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Director's Report to the National Advisory Council on Drug Abuse - May, 2005



Research Findings - Research on Medical Consequences of Drug Abuse

Integration of Motivational Interviewing and Cognitive Behavioral Therapy to Improve HIV Medication Adherence and Reduce Substance Use Among HIV Positive Men and Women: Results of a Pilot Project

In this pilot study a combined motivational interviewing and cognitive behavioral therapy intervention was used to increase adherence to highly active antiretroviral therapy and reduce substance use in HIV infected adults. The aims of this study were 1) to confirm the ability to recruit HIV+ substance abusers taking antiretroviral medications; 2) to demonstrate the ability to retain participants over the course of the eight-session intervention; and 3) to examine changes in substance use and HAART adherence from pretreatment to posttreatment. Twelve HIV+ adults with a substance use disorder participated in the 8-week intervention, which consisted of weekly individual sessions with a trained therapist. Preliminary results showed that there was a significant reduction in substance use during treatment. Retention for all 8 sessions was 73.3%. No statistically significant differences were found for changes in HIV medication adherence, but the trends suggest the potential for positive results with a larger sample. This pilot study demonstrated the feasibility and acceptability of the treatment. However, additional research is needed to determine if this may be an effective intervention to improve HIV medication adherence in HIV + drug abusers. Parsons, J.T., Rosof, E., Punzalan, J.C. and Di Maria, L. AIDS Patient Care STDS. 19(1), pp. 31-39, January 2005.

Patient-Clinician Relationships and Treatment System Effects on HIV Medication Adherence

The aims of this study were to determine the impact of the patient-clinician relationship on patient adherence to HIV medication, to identify which aspects of the patient-clinician and the treatment system influenced adherence, and to determine which of these variables remained important when the impact of mental distress and substance abuse was considered. This was a cross-sectional study using a sample of 120 HIV+ clinic patients. The Primary Care Assessment Survey (PCAS) assessed the clinician-patient relationship and the treatment system. The Composite International Diagnostic Inventory-Short Form ( CIDI-SF) screened for mental disorders, and the Brief Substance Abuse History Form measured recent and remote substance use. Patient adherence was assessed using five markers including 3 interview-elicited self-reports, 1 medical chart review, and 1 summary score. Logistic regression analyses identified independent predictors of each adherence behavior. PCAS scores contributed to all five models, and their effects persisted when mental distress and substance abuse were considered. Adherence behaviors are explained by a variety of factors and should be assessed using multiple methods. Further research is needed to illuminate the mechanisms of action of the clinician-patient relationship on adherence to HIV medication. Ingersoll, K.S. and Heckman, C.J. AIDS and Behavior 9(1), pp. 89-101, March 2005.

Human Immunodeficiency Virus 1 Infection, Cocaine, and Coronary Calcification

Although cocaine use and human immunodeficiency virus (HIV) infection have been linked with clinical cardiovascular disease, the effects of cocaine use and HIV infection, especially the combination of the 2, on subclinical disease have rarely been reported. The objective of this study was to evaluate whether cocaine use alone, HIV infection alone, or a combination of the 2 is associated with coronary calcification, a marker of subclinical atherosclerosis. Between May 20, 2000, and March 31, 2003, 224 African-American study participants from Baltimore were enrolled in an observational study of subclinical atherosclerosis as related to HIV and cocaine use. Interviews about sociodemographic characteristics and drug use behaviors, clinical examinations, echocardiographic examinations, lipid profiles, high-sensitivity C-reactive protein tests, and computed tomographic scans for coronary calcium were performed. Although the overall investigation is a cohort study, the data presented herein are cross sectional only. Results indicated that the highest proportion (37.6%) of presence of coronary calcification was in the HIV-positive and cocaine-positive group, followed by 29.8% in the HIV-negative and cocaine-positive group, 28.6% in the HIV-positive and cocaine-negative group, and 18.8% in the HIV-negative and cocaine-negative group. Univariate analysis showed that HIV, cocaine use, and both were associated with a higher number of lesions, calcified area, volume, and calcium score. In multiple regression analysis with adjustment for age, body mass index, low-density lipoprotein cholesterol level, triglyceride level, mean corpuscular volume, and systolic blood pressure, HIV, cocaine use, and both were independently associated with coronary calcification. These results suggest that HIV infection alone, cocaine use alone, or the 2 combined may contribute to early subclinical atherosclerotic cardiovascular disease. Lai, S., Lima, J.A., Lai, H., Vlahov, D., Celentano, D., Tong, W., Bartlett, J.G., Margolick, J. and Fishman, E.K. Human Immunodeficiency Virus 1 Infection, Cocaine, and Coronary Calcification. Arch Intern Med. 165, pp. 690-695, March 28, 2005.

Long-Term Cocaine Use is Related to Cardiac Diastolic Dysfunction in an African-American Population in Baltimore, Maryland

Only limited studies have been done on the effects of long-term cocaine use on the human heart, and the results remain controversial. In this study, the authors examined and compared the diastolic function of non-cocaine users and chronic cocaine users to reveal the impact of long-term cocaine use on the human heart. Two-dimensional echocardiogram and pulsed Doppler transmitral blood flow pattern were obtained from 138 recruited study participants with different cocaine histories. The indices of cardiac structure and function were measured from the echocardiogram of each participant. Student's t-test was used to compare the average echocardiographic measurements of the non-cocaine user group and the cocaine user group. Multivariate regression analysis was deployed to eliminate the effects of age, gender, blood pressure, and HIV infection on the functional measurements of the two groups. Results indicated that the cocaine user group had a significantly longer average deceleration time than did the non-cocaine user group (208.1 38.2 vs. 167.5 39.1 ms, P< 0.001). A linear association existed between the deceleration time and the log-transformed duration of cocaine use (beta=0.00351, S.E.=0.00104, P=0.001). Cocaine users in this study were approximately five times more likely to have an elongated deceleration time (>200 ms) than were non-users (OR, 4.799; 95% CI, 1.000-23.044; P=0.05). No significant differences were observed in the other measured diastolic functional parameters, such as isovolumic ventricular relaxation time, E wave, A wave, and E/A ratio. Authors conclude that Long-term cocaine use is linked to decline in diastolic function. Tong, W., Lima, J.A., Meng, Q., Flynn, E. and Lai, S. Long-term Cocaine Use is Related to Cardiac Diastolic Dysfunction in an African-American Population in Baltimore, Maryland. Int J Cardiol. 97(1), pp. 25-28, October 2004.

Sexual Risk Among Injection Drug Users Recruited from Syringe Exchange Programs in California

The objective of this study was to examine correlates of sexual risk among injection drug users (IDUs). A total of 1445 IDUs were recruited from California syringe exchange programs. Consistent condom use was independently related to being HIV-positive, having multiple sex partners, not having a steady partner, not sharing syringes, and not injecting amphetamines for men; and engaging in sex work, not sharing syringes, and not having a steady partner for women. Having multiple recent sexual partnerships that included a steady partner was related to engaging in sex work, speedball injection, and amphetamine use among men; and younger age, having had a sexually transmitted disease (STD), engaging in sex work, and using alcohol among women. Having heterosexual anal sex was related to having had an STD, having multiple sexual partners, using amphetamines, and syringe-sharing for men; and younger age and amphetamine use for women. Authors conclude that comprehensive prevention interventions addressing multiple sexual and injection risk behaviors are needed for IDUs. Bogart, L.M., Kral, A.H., Scott, A., Anderson, R., Flynn, N., Gilbert, M.L. and Bluthenthal, R.N. Sexual Risk Among Injection Drug Users Recruited from Syringe Exchange Programs in California. Sex Transm Dis. 32(1), pp. 27-34, January 2005.

Injection Risk Behaviors Among Clients of Syringe Exchange Programs With Different Syringe Dispensation Policies

While there have been numerous papers published in the medical, social, and epidemiologic literature about the effectiveness of syringe exchange programs (SEPs), few papers identify operational characteristics of the SEPs they study or assess which of those characteristics are associated with optimal HIV risk reduction among clients. The objective of this study was to examine whether different syringe dispensation policies were associated with client-level injection-related HIV risk. Injection drug users (IDUs) were recruited at 23 SEPs in California in 2001 (n = 531). SEPs were classified by their executive directors as to whether they provided a strict one-for-one syringe exchange, gave a few extra syringes above the one-for-one exchange, or distributed the amount of syringes based upon need as opposed to how many syringes were turned in by the clients. Injection-related risk was compared by SEP program type. In multivariate logistic regression analysis, clients of distribution-based programs had lower odds of reusing syringes (adjusted odds ratio = 0.43; 95% CI = 0.27, 0.71) when adjusting for confounding variables. There were no statistical differences with regards to distributive or receptive syringe sharing by dispensation policy. It is concluded that SEPs that base syringe dispensation policy upon need may facilitate reductions in reuse of syringes. Kral, A.H., Anderson, R., Flynn, N.M. and Bluthenthal, R.N. Injection Risk Behaviors Among Clients of Syringe Exchange Programs With Different Syringe Dispensation Policies. J Acquir Immune Defic Syndr. 37(2) pp. 1307-1312, October 1, 2004.

Injection Drug Use and Crack Cocaine Smoking: Independent and Dual Risk Behaviors for HIV Infection

Previous studies have examined the practices of injecting drugs or smoking crack cocaine as high-risk, but independent, factors for HIV transmission. To explore the independent and dual risks of injection practices and crack smoking, this study examined HIV seroprevalence rates among distinct drug user groups, based on patterns of daily administration. A sample of 3,555 drug users and neighborhood controls in urban Miami, FL and rural Belle Glade and Immokalee, FL were partitioned into four mutually-exclusive groups: 1) injection drug users (IDUs); 2) crack-cocaine smokers; 3) dual users who both smoked crack and injected drugs; and 4) non-drug-user controls. HIV seroprevalence rates were 45.1% for IDUs, 30.5% for dual users, 20.1% for crack smokers and 7.3% for controls. Multivariate logistic regression analysis found that when compared with controls odds ratios for HIV seropositivity were 9.81 for IDUs, 5.27 for dual users, and 2.24 for crack smokers. These findings provide evidence of: 1) behavioral and structural co-factors that influence HIV exposure patterns among drug users; and 2) the substantially higher risk of HIV infection among IDUs compared with other drug users. Intervention strategies must be tailored for the specific drug use subpopulations to optimize efficacy. McCoy, C.B., Lai, S., Metsch, L.R., Messiah, S.E. and Zhao, W. Injection Drug Use and Crack Cocaine Smoking: Independent and Dual Risk Dehaviors for HIV Infection. Ann Epidemiol. 14(8), pp. 535-542, September 2004.

Drug Abuse and Neuropathogenesis of HIV Infection: Role of DC-SIGN and IDO

Dendritic cells are the critical mediators of various immune responses and are the first line of defense against any infection including HIV. They play a major role in harboring HIV and the subsequent infection of T cells and passage of virus through the blood-brain barrier (BBB). The recently discovered DC-specific, CD4-independent HIV attachment receptor, DC-SIGN, and T-cell suppressing factor, indolamine 2,3-dioxygenase (IDO), are known to play a critical role in the immuno-neuropathogenesis of HIV infection. Since brain microvascular cells (BMVEC) express dendritic cell (DC)-specific C type ICAM-3 grabbing nonintegrin (DC-SIGN), it is possible that DC-SIGN may play a critical role in human immunodeficiency virus-type 1 (HIV-1) infection and migration of infected DC across BBB. Matrix metalloproteinases (MMPs) are proteolytic enzymes known to be responsible for maintenance, turnover and integrity of extracellular matrix. Results show that cocaine upregulates IDO and DC-SIGN expression by DC. Further, cocaine upregulates DC-SIGN and MMPs in BMVEC supporting the hypothesis that cocaine causes membrane permeability facilitating endothelial transmigration of infected DC into the CNS. Targeting DC-SIGN and IDO with specific monoclonal antibodies, inexpensive synthetic antagonists, antisense oligonucleotides and siRNA may lead to the development of novel treatment strategies particularly in high-risk populations such as cocaine users. Nair, M.P., Schwartz, S.A., Mahajan, S.D., Tsiao, C., Chawda, R.P., Whitney, R., Don Sykes, B.B. and Hewitt, R. Drug Abuse and Neuropathogenesis of HIV Infection: Role of DC-SIGN and IDO. J Neuroimmunol. 57(1-2), pp. 56-60, December 2004.

Association of Drug Abuse with Inhibition of HIV-1 Immune Responses: Studies with Long-term of HIV-1 Non-progressors

Recreational drug use has been proposed to affect the course of human immunodeficiency virus (HIV) infections. To investigate the effects of substance abuse on HIV infections, the authors compared virus-specific cytotoxic T lymphocyte (CTL) responses and the expression of IL-16, TGF-beta1, and CXCR4 in three different cohorts of HIV-infected patients: (1) long-term nonprogressors (LT-NPs) of HIV infection who do not use recreational drugs; (2) nondrug using normal progressors (NPs), and (3) drug using NPs. Results show that LT-NPs manifest increased CTL activity and IL-16 expression and decreased expression of TGF-beta1 and CXCR4 compared to NPs, regardless of recreational drug usage. Furthermore, drugs using NPs showed significantly lower levels of CTL and IL-16 expression and increased TGF-beta1 and CXCR4 expression compared to nondrugs using NPs. Results suggest that recreational drug use may reduce CTL and IL-16 expression and increase the expression of TGF-beta1 and CXCR4, all of which may facilitate progression of HIV infections Nair, M.P., Mahajan, S., Hewitt, R., Whitney, Z.R. and Schwartz, S.A. Association of Drug Abuse with Inhibition of HIV-1 Immune Responses: Studies with Long-term of HIV-1 Nonprogressors. J Neuroimmunol. 147(1-2), pp. 21-25, February 2004.

Body Habitus in a Cohort of HIV-seropositive and HIV-seronegative Injection Drug Users

Authors determined anthropometric measurements (including height, weight, circumferences, and skinfolds) and self-reported symptoms related to body habitus changes in 324 HIV-seropositive and HIV-seronegative inner city injection drug users (IDUs) who participated in a substudy from the ALIVE (AIDS Linked to Intravenous Experiences) cohort. Participants who reported lipoatrophy in body parts had consistently lower anthropometric measurements and those reporting adiposity had correspondingly higher anthropometric measurements than participants who did not report these changes. Peripheral lipoatrophy was more common among all HIV-seropositive than HIV-seronegative participants, however, it was not associated with highly active antiretroviral therapy (HAART) (39% HIV-seronegatives; 58% HIV-seropositive not receiving HIV treatment [No Tx]; 49% HAART, p = 0.04). Central adiposity was more common among HAART (52%) than No Tx (26.6%) and HIV-seronegative (42%) participants (p = 0.001). However, waist circumference, while somewhat higher among HAART than No Tx participants, did not differ significantly from HIV-seronegative participants (85.2 cm HIV-seronegatives; 83.3 cm No Tx; 85.8 cm HAART). A large proportion of those who reported peripheral lipoatrophy also reported central lipoatrophy (76.9% HIV-seronegatives; 69.6% No Tx; 66.2% HAART). A large proportion of those who reported central adiposity also reported adiposity of the peripheral sites (88.1% HIV seronegatives; 66.7% No Tx; 74.3% HAART). The combination of lipoatrophy and adiposity was associated with HAART treatment (6% HIV-seronegatives; 3% No Tx; 16% HAART, p = 0.002), but may be driven by the association with adiposity. These data suggest validity of self-reports for body habitus changes among injection drug users. Smit, E., Semba, R.D., Pilibosian, E., Vlahov, D., Tun, W., Purvis, L. and Tang, A.M. Body Habitus in a Cohort of HIV-seropositive and HIV-seronegative Injection Drug Users. AIDS Patient Care STDS. 19(1), pp. 19-30, January 2005.

The Effect of Drug Abuse on Body Mass Index in Hispanics with and without HIV Infection

There is a widely held view that the lower weight of drug abusers is attributable to diet. However, many studies on the dietary intake of drug abusers have failed to find energy insufficiency, while non-dietary factors have rarely been examined. The purpose of this study was to examine non-dietary factors that could affect the weight of drug abusers with and without HIV infection. Participants were recruited into one of three groups: HIV-positive drug abusers (n=85), HIV-negative drug abusers (n=102) and HIV-positive persons who do not use drugs ('non-drug abusers', n=98). Non-dietary factors influencing weight included infection with HIV and/or hepatitis, malabsorption, resting energy expenditure and physical activity. The baseline data was from a prospective cohort study of the role of drug abuse in HIV/AIDS weight loss conducted in Boston, USA. The first 286 participants to enroll in the study served as subjects. HIV-positive drug abusers had a body mass index (BMI) that was significantly lower than that of HIV-positive non-drug abusers. The differences in weight were principally differences in fat. In the men, cocaine abuse, either alone or mixed with opiates, was associated with lower BMI, while strict opiate abuse was not. Infection with HIV or hepatitis, intestinal malabsorption, resting energy expenditure and physical activity, as measured in this study, did not explain the observed differences in weight and BMI. Drug abuse, and especially cocaine abuse, was associated with lower weight in men. However, infection with HIV and/or hepatitis, malabsorption and resting energy expenditure do not explain these findings. Forrester, J.E., Tucker, K.L. and Gorbach, S.L. The Effect of Drug Abuse on Body Mass Index in Hispanics with and without HIV Infection. Public Health Nutr. 8(1), pp. 61-68, February 2005.

Dietary Intake and Body Mass Index in HIV-positive and HIV-negative Drug Abusers of Hispanic Ethnicity

Malnutrition in drug abusers has been attributed to poor diet. However, previous studies are conflicting. Many studies have not considered possible concurrent HIV disease. The purpose of this study was to determine the relationship between drug abuse and dietary intake in Hispanic Americans with and without HIV infection. Dietary intake was measured using 3-day food records and 24-hour dietary recalls in three groups: HIV-positive drug abusers, HIV-negative drug abusers and HIV-positive persons who do not use drugs ('non-drug abusers'). The baseline data was from a prospective cohort study of the role of drug abuse in HIV/AIDS weight loss and malnutrition conducted in Boston, Massachusetts. The first 284 participants to enroll in the study served as subjects. HIV-positive drug abusers had a body mass index (BMI) that was significantly lower than that of HIV-positive non-drug abusers. Reported energy, fat and fiber intakes did not differ between groups. All groups had median reported intakes of vitamin A, vitamin B6, vitamin B12, selenium and zinc that were in excess of the dietary reference values (DRI). Intakes of alpha-tocopherol were below the DRI, but did not differ from intakes of the general US population. However, increasing levels of drug abuse were associated with lower reported intakes of vitamin B6, vitamin B12, selenium and zinc. Overall, this study does not support the notion that dietary intake can explain the lower BMI of HIV-positive drug abusers. Further studies examining non-dietary determinants of nutritional status in drug abusers are warranted. Forrester, J.E., Tucker, K.L. and Gorbach, S.L. Dietary Intake and Body Mass Index in HIV-positive and HIV-negative Drug Abusers of Hispanic Ethnicity. Public Health Nutr. 7(7), pp. 863-870, October 2004.

HIV Prevalence and Risk Behaviors Among Men Who Have Sex with Men and Inject Drugs in San Francisco

The dual risks of male-to-male sex and drug injection have put men who have sex with men and inject drugs (MSM-IDU) at the forefront of the HIV epidemic, with the highest rates of infection among any risk group in the United States. This study analyzes data collected from 357 MSM-IDU in San Francisco between 1998 and 2002 to examine how risk behaviors differ by HIV serostatus and self-identified sexual orientation and to assess medical and social service utilization among HIV-positive MSM-IDU. Twenty-eight percent of the sample tested HIV antibody positive. There was little difference in risk behaviors between HIV-negative and HIV-positive MSM-IDU. Thirty percent of HIV-positive MSM-IDU reported distributive syringe sharing, compared to 40% of HIV negatives. Among MSM-IDU who reported anal intercourse in the past 6 months, 70% of positives and 66% of HIV negatives reported unprotected anal intercourse. HIV status varied greatly by self-identified sexual orientation: 46% among gay, 24% among bisexual, and 14% among heterosexual MSM-IDU. Heterosexual MSM-IDU were more likely than other MSM-IDU to be homeless and to trade sex for money or drugs. Gay MSM-IDU were more likely to have anal intercourse. Bisexual MSM-IDU were as likely as heterosexual MSM-IDU to have sex with women and as likely as gay-identified MSM-IDU to have anal intercourse. Among MSM-IDU who were HIV positive, 15% were currently on antiretroviral therapy and 18% were currently in drug treatment, and 87% reported using a syringe exchange program in the past 6 months. These findings have implications for the development of HIV interventions that target the diverse MSM-IDU population. Kral A.H., Lorvick, J., Ciccarone, D., Wenger, L., Gee, L., Martinez, A. and Edlin, B.R. HIV Prevalence and Risk Behaviors Among Men Who Have Sex with Men and Inject Drugs in San Francisco. J Urban Health. 82(1 Suppl 1):i43-i50, March 2005. Epub February 28, 2005.

Early Puberty in Girls: The Case of Premature Adrenarche

In this article authors examine the issue of early puberty in girls. First, a brief overview of normal pubertal development is provided, including the two endocrine components of puberty: gonadarche and adrenarche. Second, authors critically discuss the controversy regarding whether puberty truly is occurring earlier in girls. Third, they emphasize one type of early puberty, the case of premature adrenarche (PA). PA is used to illustrate the importance of identifying types of early puberty, evaluating the types to determine causality, determining whether follow-up of early puberty is necessary, and showing the potential ramifications of ignoring this variation in pubertal development. Findings from a pilot study comparing PA and on-time puberty children are used to show the importance of determining whether early puberty is normal in all cases. Dorn, L.D. and Rotenstein, D. Early Puberty in Girls: The Case of Premature Adrenarche. Womens Health Issues 14(6), pp. 177-183, November-December 2004.

Vitamin D Deficiency and Seasonal Variation in an Adult South Florida Population

Hypovitaminosis D is associated with impaired neuromuscular function, bone loss, and fractures. If a person is not taking a vitamin supplement, sun exposure is often the greatest source of vitamin D. Thus, vitamin D deficiency is not uncommon in the winter, particularly in northern latitudes. The goal of this study was to establish the prevalence of vitamin D deficiency in south Florida (U.S.), a region of year-round sunny weather. At the end of the winter, 212 men and women attending an internal medicine clinic at a local county hospital were enrolled for measurements of 25-hydroxyvitamin D [25(OH)D], 1,25-dihydroxyvitamin D, and PTH; 99 participants returned at the end of summer. The mean (sd) winter 25(OH)D concentration was 24.9 8.7 ng/ml (62.3 21.8 nmol/liter) in men and 22.4 8.2 ng/ml (56.0 20.5 nmol/liter) in women. In winter, the prevalence of hypovitaminosis D, defined as 25(OH)D less than 20 ng/ml (50 nmol/liter), was 38% and 40% in men and women, respectively. In the 99 subjects who returned for the end of summer visit, the mean 25(OH)D concentration was 31.0 11.0 ng/ml (77.5 27.5 nmol/liter) in men and 25.0 9.4 ng/ml (62.5 23.5 nmol/liter) in women. Seasonal variation represented a 14% summer increase in 25(OH)D concentrations in men and a 13% increase in women, both of which were statistically significant. The prevalence of hypovitaminosis D is considerable even in southern latitudes and should be taken into account in the evaluation of postmenopausal and male osteoporosis. Levis, S., Gomez, A., Jimenez, C., Veras, L., Ma, F., Lai, S., Hollis, B. and Roos, B.A. Vitamin D Deficiency and Seasonal Variation in an Adult South Florida Population. J Clin Endocrinol Metab. 90(3), pp. 1557-1562, March 2005.


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