NIDA Research Priorities and Highlights

Role of Research

Drug Use, HIV, and Other Infectious Diseases

There is little doubt today about the connection between drug use and HIV infection, which leads to AIDS. What might be less well appreciated, but just as true, is the strong connection between drug use and other infectious diseases, particularly hepatitis C and tuberculosis. Drug use is now the major risk factor identified in new cases of AIDS, hepatitis C, and tuberculosis in the United States, and a growing number of cases of these infectious diseases are now 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. [37] Therefore, NIDA's top priorities in dealing with this issue continue to be 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 and AIDS as well as other infectious diseases, and fund research on drug use behaviors that lead to the transmission of HIV and other infectious diseases.

Because of the magnitude of this problem, NIDA has established a Center for AIDS and Other Medical Consequences of Drug Abuse. This office is spearheading the Institute's efforts to expand outreach to educate populations at risk about the relationship between drug use and serious infectious diseases. Research has repeatedly shown that even small amounts of education and counseling can help drug users modify those behaviors that put them at risk for acquiring and transmitting HIV, hepatitis, or tuberculosis, even without total abstinence.

With the establishment of this Center, NIDA has the unique opportunity to assess both short- and long-term consequences associated with drug use, many of which are not well understood. In addition to studying infectious diseases, the Center will also assess other health consequences associated with continued exposure to various illicit drugs, such as the respiratory and pulmonary effects of long-term marijuana smoking.

Identifying AIDS Prevention Guidelines Among Drug Users

Recently, NIDA sponsored the first national Research Synthesis Symposium on the Prevention of HIV in Drug Abuse. Discussions centered on approaches to stem the trend that more drug users, and not just those that inject drugs, are becoming infected with HIV and other infectious diseases, such as hepatitis and tuberculosis. Participants identified several HIV prevention principles that would be effective for guiding practitioners and policymakers. For example, the symposium recommended that NIDA implement multiple intervention strategies, such as outreach to active drug users, recruitment and referral to treatment, and risk behavior reduction. The symposium also recommended that such intervention programs should include other elements of comprehensive HIV programs, including the use of sterile injection equipment by those who will not stop drug use and drug use treatments that have been shown to be effective in reducing risk behaviors for injection drug users and in preventing the spread of HIV.

Symposium participants also recommended that any efforts should create opportunities for increased exposure to interventions through booster sessions to reinforce skills and knowledge learned in the initial intervention to increase the effectiveness of interventions. At the same time, successful programs have to recognize that populations at risk for HIV are in various stages of readiness to participate in an intervention and need to be engaged appropriately to maintain them in the interventions by, for example, using motivational techniques, contingency management, cognitive strategies, and/or peer-driven interventions.

Characterizing HIV Risk Behaviors

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. A group of investigators in Seattle, where methamphetamine abuse is a growing problem, have characterized drug use and sexual risk behaviors, social and ecological contexts, and service needs of men who use drugs and have sex with men. Three methods were used for this research: unobtrusive observations, focus group interviews, and individual interviews. Nearly all the men interviewed were HIV positive or had an AIDS diagnosis, and almost all identified themselves as gay or bisexual. A number of common themes emerged from the interviews: Almost all those interviewed injected methamphetamine and used other drugs (e.g., cocaine, MDMA, alcohol, marijuana, heroin); almost all described an intense association between methamphetamine use and sex; and some of the men said they had moved to Seattle specifically because it had a reputation as "the hot spot" for men who use drugs and have sex with men. Although some respondents had completed treatment and remained abstinent from methamphetamine for a period of time, most had also relapsed, explaining that they were unable to enjoy sex without methamphetamine. Abstaining from methamphetamine use was perceived as equivalent to abstaining from sex and therefore made treatment entry and compliance options of last resort. The researchers learned that methamphetamine was sometimes used by respondents to manage the depression they felt from being HIV positive or having AIDS. At the same time, they learned that needle-sharing and unprotected sex were common among the men who reported being HIV seropositive or having AIDS, either because they assumed their injecting drug and sexual partners were also HIV positive or because they would become so intoxicated that they would forget that they were HIV positive. [38]

Another group of researchers in Dayton, Ohio, conducted a study to determine factors that affect the self-reported use of condoms among heterosexual injection drug users and crack cocaine smokers. More than 70 percent of the participants reported that they frequently used drugs when having sex. Persons who were high when they had sex were significantly less likely to use condoms than persons who were not high, but those whose partners got high when having sex were more likely to report condom use. Individuals said that they were less likely to use condoms when they had sex with a main partner. Those who believed it was important to use condoms were more likely to use them, whereas persons who believed condoms reduced sexual pleasure were significantly less likely to use them. A key result of this research is that drug users frequently use substances before and during sex, presenting a significant impediment to employing safer sex techniques that rely on condoms. This study shows that it is also critical that sexual risk-reduction interventions targeting heterosexual users of injection drugs or crack address the widespread practice of simultaneous use of psychoactive drugs. Until such dually focused interventions are in place, access to drug use treatment will continue to play a critical role in preventing the spread of HIV and other sexually transmitted diseases in this population. [39]

Outreach and Intervention Strategies To Reduce Drug Use and AIDS

NIDA-funded research has found that through drug use treatment, prevention, and community-based outreach programs, drug users, even those who refuse treatment, can still change their behaviors to reduce or eliminate drug use or drug-related HIV risk behaviors, such as needle-sharing and unsafe sex practices. Not surprisingly, drug use treatment has been shown to be highly effective in preventing the spread of HIV and other infectious diseases. Unfortunately, for a wide variety of reasons, only a small percentage of those who actually need drug use treatment receive it. To reach the almost 85 percent of chronic drug users who are not in treatment, NIDA has been conducting extensive research to develop community-based outreach interventions to reduce the spread of HIV and other infectious diseases among drug users.

The National AIDS Demonstration Research (NADR) program, for example, was the first multisite research program to deliver and evaluate HIV risk-reduction outreach programs to drug users not in treatment. As part of the interventions, outreach staff indigenous to the selected communities met with intravenous drug users in their natural settings to distribute HIV risk-reduction information and to offer additional counseling and HIV testing. The outreach workers acted as credible messengers, provided risk-reduction materials and education, and arranged for intravenous drug users to receive free, confidential HIV testing and counseling. The ongoing Cooperative Agreement for AIDS Community-Based Outreach/ Intervention Research Program uses similar manualized behavioral interventions to reduce HIV risk-taking and to increase protective behaviors.

As part of an HIV risk-reduction intervention for out-of-treatment drug injectors and crack smokers, one group of investigators has instituted regularly scheduled social gatherings in the Long Beach, California, community as a means to provide social support for modifications of HIV risk behaviors. These events are one component of a 4- to 6-month HIV risk-reduction intervention that also includes HIV counseling and testing, individual and group risk-reduction sessions, "support buddies," and followup by outreach workers. The monthly HIV-focused social gatherings provide peer support and opportunities for social modeling by staff and peers, influence perceived social norms, and increase personal self-efficacy for reducing HIV risks. The socials last about 2 hours and include lunch. They are structured around risk-reduction activities, including highly effective role model panels in which outreach workers, staff with prior drug experience, and clients who have successfully reduced their risk behaviors discuss a variety of topics. Discussions have focused on such issues as the role of social support in modifying risk behaviors, techniques for dealing with relapse and backsliding, and techniques for quitting drugs and maintaining sobriety. Over a 3-year period, 68 percent of the active clients in the intervention program attended at least one social event, and 66 percent attended more than one. At followup, significant differences were found between clients who attended social events and those who did not; the former were more likely to report that the program helped them get off drugs, that they had discussed staying safe from AIDS with friends and family members, that they had asked an outreach worker for assistance with a personal problem, and that they were acquainted with other program participants. The popularity of these social events, which are relatively cost-effective and easily implemented, makes this intervention mechanism especially valuable for maintaining the participation of active drug users in programs of this type. [40]

Another group of researchers compared the efficacy of three HIV and drug use intervention approaches in two midsized towns: an intensive outreach program using indigenous outreach workers providing reinforcement of an HIV risk-reduction program and a low-intensity outreach program combined with a more intensive office-based HIV risk-reduction program, and the NADR intervention discussed above. Each of the enhanced interventions was effective in reducing both drug-related and sexual risks for HIV transmission in active drug users. However, the intensive outreach combined with office intervention and the intensive office intervention without outreach reinforcement each produced significant reductions in sexual risk-taking among active drug users, beyond the reductions found in the standard intervention. One important finding was that intensive outreach had a significant effect on the reduction of sexual risk behaviors of men, but not of women, whereas the more intensive, office-based risk-reduction program significantly related to improvement in the sexual risk behavior of women, but not of men. [41]

In Detroit, investigators compared the effectiveness of two outreach interventions in decreasing the AIDS-related high-risk behaviors of active intravenous drug users and crack cocaine users not in treatment. Half the drug users were assigned to the NADR intervention, and another half to a nursing intervention developed by the investigators. An optional component of this intervention was a weekly "Tuesday Group," when caregivers and clients would meet as a group to discuss client concerns and provide peer support and encouragement. Followup evaluations indicated a dose-response relationship, with participants in the enhanced intervention plus weekly Tuesday Group showing significantly more improvement in reducing their use of drugs and in engaging in unprotected sex, followed by clients in the enhanced only, then by clients in the standard intervention. The findings show the importance of positive peer support and encouragement; group counseling; and consistent, planned opportunities to participate in group sessions for reducing drug use and sexual risk behaviors and for preventing relapse. [42]

The collective findings from NIDA-funded drug use and HIV research suggest that a range of HIV intervention strategies should be introduced early to control the spread of the HIV epidemic. Interventions have to be introduced in a variety of settings to reach at-risk and drug-using populations and to provide them with the means for changing their drug use, needle practices, and sexual behaviors simultaneously. The empirical data reported from the NIDA-funded research studies consistently demonstrate that among those participating in interventions, decreases in the prevalence of risk behaviors and increases in protective behaviors are linked to declines in incident HIV infections. [43]

A comprehensive approach must be taken when one is simultaneously addressing the public health problems of drug use and HIV/AIDS. We know that HIV infections can come from direct transmission of the virus through the sharing of contaminated needles and paraphernalia among injecting drug users (IDUs) or from indirect transmission, such as when a mother who has HIV as a result of her own drug use or through sex with an IDU transmits the virus perinatally to her child. "Sex for crack" is viewed as a major cause of the spread of HIV in the heterosexual population. In addition, we know that that drug use can interfere with judgment about risk-taking behavior and can potentially lead to reduced precautions about having sex and sharing needles and injection paraphernalia.

For these reasons, research shows that needle-exchange programs can play a significant role in a comprehensive approach to reduce HIV infections.

Meta-analytic techniques were used to examine whether participation in syringe-exchange programs leads to individual-level protection against incident HIV infection. HIV incidence data from injecting drug users were combined for three studies: the Syringe Exchange Evaluation, the Vaccine Preparedness Initiative Cohort, and a study involving very-high-seroprevalence cities in the NADR program. HIV incidence among continuing exchangers in the Syringe Exchange Evaluation was 1.58 per 100 person-years at risk; among continuing exchange users in the Vaccine Preparedness Initiative, it was 1.38 per 100 person-years at risk. Incidence among nonusers of the exchange in the Vaccine Preparedness Initiative was 5.26 per 100 person-years at risk and in the NADR cities, 6.23 per 100 person-years at risk. When the data were pooled, not using the syringe exchanges was associated with a hazard ratio of 3.35 for incident HIV infection compared with using the exchanges, indicating that a significant protective effect against HIV infection is associated with participation in syringe-exchange programs. [44]

Findings from a national survey indicate that there has been an expansion in the number of syringe-exchange programs and in the scope of activities since 1994. From 1994 to 1996, there were increases in the number of syringe-exchange programs participating in the surveys and in the numbers of cities and States with syringe-exchange programs. The number of syringes exchanged increased by 75 percent, from 8 to 14 million, between 1994 and 1996. The 10 most active syringe-exchange programs exchanged 500,000 syringes each, approximately 9.4 million of all syringes exchanged. The syringe-exchange program in San Francisco reported exchanging the largest number of syringes in 1996 (1,461,096). All syringe-exchange programs provided intravenous drug users with information about safer injection techniques and/or use of bleach to disinfect injection equipment. Other services included referral of clients to substance use treatment programs, instruction in the use of condoms and dental dams to prevent sexual transmission of HIV and other sexually transmitted diseases, and sexually transmitted disease prevention education. Health services offered on site included HIV counseling and testing, primary health care, tuberculosis skin testing, and screening for sexually transmitted diseases. [45]

Despite our best efforts, many intravenous drug users continue to share syringes. To understand the factors influencing this risky behavior, investigators examined the psychosocial correlates of needle-sharing behavior at two points in time by use of a prospective longitudinal design. The results supported a mediational model, in which personality and peer factors predicted needle-sharing at the beginning of the study, which served as the mediator for needle-sharing at the end of the study. These findings have important implications for intervention; an intervention earlier in the sequence might focus on the personality and friendship networks, whereas an intervention a little later in the developmental sequence would focus on altering needle-sharing behavior. The study also showed that earlier therapeutic interventions focusing on personality disposition, family alienation, or peer group affiliations should reduce the risk of later needle-sharing behavior. [46]

HIV transmission in drug-using populations is preventable. The challenge for prevention researchers is to anticipate the changing dynamics of the co-occurring and interrelated epidemics of drug use and HIV/AIDS and to respond rapidly and effectively to prevent increasing drug use and further spreading of HIV. Early in the epidemic, behavioral interventions were the only means available to prevent HIV infection. Comprehensive programs that include community-based outreach, needle-exchange programs, and drug treatment as HIV prevention remain, in the absence of an AIDS vaccine or a cure, the most cost-effective and reliable strategies for averting new HIV infections.

Drug Use and Other Infectious Diseases

In addition to its role in the spread of AIDS, illicit drug injection is becoming an increasingly more important niche for the transmission of other diseases, such as tuberculosis, that have significant interactions with HIV-related immunosuppression. For many emerging and re-emerging infectious diseases, protecting the health of the community as a whole will depend on protecting the health of intravenous drug users. Therefore, it is important to learn more about the incidence of infectious diseases in the population of those who abuse drugs.

One study of intravenous drug users found that this population is an important reservoir for hepatitis A infection. The data indicated that intravenous drug users are at increased risk for hepatitis A infection but that factors related to low socioeconomic status, such as poor hygiene or overcrowding, contribute more to the occurrence of hepatitis A infection than does injection drug use. The findings from this study indicate the need for hepatitis A vaccination of intravenous drug users and persons at risk for injection drug use. [47]

Another investigation examined the prevalence and correlates of four blood-borne viral infections among illicit drug users with up to 6 years of injecting history, and data were analyzed for hepatitis C, hepatitis B, and HIV. Overall seroprevalence of hepatitis C, hepatitis B, and HIV was 76.9 percent, 65.7 percent, and 20.5 percent, respectively, for those injecting for up to 6 years. Among those injecting for 1 year or less, rates were 64.7 percent for hepatitis C, 49.8 percent for hepatitis B, and 13.9 percent for HIV. The high rates of viral infections among even short-term injectors emphasize the need to target both parenteral and sexual risk-reduction interventions early. [48]

The danger of these viral infections does not stop with the infected individual. A study from the Women and Infant Transmission Study demonstrated that maternal infection with hepatitis C virus is associated with increased HIV maternal-infant transmission. Among women infected with HIV either heterosexually or through injection drug use, 33 percent were found to be infected with hepatitis C, and HIV transmission to infants occurred in 26 percent of the HIV/hepatitis C-infected mothers versus 16 percent of mothers not infected with hepatitis C virus. These data suggest that maternal HCV infection either enhances HIV transmission to the fetus directly or is a marker for another cofactor, such as maternal drug use. Further study is needed to confirm the findings of this study and to determine whether the association represents a biologic effect of hepatitis C infection or is due to a confounding interaction with drug use or other factors. [49]

Tuberculosis and other diseases caused by mycobacteria are growing problems among intravenous drug users. A study of tuberculosis screening at a syringe exchange found a high success rate of consent and return rates for skin-test reading and followup. Tuberculosis screening was conducted during syringe-exchange sessions, at which skin-test reading, tuberculosis education, and HIV testing and counseling were offered. Of the exchange participants approached, 96.5 percent consented to tuberculosis screening. Of these, 91.5 percent returned for their skin-test reading, and 78 percent completed followup tuberculosis screening, including chest radiographs if indicated. Of those who consented to screening, 39 percent were homeless or unstably housed, 35 percent had no health insurance, and 60 percent were not in drug treatment. Data indicate that participating intravenous drug users were aware of their tuberculosis risk, frequently confused tuberculosis infection with active tuberculosis, and were receptive to the availability of tuberculosis services at a syringe exchange. More than 60 percent reported using the syringe exchange two or more times per week, and 52 percent reported using the exchange for 6 months or more, suggesting that the population of intravenous drug users at this syringe exchange may be sufficiently stable to allow administration of twice weekly directly observed therapy for those identified with tuberculosis infection. [50]

In fact, a study of directly observed prophylaxis and treatment among drug users ongoing in a methadone program in New York City found that this setting worked well for providing tuberculosis therapy and for monitoring that patients completed their therapy. This is particularly important because not completing tuberculosis therapy is the main factor for the resurgence of tuberculosis among intravenous drug users. In this study, 88 percent of eligible patients agreed to directly observed therapy, and there was an 80-percent adherence rate to completion. These results indicate that successful adherence to and completion of tuberculosis therapy can be attained by drug users in drug treatment, despite ongoing substance use and lack of material incentives. [51]

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