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Many addicts need to "hit bottom" before they seek help; Pedro was always able to find "a trap door". In 1986, however, at age 29, he found himself at a turning point when he discovered he was infected with the AIDS virus. "At the time I was high on heroin, so I didn't really get it. When the diagnosis finally sank in, it was a shocking wake-up call."
Source: Moyers on Addiction: Close to Home
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Drug abuse not only weakens the immune system but is also linked to risky behaviors like needle sharing and unsafe sex. The combination greatly increases the likelihood of acquiring HIV-AIDS, hepatitis and many other infectious diseases.
| Drugs that can lead to HIV, Hepatitis and other infectious diseases: |
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| Selected Research Findings on HIV and Other Infectious Diseases |
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Incidence and Outcomes of Malignancy in the HAART Era in an Urban Cohort of HIV-infected Individuals
This study sought to investigate trends, patient characteristics, and survival associated with AIDS-defining cancer (ADC) and non-AIDS defining cancer (NADC) in the HAART era. Retrospective analysis was conducted of all incident malignancies occurring in 1996-2005 among 2566 patients in an urban HIV clinic. Clinical profiles of NADC were compared with ADC and the general cohort. Incidence was examined by Poisson analysis. Standardized incidence ratios (SIR) compared cancer risk with that in the general population. Survival was analyzed by Kaplan-Meier and Cox proportional hazards models. Between 1996 and 2005, 138 ADC and 115 NADC were diagnosed. ADC rates decreased from 12.5 to 3.5 cases/1000 person-years (P < 0.001 for trend) while NADC rates increased from 3.9 to 7.1 cases/1000 person-years (P = 0.13 for trend). Incidence of the most common NADC was higher than expected, including cancers of the lung [n = 29; SIR, 5.5; 95% confidence interval (CI), 3.7-8.0], liver (n = 13, SIR, 16.5; 95% CI, 8.8-28.2), anus (n = 10; SIR, 39.0; 95% CI, 18.7-71.7), head and neck (n = 14; SIR, 5.1; 95% CI, 2.8-8.6), and Hodgkin's lymphoma (n = 8; SIR, 9.8; 95% CI, 4.2-19.2). Survival after cancer diagnosis did not differ between ADC and NADC. Advanced age was associated with NADC (P < 0.01 for trend) and increased mortality in ADC (age > or = 50 years adjusted hazard ratio, 2.21; 95% CI, 1.00-4.89). These findings show that rates of ADC decreased while NADC increased within this cohort. Several NADC occurred at rates significantly higher than expected, indicating that screening and suspicion for NADC should increase in care for HIV-infected patients. Long, J., Engels, E., Moore, R., and Gebo, K. Incidence and Outcomes of Malignancy in the HAART Era in an Urban Cohort of HIV-Infected Individuals. AIDS, 22(4), pp. 489-496, 2008.
HCV Synthesis Project: Preliminary Analyses of HCV Prevalence in Relation to Age and Duration of Injection
Early acquisition of hepatitis C virus (HCV) infection appears to affect a substantial proportion of IDUs--between 20 percent and 90 percent. Analyzing the range of HCV prevalence estimates in new injectors may help identify factors that can be modified to reduce HCV transmission. The HCV Synthesis Project is a meta-analysis of studies of HCV epidemiology and prevention in drug users worldwide. In this preliminary analysis, researchers examined data from 127 studies of IDUs that reported HCV prevalence in relation to age or year since onset of drug injection, analyzing heterogeneity and calculating summary statistics where appropriate. Six studies reported gender-specific HCV prevalence rates among young or new injectors; the group mean prevalence was 47 percent for men and 44 percent for women (NS). Group mean age for HCV-negatives was 24.7 years (range 24-28) and 26.1 years (range 21-31) for HCV-positives (n=8 studies). Data were examined from 13 studies that compared HCV prevalence among young injectors to older injectors using 5-year age categories; substantial variation was present within these categories such that measures of central tendency were not calculated. Similarly, among studies reporting HCV prevalence among IDUs in relation to 1-year intervals of duration of injection (<1 year, <2 years, and <3 years), considerable variability was observed. Notably, there were studies in each category that reported prevalence of 70 percent or higher among recent-onset drug injectors. These findings confirm previous studies reporting high risk of acquiring HCV shortly after onset of injection; thus, HCV prevention programmes must emphasize methods to reach new injectors. Future research should (1) report data on time to infection in depth, (2) provide detailed information on study methodology, and (3) characterize the research setting with respect to underlying factors that affect injection practices and networks. This will permit synthesis of a greater number of studies and may lead to the identification of factors that impede HCV transmission. Hagan, H., Des Jarlais, D., Stern, R., Lelutiu-Weinberger, C., Scheinmann, R., Strauss, S., and Flom, P. HCV Synthesis Project: Preliminary Analyses of HCV Prevalence in Relation to Age and Duration of Injection. Int. J. Drug Policy, 18(5), pp. 341-351, 2007.
CD4+ T Cell-dependent Reduction in Hepatitis C Virus-specific Humoral Immune Responses after HIV Infection
Human immunodeficiency virus (HIV) infection adversely affects all stages of hepatitis C virus (HCV) infection, leading to increased rates of viral persistence, higher levels of HCV viremia, and accelerated progression of HCV-related liver disease. These disease interactions may result in part from impairment of B cell function, which is CD4(+) T cell dependent. To determine the effect of HIV infection on B cell function, authors compared HCV antibody levels and specificities in 29 HCV-infected persons before and after they acquired HIV and assessed the temporal correlation of these changes with overall CD4(+) T lymphocyte counts. The pre-HIV infection HCV antibody titer was a predictor of the subsequent titer for all antigens, and decreasing CD4(+) T cell numbers was strongly associated with a decrease in anti-HCV titers for several antigens. CD4(+) T cells counts of <500 cells/mm(3) were significantly associated with lower HCV antibody end-point titers. Higher HCV end-point titers were associated with fewer years from HIV infection and, for Core antigen, current drug use. The authors conclude that HCV-specific antibody production is impaired by HIV infection, and loss of antibody production depends on CD4(+) T cell depletion. However, the decrease in titers is less significant in those who continue to actively inject drugs. Netski, D.M., Mosbruger, T., Astemborski, J., Mehta, S., Thomas, D., and Cox, A. J. Infect. Dis. 195(6), pp. 857-863, 2007.
Hepatitis C Virus Infection is Associated with Insulin Resistance Among Older Adults with or at Risk of HIV Infection
The objectives of this research was to determine the associations of hepatitis C virus (HCV) infection with insulin resistance and abnormal glucose tolerance in a cohort of older adults with or at risk of HIV infection. A cross-sectional study of 267 HIV-infected and 179 at-risk-uninfected adults without a history of diabetes mellitus was employed. HCV antibody assays and RNA levels were performed to assess HCV status. Antiretroviral use, family history of diabetes, sedentary behavior, and sociodemographic data were obtained using standardized interviews. Fasting insulin levels and oral glucose tolerance tests were performed to assess two outcomes, the homeostasis model assessment of insulin resistance and abnormal glucose tolerance [impaired glucose tolerance (IGT) or diabetes]. Of 446 participants, 265 (59%) were HCV seropositive; of these, 199 (75%) had detectable HCV-RNA levels. Insulin resistance was greater among HCV-seropositive compared with seronegative participants, adjusting for body mass index, Hispanic ethnicity, age greater than 55 years, sedentary behavior (watching television > 4h/day), HIV status, HAART, and protease inhibitor (PI) use. Ninety-eight participants (22%) had abnormal glucose tolerance (69 with IGT and 29 with diabetes). Among HIV-infected participants, 25% were on non-PI HAART and 52% were on PI HAART, but HAART and PI use were not associated with insulin resistance or abnormal glucose tolerance. Among obese participants, abnormal glucose tolerance was more common in HCV-seropositive than seronegative individuals, whereas among non-obese participants there was no association. The potential impact of HCV co-infection and obesity on glucose metabolism should be recognized in clinical care, and addressed in future research studies of HIV-infected individuals. Howard, A.A., Lo, Y., Floris-Moore, M., Klein, R.S., Fleischer, N., and Schoenbaum, E.E. AIDS. 21(5), pp. 633-641, 2007.
Co-morbid Medical and Psychiatric Illness and Substance Abuse in HCV-infected and Uninfected Veterans
Comorbidities may affect the decision to treat chronic hepatitis C virus (HCV) infection. The authors undertook this study to determine the prevalence of these conditions in HCV-infected persons compared with HCV-uninfected controls. Demographic and comorbidity data were retrieved for HCV-infected and -uninfected subjects from the VA National Patient Care Database using ICD-9 codes. Logistic regression was used to determine the odds of comorbid conditions in the HCV-infected subjects. HCV-uninfected controls were identified matched on age, race/ethnicity and sex. Authors identified 126,926 HCV-infected subjects and 126,926 controls. The HCV-infected subjects had a higher prevalence of diabetes, anemia, hypertension, chronic obstructive pulmonary disease (COPD)/asthma, cirrhosis, hepatitis B and cancer, but had a lower prevalence of coronary artery disease and stroke. The prevalence of all psychiatric comorbidities and substance abuse was higher in the HCV-infected subjects. In the HCV-infected persons, the odds of being diagnosed with congestive heart failure, diabetes, anemia, hypertension, OPD/asthma, cirrhosis, hepatitis B and cancer were higher, but lower for coronary artery disease and stroke. After adjusting for alcohol and drug abuse and dependence, the odds of psychiatric illness were not higher in the HCV-infected persons. The prevalence and patterns of comorbidities in HCV-infected veterans are different from those in HCV-uninfected controls. The association between HCV and psychiatric diagnoses is at least partly attributable to alcohol and drug abuse and dependence. These factors should be taken into account when evaluating patients for treatment and designing new intervention strategies. Butt, A., Khan, U., McGinnis, K. Et al. J. Viral Hepat.14, pp. 890-896, 2007.
Drug Use and Other Risk Factors Related to Lower Body Mass Index Among HIV-Infected Individuals
Malnutrition is associated with morbidity and mortality in HIV-infected individuals. Little research has been conducted to identify the roles that clinical, illicit drug use and socioeconomic characteristics play in the nutritional status of HIV-infected patients. This cross-sectional analysis included 562 HIV-infected participants enrolled in the Nutrition for Healthy Living study conducted in Boston, MA and Providence, RI. The relationship between body mass index (BMI) and several covariates (type of drug use, demographic, and clinical characteristics) were examined using linear regression. Overall, drug users had a lower BMI than non-drug users. The BMI of cocaine users was 1.4kg/m(2) less than that of patients who did not use any drugs, after adjusting for other covariates (p=0.02). The BMI of participants who were over the age of 55 years was 2.0kg/m(2) less than that of patients under the age of 35, and BMI increased by 0.3kg/m(2) with each 100cells/mm(3) increase in CD4 count. HAART use, adherence to HAART, energy intake, AIDS status, hepatitis B and hepatitis C co-infections, cigarette smoking and depression were not associated with BMI in the final model. In conclusion, BMI was lower in drug users than non-drug users, and was lowest in cocaine users. BMI was also directly associated with CD4 count and inversely related to age more than 55 years old. HIV-infected cocaine users may be at higher risk of developing malnutrition, suggesting the need for anticipatory nutritional support. Quach, L.A., Wanke, C.A., Schmid, C.H., Gorbach, S.L., Mkaya Mwamburi, D., Mayer, K.H., Spiegelman, D., and Tang, A.M. Drug Alcohol Depend. 95(1-2), pp. 30-36. Epub February 19, 2008.
Rapid Fibrosis Progression Among HIV/Hepatitis C Virus-Co-Infected Adults
The objectives of this study were to define the incidence of fibrosis progression among hepatitis C virus (HCV)/HIV-co-infected adults, to assess whether HCV or HIV treatment alters the risk of progression, and to determine the utility of liver biopsy to predict future disease. This prospective cohort evaluated 184 HIV/HCV-co-infected individuals who had at least two liver biopsies (median interval 2.9 years). Biopsies were scored according to the Ishak modified histological activity index scoring system by a single pathologist blind to biopsy sequence. Significant fibrosis progression was defined as an increase of at least two Ishak fibrosis units between the first and second liver biopsy. Logistic regression analysis was used to assess determinants of fibrosis progression. A total of 174 non-cirrhotic patients were eligible; the majority were African-American men undergoing HIV treatment. On initial biopsy, no or minimal fibrosis was identified in 136 patients (77%). Significant fibrosis progression occurred in 41 patients (24%). Measures of HIV disease and its treatment before and after initial biopsy were not significantly different in progressors and non-progressors. Fibrosis progression was not associated with HCV treatment, which was received by 37 patients (21%) but only three sustained HCV-RNA suppression. In adjusted analysis, only an elevated serum aspartate aminotransferase level between biopsies was associated with progression (odd ratio 3.4, 95% confidence interval 1.4-7.9). The authors conclude that over a 3-year interval, significant fibrosis progression can occur in co-infected individuals even if minimal disease was detected on initial biopsy. In this context, factors other than treatment for HIV or HCV modify the risk of fibrosis progression. Sulkowski, M.S., Mehta, S.H., Torbenson, M.S., Higgins, Y., Brinkley, S.C., de Oca, R.M., Moore, R.D., Afdhal, N.H., and Thomas, D.L. AIDS. 21(16), pp. 2209-2216, 2007.
Impact of Hepatitis C Virus Infection and other Comorbidities on Survival in Patients on Dialysis
The impact of hepatitis C virus (HCV) and other comorbid conditions upon survival is not well quantified in patients on dialysis. The authors identified HCV-infected and uninfected persons in the USRDS using claims data in 1997-1998 and followed until September 22, 2002 or death. They used Gray's time-varying coefficients model to examine factors associated with survival. Subjects with a renal transplant were excluded. A total of 5737 HCV-infected and 11 228 HCV-uninfected persons were identified. HCV-infected subjects were younger (mean age 57.8 vs 65.3 years), more likely to be male (57.6%vs 49.6%) and black (54.0%vs 36.4%). They were more likely to have a diagnosis of drug (16.5%vs 4.6%) and alcohol use (14.0%vs 3.1%), and to be human immunodeficiency virus (HIV) co-infected (7.4%vs 1.8%) (all comparisons, P < 0.0005). In an adjusted Gray's time-varying coefficient model, HCV was associated with an increased risk of mortality (P < 0.0005). The hazards were highest at the time of HCV diagnosis and decreased to a stable level 2 years after diagnosis. Other factors associated with increased risk of mortality were (P < 0.0005 unless stated) HIV coinfection; diagnosis of drug use (P = 0.001); coronary artery disease (P = 0.006); stroke; diabetes as the primary cause for renal failure; peripheral vascular disease; depression and presence of anemia. HCV was associated with higher risk of death in patients on dialysis, even after adjusting for concurrent comorbidities. The risk was highest at the time of HCV diagnosis and stabilized over time. Clinical trials of HCV screening and treatment to reduce mortality in this population are warranted. Butt, A.A., Skanderson, M., McGinnis, K.A., Ahuja, T., Bryce, C.L., Barnato, A.E., and Chang, C.C. J. Viral Hepat. 14(10), pp. 688-696, 2007.
Herpes Simplex Virus-2 and HIV among Noninjecting Drug Users in New York City
This study sought to examine the relationship between herpes simplex virus 2 (HSV-2) seroprevalence and HIV seroprevalence among noninjecting heroin and cocaine users in New York City. Four hundred sixty-two noninjecting cocaine and heroin users were recruited from a drug detoxification program in New York City. Smoking crack cocaine, intranasal use of heroin, and intranasal use of cocaine were the most common types of drug use. A structured interview was administered and a serum sample was collected for HIV and HSV testing. HIV prevalence was 19% (95% CI 15%-22%) and HSV-2 seroprevalence was 60% (95% CI 55%-64%). The adjusted risk ratio for the association between HSV-2 and HIV was 1.9 (95% CI 1.21%-2.98%). The relationship between HSV-2 and HIV was particularly strong among females, among whom 86% were HSV-2 seropositive, 23% were HIV seropositive, and all HIV seropositives were also HSV-2 seropositive. The findings suggest that HSV-2 is an important factor in sexual transmission of HIV among noninjecting cocaine and heroin users in New York City, especially among females. The estimated population attributable risk for HIV infection attributable to HSV-2 infection in this sample was 38%, underscoring the importance of programs to manage HSV-2 infection as part of comprehensive HIV prevention for noninjecting drug users. Des Jarlais, D., Hagan, H., Arasteh, K., McKnight, C., Perlman, D., and Friedman, S. Herpes Simplex Virus-2 and HIV among Non Injecting Drug Users in New York City. Sex Transm. Dis., 34(11), pp. 923-927, 2007.
Studies of Drug Actions on Basic HIV Infection and Growth
Several different laboratories have recently published data on drug action on HIV proliferation in various mammalian systems. There are three papers recently published that describe different types of drug action (cannabinoid or opioid) on immune systems; the third paper describes the basic mechanism of action (describing enzyme systems conducting the message) through which these drugs exert their actions. (1) The first paper describes the inhibition of growth of HIV in cell cultures by a synthetic cannabinoid. NIDA researcher Guy Cabral and colleagues observed that this action was mediated primarily through the "peripheral" cannabinoid system. They also observed, unexpectedly, that the more "central" cannabinoid system, also present, exerted the opposite effect. This occurred not through the action of the agonist (the usual mode of "pro" action through a receptor), but via the antagonist. Rock, R.B., Gekker, G., Hu, S., Sheng, W.S., Cabral, G.A., Martin, B.R. and Peteron, P.K. WIN55,212-2-Mediated Inhibition of HIV-1 Expression in Microglial Cells: Involvement of Cannabinoid Receptors. Journal of Neuroimmune Pharmacology, 2, pp. 178-183, 2007. (2) The second study, reported by NIDA research Dr. S.L. Chang focuses on opioid actions. In a special rat model which expresses some HIV viral proteins, these circulating viral entities enhanced the expression of morphine receptor activity through which increased levels of HIV viral growth could occur, especially in humans. This would demonstrate that not only bacterial, but viral growth (including HIV) could be enhanced by opiates administered to humans. Chang, S.L., Beltran, J.A. and Swarup, S. Expression of the Mu Opioid Receptor in the Human Immunodeficiency Virus Type 1 Transgenic Rat Model. Journal of Virology, 81, pp. 8406-8411, 2007. (3) A CXCR4 receptor system resides on immune and neural supporting cells. This receptor plays a pivotal role in immune responses, the pathogenesis of infection such as HIV, and cellular trafficking. However, the signaling mechanisms regulating SDF-driven (the agent acting on the CXCR4 receptor) T cell migration are not well defined. Dr. Burt Sharp and colleagues have focused on understanding how the signal is transmitted from CXCR4 receptor to accomplish its actions: i.e. alter HIV actions and reproduction and have characterized the kinases involved (enzyme systems which are involved in many cellular functions), which are different from those primarily associated with HIV type actions. Shahabi, N.A., McAllen, K. and Sharp, B.M. Stromal Cell-Derived Factor 1-_ (SDF)-Induced Human T Cell Chemotaxis Becomes Phosphoinositide 3-Kinase (PI3K-Independent: Role of PKC-_. Journal of Leukocyte Biology, 83, 2008. (epub ahead of print)
HIV Risk Behavior Among Patients with Co-Occurring Bipolar and Substance Use Disorders: Associations with Mania and Drug Abuse
Bipolar and substance use disorders frequently co-occur, and both are associated with impulsivity, impaired judgment, and risk-taking. In this study, Dr. Meade and colleagues at Harvard Medical School and McLean Hospital, aimed to: (1) describe the rates of HIV sexual and drug risk behaviors among patients with co-occurring bipolar and substance use disorders, (2) test whether acute mania, psychiatric severity, and drug severity independently predict HIV risk, and (3) examine the relationship between specific substance dependencies and sexual risk behaviors. Participants (N=101) were assessed for psychiatric diagnoses, substance abuse, and HIV risk behavior using structured clinical interviews and self-report questionnaires. The majority (75%) were sexually active in the past 6 months and reported high rates of sexual risk behaviors, including unprotected intercourse (69%), multiple partners (39%), sex with prostitutes (24%, men only), and sex trading (10%). In a multivariate linear regression model, recent manic episode, lower psychiatric severity, and greater drug severity were independent predictors of total HIV risk. Cocaine dependence was associated with increased risk of sex trading. Results underscore the importance of HIV prevention for this population. Meade, C.S., Graff, F.S., Griffin, M.L., and Weiss, R.D. HIV Risk Behavior Among Patients with Co-occurring Bipolar and Substance Use Disorders: Associations with Mania and Drug Abuse. Drug and Alcohol Dependence, 92(1-3), pp. 296-300, 2008.
| Relevant NIDA Meetings |
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Allison Chausmer (NIDA), Diane Lawrence (NIDA), Cathy Backinger (NCI), Gerald Sharp (NIAID), Xingzhu Liu (FIC), and Francisco Sy (NCMHD) organized a workshop on Current Issues in Cigarette Smoking and HIV/AIDS, October 2007, Natcher Conference Center, NIH. The purpose of this workshop was to highlight understudied issues related to cigarette smoking in HIV-infected persons. This workshop featured 13 presentations followed by breakout groups discussing opportunities for accelerating scientific breakthroughs and a list of priority research areas. As a result of the meeting, A special, peer-reviewed supplement of AIDS Education and Prevention: An Interdisciplinary Journal is anticipated to be published in March/April 2008. Submissions will be by invitation only and will be based on several areas of interest that follow directly from this workshop, including:
- Biological and behavioral foundation of the relationship between tobacco smoking and HIV/AIDS
- Interactions between smoking, HIV/AIDS and other diseases or infections
- Interactions between smoking and HAART
- Smoking cessation strategies for smokers with HIV/AIDS
- Global implications of tobacco use and HIV/AIDS
Sponsored by NIDA, in collaboration with other NIH Institutes and the Centers for Disease Control and Prevention, 2007 Drug Abuse and Risky Behaviors: The Evolving Dynamics of HIV/AIDS meeting, held May 8-9, 2007, highlighted the drug abuse-HIV link. This meeting was held in response to deep concerns about the continuing spread of HIV/AIDS in the United States and abroad and invited the scientific community to engage in a dialog to further our understanding of the problem and how it is changing. To address this significant public health threat, research has focused on the multiple ways that HIV/AIDS and drug abuse are entwined, including: risk behaviors associated with both injection and non-injection drug abuse; how drugs of abuse alter brain function and impair decision making; and HIV prevention and treatment strategies for diverse groups. This conference provided a broad understanding of the multiple ways drug abuse and addiction impact HIV/AIDS and how research can inform public health policy. Presentations focused on successes, research challenges, and opportunities for addressing the evolving HIV/AIDS pandemic. Collaborators included: the National Institute on Alcohol Abuse and Alcoholism, the National Institute of Allergy and Infectious Diseases, the National Institute of Child Health and Human Development, the National Institute of Mental Health, and the Centers for Disease Control and Prevention.
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