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1.  Improvement in Posttraumatic Stress Disorder in Postconflict Rwandan Women 
Journal of Women's Health  2011;20(9):1325-1332.
Abstract
Background
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.
Methods
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.
Results
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.
Conclusions
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.
doi:10.1089/jwh.2010.2404
PMCID: PMC3168969  PMID: 21732802
2.  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.
Abstract
Objective
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.
Methods
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).
Results
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.
Conclusions
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.
doi:10.1089/jwh.2009.1367
PMCID: PMC2828188  PMID: 19951212
3.  Comparison of Antibodies That Mediate HIV Type 1 gp120 Antibody-Dependent Cell-Mediated Cytotoxicity in Asymptomatic HIV Type 1-Positive Men and Women 
Abstract
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.
doi:10.1089/aid.2012.0377
PMCID: PMC3887406  PMID: 23972002
4.  Gender Roles and Mental Health in Women With and at Risk for HIV 
Psychology of women quarterly  2014;38(3):311-326.
Predominantly low-income and African American women from the same community, HIV-infected (n = 100; HIV+) and uninfected (n = 42; HIV−), were assessed on reported gender roles in sexual and other close relationships—including levels of self-silencing, unmitigated communion, and sexual relationship power—at a single recent study visit during 2008–2012. Recent gender roles were investigated in relation to depressive symptoms and health-related quality of life assessed both at a single visit during 2008–2012 and averaged over semiannual visits (for depressive symptoms) and annual visits (for quality of life) occurring between 1994 and 2012. Compared to HIV− women, HIV+ women reported significantly higher levels of several aspects of self-silencing, unmitigated communion, and multi-year averaged depressive symptoms as well as lower levels of sexual relationship power and recent and multi-year averaged quality of life. For both HIV+ and HIV− women, higher self-silencing and unmitigated communion significantly related to recent or multi-year averaged higher depressive symptoms and lower quality of life. Intervention strategies designed to increase self-care and self-advocacy in the context of relationships could potentially minimize depressive symptoms and enhance quality of life in women with and at risk for HIV.
doi:10.1177/0361684314525579
PMCID: PMC4258411  PMID: 25492991
sex roles; HIV; depression; quality of life; silencing the self; communion; health; empowerment
5.  Understanding the disparity: Predictors of virologic failure in women using highly active antiretroviral therapy vary by race and/or ethnicity 
Journal of acquired immune deficiency syndromes (1999)  2013;64(3):10.1097/QAI.0b013e3182a095e9.
Background
Stark racial/ethnic disparities in health outcomes exist among those living with HIV in the United States. One of three primary goals of the National HIV/AIDS Strategy is to reduce HIV-related disparities and health inequities.
Methods
Using data from HIV-infected women participating in the Women’s Interagency HIV Study from April 2006 to March 2011, we measured virologic failure (HIV RNA >200 copies/mL) following suppression (HIV RNA <80 copies/mL) on HAART. We identified predictors of virologic failure using discrete-time survival analysis and calculated racial/ethnic-specific population attributable fractions (PAFs).
Results
Of 887 eligible women, 408 (46%) experienced virologic failure during the study period. Hispanic and White women had significantly lower hazards of virologic failure than African-American women (Hispanic hazard ratio, HR=0.8, 95% confidence interval [0.6, 0.9]; White HR=0.7 [0.5, 0.9]). The population attributable fraction of virologic failure associated with low income was higher in Hispanic (aHR=2.2 [0.7, 6.5], PAF=49%) and African-American women (aHR=1.8 [1.1, 3.2], PAF=38%) than among White women (aHR=1.4 [0.6, 3.4], PAF=16%). Lack of health insurance compared to public health insurance was associated with virologic failure only among Hispanic (aHR=2.0 [0.9, 4.6], PAF=22%) and White women (aHR=1.9 [0.7, 5.1], PAF=13%). By contrast, depressive symptoms were associated with virologic failure only among African-American women (aHR=1.6 [1.2, 2.2], PAF=17%).
Conclusions
In this population of treated HIV-infected women, virologic failure was common, and correlates of virologic failure varied by race/ethnicity. Strategies to reduce disparities in HIV treatment outcomes by race/ethnicity should address racial/ethnic-specific barriers including depression and low income to sustain virologic suppression.
doi:10.1097/QAI.0b013e3182a095e9
PMCID: PMC3816935  PMID: 23797695
disparities; race/ethnicity; virologic failure; HAART; HIV; women
6.  The Impact of HIV Status, HIV Disease Progression and Post-Traumatic Stress Symptoms on the Health-Related Quality of Life of Rwandan Women Genocide Survivors 
Purpose
We examined whether established associations between HIV disease and HIV disease progression on worse health-related quality of life (HQOL) were applicable to women with severe trauma histories, in this case Rwandan women genocide survivors, the majority of whom were HIV infected. Additionally, this study attempted to clarify whether post-traumatic stress symptoms were uniquely associated with HQOL or confounded with depression.
Methods
The Rwandan Women’s Interassociation Study and Assessment (RWISA) was a longitudinal prospective study of HIV-infected and uninfected women. At study entry 922 women (705 HIV+ and 217 HIV−) completed measures of symptoms of post-traumatic stress and HQOL as well as other demographic, clinical and behavioral characteristics.
Results
Even after controlling for potential confounders and mediators, HIV+ women, in particular those with the lowest CD4 counts, scored significantly worse on HQOL and overall QOL than did HIV− women. Even after controlling for depression and HIV disease progression, women with more post-traumatic stress symptoms scored worse on HQOL and overall QOL than women with fewer post-traumatic stress symptoms.
Conclusions
This study demonstrated that post-traumatic stress symptoms were independently associated with HQOL and overall QOL, independent of depression and other confounders or potential mediators. Future research should examine whether the long term impact of treatment on physical and psychological symptoms of HIV and post-traumatic stress symptoms would generate improvement in HQOL.
doi:10.1007/s11136-012-0328-y
PMCID: PMC4084826  PMID: 23271207
Quality of Life; Posttraumatic Stress Disorder; HIV; Women; Rwanda
7.  Microbial Translocation and Liver Disease Progression in Women Coinfected With HIV and Hepatitis C Virus 
The Journal of Infectious Diseases  2013;208(4):679-689.
Background. Microbial translocation has been implicated in the pathogenesis of liver fibrosis and cirrhosis. We sought to determine whether markers of microbial translocation are associated with liver disease progression during coinfection with human immunodeficiency virus (HIV) and hepatitis C virus (HCV).
Methods. We measured serial plasma lipopolysaccharide (LPS), endotoxin core antibody, intestinal fatty acid–binding protein (I-FABP), soluble CD14 (sCD14), interleukin 6 (IL-6), interleukin 10, and tumor necrosis factor α (TNF-α) levels over a 5-year period in 44 HIV/HCV-coinfected women, 21 of whom experienced liver disease progression and 23 were nonprogressors.
Results. While LPS levels did not differ significantly over time between progressors and nonprogressors (P = .60), progressors had significantly higher plasma levels of sCD14, a marker of monocyte activation by LPS, at the first time point measured (P = .03) and throughout the study period (P = .001); progressors also had higher IL-6 and I-FABP levels over the 5-year study period (P = .02 and .03, respectively). The associations between progression and sCD14, I-FABP, and IL-6 levels were unchanged in models controlling for HIV RNA and CD4+ T-cell count.
Conclusions. Although LPS levels did not differ between liver disease progressors and nonprogressors, the association of sCD14, I-FABP, and IL-6 levels with liver disease progression suggests that impairment of gut epithelial integrity and consequent microbial translocation may play a role in the complex interaction of HIV and HCV pathogenesis.
doi:10.1093/infdis/jit225
PMCID: PMC3719907  PMID: 23687224
HIV; hepatitis C; microbial translocation; fibrosis; liver disease progression; soluble CD14
8.  Critical Consciousness, Racial and Gender Discrimination, and HIV Disease Markers in African American Women with HIV 
AIDS and behavior  2014;18(7):1237-1246.
Critical consciousness, the awareness of social oppression, is important to investigate as a buffer against HIV disease progression in HIV-infected African American women in the context of experiences with discrimination. Critical consciousness comprises several dimensions, including social group identification, discontent with distribution of social power, rejection of social system legitimacy, and a collective action orientation. The current study investigated self-reported critical consciousness as a moderator of perceived gender and racial discrimination on HIV viral load and CD4+ cell count in 67 African American HIV-infected women. Higher critical consciousness was found to be related to higher likelihood of having CD4+ counts over 350 and lower likelihood of detectable viral load when perceived racial discrimination was high, as revealed by multiple logistic regressions that controlled for highly active antiretroviral therapy (HAART) adherence. Multiple linear regressions showed that at higher levels of perceived gender and racial discrimination, women endorsing high critical consciousness had a larger positive difference between nadir CD4+ (lowest pre-HAART) and current CD4+ count than women endorsing low critical consciousness. These findings suggest that raising awareness of social oppression to promote joining with others to enact social change may be an important intervention strategy to improve HIV outcomes in African American HIV-infected women who report experiencing high levels of gender and racial discrimination.
doi:10.1007/s10461-013-0621-y
PMCID: PMC4010552  PMID: 24077930
Critical consciousness; HIV; African American women; Protective factor; Perceived racial discrimination; Perceived gender discrimination
9.  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.
doi:10.1007/s10461-012-0270-6
PMCID: PMC3534826  PMID: 22836592
Alcohol consumption; women; HIV-infection; trajectories
10.  Do HIV-Positive Women Receive Depression Treatment that Meets Best Practice Guidelines? 
AIDS and behavior  2014;18(6):1094-1102.
This study addressed whether psychopharmacologic and psychotherapeutic treatment of depressed HIV+ women met standards defined in the best practice literature, and tested hypothesized predictors of standard-concordant care. 1,352 HIV-positive women in the multi-center Women’s Interagency HIV Study were queried about depressive symptoms and mental health service utilization using standards published by the American Psychiatric Association and the Agency for Healthcare Quality and Research to define adequate depression treatment. We identified those who: 1) reported clinically significant depressive symptoms (CSDS) using Centers for Epidemiological Studies – Depression Scale (CES-D) scores of ≥ 16; or 2) had lifetime diagnoses of major depressive disorder (MDD) assessed by World Mental Health Composite International Diagnostic Interviews plus concurrent elevated depressive symptoms in the past 12 months. Adequate treatment prevalence was 46.2% (n=84) for MDD and 37.9% (n=211) for CSDS. Multivariable logistic regression analysis found that adequate treatment was more likely among women who saw the same primary care provider consistently, who had poorer role functioning, who paid out-of-pocket for healthcare, and who were not African American or Hispanic/Latina. This suggests that adequate depression treatment may be increased by promoting healthcare provider continuity, outreaching individuals with lower levels of role impairment, and addressing the specific needs and concerns of African American and Hispanic/Latina women.
doi:10.1007/s10461-013-0679-6
PMCID: PMC4020946  PMID: 24402689
Women and HIV; Depression Treatment; Psychopharmacology; Psychotherapy
11.  Illicit Drug Use, Depression and their Association with Highly Active Antiretroviral Therapy in HIV-Positive Women 
Drug and alcohol dependence  2007;89(1):74-81.
Background
We examined the interaction of illicit drug use and depressive symptoms, and how they affect the subsequent likelihood of highly active antiretroviral therapy (HAART) use among women with HIV/AIDS.
Methods
Subjects included 1,710 HIV-positive women recruited from six sites in the U.S. including Brooklyn, Bronx, Chicago, Los Angeles, San Francisco/Bay Area, and Washington, DC. Cases of probable depression were identified using depressive symptom scores on the Centers for Epidemiologic Studies Depression Scale. Crack, cocaine, heroin, and amphetamine use were self-reported at 6-month time intervals. We conducted multivariate logistic random regression analysis of data collected during sixteen waves of semiannual interviews conducted from April 1996 through March 2004.
Results
We found an interaction effect between illicit drug use and depression that acted to suppress subsequent HAART use, controlling for virologic and immunologic indicators, socio-demographic variables, time, and study site.
Conclusions
This is the first study to document the interactive effects of drug use and depressive symptoms on reduced likelihood of HAART use in a national cohort of women. Since evidence-based behavioral health and antiretroviral therapies for each of these three conditions are now available, comprehensive HIV treatment is an achievable public health goal.
doi:10.1016/j.drugalcdep.2006.12.002
PMCID: PMC4009351  PMID: 17291696
HIV; depression; HAART; drug use
12.  HIV and Recent Illicit Drug Use Interact to Affect Verbal Memory in Women 
Objective
HIV infection and illicit drug use are each associated with diminished cognitive performance. This study examined the separate and interactive effects of HIV and recent illicit drug use on verbal memory, processing speed and executive function in the multicenter Women's Interagency HIV Study (WIHS).
Methods
Participants included 952 HIV-infected and 443 HIV-uninfected women (mean age=42.8, 64% African-American). Outcome measures included the Hopkins Verbal Learning Test - Revised (HVLT-R) and the Stroop test. Three drug use groups were compared: recent illicit drug users (cocaine or heroin use in past 6 months, n=140), former users (lifetime cocaine or heroin use but not in past 6 months, n=651), and non-users (no lifetime use of cocaine or heroin, n=604).
Results
The typical pattern of recent drug use was daily or weekly smoking of crack cocaine. HIV infection and recent illicit drug use were each associated with worse verbal learning and memory (p's<.05). Importantly, there was an interaction between HIV serostatus and recent illicit drug use such that recent illicit drug use (compared to non-use) negatively impacted verbal learning and memory only in HIV-infected women (p's <0.01). There was no interaction between HIV serostatus and illicit drug use on processing speed or executive function on the Stroop test.
Conclusion
The interaction between HIV serostatus and recent illicit drug use on verbal learning and memory suggests a potential synergistic neurotoxicity that may affect the neural circuitry underlying performance on these tasks.
doi:10.1097/QAI.0b013e318289565c
PMCID: PMC3628722  PMID: 23392462
13.  Antiretroviral-Treated HIV-Infected Women Have Similar Long-Term Kidney Function Trajectories as HIV-Uninfected Women 
Abstract
Natural history studies suggest increased risk for kidney function decline with HIV infection, but few studies have made comparisons with HIV-uninfected women. We examined whether HIV infection treated with highly active antiretroviral therapy (HAART) remains associated with faster kidney function decline in the Women's Interagency HIV Study. HIV-infected women initiating HAART with (n=105) or without (n=373) tenofovir (TDF) were matched to HIV-uninfected women on calendar and length of follow-up, age, systolic blood pressure, hepatitis C antibody serostatus, and diabetes history. Linear mixed models were used to evaluate differences in annual estimated glomerular filtration rate (eGFR). Person-visits were 4,741 and 11,512 for the TDF-treated and non-TDF-treated analyses, respectively. Mean baseline eGFRs were higher among women initiated on TDF-containing HAART and lower among those on TDF-sparing HAART compared to their respective HIV-uninfected matches (p<0.05 for both). HIV-infected women had annual rates of eGFR changes similar to HIV-uninfected matches (p-interaction >0.05 for both). Adjusting for baseline eGFR, mean eGFRs at 1 and 3 years of follow-up among women initiated on TDF-containing HAART were lower than their uninfected matches (−4.98 and −4.26 ml/min/1.73 m2, respectively; p<0.05 for both). Mean eGFR of women initiated on TDF-sparing HAART was lower versus uninfected matches at 5 years (–2.19 ml/min/1.73 m2, p=0.03). HAART-treated HIV-infected women had lower mean eGFRs at follow-up but experienced rates of annual eGFR decline similar to HIV-uninfected women. Tenofovir use in HIV-infected women with normal kidney function did not accelerate long-term kidney function decline relative to HIV-uninfected women.
doi:10.1089/aid.2012.0248
PMCID: PMC3636577  PMID: 23273313
14.  Host APOL1 genotype is independently associated with proteinuria in HIV infection 
Kidney international  2013;84(4):834-840.
Proteinuria is associated with adverse clinical outcomes in HIV infection. Here we evaluated whether APOL1 risk alleles, previously associated with advanced kidney disease, is independently associated with proteinuria in HIV infection in a cross-sectional study of HIV-infected women in the Women’s Interagency HIV Study. We estimated the percent difference in urine protein excretion and odds of proteinuria (200 mg/g and higher) associated with two versus one or no APOL1 risk allele using linear and logistic regression, respectively. Of 1285 women successfully genotyped, 379 carried one and 80 carried two risk alleles. Proteinuria was present in 124 women; 78 of whom had proteinuria confirmed on a second sample. In women without prior AIDS, two risk alleles were independently associated with a 69% higher urine protein excretion (95% CI: 36%, 108%) and 5-fold higher odds of proteinuria (95% CI: 2.45, 10.37) versus one or no risk allele. No association was found in women with prior AIDS. Analyses in which women with impaired kidney function were excluded and proteinuria was confirmed by a second urine sample yielded similar estimates. Thus, APOL1 risk alleles are associated with significant proteinuria in HIV-infected persons without prior clinical AIDS, independent of clinical factors traditionally associated with proteinuria. Trials are needed to determine whether APOL1 genotyping identifies individuals who could benefit from earlier intervention to prevent overt renal disease.
doi:10.1038/ki.2013.203
PMCID: PMC3788838  PMID: 23715117
15.  Does HIV infection promote early kidney injury in women? 
Antiviral therapy  2013;19(1):79-87.
Background
In HIV-infected women, urine concentrations of novel tubulointerstitial injury markers, interleukin-18 (IL-18) and kidney injury marker-1 (KIM-1) are associated with kidney function decline and all-cause mortality. We hypothesized that HIV-infected individuals with preserved kidney filtration function would have more extensive kidney injury, as determined by urine injury markers, compared to the uninfected controls, and that risk factors for tubulointerstitial injury would differ from risk factors for albuminuria.
Methods
In this cross-sectional study, we compared urine concentrations of IL-18, KIM-1, and ACR in 908 HIV-infected and 289 HIV-uninfected women enrolled in the Women’s Interagency HIV Study, utilizing stored urine specimens from visits between 1999 and 2000.
Results
After multivariate-adjusted linear regression analysis, mean urine concentrations were higher in HIV-infected individuals by 38% for IL-18 (p<0.0001), 12% for KIM-1 (p=0.081), and 47% for ACR (p<0.0001). Higher HIV RNA level (15% per 10-fold increase, p<0.0001), lower CD4 count (8% per doubling, p=0.0025), HCV infection (30%, p=0.00018), and lower HDL (5% per 10 mg/dL, p=0.0024) were each associated with higher IL-18 concentrations. In contrast, hypertension (81%, p<0.0001) and diabetes (47%, p=0.018) were among the strongest predictors of higher ACR, though HIV RNA level (15% per 10-fold increase, p=0.0004) was also associated with higher ACR.
Conclusions
HIV-infected women had more extensive tubulointerstitial and glomerular injury than uninfected women, but the associated factors differed among the urine biomarkers. Combinations of urinary biomarkers should be investigated to further characterize early kidney injury in HIV-infected women.
doi:10.3851/IMP2677
PMCID: PMC3933452  PMID: 23970313
16.  Comparisons of creatinine and cystatin C for detection of kidney disease and prediction of all-cause mortality in HIV-infected women 
AIDS (London, England)  2013;27(14):2291-2299.
Background
Cystatin C could improve chronic kidney disease (CKD) classification in HIV-infected women relative to serum creatinine.
Design
Retrospective cohort analysis.
Methods
Cystatin C and creatinine were measured from specimens taken and stored during the 1999–2000 exam among 908 HIV-infected participants in the Women’s Interagency HIV study (WIHS). Mean follow-up was 10.2 years. The associations of baseline categories (<60, 60–90, and >90 mL/min/1.73m2) of creatinine eGFR (eGFRcr), cystatin C eGFR (eGFRcys), and combined creatinine-cystatin C eGFR (eGFRcr-cys) with all-cause mortality were evaluated using multivariable Cox regression. The net reclassification index (NRI) was calculated to evaluate the effect of cystatin C on reclassification of CKD staging.
Results
The prevalence of CKD (eGFR<60) at baseline was higher with eGFRcys (10.1%) compared to eGFRcr (6.7%, p=0.0006) and eGFRcr-cys (7.5%, p=0.011). Relative to eGFR >90, the eGFR <60 category by eGFRcys (Adjusted HR: 2.56; 95% CI: 1.63, 4.02), eGFRcr-cys (3.11; 1.94–5.00), and eGFRcr (2.34; 1.44–3.79) was associated with increased mortality risk. However, the eGFR 60–90 category was associated with increased mortality risk for eGFRcys (1.80; 1.28–2.53) and eGFRcr-cys (1.91; 1.38–2.66) but not eGFRcr (1.20; 0.85–1.67). The overall NRI for mortality was 26% when reclassifying from eGFRcr to eGFRcys (p<0.001) and was 20% when reclassifying from eGFRcr to eGFRcr-cys (p<0.001).
Conclusion
Cystatin C detected a higher prevalence of CKD relative to creatinine and improves CKD staging relative to creatinine by reclassifying individuals at the highest mortality risk to lower eGFR categories.
doi:10.1097/QAD.0b013e328362e874
PMCID: PMC3919542  PMID: 23669156
Creatinine; Cystatin C; Glomerular Filtration Rate; HIV; Mortality; Kidney; Women
17.  Vitamin D insufficiency may impair CD4 recovery among Women’s Interagency HIV Study participants with advanced disease on HAART 
AIDS (London, England)  2013;27(4):573-578.
Background
Recent studies in HIV-infected men report an association between low vitamin D (25OH-D) and CD4 recovery on HAART. We sought to test this relationship in the Women’s Interagency HIV Study (WIHS).
Methods
We examined 204 HIV-infected women with advanced disease, who started HAART after enrollment in the WIHS. We measured vitamin D (25OH-D) levels about 6 months prior to HAART initiation. The relationship between CD4 recovery (defined as increases of ≥50, 100, and 200 cells at 6, 12, and 24 months) and exposure variables was examined using logistic regression models at 6, 12 and 24 months post-HAART initiation in unadjusted and adjusted analyses, and using multivariable longitudinal Generalized Estimating Equations (GEE). Vitamin D insufficiency was defined as 25OH-D levels at least 30 ng/ml.
Results
The majority were non-Hispanic black (60%) and had insufficient vitamin D levels (89%). In adjusted analyses, at 24 months after HAART, insufficient vitamin D level (OR 0.20, 95% CI 0.05–0.83) was associated with decreased odds of CD4 recovery. The undetectable viral load (OR 11.38, 95% CI 4.31–30.05) was associated with CD4 recovery. The multivariable GEE model found that average immune reconstitution attenuated significantly (P <0.01) over time among those with insufficient vitamin D levels compared with those with sufficient vitamin D levels.
Conclusion
Vitamin D insufficiency is associated with diminished late CD4 recovery after HAART initiation among US women living with advanced HIV. The mechanism of this association on late CD4 recovery may be late vitamin D-associated production of naive CD4 cells during immune reconstitution.
doi:10.1097/QAD.0b013e32835b9ba1
PMCID: PMC3902982  PMID: 23095316
antiretroviral therapy; HIV; immune reconstitution; vitamin D; women
18.  The association between diet and physical activity on insulin resistance in the Women’s Interagency HIV Study 
Objectives
To evaluate the association of diet and physical activity with insulin resistance (IR) in HIV-infected and uninfected women.
Methods
Cross sectional analyses of summary dietary measures and physical activity intensity scores obtained from women enrolled in the San Francisco (n=113) and Chicago (n=65) Women’s Interagency HIV Study (WIHS) sites. IR was estimated using the homeostasis model assessment (HOMA-IR). Stepwise regression models assessed the association of diet and physical activity with HOMA-IR after adjustment for demographic, behavioral, and clinical factors.
Results
Compared to HIV-uninfected women, HIV-infected women were older and more likely to have health insurance. In multivariable analysis including all women, being from San Francisco (p=0.005), having a higher mean body mass index (BMI, p<0.001), and a higher percent kilocalories from sweets (p=0.025) were associated with greater HOMA-IR; heavy intensity physical activity (p=0.006) and annual household income <$36,000 (p=0.002) was associated with a lower HOMA-IR. In analysis limited to HIV-infected women, having a higher BMI (p<0.001) and a history of protease inhibitor use (0.002) were significantly associated with higher HOMA-IR; heavy intensity activity (p=0.06) was marginally associated with lower HOMA-IR and being menopausal (p=0.05) was marginally associated with higher HOMA-IR.
Conclusions
Among urban women with or at risk for HIV-infection, heavy intensity physical activity was associated with lower HOMA-IR while higher percent kilocalories from sweets were associated with higher HOMA-IR. Given the overall health benefits of physical activity and a diet low on sugar, these behaviors should be encouraged whenever possible.
doi:10.1097/QAI.0b013e318275d6a4
PMCID: PMC3529765  PMID: 23075914
HIV; HOMA-IR; insulin resistance; macronutrients; physical activity; women
19.  Relation of HLA Class I and II Supertypes with Spontaneous Clearance of Hepatitis C Virus 
Genes and immunity  2013;14(5):330-335.
Human leukocyte antigen (HLA) genotype has been associated with probability of spontaneous clearance of hepatitis C virus (HCV). However, no prior studies have examined whether this relationship may be further characterized by grouping HLA alleles according to their supertypes, defined by their binding capacities. There is debate regarding the most appropriate method to define supertypes. Therefore, previously reported HLA supertypes (46 class I and 25 class II) were assessed for their relation with HCV clearance in a population of 758 HCV-seropositive women. Two HLA class II supertypes were significant in multivariable models that included: (i) supertypes with significant or borderline associations with HCV clearance after adjustment for multiple tests, and (ii) individual HLA alleles not part of these supertypes, but associated with HCV clearance in our prior study in this population. Specifically, supertype DRB3 (prevalence ratio (PR)=0.4; p=0.004) was associated with HCV persistence while DR8 (PR=1.8; p=0.01) was associated with HCV clearance. Two individual alleles (B*57:01 and C*01:02) associated with HCV clearance in our prior study became non-significant in analysis that included supertypes while B*57:03 (PR=1.9; p=0.008) and DRB1*07:01 (PR=1.7; p=0.005) retained significance. These data provide epidemiologic support for the significance of HLA supertypes in relation to HCV clearance.
doi:10.1038/gene.2013.25
PMCID: PMC3723800  PMID: 23636221
hepatitis C virus; HLA; human leukocyte antigen; supertype
20.  Urinary Markers of Kidney Injury and Kidney Function Decline in HIV-Infected Women 
Objective
HIV-infected persons have substantially higher risk of kidney failure than persons without HIV, but serum creatinine levels are insensitive for detecting declining kidney function. We hypothesized that urine markers of kidney injury would be associated with declining kidney function among HIV-infected women.
Methods
In the Women's Interagency HIV Study (WIHS), we measured concentrations of albumin-to-creatinine ratio (ACR), interleukin-18 (IL-18), kidney injury marker-1 (KIM-1), and neutrophil gelatinase-associated lipocalin (NGAL) from stored urine among 908 HIV-infected and 289 uninfected participants. Primary analyses used cystatin C based estimated glomerular filtration rate (CKD-EPI eGFRcys) as the outcome, measured at baseline and two follow-up visits over eight years; secondary analyses used creatinine (CKD-EPI eGFRcr). Each urine biomarker was categorized into tertiles, and kidney decline was modeled with both continuous and dichotomized outcomes.
Results
Compared with the lowest tertiles, the highest tertiles of ACR (−0.15ml/min/1.73m2, p<0.0001), IL-18 (−0.09ml/min/1.73m2, p<0.0001) and KIM-1 (−0.06ml/min/1.73m2, p<0.001) were independently associated with faster eGFRcys decline after multivariate adjustment including all three biomarkers among HIV-infected women. Among these biomarkers, only IL-18 was associated with each dichotomized eGFRcys outcome: ≥3% (Relative Risk 1.40; 95%CI 1.04-1.89); ≥5% (1.88; 1.30-2.71); and ≥10% (2.16; 1.20-3.88) for the highest versus lowest tertile. In alternative models using eGFRcr, the high tertile of KIM-1 had independent associations with 5% (1.71; 1.25-2.33) and 10% (1.78; 1.07-2.96) decline, and the high IL-18 tertile with 10% decline (1.97; 1.00-3.87).
Conclusions
Among HIV-infected women in the WIHS cohort, novel urine markers of kidney injury detect risk for subsequent declines in kidney function.
doi:10.1097/QAI.0b013e3182737706
PMCID: PMC3509242  PMID: 23023103
HIV; KIM-1; NGAL; IL-18; albumin-to-creatinine ratio; cystatin C; kidney injury
21.  Correction: Computational Modeling Reveals Distinct Effects of HIV and History of Drug Use on Decision-Making Processes in Women 
PLoS ONE  2013;8(9):10.1371/annotation/5a8e6fe0-623c-4d17-8781-9a0eadf67a43.
doi:10.1371/annotation/5a8e6fe0-623c-4d17-8781-9a0eadf67a43
PMCID: PMC3770829  PMID: 24039690
22.  Computational Modeling Reveals Distinct Effects of HIV and History of Drug Use on Decision-Making Processes in Women 
PLoS ONE  2013;8(8):e68962.
Objective
Drug users and HIV-seropositive individuals often show deficits in decision-making; however the nature of these deficits is not well understood. Recent studies have employed computational modeling approaches to disentangle the psychological processes involved in decision-making. Although such approaches have been used successfully with a number of clinical groups including drug users, no study to date has used computational modeling to examine the effects of HIV on decision-making. In this study, we use this approach to investigate the effects of HIV and drug use on decision-making processes in women, who remain a relatively understudied population.
Method
Fifty-seven women enrolled in the Women's Interagency HIV Study (WIHS) were classified into one of four groups based on their HIV status and history of crack cocaine and/or heroin drug use (DU): HIV+/DU+ (n = 14); HIV+/DU− (n = 17); HIV−/DU+ (n = 14); and HIV−/DU− (n = 12). We measured decision-making with the Iowa Gambling Task (IGT) and examined behavioral performance and model parameters derived from the best-fitting computational model of the IGT.
Results
Although groups showed similar behavioral performance, HIV and DU exhibited differential relationship to model parameters. Specifically, DU was associated with compromised learning/memory and reduced loss aversion, whereas HIV was associated with reduced loss aversion, but was not related to other model parameters.
Conclusions
Results reveal that HIV and DU have differential associations with distinct decision-making processes in women. This study contributes to a growing line of literature which shows that different psychological processes may underlie similar behavioral performance in various clinical groups and may be associated with distinct functional outcomes.
doi:10.1371/journal.pone.0068962
PMCID: PMC3737214  PMID: 23950880
24.  Differences in the Nonuse of any Contraception and Use of Specific Contraceptive Methods in HIV Positive and HIV Negative Rwandan Women 
AIDS Research and Treatment  2012;2012:367604.
Contraception can reduce the dual burden of high fertility and high HIV prevalence in sub-Sahara Africa, but significant barriers remain regarding access and use. We describe factors associated with nonuse of contraception and with use of specific contraceptive methods in HIV positive and HIV negative Rwandan women. Data from 395 HIV-positive and 76 HIV-negative women who desired no pregnancy in the previous 6 months were analyzed using univariate and multivariate logistic regression models to identify clinical and demographic characteristics that predict contraceptive use. Differences in contraceptive methods used were dependent on marital/partner status, partner's knowledge of a woman's HIV status, and age. Overall, condoms, abstinence, and hormonal methods were the most used, though differences existed by HIV status. Less than 10% of women both HIV+ and HIV− used no contraception. Important differences exist between HIV-positive and HIV-negative women with regard to contraceptive method use that should be addressed by interventions seeking to improve contraceptive prevalence.
doi:10.1155/2012/367604
PMCID: PMC3533450  PMID: 23304468
25.  Relative time to pregnancy among HIV-infected and uninfected women in the Women’s Interagency HIV Study, 2002–2009 
AIDS (London, England)  2011;25(5):707-711.
Objectives
To determine the incidence rate of, and the relative time to pregnancy by HIV status in US women between 2002 and 2009.
Design
The Women’s Interagency HIV Study (WIHS) is an ongoing, multicenter prospective cohort study of the natural and treated history of HIV infection and related outcomes among women with and without HIV.
Methods
Eligible participants were ≤45 years of age; sexually active with male partner(s) or reported a pregnancy outcome within the past year; and never reported hysterectomy, tubal ligation, or oopherectomy. Poisson regression was conducted to compare pregnancy incidence rates over time by HIV status. Relative time to pregnancy was ascertained via Kaplan-Meier plots and generalized gamma survival analysis.
Results
Adjusting for age, number of male sex partners, contraception, parity, exchanging sex, and alcohol use, HIV infection was associated with a 40% reduction in the incidence rate of pregnancy (incidence rate ratio=0.60, 95% confidence interval: [C.I.] 0.46–0.78). The time for HIV-infected women to become pregnant was 73% longer relative to HIV-uninfected women (relative time=1.73, 95% C.I.: 1.35–2.36). In addition to HIV infection, decreased parity and older age were independent predictors of lower pregnancy incidence.
Conclusions
Despite the beneficial effects of modern antiretroviral therapy on survival and prevention of maternal-to-child transmission, our findings suggest that pregnancy incidence remains lower among HIV-infected women. Whether this lower incidence is due to behavioral differences or reduced biologic fertility remains an area worthy of further study.
doi:10.1097/QAD.0b013e3283445811
PMCID: PMC3496791  PMID: 21297418
women; HIV; pregnancy; time to pregnancy; parity

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