Previous studies of the association of the C17T polymorphism of the mu opiate receptor gene with substance dependence compared cases with substance dependence to controls and usually found no significant association. However, the studies were limited by small sample size - no study had more than 12 subjects with the TT genotype, a genotype that is rare in white and Asian subjects. Moreover, drug use is not dichotomous but follows a spectrum from non-use to modest, intermittent use, to use several times daily. We asked whether the Kreek-McHugh-Schluger-Kellogg (KMSK) scales for alcohol, cocaine, opiates, and tobacco that quantify substance use during the time of a subject's maximal use might be more sensitive measures than dichotomous outcomes. We administered the KMSK scales and completed C17T genotyping on 1009 HIV-infected and 469 HIV-uninfected women in The Women's Interagency HIV Study (WIHS), an ongoing study of HIV in women. Forty-two of 697 African-American, 1 of 182 Hispanic, and none of 161 white women had the TT genotype. KMSK cocaine, alcohol, and tobacco scores were significantly higher in African-American women with the TT genotype (p =0.008, 0.0001, and 0.006 respectively) but opiate scores were not. Ordinal regression models controlling for HIV-serostatus, age, education, and income had odds ratios for the TT genotype for predicting alcohol, tobacco, cocaine, and opiates scores of 2.1 (p = 0.02), 2.4 (p = 0.0004), 2.0 (p = 0.03), and 1.9 (p = 0.07). We conclude that the TT genotype of OPRM1 may increase the risk of substance use and abuse.

Abstract

Objective

Depression is common among HIV-infected women, predicts treatment nonadherence, and consequently may impact vertical transmission of HIV. We report findings from a study evaluating preconception, pregnancy, and postpartum depressive symptoms in HIV-infected vs. at-risk, HIV-uninfected women.

Methods

We examined the prevalence and predictors of elevated perinatal (i.e., pregnancy and/or postpartum) depressive symptoms using a Center for Epidemiological Studies-Depression (CES-D) scale score of ≥16 in 139 HIV-infected and 105 HIV-uninfected women (62% African American) from the Women's Interagency HIV Study (WIHS).

Results

The prevalence of elevated perinatal depressive symptoms did not differ by HIV serostatus (HIV-infected 44%, HIV-uninfected 50%, p=0.44). Among HIV-infected women, the strongest predictor of elevated symptoms was preconception depression (odds ratio [OR] 5.71, 95% confidence interval [CI] 2.67-12.19, p<0.001); crack, cocaine, and/or heroin use during preconception was marginally significant (OR 3.10, 95% CI 0.96-10.01, p=0.06). In the overall sample, additional significant predictors of perinatal depression included having multiple sex partners preconception (OR 2.20, 95% CI 1.12-4.32, p=0.02), use of preconception mental health services (OR 2.51, 95% CI 1.03-6.13, p=0.04), and not graduating from high school (OR 1.92, 95% CI 1.06-3.46, p=0.03).

Conclusions

Elevated perinatal depressive symptoms are common among HIV-infected and at-risk HIV-uninfected women. Depressive symptoms before pregnancy were the strongest predictor of perinatal symptoms. Findings underscore the importance of early and ongoing assessment and treatment to ensure low vertical transmission rates and improving postpregnancy outcomes for mothers and children.

Recent in vitro and in vivo research has suggested that cocaine has a direct effect on the pathogenesis of AIDS. These findings are confirmed by epidemiological studies linking the use of injected, inhaled, and smoked (crack) cocaine and indicators of HIV disease progression, even among adherent users of highly active antiretroviral therapy. Recent studies of vertical HIV transmission suggest that cocaine use may play a role in mother-to-child infection via alteration of maternal immune responses, enhanced viral replication in maternal immune cells, or alterations in the immune systems of neonates or infants. The purpose of this article is to review research conducted over the past several decades on associations between use of cocaine and HIV disease progression, especially among HIV+ women, and to explore its potential relevance for understanding mother-to-infant transmission of HIV.

Aims

To evaluate the effects of longitudinal patterns and types of non-injection drug use (NIDU) on HIV progression in the highly active antiretroviral therapy (HAART) era.

Design

Women’s Interagency HIV Study (WIHS), a prospective cohort study conducted at six US sites.

Methods

Data were collected semi-annually from 1994 to 2002 on 1046 HIV+ women. Multivariate Cox proportional hazards modeling was used to estimate relative hazards for developing AIDS and for death by pattern and type of NIDU.

Findings

During follow-up, 285 AIDS events and 287 deaths, of which 177 were AIDS-related, were reported. At baseline, consistent and former NIDU was associated with CD4+ counts of < 200 cells/μl (43% and 46%, respectively) and viral load > 40 000 copies/ml (53% and 55%, respectively). Consistent NIDU reported less HAART use (53%) compared with other NIDU patterns. Stimulant use was associated with CD4+ cell counts of < 200 cells/μl (53%) and lower HAART initiation (63%) compared with other NIDU types. In multivariate analyses, progression to AIDS was significantly higher among consistent (RH = 2.52), inconsistent (RH = 1.63) and former (RH = 1.56) users compared with never users; and for stimulant (RH = 2.04) and polydrug (RH = 1.65) users compared with non-users. Progression to all-cause death was higher only among former users (RH = 1.48) compared with never users in multivariate analysis. NIDU behaviors were not associated with progression to AIDS-related death.

Conclusions

In this study, pattern and type of NIDU were associated with HIV progression to AIDS and all-cause mortality. These differences were associated with lower HAART utilization among consistent NIDU and use of stimulants, and poor baseline immunological and virological status among former users.

Hazardous alcohol consumption among women with human immunodeficiency virus (HIV) infection is associated with several adverse health and behavioral outcomes, but the proportion of HIV-positive women who engage in hazardous drinking over time is unclear. The authors sought to determine rates of hazardous alcohol consumption among these women over time and to identify factors associated with this behavior. Subjects were 2,770 HIV-positive women recruited from 6 US cities who participated in semiannual follow-up visits in the Women's Interagency HIV Study from 1995 to 2006. Hazardous alcohol consumption was defined as exceeding daily (≥4 drinks) or weekly (>7 drinks) consumption recommendations. Over the 11-year follow-up period, 14%–24% of the women reported past-year hazardous drinking, with a slight decrease in hazardous drinking over time. Women were significantly more likely to report hazardous drinking if they were unemployed, were not high school graduates, had been enrolled in the original cohort (1994–1995), had a CD4 cell count of 200–500 cells/mL, were hepatitis C-seropositive, or had symptoms of depression. Approximately 1 in 5 of the women met criteria for hazardous drinking. Interventions to identify and address hazardous drinking among HIV-positive women are urgently needed.

SUMMARY

Depression is a common condition among patients with HIV. This paper uses panel data for 1,234 participants from the Women’s Interagency HIV Study (WIHS) to estimate the effect of antidepressant use on the likelihood of being employed among women receiving highly active antiretroviral therapy (HAART) in the United States from 1996 to 2004. We show that naïve regressions of antidepressant use on employment generally result in negative or non-significant coefficients, whereas the instrumental variables approach shows a positive and significant effect of antidepressant use on the employment probability of women living with HIV. We use instrumental variables to predict antidepressant use independently of outcomes; thus, addressing potential biases (e.g., more depressed women are more likely to receive antidepressant treatment, but they are also more likely to be unemployed). The results are consistent for linear (random and fixed effects) as well as non-linear (bivariate probit) specifications. Among women receiving HAART, and controlling for individual and local area labor market characteristics, the use of antidepressants is associated with a 29-percentage-point higher probability of being employed. Improved efforts to test, diagnose and treat depression among HIV-positive patients may improve not only clinical indicators but also labor market outcomes.

Background

Longitudinal associations between patterns of crack cocaine use and progression of human immunodeficiency virus (HIV-1) disease are poorly understood, especially among women. This paper explores relationships between crack use and HIV-1 disease outcomes in a multi-center cohort of infected women.

Methods

Subjects were 1686 HIV-seropositive women enrolled at six U.S. research centers in the Women’s Interagency HIV Study. Approximately 80% were nonwhite and 29% used crack during the study period. Cox survival and random regression analysis examined bi-annual observations made April 1996 through September 2004. Outcome measures included: death due to AIDS-related causes; CD4 cell count; HIV-1 RNA level; and newly acquired AIDS-defining illnesses.

Results

Persistent crack users were over three times as likely as nonusers to die from AIDS-related causes, controlling for use of highly active antiretroviral viral therapies self-reported at >=95% adherence, problem drinking, age, race, income, education, illness duration, study site, and baseline virologic and immunological indicators. Persistent crack users and intermittent users in active phases showed greater CD4 cell loss and higher HIV-1 RNA levels controlling for the same covariates. Persistent and intermittent crack users were more likely than nonusers to develop new AIDS-defining illnesses controlling for identical confounds. These results persisted when controlling for heroin use, tobacco smoking, depressive symptoms, Hepatitis C virus co-infection, and intravenous drug use.

Conclusions

Use of crack cocaine independently predicts AIDS-related mortality, immunologic and virologic markers of HIV-1 disease progression, and development of AIDS-defining illnesses among women.

Objective

This study examined the relationship between levels of depressive symptoms and subsequent increases in substance use among 784 youth with severe emotional disturbance enrolled in Medicaid-funded behavioral health care plans.

Method

Youth at five sites nationwide were interviewed about their emotional and behavior problems, as well as their use of cigarettes, alcohol, and drugs—at both baseline and follow-up.

Results

(1) Levels of depressive symptoms were significantly associated with concurrent substance use at baseline. (2) Baseline levels of depressive symptoms predicted subsequent changes in substance use, especially use of illicit drugs and multiple drugs. (3) These findings remained significant, even after controlling for sociodemographic, family, and individual characteristics.

Conclusions

These results indicate that depressive symptoms early in life may signal a risk for increasing involvement in substance use among severe emotional disturbed youth. This finding has important clinical implications for the prevention of substance misuse in this population.

BACKGROUND

Treatment guidelines recommend all HIV/HCV-co-infected persons be considered for hepatitis C virus (HCV) treatment, yet obstacles to testing and accessing treatment for HCV continue for women.

OBJECTIVE

To assess awareness of HCV, and describe diagnostic referrals and HCV treatment among women in the Women’s Interagency HIV Study (WIHS).

DESIGN

Prospective epidemiologic cohort.

PARTICIPANTS

Of 3,768 HIV-infected and uninfected women in WIHS, 1,166 (31%) were HCV antibody positive.

MEASUREMENTS AND MAIN RESULTS

Awareness of HCV infection and probability of referrals for diagnostic evaluations and treatment using logistic regression. Follow-up HCV information was available for 681 (390 died, 15 withdrew, 80 missed visit) in 2004. Of these 681, 522 (76.7%) reported knowing their HCV diagnosis. Of these, 247 of 522 (47.3%) stated their providers recommended a liver biopsy, whereas 139 of 247 or 56.3% reported having a liver biopsy. A total of 170 of 522 (32.6%) reported being offered treatment and 74.1% (n = 126 of 170) reported receiving HCV treatment. In multivariate regression analyses, African-American race, Hispanic/Latina ethnicity, poverty, and current crack/cocaine/heroin use were negatively associated with treatment referrals, whereas elevated alanine aminotransferase (ALT) was associated with increased likelihood of referral and increased likelihood of treatment.

CONCLUSION

One quarter of women with HCV in this cohort were not aware of their diagnosis. Among those aware of their HCV, 1 in 4 received liver biopsy and treatment for HCV. Both provider and patient education interventions regarding HCV testing and HCV treatment options and guidelines are needed to enhance HCV awareness and participation in HCV evaluation and treatment.

People with schizophrenia frequently have significant problems in community functioning. Progress in developing effective interventions to ameliorate these problems has been slowed by the absence of reliable and valid measures that are suitable for use in clinical trials. The National Institute of Mental Health convened a workgroup in September 2005 to examine this issue and make recommendations to the field that would foster research in this area. This article reports on issues raised at the meeting. Many instruments have been developed to assess community functioning, but overall insufficient attention has been paid to psychometric issues and many instruments are not suitable for use in clinical trials. Consumer self-report, informant report, ratings by clinicians and trained raters, and behavioral assessment all can provide useful and valid information in some circumstances and may be practical for use in clinical trials. However, insufficient attention has been paid to when and how different forms of assessment and sources of information are useful or how to understand inconsistencies. A major limiting factor in development of reliable and valid instruments is failure to develop a suitable model of functioning and its primary mediators and moderators. Several examples that can guide thinking are presented. Finally, the field is limited by the absence of an objective gold standard of community functioning. Hence, outcomes must be evaluated in part by “clinical significance.” This criterion is problematic because different observers and constituencies often have different opinions about what types of change are clinically important and how much change is significant.

Cytomegalovirus (CMV) infections have been shown to dramatically affect solid organ transplant graft survival in both human and animal models. Recently, it was demonstrated that rat CMV (RCMV) infection accelerates the development of transplant vascular sclerosis (TVS) in both rat heart and small bowel graft transplants. However, the mechanisms involved in this process are still unclear. In the present study, we determined the kinetics of RCMV-accelerated TVS in a rat heart transplant model. Acute RCMV infection enhances the development of TVS in rat heart allografts, and this process is initiated between 21 and 24 days posttransplantation. The virus is consistently detected in the heart grafts from day 7 until day 35 posttransplantation but is rarely found at the time of graft rejection (day 45 posttransplantation). Grafts from RCMV-infected recipients had upregulation of chemokine expression compared to uninfected controls, and the timing of this increased expression paralleled that of RCMV-accelerated neointimal formation. In addition, graft vessels from RCMV-infected grafts demonstrate the increased infiltration of T cells and macrophages during periods of highest chemokine expression. These results suggest that CMV-induced acceleration of TVS involves the increased graft vascular infiltration of inflammatory cells through enhanced chemokine expression.

Patients admitted to hospital by a defined group of general practitioners under their own care differ in age, diagnostic category, perceived needs, use of services and outcome, from those admitted by the same general practitioners to consultant beds. However, problems of methodology have to be kept in mind when interpreting the results.

These findings suggest that general practitioners see consultant and general-practitioner care as having different attributes but only broadly indicate the nature of these. This study has not attempted to answer the question of outcome: What are the needs of the patient which can be most satisfactorily met by different forms of care—consultant care, general-practitioner care in hospital, and general-practitioner care at home?

The next stage must be the development of both a more valid measure of a wide range of needs, and controlled trials of care into the effects of different forms and place of care on patients with differing types of needs.