Ronald C. Hershow

Perinatal Transmission of Hepatitis C Virus from Human Immunodeficiency Virus Type 1-Infected Mothers

Antepartum plasma hepatitis C virus (HCV) RNA was quantified in 155 mothers coinfected with HCV and human immunodeficiency virus type 1 (HIV-1), and HCV RNA was serially assessed in their infants. Of 155 singleton infants born to HCV antibody-positive mothers, 13 (8.4%) were HCV infected. The risk of HCV infection was 3.2-fold greater in HIV-1-infected infants compared with HIV-1-uninfected infants (17.1% of 41 vs. 5.4% of 112, P = .04). The median concentration of plasma HCV RNA was higher among the 13 mothers with HCV-infected infants (2.0 x 10(6) copies/mL) than among the 142 mothers with HCV-negative infants (3.5 x 10(5) copies/mL; P < .001), and there were no instances of HCV transmission from 40 mothers with HCV RNA concentrations of < 10(5) copies/mL. Women dually infected with HIV-1 and HCV but with little or no detectable HCV RNA should be reassured that the risk of perinatal transmission of HCV is exceedingly low.

Urinary tract infection during pregnancy: its association with maternal morbidity and perinatal outcome.

OBJECTIVES. The effects of antepartum urinary tract infection on adverse maternal and perinatal outcomes were examined. Antepartum urinary tract infection has been previously implicated as a risk factor for numerous outcomes. METHODS. Crude and multivariable analyses were performed with a perinatal registry cohort of 25,746 mother/infant pairs. RESULTS. Elevated risks were observed for exposure to urinary tract infection and low birthweight, prematurity, preterm low birthweight, premature labor, hypertension/preeclampsia, maternal anemia, and amnionitis. Urinary tract infection was associated with perinatal death only among subjects 20 to 29 years of age. CONCLUSIONS. These findings underscore the importance of antepartum urine screening to identify patients at risk for adverse outcomes.

Trends in mortality and causes of death among women with HIV in the United States: a 10-year study.

Background:To assess trends in mortality and cause of death for women with HIV, we studied deaths over a 10-year period among participants in the Womens Interagency HIV Study, a representative US cohort. Methods:Deaths were ascertained by National Death Index Plus match, and causes of death determined by death certificate. Results:From 1995 through 2004, 710 of 2792 HIV-infected participants died. During this interval, the standardized mortality ratio fell from a high of 24.7 in 1996 to a plateau with a mean of 10.3 from 2001 to 2004. Over the decade, deaths from non-AIDS causes increased and accounted for the majority of deaths by 2001-2004. The most common non-AIDS causes of death were trauma or overdose, liver disease, cardiovascular disease, and malignancy. Independent predictors of mortality besides HIV-associated variables were depressive symptoms and active hepatitis B or C. Women who were overweight or obese were significantly less likely to die of AIDS than women of normal weight. Conclusions:In the Womens Interagency HIV Study, the death rate has plateaued in recent years. Although HIV-associated factors predicted AIDS and non-AIDS deaths, other treatable conditions predicted mortality. Further gains in reducing mortality among HIV-infected women may require broader access to therapies for depression, viral hepatitis, and HIV itself.

Increased Vertical Transmission of Human Immunodeficiency Virus from Hepatitis C Virus-Coinfected Mothers

To determine if hepatitis C virus (HCV) infection affects vertical transmission of human immunodeficiency virus (HIV), 487 HIV-infected pregnant women in the prospective, multicenter, Women and Infants Transmission Study had HCV antibody (anti-HCV by second-generation ELISA) and HCV RNA (by quantitative polymerase chain reaction) measured in peripartum maternal plasma; 161 (33%) were anti-HCV-positive. HIV vertical transmission occurred from 42 HCV-infected mothers (26.1%) versus 53 HCV-uninfected mothers (16.3%; odds radio [OR], 1.82; P = .01). In a logistic regression model that included maternal drug use, a potential confounder, HCV infection was marginally associated with perinatal HIV transmission (OR, 1.64; P = .05), whereas drug use was not. Women who transmitted HIV had higher levels of HCV RNA (median, 721,254 copies/mL) than those who did not (337,561 copies/mL; P = .01). Maternal HCV infection is associated with increased HIV vertical transmission. Further studies are needed to ascertain if HCV directly affects perinatal HIV transmission or is a marker for another factor, such as maternal drug use.

The contribution of assay variation and biological variation to the total variability of plasma HIV-1 RNA measurements

OBJECTIVES To assess the specific contributions of assay variation and biological variation to the total variation of plasma HIV-1 RNA measured by the Roche Monitor assay and the extent to which batch assays reduced both assay variability and total variability compared with real-time determinations. DESIGN A retrospective analysis of data obtained from three trials conducted by the Adult and Pediatric AIDS Clinical Trials Groups (ATCG), the Women and Infants Transmission Study (WITS) and the NIAID-sponsored Virology Quality Assurance Program. METHODS Within-subject variation was assessed from stored, serially collected plasma samples from 663 subjects enrolled in the ACTG and WITS studies. Interassay and intra-assay variation were estimated from two of the clinical trials and 22 laboratories that participated in a quality assurance program and were used to estimate the effect of real-time testing on total variation. RESULTS The total variation (standard deviation) from a random effects model was 0.26 log10 RNA copies/ml. The estimated interassay variation was 0.08 log10 and intra-assay variation was 0.12 log10 RNA copies/ml. Biological variation accounted for 56-80% of total variation. The effect of real-time testing compared with batch testing was minimal. CONCLUSION Our estimates of total within-subject HIV-1 RNA variation support the current recommendation to obtain at least two specimens, preferably obtained less than 2 weeks apart, for viral RNA measurement before starting therapy. The major contribution of biological variation to the total variation supports the use of real-time HIV-1 RNA assays, provided that consistent specimen collection procedures are followed and acceptable assay proficiency is maintained.

Cervicovaginal Levels of Lactoferrin, Secretory Leukocyte Protease Inhibitor, and RANTES and the Effects of Coexisting Vaginoses in Human Immunodeficiency Virus (HIV)-Seronegative Women with a High Risk of Heterosexual Acquisition of HIV Infection

ABSTRACT Innate immune factors in mucosal secretions may influence human immunodeficiency virus type 1 (HIV-1) transmission. This study examined the levels of three such factors, genital tract lactoferrin [Lf], secretory leukocyte protease inhibitor [SLPI], and RANTES, in women at risk for acquiring HIV infection, as well as cofactors that may be associated with their presence. Women at high risk for HIV infection meeting established criteria (n = 62) and low-risk controls (n = 33) underwent cervicovaginal lavage (CVL), and the CVL fluid samples were assayed for Lf and SLPI. Subsets of 26 and 10 samples, respectively, were assayed for RANTES. Coexisting sexually transmitted infections and vaginoses were also assessed, and detailed behavioral information was collected. Lf levels were higher in high-risk (mean, 204 ng/ml) versus low-risk (mean, 160 ng/ml, P = 0.007) women, but SLPI levels did not differ, and RANTES levels were higher in only the highest-risk subset. Lf was positively associated only with the presence of leukocytes in the CVL fluid (P < 0.0001). SLPI levels were lower in women with bacterial vaginosis [BV] than in those without BV (P = 0.04). Treatment of BV reduced RANTES levels (P = 0.05). The influence, if any, of these three cofactors on HIV transmission in women cannot be determined from this study. The higher Lf concentrations observed in high-risk women were strongly associated with the presence of leukocytes, suggesting a leukocyte source and consistent with greater genital tract inflammation in the high-risk group. Reduced SLPI levels during BV infection are consistent with an increased risk of HIV infection, which has been associated with BV. However, the increased RANTES levels in a higher-risk subset of high-risk women were reduced after BV treatment.

Hepatitis C virus infection in Chicago women with or at risk for HIV infection : Evidence for sexual transmission

Background and Objectives: The importance of sexual transmission of hepatitis C virus (HCV) infection is unclear. We attempted to define its role in women with or at risk for HIV infection. Goal of this Study: To ascertain if high‐risk sexual behavior was independently associated with HCV infection. Study Design: Risk factors were assessed cross‐sectionally in Chicago women newly enrolled in the Womens Interagency HIV Study. Women who had (n = 243) or were at risk for HIV infection (n = 53) were tested for HCV antibodies (Ab). Results: Of 296 women, 123 (42%) were HCV Ab positive; prevalence was 90% in women who injected drugs (IDU) compared with 12% in noninjectors (odds ratio [OR], 64.0, 95% confidence interval [CI], 29.9 to 137.0). A multivariate model showed associations with IDU (OR, 110.3, 95% CI, 33.3 to 365.8), prior gonorrhea (OR, 3.6, 95% CI, 1.4 to 8.9), and sex with a male IDU (OR, 2.7, 95% CI, 1.1 to 7.0). Conclusion: Injection drug use is the strongest predictor of HCV infection, but sexual risk factors are also independently associated.

Underreporting of blood and body fluid exposures among health care students and trainees in the acute care setting: a 2007 survey.

BACKGROUND It has been estimated that more than 8 million health care workers (HCWs) in the United States may be exposed to blood and body fluids via sharp and mucocutaneous exposures. METHODS An anonymous questionnaire was distributed among 505 HCWs. The target sample population included all the medical students; nursing professionals; dental professionals; and residents in internal medicine, emergency medicine, surgery, and obstetrics and gynecology at the University of Illinois Medical Center, Chicago, Illinois, a metropolitan tertiary care and referral center for Northern Illinois and Northwest Indiana. The sample was limited by the number of HCWs who were available to take the survey. The number and the characteristics of occupational exposures and reporting practices were recorded and compiled. Subsequently, a review of the English literature was performed using PubMed to analyze reasons for underreporting. Secondary and tertiary articles were located based on findings from the initial searches. RESULTS One hundred three of 455 (22.6%) HCWs reported a sharps exposure during their career, including their student years; thirty-four (33.0%) of these were not reported. One hundred five of 455 (23.1%) HCWs reported a mucocutaneous exposure during their career; 87 (82.9%) of these were not reported. The most common year of exposure was the intern year. The most common reason for not reporting was the belief that the exposure was not significant, followed by the combination of believing the exposure was not significant and being too busy. CONCLUSION Underreporting of blood and body fluid exposures is common because of a belief that most exposures are not significant. More education of HCWs is needed to change this perspective.

Effect of hard-drug use on CD4 cell percentage, HIV RNA level, and progression to AIDS-defining class C events among HIV-infected women.

In vitro and animal studies suggest that cocaine and heroin increase HIV replication and suppress immune function, whereas epidemiologic studies are inconclusive regarding their effect on HIV infection progression. The authors prospectively examined the association between illicit-drug use and 4 outcome measures (CD4 cell percentage, HIV RNA level, survival to class C diagnosis of HIV infection, and death) in a national cohort of HIV-infected women. Women enrolled between 1989 and 1995 were followed for 5 years and repeatedly interviewed about illicit (“hard”)–drug use. Up to 3 periodic urine screens validated self-reported use. Outcomes were compared between hard-drug users (women using cocaine, heroin, methadone, or injecting drugs) and nonusers, adjusting for age, antiretroviral therapy, number of pregnancies, smoking, and baseline CD4 cell percentage. Of 1148 women, 40% reported baseline hard-drug use during pregnancy. In multivariate analyses, hard-drug use was not associated with change in CD4 cell percentage (P = 0.84), HIV RNA level (P = 0.48), or all-cause mortality (relative hazard = 1.10; 95% confidence interval, 0.61–1.98). Hard-drug users did, however, exhibit a higher risk of developing class C diagnoses (relative hazard = 1.65; 95% confidence interval, 1.00–2.72), especially herpes, pulmonary tuberculosis, and recurrent pneumonia. Hard-drug–using women may have a higher risk for nonfatal opportunistic infections.

Discordant CD4 T lymphocyte responses to antiretroviral therapy for HIV infection are associated with ex-vivo rates of apoptosis.

Our purpose was to determine if changes in CD4 cell counts in HIV-infected patients with good viral suppression on stable antiretroviral regimens could be predicted by ex-vivo rates of apoptosis of peripheral blood mononuclear cells (PBMC). Patients were grouped by lowest pre-treatment and highest on-treatment CD4 cell counts and classified as complete immune responders, partial responders, or non-responders. Whole blood was collected from a subgroup of patients and controls, and rates of the ex-vivo apoptosis of PBMC were assessed. Non-responders exhibited significantly increased apoptosis, whereas good immune responses were associated with decreased apoptosis. Persistently accelerated apoptosis may contribute to persisting immune deficiency independent of the viral load.