Mardge H. Cohen

Effects of depressive symptoms and mental health quality of life on use of highly active antiretroviral therapy among HIV-seropositive women.

This study examines the effects of depressive symptoms and mental health quality of life on utilization of highly active antiretroviral therapy (HAART) among HIV-seropositive women. Data were collected biannually from 1996 through 1998 in a prospective cohort study. Women reported use of antiretroviral therapy, health and mental health status, demographics, and social and behavioral factors; CD4 count and viral load also were assessed. Random effects regression models estimated the longitudinal effects of depressive symptoms and mental health quality of life on the probability of HAART utilization, controlling for clinical indicators (CD4 count, viral load, symptom presence), demographics (race, age, education), behavioral factors (drug/alcohol use, clinical trials participation), service features (insurance status, mental health service utilization), and study site. High levels of depressive symptoms and poor mental health quality of life were found, and they significantly reduced the probability of HAART utilization. Receiving mental health services significantly increased the probability of utilizing HAART. HIV-seropositive women characterized as being in poor mental health were less likely to use HAART, whereas those receiving treatment of mental health difficulties were more likely to use HAART. These findings suggest that efforts to enhance womens access to psychological treatment may increase their use of the latest HIV therapies.

Ten-Year Predicted Coronary Heart Disease Risk in HIV-Infected Men and Women

BACKGROUND Highly active antiretroviral therapy (HAART), in addition to traditional vascular risk factors, may affect coronary heart disease (CHD) risk in individuals with human immunodeficiency virus (HIV) infection. METHODS Among HIV-infected (931 men and 1455 women) and HIV-uninfected (1099 men and 576 women) adults, the predicted risk of CHD was estimated on the basis of age, sex, lipid and blood pressure levels, the presence of diabetes, and smoking status. RESULTS Among HIV-infected men, 2% had moderate predicted risk of CHD (10-year CHD risk, 15%-25%), and 17% had high predicted risk (10-year CHD risk of > or = 25% or diabetes). Among HIV-infected women, 2% had moderate predicted CHD risk, and 12% had high predicted CHD risk. Compared with users of protease inhibitor-based HAART, the adjusted odds ratio (OR) for moderate-to-high risk of CHD was significantly lower among HAART-naive individuals (OR, 0.57; 95% confidence interval [CI], 0.36-0.89). Users of HAART that was not protease inhibitor based (OR, 0.74; 95% CI, 0.53-1.01) and former HAART users (OR, 0.68; 95% CI, 0.46-1.03) were also less likely than users of protease inhibitor-based HAART to have moderate-to-high CHD risk, although 95% CIs overlapped the null. Low income was associated with increased likelihood of moderate-to-high CHD risk (for annual income <

Cause-Specific Life Expectancies After 35 Years of Age for Human Immunodeficiency Syndrome-Infected and Human Immunodeficiency Syndrome-Negative Individuals Followed Simultaneously in Long-term Cohort Studies, 1984–2008

10,000 vs. >

Utility of Amsel Criteria, Nugent Score, and Quantitative PCR for Gardnerella vaginalis, Mycoplasma hominis, and Lactobacillus spp. for Diagnosis of Bacterial Vaginosis in Human Immunodeficiency Virus-Infected Women

40,000: OR, 2.32; 95% CI, 1.51-3.56 ). Elevated body mass index (calculated as weight in kilograms divided by the square of height in meters) predicted increased likelihood of moderate-to-high CHD risk (for BMI of 18.5-24.9 vs. BMI of 25-30: OR, 1.41 [95% CI, 1.03-1.93]; for BMI of 18.5-24.9 vs. BMI > or = 30: OR, 1.79 [95% CI, 1.25-2.56]). CONCLUSIONS Among HIV-infected adults, in addition to antiretroviral drug exposures, being overweight and having a low income level were associated with increased predicted CHD risk. This suggests a need to target HIV-infected men and women with these characteristics for vascular risk factor screening.

Effects of treated and untreated depressive symptoms on highly active antiretroviral therapy use in a US multi-site cohort of HIV-positive women

Parametric and semiparametric competing risks methods were used to estimate proportions, timing, and predictors of acquired immune deficiency syndrome (AIDS)-related and non-AIDS-related mortality among individuals both positive and negative for the human immunodeficiency syndrome (HIV) in the Multicenter AIDS Cohort Study (MACS) and Womens Interagency HIV Study (WIHS) from 1984 to 2008 and 1996 to 2008, respectively. Among HIV-positive MACS participants, the proportion of deaths unrelated to AIDS increased from 6% before the introduction of highly active antiretroviral therapy (HAART) (before 1996) to 53% in the HAART era (P < 0.01); the median age of persons who died from non-AIDS-related causes after age 35 years increased from 49.0 to 66.0 years (P < 0.01). In both cohorts during the HAART era, median ages at time of non-AIDS-related death were younger for HIV-positive individuals than for comparable HIV-negative individuals (8.7 years younger in MACS (P < 0.01) and 7.6 years younger in WIHS (P < 0.01)). In a multivariate proportional cause-specific hazards model, unemployment (for non-AIDS death, hazard ratio (HR) = 1.8; for AIDS death, HR = 2.3), depression (for non-AIDS death, HR = 1.4; for AIDS death, HR = 1.4), and hepatitis B or C infection (for non-AIDS death, HR = 1.8, for AIDS death; HR = 1.4) were significantly (P < 0.05) associated with higher hazards of both non-AIDS and AIDS mortality among HIV-positive individuals in the HAART era, independent of study cohort. The results illuminate the changing face of mortality among the growing population infected with HIV.

Variation of human immunodeficiency virus type 1 viral RNA levels in the female genital tract : Implications for applying measurements to individual women

ABSTRACT Bacterial vaginosis (BV) is a clinical syndrome presenting with a malodorous vaginal discharge and increased vaginal pH. Diagnosis has been based on clinical Amsel criteria and direct Gram stain of vaginal secretions. Human immunodeficiency virus (HIV)-infected participants in the Womens Interagency HIV Study contributed cervicovaginal lavage (CVL) samples. Lactobacilli, Gardnerella vaginalis, and Mycoplasma hominis in cervicovaginal lavage samples were quantified by PCR. Gynecologic evaluation included Nugent score and Amsel criterion assessment. We compared the gold standard Nugent score to Amsel criteria and quantitative bacterial PCR for diagnosing BV in 203 CVL samples from women with Nugent scores of 7 to 10 (BV group) and 203 samples from women with BV Nugent scores of 0 to 3 (“No-BV” group). Only 75 of the 203 CVL samples from women with Nugent scores of 7 to 10 met positive Amsel criteria. Increasing levels of G. vaginalis and M. hominis and decreasing levels of lactobacilli were significantly associated with BV by Nugent score. Of the group with Nugent scores of 7 to 10, 83% and 81% had log10G. vaginalis counts and log10M. hominis counts greater than 6.81 and 4.82, respectively, while only 30% and 31% of the group with Nugent scores of 0 to 3 were above these thresholds, respectively. There was significant overlap in the log10 lactobacillus counts between the two groups. Utilizing all three log10 bacterial counts (G. vaginalis, M. hominis, and lactobacilli) in our model improved the sensitivity and specificity to 83% and 78%, respectively, in comparison with Nugent score. In this cohort, Amsel criteria were poorly predictive of BV. PCR quantification of G. vaginalis and M. hominis from CVL is significantly more sensitive than Amsel criteria for diagnosing BV.

Lymphoid follicles are generated in high-grade cervical dysplasia and have differing characteristics depending on HIV status.

Abstract This study examines the effects of treated and untreated depressive symptoms on the likelihood of utilization of highly active antiretroviral therapy (HAART) among a multi-site cohort of HIV-infected women who screened positive for probable depression. Data were collected biannually from 1996 through 2001 in a prospective cohort study. Random-effects regression analysis was used to estimate the longitudinal effects of mental health treatment on the probability of HAART utilization, controlling for clinical indicators (CD4 count, viral load), demographic features (race/ethnicity, income), and behavioural factors (recent crack, cocaine, or heroin use). Use of antidepressants plus mental health therapy, or use of mental health therapy alone significantly increased the probability of HAART utilization, compared to receiving no depression treatment. Use of antidepressants alone did not differ significantly from receiving no depression treatment. African American women and those who used crack, cocaine, or heroin also were less likely to use HAART. These findings suggest that efforts to enhance depressed womens access to psychopharmacologic treatment and therapy may increase their use of the most effective HIV therapies.

A Single-Nucleotide Polymorphism in CYP2B6 Leads to >3-Fold Increases in Efavirenz Concentrations in Plasma and Hair Among HIV-Infected Women

The short-term detection and variability of human immunodeficiency virus type 1 (HIV-1) RNA level was assessed in the blood plasma and genital tracts of 55 HIV-1-infected women. Specimens were collected weekly for 8 weeks from the endocervical canal with wicks and cytobrushes and from the ectocervix and vagina with cervicovaginal lavage. In all, 48 women (87.3%) had detectable genital tract HIV-1 RNA at > or =1 collection times. HIV-1 RNA levels varied least in specimens from endocervical canal wick and most in cervicovaginal lavage samples. The within-subject variation for genital-tract virus level was greater than that for blood. Overall, the odds for viral RNA detection in the genital tract approximately tripled for each 10-fold increase in plasma viral RNA concentration (P<.001) or with concomitant genital tract infection (P=.003). Endocervical canal wicks should be considered as an adjunct to cervicovaginal lavage, to improve the sensitivity and precision of HIV-1 RNA detection.

Mechanisms for the Negative Effects of Internalized HIV-Related Stigma on Antiretroviral Therapy Adherence in Women: The Mediating Roles of Social Isolation and Depression

The exact role of the mucosal immune response in the pathogenesis of human papillomavirus (HPV)-related premalignant and malignant diseases of the genital tract is poorly understood. We used immunohistochemical analysis to characterize immune cells in normal cervix (N = 21), HIV-negative high-grade dysplasia (N = 21), and HIV-positive high-grade dysplasia (N = 30). Classical germinal centers were present in 4.7% of normal cervix, 33% of high-grade lesions from HIV-negative women, and 3.3% of high-grade lesions from HIV-positive women (P = 0.003). HPV16 E7 antigen was detected in a subset of germinal centers, indicating that the secondary immune response was directed in part against HPV. Lymphoid follicles were present in 9.5% of normal cervix, 57% of HIV-negative high-grade dysplasia, and 50% of HIV-positive high-grade dysplasia (P = 0.001 normal versus high-grade). A novel type of lymphoid aggregate, consisting predominantly of CD8(+) T cells, was detected in 4.8% of normal cervix, 0% of HIV-negative high-grade dysplasia, and 40% of HIV-positive high-grade dysplasia (P < 0.001). The recurrence rate of high-grade dysplasia within one year was significantly higher in women with such CD8(+) T cell-dominant aggregates (P = 0.02). In summary, the types of lymphoid follicle in lesions from HIV-positive women were significantly different from those from HIV-negative women, and these differences are associated with the worse clinical outcome in HIV-positive women.

HIV Infection and Women's Sexual Functioning

BACKGROUND Efavirenz exhibits marked interindividual variability in plasma levels and toxicities. Prior pharmacogenetic studies usually measure exposure via single plasma levels, examine limited numbers of polymorphisms, and rarely model multiple contributors. We analyzed numerous genetic and nongenetic factors impacting short-term and long-term exposure in a large heterogeneous population of human immunodeficiency virus (HIV)-infected women. METHODS We performed 24-hour intensive pharmacokinetic studies in 111 women receiving efavirenz under actual-use conditions and calculated the area-under-the-concentration-time curve (AUC) to assess short-term exposure; the efavirenz concentration in hair was measured to estimate long-term exposure. A total of 182 single-nucleotide polymorphisms (SNPs) and 45 haplotypes in 9 genes were analyzed in relationship to exposure by use of multivariate models that included a number of nongenetic factors. RESULTS Efavirenz AUCs increased 1.26-fold per doubling of the alanine aminotransferase level and 1.23-fold with orange and/or orange juice consumption. Individuals with the CYP2B6 516TT genotype displayed 3.5-fold increases in AUCs and 3.2-fold increases in hair concentrations, compared with individuals with the TG/GG genotype. Another SNP in CYP2B6 (983TT) and a p-glycoprotein haplotype affected AUCs without substantially altering long-term exposure. CONCLUSIONS This comprehensive pharmacogenomics study showed that individuals with the CYP2B6 516TT genotype displayed >3-fold increases in both short-term and long-term efavirenz exposure, signifying durable effects. Pharmacogenetic testing combined with monitoring of hair levels may improve efavirenz outcomes and reduce toxicities.