New NIDA-funded research finds increased law enforcement efforts designed to deter drug abuse may instead yield the unintended consequence of an increase in HIV among injection drug users (IDUs).

Scientists from the National Development and Research Institute in New York, New York, examined associations between punitive enforcement in 89 large metropolitan areas and HIV prevalence among IDUs in those areas. The researchers found that increased arrests among drug abusers for the sale and possession of heroin and cocaine, as well as increased police presence and spending for correction systems (prison and probation) were associated with greater HIV prevalence among IDUs living in metropolitan areas. According to the researchers, punitive enforcement was not found to impact drug injection rates, but may instead contribute to riskier injection practices.

A number of other studies suggest that punitive policing policies such as increased arrests and more aggressive police enforcement, which reinforce punishment and stigmatization, may not only encourage risky behaviors such as hurried injection and increased needle sharing, but also may hinder secondary prevention efforts such as drug treatment programs.

What it means: These study findings suggest that punitive enforcement may have little or no deterring effect on injection drug abuse. In fact, increased enforcement may actually yield a high cost—increased HIV prevalence among IDUs, an unanticipated public health effect. Additional research is needed to better understand the mechanisms through which these consequences arise.

Dr. Samuel Friedman and colleagues published this study in the January 2006 issue of AIDS.

NIDA NewsScan, July 24, 2006

Researchers who previously used a mouse model to confirm that cocaine increases the rate at which HIV replicates now have identified pathways and mechanisms responsible for this increase.

Working with genetically engineered mice that have deficient immune systems, Dr. Gayle Baldwin and her colleagues at the David Geffen School of Medicine at UCLA created a practical animal model to study the effects of cocaine on HIV infection.

Based on previous studies suggesting that the immune-suppressing effects of cocaine are mediated through cell-surface proteins called sigma-1 receptors, the UCLA scientists hypothesized that sigma-1 receptors were directly involved in the cocaine/HIV interaction. To test this hypothesis, they treated HIV-positive mice for 10 days with daily injections of saline, cocaine, a sigma-1 blocker called BD1047, or a combination of cocaine and BD1047. Dr. Baldwin and her colleagues observed that the combination of BD1047 and cocaine blocked the impact of cocaine on HIV replication.

What it means: The findings suggest that the dynamic interaction between cocaine and HIV, which ultimately results in enhanced HIV replication, is accomplished in part through activation of sigma-1 receptors. Blocking sigma-1 receptors may diminish the effects of cocaine on HIV replication.

The study was published in the December 2005 issue of the Journal of Leukocyte Biology.

NIDA NewsScan, March 9, 2006

A brief educational intervention can increase HIV/AIDS knowledge among cocaine abusers in outpatient treatment .

Knowledge levels of HIV/AIDS were assessed in 83 adult cocaine abusers in outpatient t reatment through completion of the Kelly and Marsch tests (multiple item, true-false tests designed to measure knowledge in three general areas: high-risk sexual and drug practices, risk-reduction steps, and misconceptions about HIV/AIDS). They then were divided into two groups. Members of the experimental group viewed a 12-minute HIV/AIDS education video and met individually with a counselor to review an educational pamphlet on HIV/AIDS. Members of the control group viewed a 10-minute excerpt of a video on the psychopharmacology of cocaine and met individually with a counselor to review a pamphlet on the psychopharmacology of stimulants. Members of both groups again completed the two tests immediately after meeting with the counselors.

The researchers reported that participants in the experimental group had higher test scores following the intervention than participants in the control group. Scores of participants in the control group also increased after crossing over and receiving the same HIV/AIDS intervention.

What it means: The results suggest that a brief educational intervention can increase HIV/AIDS knowledge among drug abusers. Although education alone may be insufficient to drive behavior changes, a brief intervention such as this may serve as a component of more extensive interventions.

Dr. Sarah Heil and her colleagues at the University of Vermont published their findings in the August 2005 issue of Experimental and Clinical Psychopharmacology.

NIDA NewsScan, March 9, 2006

Nonadherence to antiretroviral therapy may be one of the greatest public health challenges associated with the management of HIV/AIDS. A recent study, supported in part by NIDA, suggests that depression and the inability to tolerate the adverse effects of antiretroviral therapy may influence adherence rates in adolescents with late-stage HIV.

Dr. Debra Murphy, from the University of California at Los Angeles, worked with colleagues in the Adolescent Medicine HIV/AIDS Research Network and examined adherence to highly active antiretroviral therapy (HAART) and the factors associated with adherence in 234 adolescents with HIV, nearly three-fourths of whom were African-American. The team of scientists conducted face-to-face interviews and implemented self-reporting measures to assess adherence to therapy, mental health and coping, substance abuse, and quality of life.

The researchers observed that adolescents in the late stages of HIV were less likely to adhere to antiretroviral therapy when compared with adolescents in the earlier stage of the disease. Additional research findings suggest that among other factors, depression and disease progression may contribute to low adherence by impairing an individual's desire to take medications as directed.

What it means: These study findings underscore the need for improved interventions to help adolescents with HIV adhere to antiretroviral therapy. Future research should target strategies to help adolescents overcome challenges to therapy adherence and provide additional support, such as screening and treatment for depression, in adolescents with advanced HIV.

This study was published in the August 2005 issue of Archives of Pediatrics and Adolescent Medicine.

NIDA NewsScan, October 28, 2005

Minority injection drug users (IDUs) with late-stage human immunodeficiency virus (HIV) frequently face health challenges such as limited access to life-saving treatment and increased risk of death due to drug abuse. Recent study results suggest that highly active antiretroviral therapy (HAART)--a combination of drug therapies designed to slow HIV replication in the body--improves overall survival in minority injection drug abusers with late-stage HIV.

Dr. David Vlahov and researchers from New York Academy of Medicine and the Johns Hopkins Bloomberg School of Public Health recruited 665 HIV-positive, minority injection drug abusers, and followed them for 14 years. The study participants were monitored over the course of two clinical periods--pre-HAART era (1988-1996) and the HAART era (1996-2002). The treatment group received HAART, while patients from the pre-HAART group received the standard clinical treatment for their era--antiretroviral therapy and/or medications to control opportunistic infections (caused by organisms that do not normally cause disease in humans, but can do so in people with damaged immune systems).

Scientists observed fewer deaths among HAART-era patients. Moreover, study participants from this group had higher CD4 levels--a measure of the body's ability to fight infection--and suffered from fewer HIV-related problems such as anemia, sepsis, and pneumonia.

What it means: Although lack or delayed access to treatment is a major issue among minority injection drug abusers, findings from this study suggest that HAART is an effective form of treatment for minority injection drug abusers with late-stage HIV. Further research is necessary to identify additional factors that may influence survival in minority drug abusers with late-stage HIV.

The study appears in the June 2005 issue of the American Journal of Epidemiology.

NIDA NewsScan, October 28, 2005

New study findings suggest drug abuse and HIV prevention and treatment programs should tailor interventions to match the residential status of drug abusers.

Dr. Juan Reyes and colleagues from the Center for Addiction Studies at the Universidad Central del Caribe examined the relationship between homelessness and HIV risk behaviors among 577 injection drug users (IDUs) in Puerto Rico. The study participants were assigned to one of three groups based on their residential status--housed, transitional housed (living with friends, family or others but considering themselves homeless), and on-thestreet homeless (living on the street or in a shelter). Drug-use patterns and HIV risk behaviors were self-reported by questionnaire.

The scientists found that on-the-street homeless IDUs were more likely to practice injection-related HIV risk behaviors such as sharing needles and rinse water, while transitionally housed IDUs were more likely to practice sexual risk behaviors such as exchanging sex for money or drugs. Sex workers have been found to be at very high risk of depression. Consequently, transitionally housed IDUs were more likely to report symptoms of severe depression. Housed IDUs were significantly more likely to use heroin alone than transitionally housed and on-thestreet homeless who were more likely to inject "speedballs," a mixture of heroin and cocaine. Among IDUs, injection of heroin alone (in contrast to injection of speedballs) is generally considered an indicator of a more stable lifestyle and reduced risk of HIV transmission.

What it means: Understanding the factors related to HIV risk behavior among homeless drug abusers is important in explaining why drug abusers continue to engage in HIV risk behaviors. These study findings suggest that homelessness is a risk factor for HIV among IDUs, and that HIV risk behaviors vary according to the residential status of homeless IDUs. These differences may serve as viable intervention points to prevent and reduce drug abuse and HIV risk behaviors among IDUs.

The scientists published this paper in the June 2005 issue of the Journal of Urban Health: Bulletin of the New York Academy of Medicine.

NIDA NewsScan, October 28, 2005

Hispanic adolescents between the ages of 13 and 19 are five times more likely to contract HIV than their non- Hispanic peers. Health-compromising behaviors such as increased drug use and unprotected sex have placed Hispanic adolescents at significant risk for drug abuse and HIV/AIDS.

Although Hispanic adolescents as a group appear to be at increased risk for drug abuse and risky sexual behavior, increasing evidence suggests that they may experience varying levels of risk and protective factors based on their nativity and heritage. For example, data from the Monitoring the Future survey suggest that Cuban youth have significantly higher rates of drug abuse than do Mexican-American or Puerto Rican youth. Additional evidence suggests that U.S.-born Hispanic adolescents experience higher rates of drug abuse, risky sexual behavior, and HIV contraction than foreign-born Hispanics.

Several risk and protective factors have been found to influence health behaviors in Hispanic adolescents. Factors such as parent-adolescent communication about drugs and sex, monitoring of peer relationships by parents, and differences in parent-adolescent acculturation (the adoption of American values, beliefs, and intentions) are believed to vary by nativity and heritage. Subgrouping Hispanic adolescents based on risk and protective factors may serve as the first step in designing well-tailored, flexible interventions for Hispanic adolescents.

What it means: This study suggests that subgrouping Hispanic adolescents by factors influenced by nativity and heritage may result in more effective drug abuse- and HIV-preventive interventions.

Dr. Hilda Pantin and colleagues from the University of Miami published this review in the June 2005 issue of Journal of Urban Health: Bulletin of the New York Academy of Medicine.

NIDA NewsScan, October 28, 2005

Results of a study examining drug abuse practices that influence HIV risk behaviors among incarcerated Puerto Rican drug injectors show that gang affiliations and the length of incarceration significantly increased the odds of injection drug abuse. The study also indicates that some drug abuse characteristics and practices during incarceration differed between the two populations of drug injectors jailed in Puerto Rico and New York City.

Imprisoned Puerto Rican drug injectors who were affiliated with gangs while incarcerated in New York were more than three times as likely as prisoners without gang affiliations to abuse injected drugs during their sentences; in Puerto Rico, gang membership raised the likelihood of abusing injected drugs by seven times. Among prisoners in both locations, the length of the last period of time spent in jail was related to injection drug abuse, with longer incarcerations related to a higher likelihood of drug injection.

New York participants reported more noninjection drug abuse during incarceration, while prisoners in Puerto Rico were more likely to report injecting drugs during incarceration. Among those who injected drugs while incarcerated, about 75 percent of the Puerto Rico sample and about 50 percent of the New York sample reported sharing injectionrelated equipment. The scientists say that these differences in drug use may result from differences in the ease of access to drugs and injecting equipment in prison settings. They also may be affected by inmates' experiences with drugs outside of prison.

What it means: The relationship seen between length of incarceration, gang affiliation, and increased drug abuse during incarceration may provide intervention opportunities that include recruiting and training peer gang leaders in ways to reduce drug abuse and its accompanying negative consequences. The high rates of sharing injection equipment highlight the need to increase efforts to reduce transmission of potentially fatal pathogens among prisoners. More research is needed to better understand the role of gangs in influencing inmate HIV risk behavior.

Dr. Jonny Andia, at the National Center for HIV/STD & TB Prevention at the U.S. Centers for Disease Control and Prevention, and his colleagues published their NIDA-supported findings in the September 2005 issue of The Prison Journal.

NIDA NewsScan, October 28, 2005

Young people in the juvenile justice system who are substance abusers and have major mental disorders--such as depression, mania, or psychosis--are very likely to engage in high-risk practices that greatly increase their chances of acquiring or transmitting HIV.

Dr. Linda A. Teplin, Owen L. Coon Professor of Psychiatry and Behavioral Sciences at Northwestern University's Feinberg School of Medicine, and her colleagues surveyed 800 adolescent males and females who were part of the Northwestern Juvenile Project, a long-term study that tracks 1,829 youth initially arrested between 1995 and 1998 in Chicago.

The scientists observed that the combination of co-occurring major mental disorders and substance abuse resulted in significantly more youth who engaged in high-risk behaviors that included unsafe sex practices. Among youth with co-occurring substance abuse and major mental disorders, almost all were sexually active, about twothirds had multiple partners within the previous 3 months, and more than half had recent, unprotected vaginal sex.

What it means: The study suggests that juvenile detention may be a good place to provide educational interventions to reduce the likelihood of these young people engaging in AIDS-related, high-risk behaviors when they return to the community. The researchers suggest that future investigations look at how the co-occurrence of substance abuse and major mental disorders influence the onset, persistence, discontinuation, and recurrence of HIV/AIDS risk behaviors.

The NIDA-supported study was published in the July 2005 issue of Psychiatric Services.

NIDA NewsScan, September 7, 2005

A study by NIDA Director Dr. Nora D. Volkow, Dr. Gene-Jack Wang, Dr. Linda Chang, and others at NIDA and Brookhaven National Laboratory is the first to show that people with HIV dementia experience dopamine decreases in their brains. Dopamine is a brain chemical associated with pleasure/reward and motivation.

The scientists used the brain scanning technology known as positron emission tomography (PET) to examine the brain chemistry of 15 HIV patients (some of whom had dementia) and 13 HIV-negative volunteers. The researchers found that HIV patients with dementia showed impairment in the brain's system for delivering dopamine to brain cells when compared with control subjects.

Previous research has also shown low dopamine levels in patients with conditions such as Parkinson's disease. HIV dementia is a type of cognitive decline that is more common in the later stages of HIV infection. Symptoms include slowed thinking and expression, difficulty concentrating, and apathy. Movements are slow, and muscle weakness and lack of coordination may be present.

What it means: The findings suggest that HIV patients with dementia may benefit from dopamine enhancing treatments.

The study was published in the September 2004 issue of the journal Brain.

NIDA NewsScan, March 9, 2005

Researchers have developed a mathematical formula to determine the approximate number of urban men at risk for HIV infection by estimating populations of injection drug users and men who have sex with men.

Spencer Lieb of the Florida Department of Health and his colleagues developed a model to estimate the populations of these two groups at high risk for infection with HIV and other diseases. When applied to the Miami, Florida population, the model suggests that 1.4 percent of the total adult population are injection drug users, and almost 10 percent of males aged 18 years or older are having sex with men.

What it means: Knowing the approximate number of injection drug users, as well as how many males are engaging in sex with other men, is useful for assessing current and future capabilities of services designed to reduce the burden of infectious diseases in these at-risk populations.

This NIDA-funded study was published in the September 2004 issue of the Journal of Urban Health.

NIDA NewsScan, March 9, 2005

In a study to assess the effects of age, substance abuse, and neuropsychological function on adherence to antiretroviral treatment among HIV-infected adults, researchers found that patients over the age of 50 who did not abuse drugs and who were free of cognitive impairment had the best adherence rates.

Medication adherence is critically important for HIV infected adults. Studies have shown that good adherence (typically defined as 90-95 percent of doses taken as prescribed) has been linked to improved health status and reduced mortality rates. Patients who do not meticulously adhere to the medication regimen are at risk for a worsening of their HIV disease, including possibly developing strains of the virus that no longer respond to standard HIV medications.

The investigators tracked medication usage over a one-month period in 148 HIV-infected individuals between the ages of 25 and 69, all of whom were on a self-administered antiretroviral regimen. All of the participants were tested for HIV-related cognitive impairment that can include memory problems, difficulties with planning and judgement, and a slowing of the brain’s ability to process information.

Patients over the age of 50 were three times more likely to be properly adherent to their medication schedule— defined as taking 95 percent of the prescribed medications—than were younger patients. Fifty-three percent of the patients over 50 achieved this standard compared to 26 percent of the younger patients.

Testing showed that 83 percent of the patients over the age of 50 who had poor adherence to the medication regimen had some cognitive impairment. Current drug abuse was also associated with poor medication adherence. More than 90 percent of the patients who were current drug abusers failed to adequately adhere to the medication regimen.

What it means: This study documents the importance of assessing cognitive function—particularly among older patients—and drug abuse status when treating HIV-infected adults. In order to maximize compliance, the medication regimen may need to be simplified or assistance may need to be provided for those found to have cognitive impairments.

A research team led by Dr. Charles Hinkin of the David Geffen School of Medicine at UCLA and the VA Greater Los Angeles Health Care System conducted this study with funding provided by the National Institute on Drug Abuse and the National Institute of Mental Health. The findings were published in the December 24, 2002 issue of the journal Neurology and will appear in an upcoming special issue of the journal AIDS.

NIDA NewsScan, May 23, 2003

Naltrexone, a drug used in the treatment of heroin addiction and alcoholism, may increase the effectiveness of the antiretroviral drugs zidovudine (AZT) and indinavir, which are used in the treatment of human immunodeficiency virus (HIV). Naltrexone blocks opioid receptors in the brain preventing the “high” associated with the use of heroin and other opioids. Although the mechanism of the synergistic activity of naltrexone, AZT, and indinavir is unknown, the interactionof naltrexone with opioid receptors may play a role.

Researchers at the Institute for Brain and Immune Disorders, Minneapolis Medical Research Foundation, Hennepin County Medical Center and the University of Minnesota Medical School in Minneapolis conducted an in vitro study with CD4+ T lymphocytes. These cells express opioid receptors and are the primary cells targeted by HIV.

Cells were obtained from the blood of HIV-1-seronegative individuals

and then infected with HIV-1. Cells were incubated for 4 days with AZT, indinavir, naltrexone or combinations of the drugs. HIV-1 p24 antigen levels were measured using an enzyme-linked immunoassay. The researchers found that naltrexone alone had no effect on HIV-1expression by the cells, but when the drug was added to cell cultures containing AZT or indinavir, the antiviral activity of these drugs increased.

What it means: Naltrexone is a novel approach to HIV treatment since it appears to target the cells infected with the virus rather than the virus itself, unlike current treatment medications.

The study, led by Dr. Phillip Peterson, appears in the November 2001 issue of Drug and Alcohol Dependence.

NIDA NewsScan, May 28, 2002

Drug use is now the major risk factor identified in new cases of AIDS in the United States, and a growing number of cases are being reported among the partners of intravenous drug users. In addition, the majority of HIV-infected newborns have mothers who were infected through their own drug use or through sexual activity with a drug user.

The urgency of the problem comes from statistics such as these: One study of street-recruited intravenous drug users and crack cocaine smokers found that among the intravenous drug users, HIV seroprevalence was 12.7 percent, and among crack smokers, HIV seroprevalence was 7.5 percent.

NIDA’s top priorities in dealing with this issue are to understand the behaviors that put drug users at risk for contracting HIV and other infectious diseases; expand outreach to educate populations at risk about the relationship between drug use, AIDS, and other infectious diseases; and fund research on drug use behaviors that lead to the transmission of HIV and other infectious diseases.

Source: NIDA: The Sixth Triennial Report to Congress

HIV Infections Among At-Risk Populations in America’s 96 Largest Cities

* Men and women who are at risk because they have sex with injecting drug users and/or bisexual or gay men. Estimates were compiled in 1996.

One of the most important areas of research involves understanding the behaviors that drug users engage in that put them at risk for contracting life-threatening diseases.

NIDA NewsScan, May 4, 2001

Researchers from the National Development and Research Institutes, Inc., in New York, report on information collected from a multisite HIV prevention program funded by NIDA. Data from interviews with more than 12,000 intravenous drug users (IDUs) from 22 communities were analyzed. Each community site was characterized according to seroprevalence. Ten sites were classified as low (5 percent or less), 8 sites as moderate (6-19 percent), and 4 as high (20 percent or more).

The purpose of the study was to compare HIV-related risk behaviors among IDUs in communities with various seroprevalence rates. The researchers found that drug users living in low seroprevalence communities were more likely to engage in risky injection and sex-related risk behaviors than those living in communities with higher rates of HIV infection.

IDUs living in sites with lower seroprevalence rates had the highest rates of having sex with another IDU during the past 30 days, and reported the highest level (85 percent) of unprotected sexual acts.There were significantly higher rates (about 2.5 times higher) of injection in high seroprevalence communities than in the low or moderate communities, yet more drug users (52 percent) in low seroprevalence communities reported using syringes belonging to other people compared to the other sites.

What it means: These findings, says lead investigator Dr. Sherry Deren, highlight the importance of employing prevention methods in all communities, not just those with the highest rates of HIVinfection.

The study appears in the March 2001 issue of AIDS and Behavior. NIDA NewsScan, May 4, 2001

A research team led by Dr. Mark Williams of the Center for Health Promotion Research and Development at the University of Texas-Houston School of Public Health and the Comprehensive Drug Research Center, Department of Epidemiology and Public Health, at the University of Miami School of Medicine, evaluated an educational HIV risk-reduction intervention implemented in 18 sites in the U.S. and Puerto Rico. More than 7,700 not-in-treatment drug users were targeted. The brief intervention (less than an hour and a half) reducedthe incidence of risky behaviors such as sharing needles, using needles previously used by others, or participating in unprotected sexual activity. Sexual risks were reduced to a greater extent than were risks associated with needle use.

What it means: Brief, educational interventions might be effective in reducing sexual risk behaviors. Needle risk, on the other hand, appears more resistant to change, especially among high frequency cocaine injectors. HIV prevention strategies may be more effective if drug users are matched to an intervention appropriate to their level of needle risk.

The study appears in the March 2001 issue of AIDS and Behavior.

NIDA NewsScan, May 4, 2001

A research team led by Dr. Lisa Metsch from the Comprehensive Drug Research Center at the University of Miami School of Medicine gathered information from current drug users about the practices they used to protect themselves from sexually transmitted diseases, including HIV. Members of the team interviewed 92 active usersof crack and injection drugs to ascertain their level of awareness about HIV infection through sexual contact and to determine if and how they try to avoid infection.

The investigators found that these individuals were aware of their personal risk of contracting HIV/AIDS through sexual contact and that they used a variety of methods to try to protect themselves. “Unfortunately,” Dr. Metsch says, “the actions taken are neither reliable nor sanctioned by health care professionals.” Many of the drug users used their personal assessment of a prospective partner’s cleanliness as an indication of HIV status. An individual judged as being “clean and decent” was perceived to be a safe sexual partner. Some respondents, both men and women, reported using street-bought antibiotics for prophylactic protection

against HIV infection and other sexually transmitted diseases. This practice, say the investigators, not only offers a false sense of security, but also maycontribute to the development of resistant strains of bacteria.

The investigators concluded that even though compliance with effective methods of preventing HIV infection such as abstinence or condom use is low among this drug-using population, these individuals are aware of the risks and are motivated to protect themselves. “The challenge,” Dr. Metsch says, “is to channel this motivation and these self-protective activities into behaviors that are effective in preventing disease transmission.”

What it means: Street myths about how to protect oneself from HIV infection remain among drug users and must be explicitly and directly targeted in health education messages with this population.

The study appears in the March 2001 issue of AIDS and Behavior.

NIDA NewsScan, May 4, 2001