratios were calculated using Poisson regression analyses. Survival time was assessed using Kaplan-Meier and Cox proportional hazard analyses.
Thirty-seven women and 23 men developed lung cancer (46 HIV-infected and 14 HIV-uninfected) during study follow-up. In multivariable analyses, the factors that were found to be independently associated with a higher lung cancer incidence rate ratios were older age, less education, 10 or more pack-years of smoking, and a prior diagnosis of AIDS pneumonia (vs. HIV-uninfected women). In an adjusted Cox model that allowed for different hazard functions for each cohort, a history of injection drug use was associated with shorter survival, and a lung cancer diagnosis after 2001 was associated with longer survival. In an adjusted Cox model restricted to HIV-infected participants, nadir CD4 lymphocyte cell count <200 was associated with shorter survival time.
Our data suggest that pulmonary damage and inflammation associated with HIV infection may be etiologic for the increased risk of lung cancer. Encouraging and assisting younger HIV-infected smokers to quit and to sustain cessation of smoking is imperative to reduce the lung cancer burden in this population.
PMCID: PMC4457511  PMID: 25888645
AIDS; HIV infection; incidence; lung cancer; survival
3.  Improvement in Posttraumatic Stress Disorder in Postconflict Rwandan Women 
Journal of Women's Health  2011;20(9):1325-1332.
Depression and posttraumatic stress disorder (PTSD) are common in developing and postconflict countries. The purpose of this study is to examine longitudinal changes in PTSD in HIV-infected and uninfected Rwandan women who experienced the 1994 genocide.
Five hundred thirty-five HIV-positive and 163 HIV-negative Rwandan women in an observational cohort study were followed for 18 months. Data on PTSD symptoms were collected longitudinally by the Harvard Trauma Questionnaire (HTQ) and analyzed in relationship to demographics, HIV status, antiretroviral treatment (ART), and depression. PTSD was defined as a score on the HTQ of ≥2.
There was a continuing reduction in HTQ scores at each follow-up visit. The prevalence of PTSD symptoms changed significantly, with 61% of the cohort having PTSD at baseline vs. 24% after 18 months. Women with higher HTQ score were most likely to have improvement in PTSD symptoms (p<0.0001). Higher rate of baseline depressive symptoms (p<0.0001) was associated with less improvement in PTSD symptoms. HIV infection and ART were not found to be consistently related to PTSD improvement.
HIV care settings can become an important venue for the identification and treatment of psychiatric problems affecting women with HIV in postconflict and developing countries. Providing opportunities for women with PTSD symptoms to share their history of trauma to trained counselors and addressing depression, poverty, and ongoing violence may contribute to reducing symptoms.
PMCID: PMC3168969  PMID: 21732802
4.  Prevalence and Predictors of Posttraumatic Stress Disorder and Depression in HIV-Infected and At-Risk Rwandan Women 
Journal of Women's Health  2009;18(11):1783-1791.
During the 1994 Rwandan genocide, rape was used as a weapon of war to transmit HIV. This study measures trauma experiences of Rwandan women and identifies predictors associated with posttraumatic stress disorder (PTSD) and depressive symptoms.
The Rwandan Women's Interassociation Study and Assessment (RWISA) is a prospective observational cohort study designed to assess effectiveness and toxicity of antiretroviral therapy in HIV-infected Rwandan women. In 2005, a Rwandan-adapted Harvard Trauma Questionnaire (HTQ) and the Center for Epidemiologic Studies Depression Scale (CES-D) were used to assess genocide trauma events and prevalence of PTSD (HTQ mean >2) and depressive symptoms (CES-D ≥ 16) for 850 women (658 HIV-positive and 192 HIV-negative).
PTSD was common in HIV-positive (58%) and HIV-negative women (66%) (p = 0.05). Women with HIV had a higher prevalence of depressive symptoms than HIV-negative women (81% vs. 65%, p < 0.0001). Independent predictors for increased PTSD were experiencing more genocide-related trauma events and having more depressive symptoms. Independent predictors for increased depressive symptoms were making <$18 a month, HIV infection (and, among HIV-positive women, having lower CD4 cell counts), a history of genocidal rape, and having more PTSD symptoms.
The prevalence of PTSD and depressive symptoms is high in women in the RWISA cohort. Four of five HIV-infected women had depressive symptoms, with highest rates among women with CD4 cell counts <200. In addition to treatment with antiretroviral therapy, economic empowerment and identification and treatment of depression and PTSD may reduce morbidity and mortality among women in postconflict countries.
PMCID: PMC2828188  PMID: 19951212
5.  Increased fracture incidence in middle-aged HIV-infected and uninfected women: updated results from the Women’s Interagency HIV Study 
We previously reported that fracture incidence rates did not differ by HIV status among predominantly premenopausal Women's Interagency HIV Study (WIHS) participants. We now conduct a follow-up study with 5 additional observation years, to further characterize fracture risk associated with HIV infection in women as they age.
We measured time to first new fracture at any site in 2375 (1713 HIV-infected, 662 HIV-uninfected) WIHS participants, with median 10 years follow-up. Fractures were self-reported semiannually. Proportional Hazards models assessed predictors of incident fracture.
At index visit, HIV-infected women were older (median age 40 yrs (IQR 34–46) vs. 35 (27–43), p<0.0001) and more likely to be postmenopausal, HCV-infected, and weigh less than HIV-uninfected women. Among HIV-infected women, mean CD4+ count was 480 cells/µL and 63% were taking HAART. Unadjusted incidence rates of any fracture were higher in HIV-infected than uninfected women (2.19/100 person-years (py) vs 1.54/100py, p=0.002). In multivariate models, HIV status, older age, white (vs. black) race, prior fracture, history of cocaine use, and history of injection drug use were significant predictors of incident fracture. Among HIV-infected women, age, white race, prior fracture, smoking, and prior AIDS were predictors of new fracture.
Middle-aged HIV-infected women had a higher adjusted fracture rate than uninfected women. Cocaine use and injection drug use were also associated with a greater risk of incident fracture. Further research is needed to understand whether the risk of fracture associated with cocaine use relates to increased rate of falls, or direct effects on bone metabolism.
PMCID: PMC4557627  PMID: 26322667
HIV; women; bone; fracture; fragility fracture
6.  Resilience Moderates the Association between Childhood Sexual Abuse and Depressive Symptoms Among Women with and At-Risk for HIV 
AIDS and behavior  2015;19(8):1379-1387.
Childhood sexual abuse (CSA) places women at risk for HIV infection and once infected, for poor mental health outcomes, including lower quality of life and depressive symptoms. Among HIV-positive and demographically matched HIV-negative women, we investigated whether resilience and HIV status moderated the relationships between CSA and health indices as well as the relationships among CSA, depressive symptoms, and health-related quality of life (HRQOL). Participants included 202 women (138 HIV+, 64 HIV−, 87% African American) from the Women’s Interagency HIV Study (WIHS) Chicago CORE Center site. Results indicated that in both HIV-positive and HIV-negative women, higher resilience significantly related to lower depressive symptoms and higher HRQOL. CSA related to higher depressive symptoms only for women scoring low in resilience. Interventions to promote resilience, especially in women with a CSA history, might minimize depressive symptoms and poor HRQOL among HIV-positive and HIV-negative women.
PMCID: PMC4314513  PMID: 25085079
resilience; childhood sexual abuse; HIV; depressive symptoms; quality of life
7.  Sexual behavior and risk practices of HIV positive and HIV negative Rwandan women 
AIDS and behavior  2015;19(7):1366-1378.
It is not well understood how infection with HIV and prior experience of sexual violence affects sexual behavior in African women. We describe factors influencing current sexual practices of Rwandan women living with or without HIV/AIDS. By design, 75% of participants were HIV positive and ~50% reported having experienced genocidal rape. Univariate and multivariate logistic regression models were fit to describe demographic and clinical characteristics that influenced sexual behavior in the previous 6 months, condom use, history of transactional sex, and prior infection with a non-HIV sexually transmitted disease. Respondents’ age, where they lived, whether or not they lived with a husband or partner, experience of sexual trauma, CD4 count, CES-D and PTSD scores were strongly associated with risky sexual behavior and infection with non-HIV STI. HIV positive women with a history of sexual violence in the contexts of war and conflict may be susceptible to some high-risk sexual behaviors.
PMCID: PMC4461563  PMID: 25488169
HIV/AIDS; Sexual behavior; Sexual Trauma; Genocide; Rwanda
8.  APOL1 Genotype and Glomerular and Tubular Kidney Injury in Women With HIV 
APOL1 genotype is associated with advanced kidney disease in African-Americans, but the pathogenic mechanisms are unclear. Here, associations of APOL1 genotype with urine biomarkers of glomerular and tubular injury, and with kidney function decline, were evaluated.
Study Design
Observational study.
Setting & Participants
431 HIV-infected African-American women enrolled in Women's Interagency HIV Study (WIHS).
APOL1 genotype.
Albumin-creatinine ratio (ACR), four tubular injury biomarkers (interleukin 18 [IL-18], kidney injury molecule 1 [KIM-1], neutrophil gelatinase-associated lipocalin [NGAL], and α1-microglobulin [α1m]), and kidney function estimated using the CKD-EPI cystatin C equation.
Participants were genotyped for APOL1 single-nucleotide polymorphisms rs73885319 (G1 allele) and rs71785313 (G2 allele). Urine biomarker levels were measured using stored samples from 1999-2000. Cystatin C was measured using serum collected at baseline and 4- and 8-year follow-up.
At baseline, ACR levels were higher among 47 women with 2 APOL1 risk alleles versus 384 women with 0/1 risk allele (median, 24 vs. 11 mg/g; p < 0.001). Compared to women with 0/1 risk allele, women with 2 risk alleles had 104% higher ACR (95% CI, 29-223 mg/g) and 2-fold greater risk of ACR > 30 mg/g (95% CI, 1.17-3.44) after multivariable adjustment. APOL1 genotype showed little association with urine IL-18:Cr, KIM-1:Cr, and NGAL:Cr (estimates of -5% [95% CI, -24% to 18%], -20% [95% CI, -36% to 1%], and 10% [95% CI, -26% to 64%], respectively), or detectable urine α1m (prevalence ratio, 1.13; 95% CI, 0.65-1.97) in adjusted analyses. Compared to women with 0/1 allele, women with 2 risk alleles had faster eGFR decline, by 1.2 (95% CI, -2.2 to -0.2) ml/min/1.73 m2 per year, and had 1.7- and 3.4-fold greater rates of incident chronic kidney disease (95% CI, 1.1-2.5) and 10% annual eGFR decline (95% CI, 1.7-6.7), respectively, with minimal attenuation after adjustment for glomerular and tubular injury biomarkers.
Results may not be generalizable to men.
Among HIV-infected African-American women, APOL1-associated kidney injury appears to localize to the glomerulus, rather than the tubules.
PMCID: PMC4615696  PMID: 25921719
APOL1 genotype; risk variant; risk allele; G1 allele; G2 allele; single-nucleotide polymorphism (SNP); albumin-creatinine ratio (ACR); proteinuria; tubular injury biomarker; apolipoprotein L1; kidney disease; renal function; glomerular injury; African American; Women's Interagency HIV Study (WIHS)
9.  Mechanisms for the Negative Effects of Internalized HIV-Related Stigma on Antiretroviral Therapy Adherence in Women: The Mediating Roles of Social Isolation and Depression 
Supplemental Digital Content is Available in the Text.
Internalization of HIV-related stigma may inhibit a person's ability to manage HIV disease through adherence to treatment regimens. Studies, mainly with white men, have suggested an association between internalized stigma and suboptimal adherence to antiretroviral therapy (ART). However, there is a scarcity of research with women of different racial/ethnic backgrounds and on mediating mechanisms in the association between internalized stigma and ART adherence.
The Women's Interagency HIV Study (WIHS) is a multicenter cohort study. Women living with HIV complete interviewer-administered questionnaires semiannually. Cross-sectional analyses for the current article included 1168 women on ART for whom data on medication adherence were available from their last study visit between April 2013 and March 2014, when the internalized stigma measure was initially introduced.
The association between internalized stigma and self-reported suboptimal ART adherence was significant for those in racial/ethnic minority groups (AOR = 0.69, P = 0.009, 95% CI: 0.52 to 0.91), but not for non-Hispanic whites (AOR = 2.15, P = 0.19, 95% CI: 0.69 to 6.73). Depressive symptoms, loneliness, and low perceived social support mediated the association between internalized stigma and suboptimal adherence in the whole sample, as well as in the subsample of minority participants. In serial mediation models, internalized stigma predicted less-perceived social support (or higher loneliness), which in turn predicted more depressive symptoms, which in turn predicted suboptimal medication adherence.
Findings suggest that interconnected psychosocial mechanisms affect ART adherence, and that improvements in adherence may require multifaceted interventions addressing both mental health and interpersonal factors, especially for minority women.
PMCID: PMC4868649  PMID: 26885803
adherence; stigma; depression; social support; loneliness
10.  Longitudinal Trends in Sexual Behaviors with Advancing Age and Menopause Among Women With and Without HIV-1 Infection 
AIDS and behavior  2015;19(5):931-940.
We assessed changes in self-reported sexual activity (SA) over 13 years among HIV-infected and uninfected women. The impact of aging and menopause on SA and unprotected anal or vaginal intercourse (UAVI) was examined among women in the Women’s Interagency HIV Study (WIHS), stratifying by HIV status and detectable viral load among HIV-infected women. Generalized mixed linear models were fitted for each outcome, adjusted for relevant covariates. HIV-uninfected women evidenced higher levels of SA and UAVI than HIV-infected. The odds of SA declined by 62–64 % per decade of age. The odds of SA in a 6-month interval for women aged 40–57 declined by 18–22 % post-menopause (controlling for age). Among HIV+/detectable women only, the odds of any UAVI decreased by 17 % per decade of age; the odds of UAVI were unchanged pre-menopause, and then decreased by 28 % post-menopause. Elucidating the factors accounting for ongoing unprotected sex among older women should inform interventions.
PMCID: PMC4370800  PMID: 25245474
Sexual activity; Sexual risk behaviors; Aging; Menopause; Women’s Interagency HIV Study (WIHS)
11.  Oral Glucose Tolerance Testing identifies HIV+ infected women with Diabetes Mellitus (DM) not captured by standard DM definition 
HIV-infected (HIV+) individuals may have differential risk of diabetes mellitus (DM) compared to the general population, and the optimal diagnostic algorithm for DM in HIV+ persons remains unclear. We aimed to assess the utility of oral glucose tolerance testing (OGTT) for DM diagnosis in a cohort of women with or at risk for HIV infection.
Using American Diabetic Association DM definitions, DM prevalence and incidence were assessed among women enrolled in the Women’s Interagency HIV Study. DM was defined by 2-hour OGTT ≥ 200 mg/dL (DM_OGTT) or a clinical definition (DM_C) that included any of the following: (i) anti-diabetic medication use or self-reported DM confirmed by either fasting glucose (FG) ≥126 mg/dL or HbA1c ≥ 6.5%, (ii) FG ≥ 126 mg/dL confirmed by a second FG ≥ 126 mg/dL or HbA1c 6.5%, or (iii) HbA1c 6.5% confirmed by FG ≥ 126 mg/dL cohort.
Overall, 390 women (285 HIV+, median age 43 years; 105 HIV−, median age 37 years) were enrolled between 2003-2006. Over half of all women were African American. Using DM_C, DM prevalence rates were 5.6% and 2.8% among HIV+ and HIV− women, respectively. Among HIV+ women, adding DM_OGTT to DM_C increased DM prevalence from 5.6% to 7.4%, a 31% increase in the number of diabetes cases diagnosed (p=0.02). In HIV− women, no additional cases were diagnosed by DM-OGTT.
In HIV+ women, OGTT identified DM cases that were not identified by a standardized clinical definition. Further investigation is needed to determine whether OGTT should be considered as an adjunctive tool for DM diagnosis in the setting of HIV infection.
PMCID: PMC4825684  PMID: 27066296
HIV; Women; Diabetes mellitus; Oral glucose tolerance test
12.  Post-traumatic stress is associated with verbal learning, memory, and psychomotor speed in HIV-infected and HIV-uninfected women 
Journal of neurovirology  2015;22(2):159-169.
The prevalence of post-traumatic stress disorder (PTSD) is higher among HIV-infected (HIV+) women compared with HIV-uninfected (HIV−) women, and deficits in episodic memory are a common feature of both PTSD and HIV infection. We investigated the association between a probable PTSD diagnosis using the PTSD Checklist-Civilian (PCL-C) version and verbal learning and memory using the Hopkins Verbal Learning Test in 1004 HIV+ and 496 at-risk HIV− women. HIV infection was not associated with a probable PTSD diagnosis (17 % HIV+, 16 % HIV−; p=0.49) but was associated with lower verbal learning (p<0.01) and memory scores (p<0.01). Irrespective of HIV status, a probable PTSD diagnosis was associated with poorer performance in verbal learning (p<0.01) and memory (p<0.01) and psychomotor speed (p<0.001). The particular pattern of cognitive correlates of probable PTSD varied depending on exposure to sexual abuse and/or violence, with exposure to either being associated with a greater number of cognitive domains and a worse cognitive profile. A statistical interaction between HIV serostatus and PTSD was observed on the fine motor skills domain (p= 0.03). Among women with probable PTSD, HIV− women performed worse than HIV+ women on fine motor skills (p=0.01), but among women without probable PTSD, there was no significant difference in performance between the groups (p= 0.59). These findings underscore the importance of considering mental health factors as correlates to cognitive deficits in women with HIV.
PMCID: PMC4783199  PMID: 26404435
HIV; Post-traumatic stress disorder; Women; Cognition
13.  Serum Albumin and Kidney Function Decline in HIV-Infected Women 
Serum albumin concentrations are a strong predictor of mortality and cardiovascular disease in HIV-infected individuals. We studied the longitudinal associations between serum albumin levels and kidney function decline in a population of HIV-infected women.
Study Design
Retrospective cohort analysis.
Setting & Participants
The study participants were recruited from the Women’s Interagency HIV Study (WIHS), a large observational study designed to understand risk factors for the progression of HIV infection in women living in urban communities. 908 participants had baseline assessment of kidney function and two follow-up measures over an average of 8 years.
The primary predictor was serum albumin concentration.
We examined annual change in kidney function. Secondary outcomes included rapid kidney function decline and incident reduced estimated glomerular filtration rate (eGFR).
Kidney function decline was determined by cystatin C–based (eGFRcys) and creatinine-based eGFR (eGFRcr) at baseline and follow up. Each model was adjusted for kidney disease and HIV-related risk factors using linear and relative risk regression.
After multivariate adjustment, each 0.5-g/dL decrement in baseline serum albumin concentration was associated with a 0.56-mL/min faster annual decline in eGFRcys (P<0.001), which was only slightly attenuated to 0.55-mL/min/1.73 m2 after adjustment for albuminuria. Results were similar whether using eGFRcys or eGFRcr. In adjusted analyses, each 0.5-g/dL lower baseline serum albumin was associated with a 1.71-fold greater risk of rapid kidney function decline (p<0.001) and a 1.72-fold greater risk of incident reduced eGFR (p<0.001).
The cohort is composed of only female participants from urban communities within the United States.
Lower levels of serum albumin were strongly associated with kidney function decline and incident reduced eGFR in HIV-infected women, independent of HIV disease status, BMI and albuminuria.
PMCID: PMC4177337  PMID: 25059222
albumin; kidney function; HIV; incident reduced eGFR; albuminuria; disease trajectory; chronic kidney disease (CKD) progression
14.  The association of perceived stress and verbal memory is greater in HIV-infected versus HIV-uninfected women 
Journal of neurovirology  2015;21(4):422-432.
In contrast to findings from cohorts comprised primarily of HIV-infected men, verbal memory deficits are the largest cognitive deficit found in HIV-infected women from the Women’s Interagency HIV Study (WIHS), and this deficit is not explained by depressive symptoms or substance abuse. HIV-infected women may be at greater risk for verbal memory deficits due to a higher prevalence of cognitive risk factors such as high psychosocial stress and lower socioeconomic status. Here, we investigate the association between perceived stress using the Perceived Stress Scale (PSS-10) and verbal memory performance using the Hopkins Verbal Learning Test (HVLT) in 1009 HIV-infected and 496 at-risk HIV-uninfected WIHS participants. Participants completed a comprehensive neuropsychological test battery which yielded seven cognitive domain scores, including a primary outcome of verbal memory. HIV infection was not associated with a higher prevalence of high perceived stress (i.e., PSS-10 score in the top tertile) but was associated with worse performance on verbal learning (p<0.01) and memory (p<0.001), as well as attention (p=0.02). Regardless of HIV status, high stress was associated with poorer performance in those cognitive domains (p’s< 0.05) as well as processing speed (p=0.01) and executive function (p<0.01). A significant HIV by stress interaction was found only for the verbal memory domain (p=0.02); among HIV-infected women only, high stress was associated with lower performance (p’s<0.001). That association was driven by the delayed verbal memory measure in particular. These findings suggest that high levels of perceived stress contribute to the deficits in verbal memory observed in WIHS women.
PMCID: PMC4562210  PMID: 25791344
HIV; Verbal memory; Stress; Women; Cognition
16.  An investigation of menopausal stage and symptoms on cognition in HIV-infected women 
Menopause (New York, N.Y.)  2014;21(9):997-1006.
We evaluated the separate and interactive associations of menopausal stage, menopausal symptoms, and HIV infection on cognition. We hypothesized that HIV-infected, perimenopausal women would show the greatest cognitive difficulties and that menopausal symptoms would be inversely associated with cognition.
This cross-sectional study included 708 HIV-infected and 278 HIV-uninfected, pre-, peri-, or postmenopausal women (64% African-American; median age 44 years) from the Women’s Interagency HIV Study. Participants completed tests of verbal learning and memory, attention/processing speed, and executive function. We administered a menopausal symptom questionnaire that assessed anxiety, vasomotor, and sleep symptoms and obtained measures of depressive symptoms.
In multivariable regression analyses controlling for relevant covariates, HIV infection, but not menopausal stage, was associated with worse performance on all cognitive measures (p’s<0.05). Depressive symptoms were associated with lower cognitive performance on measures of verbal learning and memory, attention, and executive function (p’s<0.05); anxiety symptoms were associated with lower performance on measures of verbal learning and memory (p’s<0.05). Vasomotor symptoms were associated with worse attention (p<0.05). HIV and anxiety symptoms interacted to influence verbal learning (p’s<0.05); elevated anxiety was associated with worse verbal learning in HIV-infected women only.
Vasomotor, depressive, and anxiety symptoms, but not menopausal stage, were associated with worse cognitive performance in both HIV-infected and uninfected women, although elevated anxiety symptoms were associated with verbal learning deficits more in HIV-infected women. Since cognitive problems can interfere with everyday functioning including treatment adherence, it may be important to screen and treat anxiety in HIV-infected women.
PMCID: PMC4119867  PMID: 24496085
HIV; Verbal Learning; Menopause; Mood; Anxiety; African American
17.  Crack cocaine use impairs anterior cingulate and prefrontal cortex function in women with HIV infection 
Journal of neurovirology  2014;20(4):352-361.
Crack cocaine use is associated with impaired verbal memory in HIV-infected women more than -uninfected women. To understand the neural basis for this impairment, this study examined the effects of crack cocaine use on activation of the prefrontal cortex (PFC) and strategic encoding during a verbal memory task in HIV-infected women.
Three groups of HIV-infected women from the Chicago Consortium of the Women’s Interagency HIV Study were compared: current users of crack cocaine (n=10), former users of cocaine (n=11), and women who had never used cocaine (n=9). Participants underwent functional magnetic resonance imaging during a verbal memory task and completed a neuropsychological test of verbal memory.
On the neuropsychological test, current crack users performed significantly worse than other groups on semantic clustering, a measure of strategic encoding, p < .05. During encoding, activation in left anterior cingulate cortex (ACC) was lower in current and former cocaine users compared to never users. During recognition, activation in bilateral PFC, specifically left dorsal medial PFC and bilateral dorsolateral PFC, was lower in current and former users compared to women who had never used cocaine. Lower activation in left dorsolateral PFC was correlated with worse performance on the recognition task, p < .05.
The verbal learning and memory deficits associated with cocaine use in women with HIV may be partially accounted for by alterations in ACC and PFC function.
PMCID: PMC4090256  PMID: 24760360
HIV; crack cocaine; African American; verbal memory; fMRI; prefrontal cortex
18.  Sexual Minority Status and Violence Among HIV Infected and At-Risk Women 
Journal of General Internal Medicine  2014;29(8):1131-1138.
Sexual minority women with and at-risk for human immunodeficiency virus (HIV) may face increased risks of violence.
To understand the relationship between sexual minority status and violence; and how high-risk sex and substance use mediate that relationship among women with and at-risk for HIV.
Longitudinal study of 1,235 HIV infected and 508 uninfected women of the Women's Interagency HIV Study (WIHS) cohort, from New York City, NY, Chicago, IL, Washington D.C., and San Francisco, CA, 1994–2012.
Primary exposures are sexual identity (heterosexual, bisexual, lesbian/gay) and sexual behavior (male, female, or male & female partners). Primary outcomes are sexual abuse, intimate partner violence (IPV) and physical violence; high-risk sex and substance use were examined as mediators.
Bisexual women were at increased odds for sexual abuse [aOR 1.56 (1.00, 2.44)], IPV [aOR 1.50 (1.08, 2.09)], and physical violence [aOR 1.77 (1.33, 2.37)] compared to heterosexual women. In a separate analysis, women who reported sex with men and women (WSMW) had increased odds for sexual abuse [aOR 1.65 (0.99, 2.77], IPV [aOR 1.50 (1.09, 2.06)] and physical violence [aOR 2.24 (1.69, 2.98)] compared to women having sex only with men (WSM). Using indirect effects, multiple sex partners, cocaine and marijuana were significant mediators for most forms of abuse. Transactional sex was only a mediator for bisexual women. Women who reported sex only with women (WSW) had lower odds of sexual abuse [aOR 0.23 (0.06, 0.89)] and physical violence [aOR 0.42 (0.21, 0.85)] compared to WSM.
Women who identify as bisexual or report both male and female sex partners are most vulnerable to violence; multiple recent sex partners, transactional sex and some types of substance use mediate this relationship. Acknowledging sexual identity and behavior, while addressing substance use and high-risk sex in clinical and psychosocial settings, may help reduce violence exposure among women with and at-risk for HIV.
PMCID: PMC4099466  PMID: 24700180
gay and lesbian health; IPV; sexual assault; HIV/AIDS; women’s health
19.  Smoking Cessation and Recidivism in the Women's Interagency Human Immunodeficiency Virus Study 
Smoking increases the risk of morbidity and mortality and is particularly harmful to HIV-infected people.
To explore smoking trends and longitudinal factors associated with smoking cessation and recidivism among participants in the Women's Interagency HIV Study.
From 1994 through 2011, 2,961 HIV-infected and 981 HIV-uninfected women were enrolled and underwent semi-annual interviews and specimen collection. Smoking prevalence was evaluated annually and risk factors associated with time to smoking cessation and recidivism were analyzed in 2013 using survival models.
The annual cigarette smoking prevalence declined from 57% in 1995 to 39% in 2011 (p-trend<0.0001). Among smokers, factors significantly associated with a longer time to smoking cessation included less education, alcohol use, having health insurance, >10-year smoking duration, self-reported poor health rating, and having hypertension. Pregnancy in the past 6 months was associated with a shorter time to cessation. Among HIV-infected women, additional risk factors for longer time to cessation included lower household income, use of crack/cocaine/heroin, CD4 cell count ≤200, and highly active antiretroviral therapy (HAART) use. Predictors of smoking recidivism included marijuana use, enrollment in 1994–1996, and not living in one's own place. Among HIV-infected women, enrollment in 2001-2002 and crack/cocaine/heroin use were associated with a shorter time to recidivism, whereas older age and HAART use were associated with a longer time to recidivism.
Despite declining rates of cigarette smoking, integrated interventions are needed to help women with and at risk for HIV infection to quit smoking and sustain cessation.
PMCID: PMC4065848  PMID: 24746376
20.  Urinary Biomarkers of Kidney Injury Are Associated with All-Cause Mortality in the Women’s Interagency HIV Study (WIHS) 
HIV medicine  2013;15(5):291-300.
Chronic kidney disease (CKD) is common in HIV; CKD is associated with mortality. Urinary markers of tubular injury have been associated with future kidney disease risk, but associations with mortality are unknown.
We evaluated the association of urinary interleukin-18(IL-18), liver fatty acid binding protein(L-FABP), kidney injury molecule-1(KIM-1), neutrophil gelatinase-associated lipocalin(NGAL), albumin-to-creatinine ratio(ACR) with 10-year, all-cause death in 908 HIV-infected women. Kidney function was estimated using cystatin C (eGFRcys).
There were 201 deaths during 9,269 person-years of follow-up. After demographic adjustment, compared to the lowest tertile, highest tertiles of IL-18 (HR 2.54,95%CI 1.75–3.68), KIM-1 (2.04,1.44–2.89), NGAL(1.50,1.05–2.14), and ACR(1.63,1.13–2.36) were associated with higher mortality. After multivariable adjustment including eGFRcys, only the highest tertiles of IL-18, (1.88,1.29–2.74) and ACR (1.46,1.01–2.12) remained independently associated with mortality. Findings with KIM-1 were borderline (1.41, 0.99–2.02). We found a J-shaped association between L-FABP and mortality. Compared to persons in the lowest tertile, HR for middle tertile of L-FABP was 0.67 (0.46–0.98) after adjustment. Findings were stronger when IL-18, ACR and L-FABP were simultaneously included in models.
Among HIV-infected women, some urinary markers of tubular injury are associated with mortality risk, independently of eGFRcys and ACR. These markers represent potential tools to identify early kidney injury in persons with HIV.
PMCID: PMC3975680  PMID: 24313986
HIV; IL-18; KIM-1; L-FABP; NGAL; urinary biomarkers
21.  Psychosocial Correlates of Gender-Based Violence Among HIV-Infected and HIV-Uninfected Women in Three US Cities 
AIDS Patient Care and STDs  2014;28(5):260-267.
Gender-based violence (GBV) is common among women with and at risk for HIV, yet little is known about the GBV associated psychological factors that could be modifiable through behavioral interventions. The current study examined the associations between some of these psychological factors (i.e., hopelessness, consideration of future consequences, self esteem), mental health symptoms, substance abuse, and GBV among a sample of 736 HIV-infected and sociodemographically similar uninfected participants in the Women's Interagency HIV Study (WIHS). Results indicated high rates of lifetime GBV among the sample (58%), as well as high rates of childhood sexual abuse (CSA) (22.2%). HIV-infected women were more likely to be hopeless and to experience lower consideration of future consequences as compared to uninfected women. Multivariable analysis indicated that current non-injection drug use and a history of injection drug use were the main correlates of GBV and CSA, even when other psychosocial variables were included in analytic models. Being born outside of the US reduced the likelihood of GBV and CSA. Future research directions and intervention implications are discussed.
PMCID: PMC4011431  PMID: 24724987
The use of single-tablet ART regimens and its implications on adherence among HIV-infected women have not been well-described.
Participants were enrolled in the Women’s Interagency HIV Study (WIHS), a longitudinal study of HIV infection in U.S. women. We examined semiannual trends in single-tablet regimen use and ART adherence, defined as self-reported 95% adherence in the past 6 months, during 2006–2013. In a nested cohort study, we assessed the comparative effectiveness of a single-tablet versus a multiple-tablet regimen with respect to adherence, virologic suppression, quality of life, and AIDS-defining events, using propensity score matching to account for demographic, behavioral, and clinical confounders. We also examined these outcomes in a subset of women switching from a multiple- to single-tablet regimen, using a case-crossover design.
15,523 person-visits, representing 1,727 women (53% black, 29% Hispanic, 25% IDU, median age 47), were included. Use of single-tablet regimens among ART users increased from 7% in 2006 to 27% in 2013; adherence increased from 78% to 85% during the same period (both p<0.001). Single-tablet regimen use was significantly associated with increased adherence (adjusted RR 1.05, 95% CI 1.03–1.08) and virologic suppression (RR 1.06, 95% CI 1.01–1.11), while associations with improved quality of life and fewer AIDS-defining events did not achieve statistical significance. Similar findings were observed among the subset of switchers.
Single-tablet regimen use was associated with increased adherence and virologic suppression. Despite this, 15% of women prescribed ART were still not optimally adherent; additional interventions are needed to maximize therapeutic benefits.
PMCID: PMC3999284  PMID: 24326606
adherence; antiretroviral therapy; HIV; time factors; United States; viral load; women
23.  RYR3 gene variants in subclinical atherosclerosis among HIV-infected women in the Women’s Interagency HIV Study (WIHS) 
Atherosclerosis  2014;233(2):666-672.
Single nucleotide polymorphisms (SNPs) in the Ryanodine receptor 3 (RYR3) gene are associated with common carotid intima media thickness (CCA cIMT) in HIV-infected men. We evaluated SNPs in the RYR3 gene among HIV-infected women participating in Women’s Interagency HIV Study (WIHS).
CCA cIMT was measured using B-mode ultrasound and the 838 SNPs in the RYR3 gene region were genotyped using the Illumina HumanOmni2.5-quad beadchip. The CCA cIMT genetic association was assessed using linear regression analyses among 1213 women and also separately among White (n=139), Black (n=720) and Hispanic (n=354) women after adjusting for confounders. A summary measure of pooled association was estimated using a meta-analytic approach by combining the effect estimates from the three races. Haploblocks were inferred using Gabriel’s method and haplotype association analyses were conducted among the three races separately.
SNP rs62012610 was associated with CCA cIMT among the Hispanics (p=4.41× 10−5), rs11856930 among Whites (p=5.62× 10−4), and rs2572204 among Blacks (p=2.45× 10−3). Meta-analysis revealed several associations of SNPs in the same direction and of similar magnitude, particularly among Blacks and Hispanics. Additionally, several haplotypes within three haploblocks containing SNPs previously related with CCA cIMT were also associated in Whites and Hispanics.
Consistent with previous research among HIV-infected men, SNPs within the RYR3 region were associated with subclinical atherosclerosis among HIV-infected women. Allelic heterogeneity observed across the three races suggests that the contribution of the RYR3 gene to CCA cIMT is complex, and warrants future studies to better understand regional SNP function.
PMCID: PMC3965606  PMID: 24561552
RYR3; single nucleotide polymorphisms; HIV infection; CCA; cIMT; subclinical atherosclerosis
24.  Resilience among women with HIV: Impact of silencing the self and socioeconomic factors 
Sex roles  2014;70(5-6):221-231.
In the U.S., women account for over a quarter of the approximately 50,000 annual new HIV diagnoses and face intersecting and ubiquitous adversities including gender inequities, sexism, poverty, violence, and limited access to quality education and employment. Women are also subjected to prescribed gender roles such as silencing their needs in interpersonal relationships, which may lessen their ability to be resilient and function adaptively following adversity. Previous studies have often highlighted the struggles encountered by women with HIV without focusing on their strengths. The present cross-sectional study investigated the relationships of silencing the self and socioeconomic factors (education, employment, and income) with resilience in a sample of women with HIV. The sample consisted of 85 women with HIV, diverse ethnic/racial groups, aged 24 – 65 enrolled at the Chicago site of the Women’s Interagency HIV Study in the midwestern region of the United States. Measures included the Connor-Davidson Resilience Scale -10 item and the Silencing the Self Scale (STSS). Participants showed high levels of resilience. Women with lower scores on the STSS (lower self-silencing) reported significantly higher resilience compared to women with higher STSS scores. Although employment significantly related to higher resilience, silencing the self tended to predict resilience over and above the contributions of employment, income, and education. Results suggest that intervention and prevention efforts aimed at decreasing silencing the self and increasing employment opportunities may improve resilience.
PMCID: PMC4051411  PMID: 24932061
resilience; silencing the self; HIV; women; socioeconomic factors
25.  Comparison of Antibodies That Mediate HIV Type 1 gp120 Antibody-Dependent Cell-Mediated Cytotoxicity in Asymptomatic HIV Type 1-Positive Men and Women 
Recent studies suggest that HIV-specific antibody-dependent cell-mediated cytotoxicity (ADCC) antibodies contribute to protective immunity against HIV. An important characteristic of future HIV vaccines will, therefore, be the ability to stimulate production of these antibodies in both men and women. Early studies suggest that men may have a better ADCC antibody response against HIV than women. Our objective was to determine whether men and women differ with respect to their ADCC response to HIV-1 gp120. HIV-positive, asymptomatic untreated men and women were matched for race, age, CD4+ T cell number, HIV-1 viral load, and treatment and HIV-1 gp120 ADCC antibody titers were compared. A standard 51Cr-release assay was used to determine HIV-1 gp120 ADCC antibody titers in HIV-1-seropositive individuals from the Multicenter AIDS Cohort Study (MACS; n=32) and the Women's Interagency HIV Study (WIHS; n=32). Both sexes had high ADCC titers against HIV-1 gp120: 34.4% (n=11) and 40.6% (n=13) of men and women, respectively, had titers of 10,000; 62.5% (n=20) and 56.3% (n=18) had titers of 100,000. Groups did not differ in percent specific release (% SR), lytic units (LU), correlations of titer to viral load, or titer to CD4+ T cells in men or women. Both groups also had similar cross-clade ADCC antibody responses (p>0.5 for % SR and LU). Comparable groups of asymptomatic HIV-1-infected men and women had comparable HIV-1 gp120 ADCC antibodies. Both sexes had significant cross-clade reactivity. Differences between men and women may become evident as disease progresses; this should be evaluated at later stages of HIV-1 infection.
PMCID: PMC3887406  PMID: 23972002

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