Joseph G. Feldman

Bio: Joseph G. Feldman is an academic researcher from SUNY Downstate Medical Center. The author has contributed to research in topics: Acquired immunodeficiency syndrome (AIDS) & Breast cancer. The author has an hindex of 26, co-authored 47 publications receiving 3387 citations. Previous affiliations of Joseph G. Feldman include Maimonides Medical Center & St. Vincent's Health System.

The Women's Interagency HIV Study. WIHS Collaborative Study Group.

Abstract: The Women's Interagency HIV Study comprises the largest U.S. cohort to date of human immunodeficiency virus (HIV)-seropositive women (N = 2,058) with a comparison cohort of seronegative women (N = 568). The methodology, training, and quality assurance activities employed are described. The study population, enrolled between October 1994 and November 1995 through six clinical consortia throughout the United States (totaling 23 sites) represents a typically hard-to-reach study population. More than half of the women in each cohort were living below the federally defined levels of poverty. The women ranged in age from 16 to 73 years; approximately one-quarter self-identified as Latina or Hispanic, over one-half as African-American not of Hispanic origin, and less than 20% as white, non-Hispanic origin. Self-reporting of HIV exposure risk included injection drug use by 34% of the seropositive women and 28% of the seronegative women, heterosexual contact (42% vs 26%), transfusion risk (4% vs 3%) and no identified risk (20% vs 43%). Demographic and HIV exposure risk characteristics of the seropositive cohort were comparable with characteristics of nationally reported AIDS cases in U.S. women. This well characterized cohort of HIV-seropositive and high-risk seronegative women represents a rich opportunity for future studies of HIV disease progression and pathogenesis.

Effect of Highly Active Antiretroviral Therapy on Time to Acquired Immunodeficiency Syndrome or Death using Marginal Structural Models

Abstract: To estimate the net (i.e., overall) effect of highly active antiretroviral therapy (HAART) on time to acquired immunodeficiency syndrome (AIDS) or death, the authors used inverse probability-of-treatment weighted estimation of a marginal structural model, which can appropriately adjust for time-varying confounders affected by prior treatment or exposure. Human immunodeficiency virus (HIV)-positive men and women (n = 1,498) were followed in two ongoing cohort studies between 1995 and 2002. Sixty-one percent (n = 918) of the participants initiated HAART during 6,763 person-years of follow-up, and 382 developed AIDS or died. Strong confounding by indication for HAART was apparent; the unadjusted hazard ratio for AIDS or death was 0.98. The hazard ratio from a standard time-dependent Cox model that included time-varying CD4 cell count, HIV RNA level, and other time-varying and fixed covariates as regressors was 0.81 (95% confidence interval: 0.61, 1.07). In contrast, the hazard ratio from a marginal structural survival model was 0.54 (robust 95% confidence interval: 0.38, 0.78), suggesting a clinically meaningful net benefit of HAART. Standard Cox analysis failed to detect a clear net benefit, because it does not appropriately adjust for time-dependent covariates, such as HIV RNA level and CD4 cell count, that are simultaneously confounders and intermediate variables.

Declining prevalence of cervicovaginal human papillomavirus infection with age is independent of other risk factors.

Abstract: Background and Objectives: Human papillomavirus (HPV) infection of the female genital tract is the most common sexually transmitted disease. Although the prevalence of HPV in women without detectable cervical disease has been shown to decline with increasing age, the relationship to sexual behavior has not been investigated. Goal: To identify risk factors for, and associated with the age-dependent decline in, genital HPV infection in women. Study Design: The prevalence of HPV was determined in a cohort of 439 sexually active inner-city women between the ages of 18 and 50 years recruited in Brooklyn, New York. Cervicovaginal cells were collected by lavage, and HPV was detected by low-stringent Southern blot hybridization. Results: The prevalence of HPV infection ranged from 36% in women younger than 25 years of age to 2.8% in women 45 years or older. Logistic regression analysis identified an increased risk for cervical HPV infection to be independently associated with number of sex partners in the past year (odds ratio [OR], 1.04 per yearly increase in age; 95% confidence interval [CI], 1.00 to 1.08), younger age (OR, 0.92 per year increase in age; 95% CI, 0.88 to 0.95), and not living with partner (OR, 2.28; 95% CI, 1.40 to 4.22). Conclusions: The lower prevalence of HPV infection in older women compared to younger women was found to be independent of sexual behavior. These results suggest that a biologic effect, such as HPV immunity acquired over time and with multiple exposures, may mediate the inverse relationship between age and HPV prevalence.

Association of Cigarette Smoking With HIV Prognosis Among Women in the HAART Era: A Report From the Women’s Interagency HIV Study

Abstract: Objective. We assessed the association of cigarette smoking with the effectiveness of highly active antiretroviral therapy (HAART) among low-income women.Methods. Data were analyzed from the Women’s Interagency HIV Study, a multisite longitudinal study up to 7.9 years for 924 women representing 72% of all women who initiated HAART between July 1, 1995, and September 30, 2003.Results. When Cox’s regression was used after control for age, race, hepatitis C infection, illicit drug use, previous antiretroviral therapy, and previous AIDS, smokers on HAART had poorer viral responses (hazard ratio [HR]=0.79; 95% confidence interval [CI]=0.67, 0.93) and poorer immunologic response (HR=0.85; 95% CI=0.73, 0.99). A greater risk of virologic rebound (HR=1.39; 95% CI=1.06, 1.69) and more frequent immunologic failure (HR=1.52; 95% CI=1.18, 1.96) were also observed among smokers. There was a higher risk of death (HR=1.53; 95% CI=1.08, 2.19) and a higher risk of developing AIDS (HR=1.36; 95% CI=1.07, 1.72) but no signifi...

Association between Renal Disease and Outcomes among HIV-Infected Women Receiving or Not Receiving Antiretroviral Therapy

Abstract: Background. The associations of proteinuria and an elevated creatinine level with progression to acquired immunodeficiency syndrome (AIDS) and death in the era of highly antiretroviral therapy (HAART) have not been fully described.Methods. This analysis includes 2038 human immunodeficiency virus (HIV)-infected women from the Women's Interagency HIV Study. Time to the development of a new AIDS-defining illness (ADI) and death was modeled using proportional hazards regression before the widespread availability of HAART and after initiation of HAART.Results. Of the 2038 subjects, the 14.1% of women with proteinuria had lower CD4 lymphocyte counts and higher viral loads (P < .0001 for all) at baseline and before initiation of HAART. Before the widespread availability of HAART, proteinuria was associated with an increased risk for development of ADI (hazard ratio [HR], 1.37; P = .005), and proteinuria and an elevated creatinine level were both associated with an increased risk of death (for proteinuria: HR, 1.35 [P = .04]; for creatinine: HR, 1.72 per decrease in the inverse unit [P = .02]). Among women initiating HAART, an elevated creatinine level remained associated with an increased risk of development of ADI (HR, 1.54 per decrease in the inverse unit; P = .03), and proteinuria and an elevated creatinine level were associated with an increased risk of death (for proteinuria: HR, 2.07 [P = .005]; for creatinine: HR, 1.96 per decrease in the inverse unit [P = .04]).Conclusions. Proteinuria and an elevated creatinine level were associated with an increased risk of death and development of ADI. These associations may reflect the direct role of the kidney in modulating HIV disease, or they may act as markers of greater comorbidity.

Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index

Abstract: Obesity is globally prevalent and highly heritable, but its underlying genetic factors remain largely elusive. To identify genetic loci for obesity susceptibility, we examined associations between body mass index and similar to 2.8 million SNPs in up to 123,865 individuals with targeted follow up of 42 SNPs in up to 125,931 additional individuals. We confirmed 14 known obesity susceptibility loci and identified 18 new loci associated with body mass index (P < 5 x 10(-8)), one of which includes a copy number variant near GPRC5B. Some loci (at MC4R, POMC, SH2B1 and BDNF) map near key hypothalamic regulators of energy balance, and one of these loci is near GIPR, an incretin receptor. Furthermore, genes in other newly associated loci may provide new insights into human body weight regulation.

Human Papillomavirus and Cervical Cancer

Abstract: Of the many types of human papillomavirus (HPV), more than 30 infect the genital tract. The association between certain oncogenic (high-risk) strains of HPV and cervical cancer is well established. Although HPV is essential to the transformation of cervical epithelial cells, it is not sufficient, and a variety of cofactors and molecular events influence whether cervical cancer will develop. Early detection and treatment of precancerous lesions can prevent progression to cervical cancer. Identification of precancerous lesions has been primarily by cytologic screening of cervical cells. Cellular abnormalities, however, may be missed or may not be sufficiently distinct, and a portion of patients with borderline or mildly dyskaryotic cytomorphology will have higher-grade disease identified by subsequent colposcopy and biopsy. Sensitive and specific molecular techniques that detect HPV DNA and distinguish high-risk HPV types from low-risk HPV types have been introduced as an adjunct to cytology. Earlier detection of high-risk HPV types may improve triage, treatment, and follow-up in infected patients. Currently, the clearest role for HPV DNA testing is to improve diagnostic accuracy and limit unnecessary colposcopy in patients with borderline or mildly abnormal cytologic test results.

Natural history of cervicovaginal papillomavirus infection in young women

Abstract: Background Genital human papillomavirus (HPV) infection is highly prevalent in sexually active young women. However, precise risk factors for HPV infection and its incidence and duration are not well known. Methods We followed 608 college women at six-month intervals for three years. At each visit, we collected information about lifestyle and sexual behavior and obtained cervicovaginal-lavage samples for the detection of HPV DNA by polymerase chain reaction and Southern blot hybridization. Pap smears were obtained annually. Results The cumulative 36-month incidence of HPV infection was 43 percent (95 percent confidence interval, 36 to 49 percent). An increased risk of HPV infection was significantly associated with younger age, Hispanic ethnicity, black race, an increased number of vaginal-sex partners, high frequencies of vaginal sex and alcohol consumption, anal sex, and certain characteristics of partners (regular partners having an increased number of lifetime partners and not being in school). The me...