Paula Schuman

Prevalence, Incidence, and Type-Specific Persistence of Human Papillomavirus in Human Immunodeficiency Virus (HIV)-Positive and HIV-Negative Women

Human immunodeficiency virus (HIV) infection and related immunosuppression are associated with excess risk for cervical neoplasia and human papillomavirus (HPV) persistence. Type-specific HPV infection was assessed at 6-month intervals for HIV-positive and HIV-negative women (median follow-up, 2.5 and 2.9 years, respectively). The type-specific incidence of HPV infection was determined, and risk factors for HPV persistence were investigated by statistical methods that accounted for repeated measurements. HIV-positive women were 1.8, 2.1, and 2.7 times more likely to have high-, intermediate-, and low-risk HPV infections, respectively, compared with HIV-negative women. In multivariate analysis, high viral signal, but not viral risk category, was independently associated with persistence among HIV-positive subjects (odds ratio [OR], 2.5; 95% confidence interval [CI], 2.1-2.9). Furthermore, persistence was 1.9 (95% CI, 1.5-2.3) times greater if the subject had a CD4 cell count <200 cells/microL (vs. >500 cells/microL). Thus, HIV infection and immunosuppression play an important role in modulating the natural history of HPV infection.

A prospective study of adherence and viral load in a large multi-center cohort of HIV-infected women

Objectives: To examine the relationship between antiretroviral adherence and viral load, and to determine the predictors of adherence over time in HIV-infected women. Design: Prospective observational study. Methods: One-hundred sixty-one HIV-infected women who were taking antiretroviral therapy for a median of 3.0 years were recruited from the HIV Epidemiology Research Study, a multicenter cohort study of HIV infection in women. Antiretroviral adherence (percent of doses taken as prescribed) was measured over a 6-month period using MEMS caps. At baseline and follow-up, CD4 lymphocyte count and viral load were measured, and a standardized interview was administered to elicit medication history and drug use behaviors. To examine changes in adherence over time, the mean adherence to all antiretroviral agents was calculated for each monitored month. Results: Adherence varied significantly over time (P < 0.001), ranging from a mean of 64% in month 1 to 45% in month 6. Nearly one-fourth of the participants had a 10% or greater decrease in adherence between consecutive months. Virologic failure occurred in 17% of women with adherence of ⩾ 88%, 28% of those with 45–87% adherence, 43% of those with 13–44% adherence, and 71% of those with ⩽ 12% adherence. In multivariate analysis, factors predicting lower adherence included active drug use, alcohol use, more frequent antiretroviral dosing, shorter duration of antiretroviral use, younger age, and lower initial CD4 lymphocyte count. Conclusions: Antiretroviral adherence is not stable over time. Interventions aimed at monitoring and improving long-term adherence in women are urgently needed.

Blood-borne and sexual transmission of human herpesvirus 8 in women with or at risk for human immunodeficiency virus infection

BACKGROUND Human herpesvirus 8 (HHV-8), the causal agent of Kaposis sarcoma, is transmitted sexually among homosexual men, but little is known of its transmission among women. Although HHV-8 has been detected in blood, there has been no clear evidence of blood-borne transmission. METHODS We identified risk factors for HHV-8 infection in 1295 women in Baltimore, Detroit, New York, and Providence, Rhode Island, who reported high-risk sexual behavior or drug use. HHV-8 serologic studies were performed with two enzyme-linked immunosorbent assays. RESULTS In univariate analyses, HHV-8 was associated with black race, Hispanic ethnic background, a lower level of education, and infection with syphilis, the human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV). The risk of seropositivity for HHV-8 increased with the frequency of injection-drug use (P<0.001); HHV-8 seroprevalence among the women who used drugs daily was three times that among women who never injected drugs. Among the women with a low risk of sexual transmission, HHV-8 seroprevalence was 0 percent in those who had never injected drugs and 36 percent in those who had injected drugs (P<0.001). However, injection-drug use was linked less strongly to HHV-8 infection than to infection with HBV or HCV. In a multivariate analysis, independent predictors of HHV-8 seropositivity included HIV infection (odds ratio, 1.6; 95 percent confidence interval, 1.1 to 2.2), syphilis infection (odds ratio, 1.8; 95 percent confidence interval, 1.1 to 2.8), and daily injection-drug use (odds ratio, 3.2; 95 percent confidence interval, 1.4 to 7.6). CONCLUSIONS Both injection-drug use and correlates of sexual activity were risk factors for HHV-8 infection in the women studied. The independent association of HHV-8 infection with injection-drug use suggests that HHV-8 is transmitted through needle sharing, albeit less efficiently than HBV, HCV, or HIV.

Longitudinal Study of Cervical Squamous Intraepithelial Lesions in Human Immunodeficiency Virus (HIV)-Seropositive and At-Risk HIV-Seronegative Women

We examined incidence and correlates of progression and regression of abnormal cervical cytologic test results, defined as at least low-grade squamous intraepithelial lesions (SILs), in 774 human immunodeficiency virus (HIV)-seropositive and 391 HIV-seronegative women monitored semiannually for up to 5.5 years. During follow-up, 224 (35%) HIV-seropositive women and 34 (9%) HIV-seronegative women had incident SILs detected by Pap test; 47 (7%) HIV-seropositive women developed high-grade lesions. The incidence of SILs was 11.5 cases among HIV-seropositive and 2.6 cases among HIV-seronegative women per 100 person-years of observation (rate ratio, 4.5; 95% confidence interval, 3.1-6.4; P<.001). Risk of incident SILs and likelihood of Pap test progression were increased among HIV-seropositive women with CD4(+) lymphocyte counts <500 cells/mm(3) and among women with human papillomavirus (HPV) infection, with risk-ordering from low- to high-risk HPV type. SIL regression was less likely among HIV-seropositive women with higher HIV loads. No beneficial effect of highly active antiretroviral therapy was demonstrated.

Development of proteinuria or elevated serum creatinine and mortality in HIV-infected women.

BackgroundData on the incidence and prognostic significance of renal dysfunction in HIV disease are limited. ObjectiveTo determine the incidence of proteinuria and elevated serum creatinine in HIV-positive and HIV-negative women and to determine whether these abnormalities are predictors of mortality or associated with causes of death listed on the death certificate in HIV-positive women. DesignThe incidence of proteinuria or elevated serum creatinine and mortality was assessed in a cohort of 885 HIV-positive women and 425 at-risk HIV-negative women. SettingWomen from the general community or HIV care clinics in four urban locations in the United States. Outcome MeasuresCreatinine of ≥1.4 mg/dL, proteinuria 2+ or more, or both. Deaths confirmed by a death certificate (92%) or medical record/community report (8%). ResultsAt baseline, 64 (7.2%) HIV-positive women and 10 (2.4%) HIV-negative women had proteinuria or elevated creatinine. An additional 128 (14%) HIV-positive women and 18 (4%) HIV-negative women developed these abnormalities over the next (mean) 21 months. Relative hazards of mortality were significantly increased (adjusted relative hazard = 2.5; 95% confidence interval: 1.9–3.3), and there were more renal causes recorded on death certificates (24/92 (26%) vs. 3/127 (2.7%), p < .0001) in HIV-infected women with, compared with those without these renal abnormalities. ConclusionsProteinuria, elevated serum creatinine, or both frequently occurred in these HIV-infected women. These renal abnormalities in HIV-infected women are associated with an increased risk of death after controlling for other risk factors and with an increased likelihood of having renal causes listed on the death certificate. The recognition and management of proteinuria and elevated serum creatinine should be a priority for HIV-infected persons.

Severe adverse life events and depressive symptoms among women with, or at risk for, Hiv infection in four cities in the United States of America

OBJECTIVE To examine frequency and predictors of severe adverse life events and depressive symptoms among HIV-infected women and a comparison group of uninfected women. DESIGN Analysis of baseline data collected from HIV-infected and uninfected women in a prospective cohort study of HIV infection and women, the HIV Epidemiologic Research Study. METHOD The sample of 871 HIV-infected and 439 demographically and behaviorally similar uninfected women were recruited from four metropolitan areas in the USA. Women provided interview information that included sociodemographic characteristics, sexual and drug-using behaviors, and social and psychological functioning. The outcome measures were number of severe adverse life events (e.g., insufficient money for necessities, physical attack or rape, death of a person close to them) and levels of depressive symptoms. RESULTS HIV-infected and uninfected women reported numerous adverse life events and high levels of depressive symptoms. The two groups, however, did not differ on either outcome measure. Low socio-economic status, injecting drug and crack cocaine use, and high risk sexual activity were related to reports of more adverse events and depressive symptoms for both groups. CONCLUSIONS HIV-infected and uninfected women in socially and economically disadvantaged environments experience many adverse events and high levels of depressive symptoms. HIV infection, at least during the early phase, may be less important than socio-environmental factors in predicting negative psychosocial outcomes for women.

Prevalence of Lower Genital Tract Infections Among Human Immunodeficiency Virus (HIV)—Seropositive and High-Risk HIV-Seronegative Women

This study was undertaken to assess whether the prevalence of lower genital tract infections among human immunodeficiency virus (HIV)-seropositive women was higher than among high-risk HIV-seronegative women at their baseline visit for the HIV Epidemiology Research Study. Results were available for 851 HIV-seropositive and 434 HIV-seronegative women. Human papilloma virus (HPV) infection was more prevalent among HIV-seropositive women (64% vs. 28%). Bacterial vaginosis was common (35% vs. 33%), followed by trichomoniasis (12% vs. 10%), syphilis (8% vs. 6%), Chlamydia trachomatis infection (4% vs. 5%), candidal vaginitis (3% vs. 2%), and Neisseria gonorrhoeae infection (0.8% vs. 0.3%). Alcohol use (odds ratio [OR], 1.8; 95% confidence interval [CI], 1. 3-2.4) and smoking (OR, 1.8; 95% CI, 1.3-2.5) were associated with bacterial vaginosis. Bacterial vaginosis (OR, 2.3; 95% CI, 1.5-3.4), trichomoniasis (OR, 2.3; 95% CI, 1.1-4.7), and syphilis (OR, 3.1; 95% CI, 1.3-7.4) were found to be more prevalent among black women. Our study showed no statistically significant difference in the prevalence of lower genital tract infections except for HPV between HIV-infected and demographically and behaviorally similar HIV-uninfected high-risk women.

Health services use by urban women with or at risk for HIV-1 infection: the HIV Epidemiology Research Study (HERS).

OBJECTIVE To characterize health services use by urban women with or at risk for HIV-1 infection enrolled in a prospective multicenter study. METHODS 1310 women 16 to 55 years of age who were at risk for HIV-1 infection were recruited between April 1993 and January 1995 at four urban centers (Baltimore, Maryland; The Bronx, New York; Detroit, Michigan; and Providence, Rhode Island). HIV-1-seropositive women without AIDS-defining illness were oversampled in a ratio of 2:1 in comparison with HIV-1-seronegative women. At a baseline study visit, the women received physical and laboratory examinations, including CD4+ counts, and were interviewed regarding HIV risk behavior, health services use, and clinical data. RESULTS 863 women were HIV-1-seropositive and 430 were HIV-1-seronegative. Fifty-two percent of the women reported injection drug use (IDU) since 1985, and 48% acquired HIV through sexual contact. Seventy-seven percent were African American, 23% were white, and 16% were Hispanic. The median age was 35 years. HIV-seronegative women were significantly less likely to have health insurance (19%) than were HIV-seropositive women (30%; p < .001). Among the HIV-seropositive women, 68% had CD4+ cell counts of <500/microl, and 64% were asymptomatic. Sixty-four percent of the HIV-seronegative women had had an outpatient hospital visit in the past 6 months, as had 86% of HIV-seropositive women (p < 0.001). Hospitalization in the past 6 months was also higher in HIV-seropositive women (22% vs. 12%; p < .001). Despite heavy use of health services, only 49% of women with CD4+ counts of <200/microl reported current use of antiretroviral therapy, and only 58% reported current use of Pneumocystis carinii pneumonia (PCP) prophylaxis. Among HIV-seropositive women, and after adjusting for CD4+ count, HIV symptoms, race, and study site, IDUs were significantly less likely to have a regular doctor and a recent outpatient visit and more likely to be hospitalized and use the emergency department (ED) than were non-IDUs. In multivariate analyses of HIV-seropositive persons, African American women had similar access to care and use of antiretroviral therapy and PCP prophylaxis than did white women but were less likely to have an outpatient department visit in the previous 6 months and to be taking PCP and opportunistic infection (OI) prophylaxis. Health services access and use of HIV-related therapies did not significantly differ between Hispanic and white women with HIV infection. CONCLUSION Although both HIV-seropositive and HIV-seronegative women had high levels of use of medical services, current use of antiretrovirals and OI prophylaxis was low throughout, and IDUs used HIV-related primary health services less and were more likely to receive emergency or episodic care. IDU and African American race were independently associated with decreased use of medical services.

Bacterial Pneumonia, HIV Therapy, and Disease Progression among HIV-Infected Women in the HIV Epidemiologic Research (HER) Study

BACKGROUND To determine the rate and predictors of community-acquired bacterial pneumonia and its effect on human immunodeficiency virus (HIV) disease progression in HIV-infected women, we performed a multiple-site, prospective study of HIV-infected women in 4 cities in the United States. METHODS During the period of 1993-2000, we observed 885 HIV-infected and 425 HIV-uninfected women with a history of injection drug use or high-risk sexual behavior. Participants underwent semiannual interviews, and CD4+ lymphocyte count and viral load were assessed in HIV-infected subjects. Data regarding episodes of bacterial pneumonia were ascertained from medical record reviews. RESULTS The rate of bacterial pneumonia among 885 HIV-infected women was 8.5 cases per 100 person-years, compared with 0.7 cases per 100 person-years in 425 HIV-uninfected women (P < .001). In analyses limited to follow-up after 1 January 1996, highly active antiretroviral therapy (HAART) and trimethoprim-sulfamethoxazole (TMP-SMX) use were associated with a decreased risk of bacterial pneumonia. Among women who had used TMP-SMX for 12 months, each month of HAART decreased bacterial pneumonia risk by 8% (adjusted hazard ratio [HR(adj)], 0.92; 95% confidence interval [CI], 0.89-0.95). Increments of 50 CD4+ cells/mm3 decreased the risk (HR(adj), 0.88; 95% CI, 0.84-0.93), and smoking doubled the risk (HR(adj), 2.12; 95% CI, 1.26-3.55). Bacterial pneumonia increased mortality risk (HR(adj), 5.02; 95% CI, 2.12-11.87), with adjustment for CD4+ lymphocyte count and duration of HAART and TMP-SMX use. CONCLUSIONS High rates of bacterial pneumonia persist among HIV-infected women. Although HAART and TMP-SMX treatment decreased the risk, bacterial pneumonia was associated with an accelerated progression to death. Interventions that improve HAART utilization and promote smoking cessation among HIV-infected women are warranted.

Neurocognitive performance enhanced by highly active antiretroviral therapy in HIV-infected women

ObjectiveTo determine whether highly active retroviral therapy (HAART) is associated with better neurocognitive outcome over time among HIV-infected women with severely impaired immune function. MethodsA semiannual neurocognitive examination on four tasks was administered: Color Trail Making, Controlled Oral Word Association, Grooved Pegboard and Four-Word Learning. This protocol was initiated in the HIV Epidemiological Research study (HERS) study when a womans CD4 cell count fell to < 100 × 106 cells/l. Immune function (CD4), viral load status and depression severity (CESD) were also assessed semi-annually, along with an interview to determine medication intake and illicit drug use. ResultsHAART was not available to any participant at the time of enrollment (baseline), while 44% reported taking HAART at their most recent visit (mean duration of HAART 36.3 ± 12.6 months). HAART-treated women had improved neurocognitive performance compared with those not treated with HAART. Women taking HAART for 18 months or more showed the strongest neurocognitive performance with improved verbal fluency, psychomotor and executive functions. These functions worsened among women not taking HAART. Substance abuse status, severity of depressive symptoms, age and educational level did not influence the HAART treatment effects on neurocognitive performance. Neurocognitive improvements were strongly associated with the magnitude of CD4 cell count increases. ConclusionsHAART appeared to produce beneficial effect on neurocognitive functioning in HIV-infected women with severely impaired immune systems. Benefits were greatest for women who reported receiving HAART for more than 18 months.