Geetanjali Chander

Substance abuse and psychiatric disorders in HIV-positive patients : Epidemiology and impact on antiretroviral therapy

There is a high prevalence of substance abuse and psychiatric disorders among HIV-infected individuals. Importantly, drug and alcohol-use disorders are frequently co-morbid with depression, anxiety and severe mental illness. Not only do these disorders increase the risk of contracting HIV, they have also been associated with decreased highly active antiretroviral therapy (HAART) utilisation, adherence and virological suppression. The literature evaluating the relationship between substance abuse and HIV outcomes has primarily focused on injection drug users, although there has been increasing interest in alcohol, cocaine and marijuana. Similarly, the mental health literature has focused largely on depression, with a lesser focus on severe mental illness or anxiety. To date, there is little literature evaluating the association between co-occurring HIV, substance abuse and mental illness on HAART uptake, adherence and virological suppression. Adherence interventions in these populations have demonstrated mixed efficacy. Both directly observed therapy and pharmacist-assisted interventions appear promising, as do integrated behavioural interventions. However, the current intervention literature has several limitations: few of these studies are randomised, controlled trials; the sample sizes have generally been small; and co-occurring substance abuse and mental illness has not specifically been targeted in these studies. Future studies examining individual substances of abuse, psychiatric disorders and co-occurring substance abuse and psychiatric disorders on HIV outcomes will inform targeted adherence interventions.

Hazardous alcohol use: a risk factor for non-adherence and lack of suppression in HIV infection.

Objective:We examined the independent effect of alcohol and combined effects of drug and alcohol use on antiretroviral (ART) utilization, adherence, and viral suppression in an urban cohort of HIV-infected individuals. Methods:In an observational clinical cohort, alcohol use, active drug use, and adherence were prospectively assessed at 6-month intervals. We classified hazardous alcohol use as >7 drinks/week or >3 drinks/occasion in women, and >14 drinks/week or >4 drinks/occasion in men and active drug use as any use in the previous 6 months. Our outcomes included ART utilization, 2-week adherence, and viral suppression. We used generalized estimating equations to analyze the association between independent variables and outcomes. Analyses were adjusted for age, sex, race, years on ART, and clinic enrollment time. Results:Between 1998 and 2003, 1711 individuals participated in 5028 interviews. 1433 of these individuals received ART accounting for 3761 interviews. The prevalence of any alcohol use at the first interview was 45%, with 10% classified as hazardous drinkers. One-third of the sample used illicit drugs. In multivariate analyses adjusting for age, sex, race, active drug use, years on ART, and clinic enrollment time, hazardous alcohol use was independently associated with decreased ART utilization (AOR, 0.65; 95% CI: 0.51 to 0.82), 2-week adherence (AOR, 0.46; 95% CI: 0.34 to 0.63), and viral suppression (AOR, 0.76; 95% CI: 0.57 to 0.99) compared to no alcohol use. Concurrent injection drug use (IDU) exacerbated this negative effect on ART use, adherence, and suppression. Conclusions:Hazardous alcohol use alone and combined with IDU was associated with decreased ART uptake, adherence, and viral suppression. Interventions targeting alcohol use may improve HIV outcomes in individuals with hazardous alcohol use.

Impact of Tobacco Control Interventions on Smoking Initiation, Cessation, and Prevalence: A Systematic Review

Background. Policymakers need estimates of the impact of tobacco control (TC) policies to set priorities and targets for reducing tobacco use. We systematically reviewed the independent effects of TC policies on smoking behavior. Methods. We searched MEDLINE (through January 2012) and EMBASE and other databases through February 2009, looking for studies published after 1989 in any language that assessed the effects of each TC intervention on smoking prevalence, initiation, cessation, or price participation elasticity. Paired reviewers extracted data from studies that isolated the impact of a single TC intervention. Findings. We included 84 studies. The strength of evidence quantifying the independent effect on smoking prevalence was high for increasing tobacco prices and moderate for smoking bans in public places and antitobacco mass media campaigns. Limited direct evidence was available to quantify the effects of health warning labels and bans on advertising and sponsorship. Studies were too heterogeneous to pool effect estimates. Interpretations. We found evidence of an independent effect for several TC policies on smoking prevalence. However, we could not derive precise estimates of the effects across different settings because of variability in the characteristics of the intervention, level of policy enforcement, and underlying tobacco control environment.

A Pilot Study Assessing the Safety and Latency-Reversing Activity of Disulfiram in HIV-1–Infected Adults on Antiretroviral Therapy

BACKGROUND Transcriptionally silent human immunodeficiency virus type 1 (HIV-1) DNA persists in resting memory CD4(+) T cells despite antiretroviral therapy. In a primary cell model, the antialcoholism drug disulfiram has been shown to induce HIV-1 transcription in latently infected resting memory CD4(+) T cells at concentrations achieved in vivo. METHODS We conducted a single-arm pilot study to evaluate whether 500 mg of disulfiram administered daily for 14 days to HIV-1-infected individuals on stable suppressive antiretroviral therapy would result in reversal of HIV-1 latency with a concomitant transient increase in residual viremia or depletion of the latent reservoir in resting memory CD4(+) T cells. RESULTS Disulfiram was safe and well tolerated. There was a high level of subject-to-subject variability in plasma disulfiram levels. The latent reservoir did not change significantly (1.16-fold change; 95% confidence interval [CI], .70- to 1.92-fold; P = .56). During disulfiram administration, residual viremia did not change significantly compared to baseline (1.53-fold; 95% CI, .88- to 2.69-fold; P = .13), although residual viremia was estimated to increase by 1.88-fold compared to baseline during the postdosing period (95% CI, 1.03- to 3.43-fold; P = .04). In a post hoc analysis, a rapid and transient increase in viremia was noted in a subset of individuals (n = 6) with immediate postdose sampling (HIV-1 RNA increase, 2.96-fold; 95% CI, 1.29- to 6.81-fold; P = .01). CONCLUSIONS Administration of disulfiram to patients on antiretroviral therapy does not reduce the size of the latent reservoir. A possible dose-related effect on residual viremia supports future studies assessing the impact of higher doses on HIV-1 production. Disulfiram affects relevant signaling pathways and can be safely administered, supporting future studies of this drug.

A Systematic Review of Randomized Controlled Trials: Web-Based Interventions for Smoking Cessation Among Adolescents, College Students, and Adults

INTRODUCTION Web-based treatments can deliver broad reaching, relatively inexpensive, and clinically tested methods for smoking cessation. We performed a systematic review of randomized controlled trials (RCTs) of smoking cessation to evaluate the efficacy of Web-based interventions in adults, college students, and adolescents. METHODS MEDLINE, EMBASE, The Cochrane Library, CINAHL, and PsycINFO were searched from January 1, 1990 through February 12, 2010 for RCTs examining the efficacy of Web-based smoking cessation programs. Paired reviewers abstracted data on study design, patient characteristics, and outcomes sequentially and did quality assessments independently. RESULTS Twenty-one RCTs met eligibility criteria, with 15 conducted among adults. Among adults, 2 RCTs found that a multicomponent intervention with Web and non-Web-based elements was more efficacious than a self-help manual, and one of 2 RCTs found that Web-based interventions may be more effective than no treatment. Three trials provided insufficient evidence to demonstrate whether Web-based interventions were more efficacious than counseling. By contrast, tailored Web sites in 2 RCTs and greater Web site exposure in 6 of 7 RCTs were associated with higher rates of abstinence. Among college students, evidence supporting use of Web-based interventions was insufficient because the one RCT conducted was also a multicomponent intervention. Five RCTs among adolescents demonstrated mixed results, with insufficient evidence supporting their efficacy. CONCLUSIONS Evidence supporting the use of Web-based interventions for smoking cessation is insufficient to moderate in adults and insufficient in college students and adolescents. These RCTs have, however, elucidated clinical, methodological, and statistical practices that are likely to improve future trial design and treatment delivery.

The impact of illicit drug use and substance abuse treatment on adherence to HAART

Abstract High levels of adherence to highly active antiretroviral therapy (HAART) are essential for virologic suppression and longer survival in patients with HIV. We examined the effects of substance abuse treatment, current versus former substance use, and hazardous/binge drinking on adherence to HAART. During 2003, 659 HIV patients on HAART in primary care were interviewed. Adherence was defined as ≥95% adherence to all antiretroviral medications. Current substance users used illicit drugs and/or hazardous/binge drinking within the past six months, while former users had not used substances for at least six months. Logistic regression analyses of adherence to HAART included demographic, clinical and substance abuse variables. Sixty-seven percent of the sample reported 95% adherence or greater. However, current users (60%) were significantly less likely to be adherent than former (68%) or never users (77%). In multivariate analysis, former users in substance abuse treatment were as adherent to HAART as never users (Adjusted Odds Ratio (AOR)=0.82; p>0.5). In contrast, former users who had not received recent substance abuse treatment were significantly less adherent than never users (AOR=0.61; p=0.05). Current substance users were significantly less adherent than never users, regardless of substance abuse treatment (p<0.01). Substance abuse treatment interacts with current versus former drug use status to affect adherence to HAART. Substance abuse treatment may improve HAART adherence for former substance users.

Co-occurring psychiatric disorders in women with addictions

There is clinically important comorbidity between psychiatric and substance use disorders, particularly in women. Women with affective and anxiety disorders are more likely to present with alcohol or drug abuse/dependence. In turn, substance-abusing women are more likely to experience clinically significant depression and anxiety. Emerging evidence is pointing to an etiological role for anxiety disorders in the development of substance abuse/dependence; however, etiologic evidence is not as clear-cut for major depressive disorder. PTSD appears to be a particularly important factor for alcohol and drug dependence in women who have experienced childhood or adult sexual and or physical abuse. Although pharmacotherapy for affective or anxiety disorders is useful for ameliorating psychiatric symptoms, research is mixed on the effectiveness for improving alcohol- and drug-related outcomes. There is some limited evidence that women-specific services can improve treatment retention, substance use outcomes, and possibly psychosocial functioning compared with traditional mixed-gender programs. However, it is clear that women with co-occurring psychiatric and substance use problems are challenging to engage and retain in care. Physicians providing womens reproductive health services can serve a vital role in the identification and referral of substance-abusing women. Particular attention should be focused on screening and assessment of alcohol and drug use and problem severity among women who have identified psychiatric disorders or who are receiving antidepressant or anxiolytic medications. Recognition and referral for both psychiatric and substance use disorders are critical for long-term health and psychosocial improvement.

Alcohol use among HIV-infected persons in care: results of a multi-site survey

We sought to determine the prevalence of any alcohol use and hazardous alcohol consumption among HIV‐infected individuals engaged in care and to identify factors associated with hazardous alcohol use.

HIV patients with psychiatric disorders are less likely to discontinue HAART

Objective:We examined whether having a psychiatric disorder among HIV-infected individuals is associated with differential rates of discontinuation of HAART and whether the number of mental health visits impact these rates. Design:This longitudinal study (fiscal year: 2000–2005) used discrete time survival analysis to evaluate time to discontinuation of HAART. The predictor variable was presence of a psychiatric diagnosis (serious mental illness versus depressive disorders versus none). Setting:Five United States outpatient HIV sites affiliated with the HIV Research Network. Patients:The sample consisted of 4989 patients. The majority was nonwhite (74.0%) and men (71.3%); 24.8% were diagnosed with a depressive disorder, and 9% were diagnosed with serious mental illness. Main outcome measures:Time to discontinuation of HAART adjusting for demographic factors, injection drug use history, and nadir CD4 cell count. Results:Relative to those with no psychiatric disorders, the hazard probability for discontinuation of HAART was significantly lower in the first and second years among those with SMI [adjusted odds ratio: first year, 0.57 (0.47–0.69); second year, 0.68 (0.52–0.89)] and in the first year among those with depressive disorders [adjusted odds ratio: first year, 0.61 (0.54–0.69)]. The hazard probabilities did not significantly differ among diagnostic groups in subsequent years. Among those with psychiatric diagnoses, those with six or more mental health visits in a year were significantly less likely to discontinue HAART compared with patients with no mental health visits. Conclusion:Individuals with psychiatric disorders were significantly less likely to discontinue HAART in the first and second years of treatment. Mental health visits are associated with decreased risk of discontinuing HAART.

HAART receipt and viral suppression among HIV-infected patients with co-occurring mental illness and illicit drug use

Abstract Mental illness (MI) and illicit drug use (DU) frequently co-occur. We sought to determine the individual and combined effects of MI and DU on highly active antiretroviral therapy (HAART) receipt and HIV-RNA suppression among individuals engaged in HIV care. Using 2004 data from the HIV Research Network (HIVRN), we performed a cross-sectional study of HIV-infected patients followed at seven primary care sites. Outcomes of interest were HAART receipt and virological suppression, defined as an HIV-RNA <400 copies/ml. Independent variables of interest were: (1) MI/DU; (2) DU only; (3) MI only; and (4) Neither. We used chi-squared analysis for comparison of categorical variables, and logistic regression to adjust for age, race, sex, frequency of outpatient visits, years in clinical care, CD4 nadir, and study site. During 2004, 10,284 individuals in the HIVRN were either on HAART or HAART eligible defined as a CD4 cell count ≤350. Nearly half had neither MI nor DU (41%), 22% MI only, 15% DU only, and 22% both MI and DU. In multivariate analysis, co-occurring MI/DU was associated with the lowest odds of HAART receipt (Adjusted Odds Ratio: 0.63 (95% CI: (0.55–0.72]), followed by those with DU only (0.75(0.63–0.87)), compared to those with neither. Among those on HAART, concurrent MI/DU (0.66 (0.58–0.75)), DU only (0.77 (0.67–0.88)), were also associated with a decreased odds of HIV-RNA suppression compared to those with neither. MI only was not associated with a statistically significant decrease in HAART receipt (0.93(0.81–1.07)) or viral suppression (0.93 (0.82–1.05)) compared to those with neither. Post-estimation testing revealed a significant difference between those with MI/DU and DU only, and MI/DU and MI only. Co-occurring MI and DU is associated with lower HAART receipt and viral suppression compared to individuals with either MI or DU or neither. Integrating HIV, substance abuse, and mental healthcare may improve outcomes in this population.