Sylvia Silver

George Washington University, Washington, Washington, D.C., United States

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Publications (11)58.14 Total impact

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    ABSTRACT: Background: There is increasing evidence that chronic immune activation predisposes to non-Hodgkin's lymphoma (NHL). Whether this association exists among women representative of the current HIV epidemic in the U.S. who are at high risk of HIV-associated NHL (AIDS-NHL), remains to be determined. Methods: We conducted a nested case-control study within the Women's Interagency HIV Study with longitudinally collected risk factor data and sera. Cases were HIV-infected women with stored sera collected at three time-windows 3-5 years, 1-3 years, and 0-1 year prior to AIDS-NHL diagnosis (n=22). Three to six HIV-infected controls, without AIDS-NHL, were matched to each case on age, race, CD4+ T cell count, and study follow-up time (n=78). Odds ratios (ORs) and 95% confidence intervals (CIs) for the association between one unit increase in log-transformed biomarker levels and AIDS-NHL were computed using random effect multivariate logistic regression models. Results: Elevated levels of sCD27 (OR=7.21, 95% CI=2.62-19.88), sCD30 (OR=2.64, 95% CI=1.24-5.64), and CXCL13 (OR=2.56, 95% CI=1.32-4.96) were associated with subsequent diagnosis of AIDS-NHL overall. Elevated sCD23 was associated with a 2-to 4-fold increased risk of AIDS-NHL in certain subgroups, while elevated IL6 was associated with a 2-fold increased risk in the 0-1 year time-window, only. Conclusion: These findings support the hypothesis that chronic B cell activation contributes to the development of AIDS-NHL in women. Impact: sCD23, sCD27, sCD30, and CXCL13 may serve as biomarkers for AIDS-NHL.
    Cancer Epidemiology Biomarkers &amp Prevention 09/2013; · 4.56 Impact Factor
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    ABSTRACT: The AIDS and Cancer Specimen Resource (ACSR) is a cooperative agreement among the United States National Cancer Institute (NCI) (Office of the Director, Office of HIV and AIDS Malignancy (OHAM)) and regional US consortia, University of California, San Francisco (West Coast), George Washington University (East Coast), and The Ohio State University (Mid-Region). The ACSR's main objective is to collect, preserve, and disperse HIV-related tissues and biologic fluids along with clinical data to qualified investigators with a focus on HIV/AIDS-related malignancies. The ACSR biorepository has more than 265,000 human HIV-positive and control samples available from 39 processing types, 16 specimen types, and 52 anatomical site types. These HIV-infected biological fluids and tissues are made available to funded approved investigators at no fee. Technical support such as HIV DNA identification in tissues and tissue microarray (TMA) blocks are available to assist approved investigators. Research needs may be filled through ACSR cooperative arrangements when not met by currently banked material. Those participating with the ACSR are expected to share their research findings with the scientific community. Some 117 abstract/poster and podium reports at national and international scientific meetings and 94 publications have been contributed to the scientific literature (as of 2010). Investigators can browse the ACSR Internet site at http://acsr.ucsf.edu for biospecimens to support their scientific initiatives, including basic, translational, biomarker discovery, and molecular epidemiology studies.
    Methods in molecular biology (Clifton, N.J.) 01/2011; 675:193-203. · 1.29 Impact Factor
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    ABSTRACT: Prior reports of an increased risk of lung cancer in HIV-infected individuals have not always included control groups, nor considered other risk factors such as tobacco exposure. We sought to determine the role of HIV infection and highly active antiretroviral therapy (HAART) on lung cancer incidence in 2,651 HIV-infected and 898 HIV-uninfected women from the Women's Interagency HIV Study (WIHS). A prospective study of the incidence rates of lung cancer was conducted, with cases identified through medical records, death certificates, and state cancer registries. Standardized incidence ratios (SIRs) were calculated to compare lung cancer incidence among HIV-infected and uninfected WIHS participants, with population-based expectations using the Surveillance, Epidemiology, and End Results registry. Behavioral characteristics in the WIHS were compared to US women by age and race adjusting the population-based data from the National Health and Nutritional Examination Survey (NHANES) III. Incidence rates of lung cancer were similar among HIV-infected and uninfected WIHS women. Lung cancer SIRs were increased in both HIV-infected and -uninfected women compared with population expectations, but did not differ by HIV status. Among HIV-infected women, lung cancer incidence rates were similar in pre-HAART and HAART eras. All WIHS women with lung cancer were smokers; the risk of lung cancer increased with cumulative tobacco exposure. WIHS women were statistically more likely to smoke than US women studied in NHANES III. HIV infection is strongly associated with smoking behaviors that increase lung cancer risk. The role of HIV itself remains to be clarified.
    Journal of Clinical Oncology 02/2010; 28(9):1514-9. · 18.04 Impact Factor
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    ABSTRACT: The objective of the study was to investigate the relationship between human immunodeficiency virus (HIV) infection and childbearing before and after the availability of highly active antiretroviral therapy (HAART). Enrollment in the Women's Interagency HIV study took place in 1994-1995 (pre-HAART era) and again in 2001-2002 (HAART era). Live birth rates prior to enrollment were compared between treatment era cohorts for HIV-infected and HIV-uninfected women aged 15-44 years using Poisson regression. For HIV-infected women, we included live births between HIV diagnosis date and study entry; the HAART era cohort included only women diagnosed with HIV in 1996 and afterward. Among HIV-infected women, the HAART era live birth rate was 150% higher than in the pre-HAART era (P = .001) vs a 5% increase among HIV-uninfected women. The rate of increase in live birth rate was higher for women > or = 35 years old (vs younger than 25 years, P = .02), and with more than a high school education (vs. less than high school, P = .05). The availability of effective therapeutic interventions has had a profound impact on child-bearing among HIV-infected women.
    American journal of obstetrics and gynecology 07/2007; 196(6):541.e1-6. · 3.28 Impact Factor
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    ABSTRACT: The AIDS Cancer and Specimen Resource (ACSR) supports scientific discovery in the area of HIV/AIDS-associated malignancies. The ACSR was established as a cooperative agreement between the NCI (Office of the Director, Division of Cancer Treatment and Diagnosis) and regional consortia, University of California, San Francisco (West Coast), George Washington University (East Coast) and Ohio State University (Mid-Region) to collect, preserve and disperse HIV-related tissues and biologic fluids and controls along with clinical data to qualified investigators. The available biological samples with clinical data and the application process are described on the ACSR web site. The ACSR tissue bank has more than 100,000 human HIV positive specimens that represent different processing (43), specimen (15), and anatomical site (50) types. The ACSR provides special biospecimen collections and prepares speciality items, e.g., tissue microarrays (TMA), DNA libraries. Requests have been greatest for Kaposi's sarcoma (32%) and non-Hodgkin's lymphoma (26%). Dispersed requests include 83% tissue (frozen and paraffin embedded), 18% plasma/serum and 9% other. ACSR also provides tissue microarrays of, e.g., Kaposi's sarcoma and non-Hodgkin's lymphoma, for biomarker assays and has developed collaborations with other groups that provide access to additional AIDS-related malignancy specimens. ACSR members and associates have completed 63 podium and poster presentations. Investigators have submitted 125 letters of intent requests. Discoveries using ACSR have been reported in 61 scientific publications in notable journals with an average impact factor of 7. The ACSR promotes the scientific exploration of the relationship between HIV/AIDS and malignancy by participation at national and international scientific meetings, contact with investigators who have productive research in this area and identifying, collecting, preserving, enhancing, and dispersing HIV/AIDS-related malignancy specimens to funded, approved researchers at no fee. Scientific discovery has been advanced by this unique biorepository. Investigators are encouraged to browse the ACSR Internet site for materials to enhance their own scientific initiatives.
    Infectious Agents and Cancer 02/2007; 2:7.
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    ABSTRACT: The Cooperative Prostate Cancer Tissue Resource (CPCTR) is a National Cancer Institute-supported tissue bank that provides large numbers of clinically annotated prostate cancer specimens to investigators. This communication describes the CPCTR to investigators interested in obtaining prostate cancer tissue samples. The CPCTR, through its four participating institutions, has collected specimens and clinical data for prostate cancer cases diagnosed from 1989 onward. These specimens include paraffin blocks and frozen tissue from radical prostatectomy specimens and paraffin blocks from prostate needle biopsies. Standardized histopathological characterization and clinical data extraction are performed for all cases. Information on histopathology, demography (including ethnicity), laboratory data (prostate-specific antigen values), and clinical outcome related to prostate cancer are entered into the CPCTR database for all cases. Materials in the CPCTR are available in multiple tissue formats, including tissue microarray sections, paraffin-embedded tissue sections, serum, and frozen tissue specimens. These are available for research purposes following an application process that is described on the CPCTR web site (www.prostatetissues.org). The CPCTR currently (as of October 2003) contains 5135 prostate cancer cases including 4723 radical prostatectomy cases. Frozen tissues, in some instances including patient serum samples, are available for 1226 cases. Biochemical recurrence data allow identification of cases with residual disease, cases with recurrence, and recurrence-free cases. The CPCTR offers large numbers of highly characterized prostate cancer tissue specimens, including tissue microarrays, with associated clinical data for biomarker studies. Interested investigators are encouraged to apply for use of this material (www.prostatetissues.org).
    Clinical Cancer Research 08/2004; 10(14):4614-21. · 7.84 Impact Factor
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    ABSTRACT: We assessed the association between initiation of highly active antiretroviral treatment (HAART) regimens and sexual risk behaviors among HIVinfected women. We analyzed data from 724 women who initiated HAART between January 1996 and January 2001 and who had pre-HAART viral loads at or above 400 copies per milliliter. Sexually active women were less likely (odds ratio [OR] = 0.79) to report 2 or more partners during a 6-month period after HAART initiation than before HAART initiation. However, the risk for unprotected sex was higher after HAART initiation than before HAART initiation among all sexually active women (both those who reported 2 or more partners [OR = 1.84] and those who reported 1 partner [OR = 1.22]). Sexual risk behaviors are associated with receipt of therapy but not with therapeutic response, indicating a risk for transmission among female HAART recipients.
    American Journal of Public Health 08/2004; 94(7):1141-6. · 3.93 Impact Factor
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    ABSTRACT: The HIV epidemic has been associated with an increased incidence of specific cancers. However, less is known about cancers occurring in HIV-infected women than men. To determine the risk of cancer among HIV-infected and at-risk HIV-uninfected women, cancer incidence data from the Women's Interagency HIV Study (WIHS) were compared with data from the population-based United States Surveillance, Epidemiology, and End Results (SEER) registry. Age- and race-adjusted standardized incidence ratios (SIRs) were computed and exact statistical tests were used to measure significance. Among the 1950 women participants (1554 HIV infected, 391 HIV uninfected, and 5 HIV seroconverters), 48 cancers were diagnosed during study follow-up. Among HIV-infected women, significantly (P < 0.05) increased incidence rates were observed for all cancer types (SIR = 1.9), Kaposi sarcoma (SIR = 213.5), non-Hodgkin lymphoma (NHL) (SIR = 19.0), and lung cancer (SIR = 6.3) when compared with SEER rates. Lung cancer incidence was also elevated (P = 0.07) among the HIV-uninfected women (SIR = 6.9), when compared with SEER rates, and was similar to the SIR for HIV-infected women. While the incidence rate of NHL among HIV-infected women was significantly lower during the era of highly active antiretroviral therapy (HAART) compared with the pre-HAART era (relative risk = 0.15, P = 0.005), the incidence of NHL among HIV-infected WIHS participants remained significantly higher than in the US population (SIR = 6.4, 95% CI = 1.3-15.5). In the HAART era, the higher rates of cancer among HIV-infected women, coupled with increased life expectancy, should lead to more intensive cancer screening and prevention efforts in this population.
    JAIDS Journal of Acquired Immune Deficiency Syndromes 08/2004; 36(4):978-85. · 4.65 Impact Factor
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    ABSTRACT: To measure the incidence of invasive cervical cancer (ICC) in US women infected with HIV. Multicenter prospective cohort study, conducted between October 1994, and September 2001. HIV research centers operating as six urban consortia in the Women's Interagency HIV Study. A total of 2131 women (462 HIV seronegative, 1661 HIV seropositive, and eight seroconverters). Women with a history of hysterectomy or of cervical cancer at baseline evaluation were excluded. Cervical cytology obtained at 6-month intervals, with a colposcopy referral threshold of atypia, followed by individualized treatment. ICC diagnoses obtained from study databases and regional cancer registries and confirmed by a gynecologic pathologist. No incident ICC were observed in HIV seronegative women during 2375 woman-years of observation. During 8260 woman-years of observation, eight putative incident cases of cervical cancer were identified in HIV seropositive women, but only one was confirmed, yielding an incidence rate of 1.2/10 000 woman-years (95% confidence interval, 0.3-6.7/10 000 woman-years). The difference in incidence between HIV seropositive and seronegative women was not significant (P = 1.0). ICC is uncommon in HIV-infected US women participating in a regular prevention program.
    AIDS 02/2004; 18(1):109-13. · 6.41 Impact Factor
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    ABSTRACT: The purpose of this study was to describe the variability in highly active antiretroviral therapy (HAART) regimens over time, the extent to which individuals switch, and the characteristics of those who are switching. We evaluated data collected between 1994 and 2000 from 1056 HIV-positive women enrolled in the Women's Interagency HIV Study (WIHS) who reported initiating HAART. We described the variability and prevalence of changes in HAART regimens between semiannual visits, estimated time to switch using Kaplan-Meier methods, investigated factors associated with a first switch using Cox proportional hazards models, and compared disease markers among women switching or remaining on unchanged HAART regimens. We demonstrated a 13-fold increase in the number of unique HAART regimens reported since mid-1996 and showed that the amount of time spent on the first, second, or third regimen is similar, with an 8-month median time to switching or discontinuing the initial HAART regimen. Women who switched had a lower mean CD4 cell count and were more likely to have HIV RNA levels greater than 400 copies/mL. Overall, the percentage of women switching decreased over the course of follow-up (to 37% in September 2000), although the percentage discontinuing therapy altogether increased 2-fold. Our findings on the relatively high rate of HAART switching emphasize the complexity of managing and evaluating these therapies.
    JAIDS Journal of Acquired Immune Deficiency Syndromes 05/2002; 29(5):495-503. · 4.65 Impact Factor
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    ABSTRACT: Although HIV-positive women may be less likely than women in general to receive mammography due to socioeconomic disadvantage, HIV diagnosis may increase opportunities for medical interactions which encourage mammography. HIV-positive (2,059) and HIV-negative (569) Women's Interagency HIV Study (WIHS) participants reported ever/never history of mammography at baseline (in 1994, 1995) and, at each 6-month follow-up visit, if they had been screened since their last visit. National Health Interview Survey (NHIS) data for 1994 were used to compare WIHS participants to U.S. women. Factors independently related to mammography were determined using logistic regression for baseline data and proportional hazards for follow-up data. Results were adjusted for age. Among women > or =40, fewer WIHS women, regardless of HIV status, reported screening than U.S. women (67% HIV-positive, 62% HIV-negative, 79% NHIS; P < 0.0001). First-time screening while on study was associated with being HIV-positive [rate ratio (95% confidence interval) = 1.6 (1.1, 2.3)]. Factors independently associated with screening were related to health care access and usage. WIHS women, a disadvantaged population, reported less mammography than the general population. HIV-positive women reported more screening than HIV-negative women, possibly because of greater opportunity to interact with the health care system.
    Preventive Medicine 03/2002; 34(3):386-92. · 3.50 Impact Factor