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1.  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
2.  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
3.  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
4.  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
5.  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
6.  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
7.  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
8.  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
9.  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
10.  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
11.  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
12.  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
14.  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
15.  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
16.  The Association of HIV Status with Bacterial Vaginosis and Vitamin D in the United States 
Journal of Women's Health  2011;20(10):1497-1503.
Abstract
Objective
To estimate the association between vitamin D deficiency and bacterial vaginosis (BV) among nonpregnant HIV-infected and uninfected women.
Methods
In a substudy of the Women's Interagency HIV Study, including women from Chicago and New York, the association between BV and vitamin D deficiency, demographics, and disease characteristics was tested using generalized estimating equations. Deficiency was defined as <20 ng/mL 25 (OH) vitamin D and insufficiency as >20 and ≤30 ng/mL. BV was defined by the Amsel criteria.
Results
Among 602 observations of nonpregnant women (480 HIV infected and 122 uninfected), BV was found in 19%. Vitamin D deficiency was found in 59.4%, and insufficiency was found in 24.4%. In multivariable analysis, black race was the most significant predictor of BV (adjusted odds ratio [AOR] 5.90, (95% confidence interval [CI] 2.52-13.8). Vitamin D deficiency was independently associated with BV among HIV-infected women (AOR 3.12, 95% CI 1.16-8.38) but not among HIV-uninfected women. There was a negative linear correlation between vitamin D concentration and prevalence of BV in HIV-infected women (r=−0.15, p=0.001).
Conclusions
Vitamin D deficiency was very common in this cohort and significantly associated with BV among HIV-infected women. These preliminary findings suggest that further epidemiologic and mechanistic exploration of the relationship between vitamin D and BV in HIV-infected women is warranted.
doi:10.1089/jwh.2010.2685
PMCID: PMC3233211  PMID: 21875343
17.  The effect of HIV infection and HAART on inflammatory biomarkers in a population-based cohort of US women 
AIDS (London, England)  2011;25(15):1823-1832.
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 non-controllers (NC), and HIV-uninfected (NEG).
Methods
Multiplex assays were used to measure 32 cytokines in a cross-sectional study of participants in the Women's Interagency HIV Study (WIHS). Participants from 3 groups were included: HAART (n=17), NC (n=14), and HIV NEG (n=17).
Results
Several cytokines and chemokines showed significant differences between NC and NEG participants, including elevated IP-10 and TNF-α and decreased IL-12(p40), IL-15, and FGF-2 in NC participants. Biomarker levels among HAART women more closely resembled the NEG, with the exception of TNF-α and FGF-2. Secondary analyses of the combined HAART and NC groups revealed that IP-10 showed a strong, positive correlation with viral load and negative correlation with CD4+ T cell counts. The growth factors VEGF, EGF, 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-α. HAART was associated with cytokine profiles that more closely resembled those of HIV uninfected women. The distinctive pattern of cytokine levels in the 3 study groups may provide insights into HIV pathogenesis, and responses to therapy.
doi:10.1097/QAD.0b013e3283489d1f
PMCID: PMC3314300  PMID: 21572306
HIV; CD4+ T cells; cytokines; chemokines; HAART
18.  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
19.  The Relation of HLA Genotype to Hepatitis C Viral Load and Markers of Liver Fibrosis in HIV-Infected and HIV-Uninfected Women 
The Journal of Infectious Diseases  2011;203(12):1807-1814.
Background. Human leukocyte antigen (HLA) class I and II genotype is associated with clearance of hepatitis C virus (HCV) infection, but little is known regarding its relation with HCV viral load or risk of liver disease in patients with persistent HCV infection.
Methods. High-resolution HLA class I and II genotyping was conducted in a prospective cohort of 519 human immunodeficiency virus (HIV)–seropositive and 100 HIV-seronegative women with persistent HCV infection. The end points were baseline HCV viral load and 2 noninvasive indexes of liver disease, fibrosis-4 (FIB-4), and the aspartate aminotransferase to platelet ratio index (APRI), measured at baseline and prospectively.
Results. DQB1*0301 was associated with low baseline HCV load (β = −.4; 95% confidence interval [CI], −.6 to −.3; P < .00001), as well as with low odds of FIB-4–defined (odds ratio [OR], .5; 95% CI, .2–.9; P = .02) and APRI-defined liver fibrosis (OR, .5; 95% CI, .3–1.0; P = .06) at baseline and/or during follow-up. Most additional associations with HCV viral load also involved HLA class II alleles. Additional associations with FIB-4 and APRI primarily involved class I alleles, for example, the relation of B*1503 with APRI-defined fibrosis had an OR of 2.0 (95% CI, 1.0–3.7; P = .04).
Conclusions. HLA genotype may influence HCV viral load and risk of liver disease, including DQB1*0301, which was associated with HCV clearance in prior studies.
doi:10.1093/infdis/jir192
PMCID: PMC3100515  PMID: 21606539
20.  Atazanavir Concentration in Hair Is the Strongest Predictor of Outcomes on Antiretroviral Therapy 
In a longitudinal study of outcomes on atazanavir-based therapy in a large cohort of HIV-infected women, hair levels of atazanavir were the strongest independent predictor of virologic suppression. Hair antiretroviral concentrations may serve as a useful tool in HIV care.
Background. Adequate exposure to antiretrovirals is important to maintain durable responses, but methods to assess exposure (eg, querying adherence and single plasma drug level measurements) are limited. Hair concentrations of antiretrovirals can integrate adherence and pharmacokinetics into a single assay.
Methods. Small hair samples were collected from participants in the Women's Interagency HIV Study (WIHS), a large cohort of human immunodeficiency virus (HIV)-infected (and at-risk noninfected) women. From 2003 through 2008, we analyzed atazanavir hair concentrations longitudinally for women reporting receipt of atazanavir-based therapy. Multivariate random effects logistic regression models for repeated measures were used to estimate the association of hair drug levels with the primary outcome of virologic suppression (HIV RNA level, <80 copies/mL).
Results. 424 WIHS participants (51% African-American, 31% Hispanic) contributed 1443 person-visits to the analysis. After adjusting for age, race, treatment experience, pretreatment viral load, CD4 count and AIDS status, and self-reported adherence, hair levels were the strongest predictor of suppression. Categorized hair antiretroviral levels revealed a monotonic relationship to suppression; women with atazanavir levels in the highest quintile had odds ratios (ORs) of 59.8 (95% confidence ratio, 29.0–123.2) for virologic suppression. Hair atazanavir concentrations were even more strongly associated with resuppression of viral loads in subgroups in which there had been previous lapses in adherence (OR, 210.2 [95% CI, 46.0–961.1]), low hair levels (OR, 132.8 [95% CI, 26.5–666.0]), or detectable viremia (OR, 400.7 [95% CI, 52.3–3069.7]).
Conclusions. Antiretroviral hair levels surpassed any other predictor of virologic outcomes to HIV treatment in a large cohort. Low antiretroviral exposure in hair may trigger interventions prior to failure or herald virologic failure in settings where measurement of viral loads is unavailable. Monitoring hair antiretroviral concentrations may be useful for prolonging regimen durability.
doi:10.1093/cid/cir131
PMCID: PMC3079399  PMID: 21507924
22.  Human Leukocyte Antigen Genotype and Risk of HIV Disease Progression before and after Initiation of Antiretroviral Therapy▿‡ 
Journal of Virology  2011;85(20):10826-10833.
While the human leukocyte antigen (HLA) genotype has been associated with the rate of HIV disease progression in untreated patients, little is known regarding these relationships in patients using highly active antiretroviral therapy (HAART). The limited data reported to date identified few HLA-HIV disease associations in patients using HAART and even occasional associations that were opposite of those found in untreated patients. We conducted high-resolution HLA class I and II genotyping in a random sample (n = 860) of HIV-seropositive women enrolled in a long-term cohort initiated in 1994. HLA-HIV disease associations before and after initiation of HAART were examined using multivariate analyses. In untreated HIV-seropositive patients, we observed many of the predicted associations, consistent with prior studies. For example, HLA-B*57 (β = −0.7; 95% confidence interval [CI] = −0.9 to −0.5; P = 5 × 10−11) and Bw4 (β = −0.2; 95% CI = −0.4 to −0.1; P = 0.009) were inversely associated with baseline HIV viral load, and B*57 was associated with a low risk of rapid CD4+ decline (odds ratio [OR] = 0.2; 95% CI = 0.1 to 0.6; P = 0.002). Conversely, in treated patients, the odds of a virological response to HAART were lower for B*57:01 (OR = 0.2; 95% CI = 0.0 to 0.9; P = 0.03), and Bw4 (OR = 0.4; 95% CI = 0.1 to 1.0; P = 0.04) was associated with low odds of an immunological response. The associations of HLA genotype with HIV disease are different and sometimes even opposite in treated and untreated patients.
doi:10.1128/JVI.00804-11
PMCID: PMC3187522  PMID: 21849458
23.  PRE-EXISTING ALBUMINURIA PREDICTS AIDS AND NON-AIDS MORTALITY IN WOMEN INITIATING ANTIRETROVIRAL THERAPY 
Antiviral therapy  2011;16(4):591-596.
Background
We previously reported an increased risk of all-cause and AIDS mortality among HIV-infected women with albuminuria (proteinuria or microalbuminuria) enrolled in the Women’s Interagency HIV Study (WIHS) prior to the introduction of highly active antiretroviral therapy (HAART).
Methods
The current analysis includes 1,073 WIHS participants who subsequently initiated HAART. Urinalysis for proteinuria and semi-quantitative testing for microalbuminuria from two consecutive study visits prior to HAART initiation were categorized as follows: confirmed proteinuria (both specimens positive for protein), confirmed microalbuminuria (both specimens positive with at least one microalbuminuria), unconfirmed albuminuria (one specimen positive for proteinuria or microalbuminuria), or negative (both specimens negative). Time from HAART initiation to death was modeled using proportional hazards analysis.
Results
Compared to the reference group of women with two negative specimens, the hazard ratio (HR) for all-cause mortality was significantly elevated for women with confirmed microalbuminuria (HR 1.9; 95% CI 1.2–2.9). Confirmed microalbuminuria was also independently associated with AIDS death (HR 2.3; 95% CI 1.3–4.3), while women with confirmed proteinuria were at increased risk for non-AIDS death (HR 2.4; 95% CI 1.2–4.6).
Conclusions
In women initiating HAART, pre-existing microalbuminuria independently predicted increased AIDS mortality, while pre-existing proteinuria predicted increased risk of non-AIDS death. Urine testing may identify HIV-infected individuals at increased risk for mortality even after the initiation of HAART. Future studies should consider whether these widely available tests can identify individuals who would benefit from more aggressive management of HIV infection and comorbid conditions associated with mortality in this population.
doi:10.3851/IMP1766
PMCID: PMC3119869  PMID: 21685547
HIV; microalbuminuria; proteinuria; mortality; non-AIDS death
24.  Fracture incidence in HIV-infected women: results from the Women’s Interagency HIV Study 
AIDS (London, England)  2010;24(17):2679-2686.
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 Women’s 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.
doi:10.1097/QAD.0b013e32833f6294
PMCID: PMC3108019  PMID: 20859192
fracture; fragility fracture; HIV-infected women; premenopausal
25.  MICROALBUMINURIA IS ASSOCIATED WITH ALL-CAUSE AND AIDS MORTALITY IN WOMEN WITH HIV INFECTION 
Prevalence of microalbuminuria is increased in patients with HIV. Microalbuminuria is associated with increased mortality in other populations, including diabetics, for whom microalbuminuria testing is standard of care. We investigated whether microalbuminuria is associated with mortality in HIV-infected women not receiving antiretroviral therapy.
Methods
Urinalysis for proteinuria and semi-quantitative testing for microalbuminuria were performed in specimens from two consecutive visits in 1,547 HIV-infected women enrolled in the Women’s Interagency HIV Study in 1994–1995. Time to death was modeled using proportional hazards analysis.
Results
Compared to women without albuminuria, the hazard ratio (HR) for all-cause mortality was increased in women with one (HR 3.4; 95% CI 2.2–5.2) or two specimens positive for either proteinuria or microalbuminuria (HR 3.9; 95% CI 2.1–7.0). The highest risk was observed in women with both specimens positive for proteinuria (HR 5.8; 95% CI 3.4–9.8). The association between albuminuria and all-cause mortality risk remained significant after adjustment for demographics, HIV disease severity, and related comorbidities. Similar results were obtained for AIDS death.
Conclusions
We identified a graded relationship between albuminuria and the risk of all-cause and AIDS mortality.
doi:10.1097/QAI.0b013e3181cc1070
PMCID: PMC2888617  PMID: 20098331
HIV; microalbuminuria; proteinuria; mortality

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