## National Institute on Drug Abuse

**FY08 Priorities**

**Title of Project: Drug Abuse and HIV Prevention**

**Area of Emphasis: 5**

**Plan Objective(s): 1A, 1B, 5A, 5C, 5D, 7A, 7B**

**SIC: M50%, I20%,**

**Mechanism: RPGs/Centers/Other**

**New or Expansion: CR/EXP/NEW**

**Co-Funding: possibly NIAID, NIMH, NIAAA, NICHD**

**Roadmap Area (if applicable):**

**Project Descriptions:**

These priorities include new, continuing, and expanded research to
prevent the intertwined HIV and drug abuse epidemics and their
associated health and social consequences. Of critical interest are
studies that address both the acquisition (i.e., primary prevention) and
transmission (i.e., secondary prevention) of HIV among drug abusers.
Over the past two decades NIDA's prevention research efforts (e.g.,
outreach, drug abuse treatment) have focused on injection drug use,
which has led to significant decreases in the number of new AIDS cases
associated with this transmission category. Given the sustained
importance of sexual transmission in new HIV infections, new HIV
prevention research questions of great public health relevance have
emerged. That is, "How much of a role does non-injection drug use play
in facilitating sexual transmission of HIV?" and "What are the
mechanisms involved?" and "What strategies are needed to prevent
drug-related sexual acquisition and transmission of HIV?" NIDA's ongoing
secondary HIV prevention research priorities also include the
development and testing of interventions to improve and maintain
adherence to ART and OI treatment medications among drug users,
including those in high risk groups and environments such as criminal
justice settings; linking HIV prevention to drug treatment and
prevention services; and cost-benefit and cost-effectiveness evaluations
of interventions. A major new priority area is the expansion of HIV
Testing and Counseling in drug abusing populations. These areas of
research are more fully described below.

**A) Secondary Prevention: HIV education, testing and counseling, and
referral to treatment**

CDC estimates that one quarter of the persons living with HIV in the
U.S. do not know that they are infected. This puts them at greater risk
for transmitting HIV. It also makes it likely that they will not receive
treatment early in their disease; many do not learn their serostatus
until they receive a diagnosis of AIDS. Mounting evidence suggests that
starting antiviral therapy earlier, i.e., at higher CD4 counts, is more
likely to lead to normalized CD4 counts and virologic suppression and
slower disease progression. Advances in HIV testing technology (rapid
testing) make it possible to give HIV-seronegative and provisional
HIV-seropositive results in a single visit so that it is now much more
likely that those who are tested will receive the results of testing.
Despite increased emphasis on HIV education, testing, counseling, and
referral to treatment as important elements in HIV prevention, there is
relatively little information about how to optimize each phase of the
process for drug abusing populations. For example, racial and ethnic
minority populations are most affected by IDU-associated AIDS.
Minorities are disproportionately affected by AIDS. Data indicate that
minorities are less well-informed about the benefits of HIV treatment,
and racial and ethnic minorities experience delays in linkage to care
following HIV diagnosis. Emphasis will be given to how to best
incorporate education, testing and counseling, referral to HIV/AIDS
treatment into sites such as drug treatment and outreach facilities and
social institutions (e.g., prisons, churches); assessing structural and
individual barriers to testing and accessing care; addressing concerns
of ethnic, racial, and other minorities about stigmatization. In light
of the fact that a large proportion of HIV infected people pass through
correctional facilities in a given year (e.g., 20% to 26% of all people
living with HIV in 1997); this initiative will give special emphasis to
correctional settings and other criminal justice institutions. Given the
current disproportional rates of HIV infections among minorities it is
anticipated that 70% of study participant will be minorities. Therefore
the SIC minority code for this priority is 70% (i.e., M70%).

**B) HIV/AIDS Health Disparities Among African Americans:** Over the
past 20 years, empirical findings have shown that HIV prevention
interventions are effective in reducing behavioral risks for HIV/AIDS,
as evidenced by declines in the incidence of HIV among many risk groups.
There are disparities in the effectiveness of these prevention
interventions, however, as indicated by the disproportionate prevalence
and incidence of HIV/AIDS in the African American population. Although
African Americans comprise about 12-13% of the U.S. population, they
account for a growing number of HIV/AIDS cases. For example, among
females, the majority (over half) of all new cases of HIV/AIDS occur
among African Americans. In light of the scope and magnitude of this
problem, NIDA proposes to develop and evaluate comprehensive strategies
to decrease HIV transmission and to improve access to treatment as well
as treatment options and treatment outcomes in order to address the
disproportionate burden of HIV/AIDS among the African American
population. Special emphasis will be given to focusing increased
attention to sexual transmission and acquisition among heterosexuals and
MSM minority populations. The proposed research initiatives will
encourage investigators to develop new primary (i.e., prevent
acquisition) and secondary interventions (i.e., prevent transmission)
that target minority drug using populations. These include interventions
that address the co-occurrence of other STDs, hepatitis, and psychiatric
disorders; and interventions that consider the role of culture, family,
contextual/environmental factors. Social factors such as characteristics
of social, drug use, and sexual networks in facilitating transmission
and acquisition of HIV will also be studied. This priority focuses on
minorities, the SIC is 80% (i.e., M80%).

**C) HIV/AIDS Prevention within Drug Abuse Treatment:** While effective
drug abuse treatments, in and of themselves, reduce HIV risk behaviors
and transmission, these treatments do not typically focus on preventing
HIV risk and do not address sexual transmission very effectively.
Presumably, integrating targeted HIV risk-reduction interventions into
treatment could improve HIV risk outcomes for highly vulnerable
populations. This research priority will support research to develop,
modify, and/or test behavioral interventions to reduce HIV risk behavior
among drug using populations in drug abuse treatment programs. Specific
research areas of interest include: 1) the development and testing of
new age-appropriate behavioral HIV risk reduction interventions based on
research findings from basic behavioral, cognitive, and social
epidemiology; or based on clinical theories of behavior change,
intervention, etc.; 2) the adaptation and testing of behavioral
interventions developed for other target problems (*e.g.,*
impulsiveness, ADHD, conduct disorder) to HIV risk reduction among drug
users in treatment. Given the unique nature of the risks of HIV among
women who abuse drugs, this priority will also address the pressing need
to develop targeted HIV risk-reduction interventions for women in drug
treatment. The proposed research priority will also support the
development and evaluation of HIV prevention strategies within
pharmacotherapeutic drug abuse treatment programs. Given that a
substantial proportion of patients in drug treatment are minorities, the
SIC Minority code is M40%.

**D) HIV/AIDS Prevention within Drug Abuse Prevention among Youth:** In
the US, women, youth, and minorities account for growing proportions of
new HIV/AIDS cases in both rural and urban areas and among drug users,
cases are increasingly linked to sexual exposure. Thus, it is important
that youth be a major focus of research efforts examining prevention of
drug abuse and HIV/AIDS. In many areas of the world, adolescents and
young adults represent the component of the population at greatest risk
for HIV infection and young females are often at highest risk. This
priority will support domestic and international research on
drug-related HIV/AIDS epidemiology and prevention among general
population and highly vulnerable youth (including minority youth, status
offenders, non-institutionalized youth in the juvenile justice system,
youth who are incarcerated or under supervision of the criminal justice
system, and youth in foster care, on the street, runaways, or victims of
sexual abuse). The initiative will support drug abuse prevention
research to better reduce health risking sexual behaviors in adolescents
and young adults. This priority will also encourage researchers to
examine the effects of drug abuse prevention interventions on reducing
both HIV transmission and acquisition.

**E) Prevention of HIV/AIDS and Other Co-morbid Conditions among
Substance Abusing Individuals Involved in the Criminal Justice System.**
This priority focuses on supporting new research to prevent further
spread of HIV and to treat HIV/AIDS among diverse drug-using individuals
involved in the criminal justice system at all levels including
community-based diversion programs, drug courts, jails, prisons, and
those re-integrating in the community after release from prison or jail.
Drug users returning to their communities following incarceration are at
particularly high risk of relapse to drug use and risky sexual behaviors
associated with the spread of HIV/AIDS and other infectious diseases.
Many of these individuals experience difficulty in accessing medical
care. For these reasons, novel HIV/AIDS interventions need to be
integrated within the criminal justice system. In addition,
community-based interventions are needed to more efficiently link drug
users transitioning from prison or other criminal justice system
involvement to HIV/AIDS interventions. NIDA is encouraging new
approaches for making HIV/AIDS prevention and treatment interventions
more responsive and adaptive to the needs of drug users in and/or
transitioning from the criminal justice system. Researchers are
encouraged develop, test, and evaluate interventions that target both
HIV transmission (i.e., HIV+) and acquisition (i.e., HIV-). Given the
over representation of minorities in the criminal justice system the SIC
code for minorities is M50%.

**F) International HIV Prevention:** Given that drug users and their
sexual partners are one of the fastest growing segment of HIV/AIDS cases
in many parts of the world, NIDA is encouraging researchers to evaluate
innovative, culturally relevant, contextually appropriate drug abuse
treatment programs for their utility as HIV and HCV prevention
approaches in different international settings; identify and compare
common and unique elements of effective HIV/AIDS prevention and
treatment interventions, and adapt, and test these elements in a variety
of social and cultural contexts; design, implement and assess the
effectiveness of combined behavioral and biomedical HIV intervention
models in and across different socio-cultural and geographic contexts;
and develop innovative methodologies for the application,
implementation, and cost-effectiveness analysis of prevention and
treatment interventions. Given that this priority area focuses on
international HIV prevention initiatives, the SIC code for International
is I100%.

**G) Assessment of the Public Health Impact and Effectiveness of
Interventions:** This initiative has short-term and longer-term goals
which include, but are not limited to: 1) characterizing and forecasting
the epidemiology of HIV/STI infections within and across different
drug-using and non-drug-using populations; and 2) characterizing the
influence of macro-level factors -- that is, social, physical, health,
environmental, and their interaction on multiple risk behaviors,
behavioral changes, new patterns of drug use, and changes in the
incidence and prevalence of HIV and co-infections; and 3) analyzing the
benefits and cost effectiveness of different HIV prevention strategies,
HIV/AIDS treatment, health services organizational models to improve
access, utilization, availability, financing, and cost-effectiveness for
HIV and its co-occurring conditions.

**H) Dissemination of HIV Prevention Research:** This program will
support research on factors influencing the dissemination of research
findings on substance abuse and HIV infections to prevention programs,
facilities and clinics that address these problems. The program will
stimulate research on the array of influences, and their interaction,
that beneficially affect the adoption of valid HIV prevention and drug
abuse prevention research findings into clinical practice, and promote
the development of an empirical base on the effectiveness of knowledge
dissemination interventions. There is a need for research on strategies
for moving evidence-based practices into broader use in clinical care,
and for examining the factors that, adversely or beneficially, influence
the adoption of current state of the art practices into clinical
practice and policy. The initiative will support research on: (1) the
factors that beneficially or adversely affect the adoption of
evidence-based HIV prevention and drug abuse prevention interventions
into clinical practice and health care service systems; (2) test of
alternative approaches to dissemination of effective interventions; (3)
promote of the development of an empirically-supported knowledge base on
the effectiveness and applicability of knowledge dissemination
interventions; and 4) test the utility of alternative dissemination
strategies for service delivery systems targeting rural, minority,
and/or other underserved populations.

**National Institute on Drug Abuse**

**FY08 Priorities**

Title of Project: Drug use and HIV/AIDS Treatment

**Area of Emphasis: 3**

**Plan Objective(s): 1B, 3C, 3D, 5B, 5C**

**SIC: M30%, I10%**

**Mechanism: RPGs**

**New or Expansion: New/CR/EXP**

**Co-funding: possibly NIAID, NIMH, NIAAA, NIDDK, NICHD**

**Roadmap area: multi- and interdisciplinary research teams**

**Program Description**:

These priorities include new, continuing, and expanded research to
develop better therapeutic regimens, limit development of drug
resistance, promote adherence, and make treatment more accessible for
drug abusing populations. NIDA supports domestic and international
research on treatment of HIV/AIDS and co-occurring infections such as
hepatitis C, TB, STIs among drug abusers. This research program includes
studies to: 1) develop and test interventions to improve and maintain
adherence to ART and OI treatment medications among drug users,
including those in high risk groups and environments; 2) link and
integrate treatment services for drug abuse, HIV, and co-occurring
infections and conditions; 3) understand drug interactions among drugs
of abuse or medications used in the treatment of addiction (e.g.,
methadone, buprenorphine) and medications to treat HIV infection and HCV
infection; 4) investigate the development of viral resistance linked to
non-compliance and/or treatment failure; 5) conduct basic research on
host factors relevant to development of new therapies for HIV in drug
abusers, e.g., research on opiate/CCR5 cross-desensitization is relevant
to the development of CCR5 antagonists; and 6) conduct functional
genomics studies of HIV infection in drug abusers, including those
co-infected with HCV.

**A) Adherence to HIV/AIDS Treatment Regimens.** Antiretroviral therapy
has dramatically reduced the morbidity and mortality of infection due to
HIV/AIDS. It is important to understand the extent to which HIV + drug
users adhere to their HIV medications and the role that substance abuse
may have on adherence. This research priority will focus on improving
our understanding of antiretroviral drug adherence among HIV-positive
substance abusers. This research will encourage studies that address the
interaction between abuse of particular drugs of abuse or combinations
of drugs of abuse with individual and environmental factors to influence
adherence, e.g., it has been suggested that stimulant abuse is
associated with poor adherence. Understanding the effects and
interactions of clinical, behavioral, neurocognitive, social, and
environmental factors on the attitudes, beliefs, and motivations of
substance abusers toward antiretroviral adherence will ultimately help
in the development of improved behavioral and therapeutic interventions
for antiretroviral adherence among drug users across the stages of HIV
infection and disease. NIDA also proposes to support research on the
effectiveness of pharmacological approaches, behavioral interventions,
and other methods to facilitate adherence to HART regimens among drug
users. Moreover, NIDA will encourage researchers to develop better
methods to assess adherence to treatment regimens across a variety of
affected populations domestically and internationally.

**B) HIV/AIDS Treatment for Adolescents and Young Adults; Implications
of Drug Abuse:** This initiative will support domestic and international
research that examines the intersection of HIV, HAART, and drug use in
the context of biology, cognition and behavior unique to the
developmental period of adolescence and young adulthood. Research areas
include: (1) studies on the effects of drug use including nicotine,
marijuana, inhalants, abused prescription drugs, stimulants, cocaine,
opiates, and club drugs on HIV disease progression and treatment during
adolescence and young adulthood, (2) studies to examine the effects of
substance use and abuse on HIV medication and treatment adherence for
youth living with HIV, and (3) studies to examine the effects of
combined exposure to HIV, HAART, and drugs of abuse on cognitive,
emotional, and social development, behavior (including risk-taking
behaviors associated with HIV/AIDS), psychiatric, psychological and
neurological conditions, educational and vocational outcomes, health and
development. Given that a large proportion of infected individuals are
minorities, the SIC code for minorities is M40%. Moreover, given that
many of the youth infected with HIV are in foreign countries, the
International SIC code is I30%.

**C) Pharmacogenetics and Pharmacoepidemiology of Drug Interactions**

Research is needed on pharmacokinetic and pharmacodynamic drug-drug
interactions among drugs of abuse and medications used in the treatment
of addiction (e.g., methadone, buprenorphine) and medications to treat
HIV infection and HCV infection and other co-occurring infections and
disorders**.** Studies have shown that there can be interactions among
various classes of antiretroviral and anti-infective drugs (e.g., PIs,
NNRTIs, NRTIs, or combinations \[HAART\]) and drug abuse treatments,
e.g, methadone, resulting in adverse consequences. The variability in
outcome of drug therapy may be contingent upon multiple factors,
including the patient's medical history, nutritional status, disease
severity, viral variant, ethnicity, gender, age, etc. Pharmacogenomic
research has shown that many cytochrome P450 genes have polymorphisms
that directly contribute to varying metabolism of antiretroviral agents,
and have a large impact on drug interactions among drugs of abuse, drug
addiction medications, and medications for mental disorders. Research is
needed to determine the incidence and prevalence of such interactions,
underlying genetic contributions to drug interactions, and the effect of
drug-drug interactions on adherence to antiretroviral therapies in those
addicted or being treated for addiction.

D\) Linking and Integrating Treatment for HIV and HCV and Other
Co-morbid Conditions with Drug Abuse Treatment Services.

Drug abusers with HIV/AIDS frequently have co-morbid conditions such as
hepatitis C (HCV), hepatitis B (HBV), tuberculosis, sexually transmitted
diseases, and mental health disorders. Programs that offer
comprehensive, accessible services as well as improved outreach and
referral strategies are needed to optimally engage drug-using
populations in care. The U.S. healthcare system does not provide
coordinated care for HIV infected drug abusers, and issues of access to
care and coordination of care are particularly relevant for underserved
and minority drug abusing populations. For example, incorporation of
HCV-related services in drug treatment units that treat intravenous drug
users and provide HIV-related services is limited. Research is needed
to: 1) identify the organizational factors that limit provision of
coordinated drug abuse treatment, HIV, HCV, and other services; 2)
identify the behavioral and social support needed by drug abusers in
order to engage in treatment and adhere to treatment regimens; and 3)
evaluate innovative approaches to treatment coordination such as use of
nurses to monitor and support treatment or integrating mental health
assessment and treatment to improve HIV /co-infection treatment success
rates. Studies are also needed on how best to stage the introduction of
medications to treat drug abuse, HIV, and HCV and to explore different
medication combinations. Coordinated treatment settings could also
provide a unique opportunity to integrate HIV prevention with service
provision, and studies are needed on how best to accomplish this.
Research is also encouraged on health services organizational models to
improve accessibility, availability, utilization, financing, and
cost-effectiveness of services for treating HIV and co-occurring
conditions among diverse risk groups and to improve the diffusion of
evidence-based treatment and prevention technologies for HIV and
co-occurring conditions. Given that a large proportion of co-infected
individuals are minority members, the Minority SIC code is M40%.

**National Institute on Drug Abuse**

**FY08 Priorities**

Title of Project: Epidemiology and Natural History of HIV/AIDS Among
Drug Using Populations

**Area of Emphasis: 1**

**Plan Objective(s): 1A, 1B, 1C, 2B, 3C, 5A, 5B, 5C**

**SIC: I60%**

**Mechanism: RPGs**

**New or Expansion: New/CR/EXP**

**Co-funding: NIAID, NIMH, NIAAA, NIDDK, NICHD**

**Roadmap area: multi- and interdisciplinary research teams**

**Project description:**

These priority areas include new, continuing, and expanded research on
drug abuse, HIV/AIDS, and the health and social consequences associated
with these intertwined epidemics. The proposed natural history and
epidemiologic studies will improve monitoring of epidemic trends,
following of changing clinical manifestation of HIV disease and
co-morbid conditions, and measure the effects of treatment regimens
(i.e., antiretroviral and substance abuse) in drug using populations. Of
critical interest are studies that advance knowledge of the changing
behavioral and social epidemiology of drug abuse, HIV/AIDS, and other
infectious diseases; the natural history of HIV/AIDS and co-infections
among injection and other drug users and their sexual partners; and the
changing social, environmental, and behavioral contexts of risk among
drug users, their sexual partners, and among high-risk groups that
bridge HIV and AIDS-related co-infections to lower risk populations. The
spectrum of research covered by these priorities will help to elucidate
our understanding of the HIV transmission dynamics and disparate health
effects of drug use and HIV/AIDS among diverse population groups and
their communities.

**A) International Studies on HIV/AIDS and Other Infections in
Drug-Using Populations.** This is a continuation and expansion of an
ongoing international initiative to foster cross-national and
international HIV research and research training collaborations related
to HIV/AIDS and other infectious diseases among drug using populations,
and their sexual partners. HIV/AIDS associated with drug use continues
to expand globally. This is particularly true in Eastern and Central
Europe, Asia, and Southeast Asia. In Russia, for example, data suggest
that drug abuse is driving 90% of the HIV epidemic, which has been
fueling a multi-drug resistant TB epidemic, high rates of STIs, and
viral hepatitis. In Asia, in the Golden Triangle area, molecular
epidemiologic studies indicate the development of new recombinant HIV
subtypes, reflecting the intersection of the IDU and heterosexual
epidemics. HIV/ HCV co-infection is a widespread and increasing problem,
as demonstrated by rates of HCV infection in HIV-infected drug users
surpassing 80% in some areas of Southeast Asia and China. This priority
will encourage investigators to: (a) develop systematic epidemiological
approaches for monitoring changes and patterns in transmission of HIV
and other infections associated with drug use; (b) researchers are also
encouraged to assess the impact of HIV prevention interventions on the
dynamic of the HIV epidemics; and (c) characterize the risk networks,
environmental contexts, and dynamic interactions between rapid
behavioral and social changes, including natural and man-made disasters
(e.g., famines, wars) and the spread of infectious diseases among new
and vulnerable drug-using populations (e.g., migrant populations)
utilizing observational, molecular, medical and behavioral
methodologies. Moreover, researchers will be encouraged to develop and
evaluate the relative efficiency of novel epidemiological methods for
obtaining HIV accurate incidence data in cost efficient manners for
possible use in resource poor countries. For example, the use of
cross-sectional studies that use new sampling procedures (e.g.,
Respondent Driving Sampling) combined with newly available detuned
assays (e.g., Calypte BED Assay) to obtain representative incidence
rates among hard to reach populations, can not only provide more timely
and accurate estimates then the traditional longitudinal study approach
used to estimate incidence but it can also represent substantial cost
savings. This priority area focuses on international project, so the SIC
code for International is I100%.

**B) Methodology.** Initiatives in this area will seek new research that
addresses methodology and measurement issues in diverse drug-using
populations, issues in studying sensitive risk behaviors, issues of
ethics in research, issues related to confidential data and the
protection of research subjects, and issues in developing
interdisciplinary, multi-method, and multilevel approaches to natural
history and epidemiological research. Also of importance are approaches
that integrate behavioral and social science research with biomedical,
physical, or computational science research or engineering. NIDA is
encouraging collaborations among researchers to promote molecular
epidemiology studies using existing drug abuse cohorts. The many cohorts
of drug abusers that have been used in primarily behavioral studies are
a resource for conducting studies on the transmission, establishment,
and spread of HIV infection in diverse populations. For example, these
cohorts could be used for genetic studies of host factors such as
chemokine and chemokine receptor variants that affect resistance and
susceptibility to HIV infection and alter disease progression. Related
initiatives will support cohort development utilizing observational,
medical and behavioral methodologies in areas of high prevalence to
study the natural and treatment history of HIV and HIV/hepatitis
co-infection among drug users. It has long been recognized that HIV
transmission among drug users depends on multiple factors, including the
reservoir of infectious disease, the characteristics and distribution of
HIV risk behaviors among drug users and their social networks, as well
as environmental and social factors. Mathematical models that integrate
these and other parameters of drug abuse and disease (e.g.,
co-infections, mental health disorders) are critical for understanding
and predicting different trajectories of the epidemic across populations
and their communities. These models also help inform the design and
testing of HIV prevention interventions for optimal cost-effectiveness
in reaching risk groups at different phases of the epidemic curve to
avert the spread of new infections. NIDA supports the development of new
mathematical and simulation studies of drug abuse and infectious disease
transmission. Topics of interest include, but are not limited to: 1)
characterization and forecasting of the incidence of HIV and other
sexually transmitted infections (STIs) among different drug-using
populations; 2) analysis of the cost-effectiveness of behavioral HIV
prevention interventions for drug users relative to different
model-based assumptions; 3) assessments of the benefits, costs, and
consequences of antiretroviral and other medications for HIV-infected
drug users in and out of the drug treatment setting; and 4) estimations
of disease transmission dynamics relative to changing patterns of drug
abuse, background seroprevalence levels, intervention-induced changes in
risk behaviors, and the consequences of relapse or continuing HIV risk
behaviors following participation in behavioral interventions. This
priority area will support the development and refinement of
epidemiological methods for studying sensitive risk behaviors in diverse
settings. It will also encourage research on ethics and ethical issues
that arise in studies of drug abuse and HIV/AIDS, especially in the
international context. Other methodological issues relate to the
collection and handling of confidential data and the protection of
research subjects. So of the proposed modeling areas will involve
international populations. The International SIC code for this priority
is I40%.

**National Institute on Drug Abuse**

**FY08 Priorities**

Title of Project: Drug Abuse Related HIV/AIDS and Its Consequences

**Area of Emphasis: 2**

**Plan Objective(s): 1A, 1B, 2B, 2E, 2F, 2G, 3C, 3D, 3H, 5A, 5B**

**SIC: M20%, I20%**

**Mechanism: RPGs**

**New or Expansion: New/CR/EXP**

**Co-funding:**

**Roadmap area: multi- and interdisciplinary research teams**

Project Description:

These priorities include new, continuing, and expanded research to
better understand how HIV infection is established and maintained and
the bases for HIV-associated profound immunodeficiency and severe
clinical complications. Such priorities include basic behavioral
research of the mechanisms underlying the effects of drug abuse on the
valence of positive reinforcement as well as negative reinforcement and
punishment and how this influences the likelihood of engaging in HIV
risk behaviors. NIDA research on etiology and pathogenesis of HIV/AIDS
studies IDU and non-IDU drug abusers, human cells in culture, and animal
models of HIV to understand the role of drug abuse and drugs of abuse,
e.g., opioids, cocaine, and methamphetamine, on: 1) the transmission,
establishment, and spread of HIV and coinfections such as HCV; 2) the
medical and health consequences of HIV and HIV/HCV coinfection; 3) the
toxicities and long term complications of combined therapy for drug
abuse and HIV or HIV/HCV co-infection.

**A) HIV/AIDS Models:** To enhance understanding of the mechanisms
involved in cell injury and death in the immune, nervous, and other
organ systems affected by HIV, NIDA is supporting studies to increase
the number of animal models available for studies of HIV-like infection
in combination with drug administration, including further development
and validation of a mouse model (Potash et al., 2005) employing a
chimeric virus that holds promise for studies of systemic HIV infection,
antiviral immune responses, and neuroinvasiveness and the development
and validation of a Chinese rhesus macaque model of SIV. A particular
focus is the development and validation of in vitro and animal models
that allow the concurrent study of HIV, SIV or other lentivirus
infection in the brain and specific patterns of chronic or acute drug
exposure. In vitro studies with established cell cultures and primary
human cell cultures, including neurons and glial cells as well as neural
precursor cells, are being used to explore interactions of HIV, drugs of
abuse and their receptors, and chemokines and their receptors.
Mechanistic studies of these interactions and their cellular and
molecular bases may lead to new therapies for HIV such as treatment
modalities to slow progression of neuroAIDS.

**B) Health and Development of Children Affected by HIV/AIDS and Drug
Abuse:** This new initiative will support international research to
examine the cognitive, emotional, and social development, health, and
psychosocial functioning of children and adolescents affected by the
dual epidemics of substance abuse and HIV/AIDS. Worldwide it is
estimated that almost 14 million children under the age of 15 years have
lost one or both parents to AIDS. There are millions more children
affected by the virus and its medical and psychosocial consequences
vis-à-vis parents, caregivers, siblings, partners, friends, and
neighbors who are living with HIV/AIDS. Affected youth may experience
psychosocial and economic stresses associated with caring for a person
with a chronic illness, or with grieving a parent or loved one who is
dying or deceased. Children of women infected through drug use risk
behaviors may experience multiple challenges related to parental illness
and to drug abuse. Non-IDU substance abuse can also impact families
living with HIV/AIDS. Substance abuse in families may impact caregiver's
abilities to monitor their children, can be associated with negative
developmental outcomes for children and may result in the separation of
the substance using caregivers and their child. In international
settings there is a dearth of information on the children of IDUs and
non-IDU substance abusers with HIV/AIDS. Qualitative and quantitative
research is needed to understand how substance use affects these
families and child outcomes directly (e.g., care giving) and indirectly
(e.g., prenatal care, adherence to medication). This information can
guide future interventions to improve the quality of life for these
children. In addition, by understanding the health, development, and
psychosocial functioning of affected children and adolescents we can
learn which children may be vulnerable to developing substance abuse and
other HIV risk behaviors in the future. Such knowledge will inform
future initiatives aimed at preventing the dual epidemics of substance
abuse and HIV in subsequent generations. Given that the majority of
children affected by the HIV/AIDS pandemic are in foreign countries,
this priority the International SIC code for this priority area is I80%.

**C) Drug Abuse Effects on HIV Risky Behaviors:** This priority will
focus on disentangling the relative contribution of drug intoxication
and/or the role of various patterns of drug abuse (i.e., class of abused
drug, chronic versus acute or intermittent use, including withdrawal
state) on HIV risk behaviors. That is, NIDA will develop various
initiatives to further our understanding of effects of drug abuse on the
valence of positive reinforcement as well as negative reinforcement and
punishment and how this influences the likelihood of engaging in HIV
risk behaviors. As part of these initiatives, NIDA will ensure that
neurobehavioral studies of how drugs of abuse and drug abuse (dependent
state or withdrawal) affect decision making by modulating the processing
of rewarding and aversive stimuli. These initiatives will also highlight
the importance of studying these phenomena during critical stages of
human development.

Specific areas of interest include: 1) [Drug abuse, risky decision
making and HIV/AIDS]{.underline}. A fundamental question that drives
research on decision making is why do people who are presented with the
same options make different choices? And why do people choose options
that are not in their best long-term interests? Moreover, what is the
role of drug intake and alcohol intoxication on decision making?
Effective HIV/AIDS prevention and treatment for alcohol and drug abusers
would benefit from research on decision making.  Despite a wealth of
anecdotal reports and limited empirical data, there remains a great deal
to be learned about the cognitive/behavioral processes and the
neurobiological mechanisms that mediate the interactive effects of
alcohol and drug abuse, risky decision making and HIV/AIDS. NIDA is
interested in developing an interdisciplinary research portfolio that
will study the role of drug abuse on HIV transmission and acquisition.
Such a portfolio will integrate economics, psychology and neuroscience
to elucidate the complex interrelationships among drug abuse, risky
decision making and HIV/AIDS. Research on the role of emotion,
expectancies, attitudes, impulsivity, and stress on the interaction
among these factors is needed. Hypothesis driven research and modeling
approaches will help to guide empirical testing and are encouraged. Both
laboratory based research and investigations in naturalistic settings
are critically important and should be integrated into a single proposal
where it is feasible; 2) [Adolescence: Development of HIV risky
behaviors and effects of substance abuse]{.underline}. A great deal to
be learned about the cognitive/behavioral processes and the
neurobiological mechanisms that 1) lead to risky behavior and 2) mediate
the interactive effects of alcohol and drug abuse, biobehavioral
mechanisms and HIV/AIDS. Using both human and animal models, significant
differences between adolescents and adults in these processes have been
demonstrated. For example, higher death rates are seen during
adolescence in multiple species, apparently related to increased
risk-taking behaviors. Adolescent male rats show much stronger
conditioning to novelty and social rewards than do adult rats, and
alcohol seems to enhance social behavior in adolescent rats while
decreasing it in the adults. This initiative will support research to
increase understanding of developmental processes and trajectories of
HIV risky behaviors, and in turn, the effects of these risky behaviors
(e.g., drug use) on the further development of those processes and
trajectories. Adolescence is a crucial time for developing self
regulatory capacities and decision making skills as this developmental
period is marked by changing social roles, greater responsibilities and
decreased adult supervision. Recent discoveries in the area of
developmental neuroscience have provided accumulating evidence for a
shift from decisions driven by activation of subcortical pathways to
top-down control mechanisms with age. The relatively immature
neurobehavioral systems for cognitive control, emotion regulation and
decision making skills in adolescents are likely related to the
risk-taking behavior and higher rates of substance use occurring in this
developmental period. Of critical interest are studies that advance
knowledge of adolescent cognitive and affective development in high-risk
groups that may lead to a greater incidence of HIV risky behaviors
and/or drug use. Also of critical interest is advancing knowledge of how
drug use influences cognitive and affective development, and decision
making skills in these high risk groups. Improved understandings of
these developmental processes are likely to have implications for
primary/ secondary prevention and adherence to HIV treatments.

**D) Liver Disease in HIV and HCV co-infected Drug Abusers and Role of
HIV/HCV Co-infection in Other Health Outcomes.**

The advent of HAART therapy has had profound changes on morbidity and
mortality associated with HIV disease and co-infections. For example
liver disease has increased as a cause of morbidity and mortality among
those co-infected with HIV and HCV. Many injection drug users (IDUs) are
co-infected with both HIV and hepatitis C (HCV); co-infection rates
range from 50 to 90 percent. Progression of liver disease is more rapid
in co-infected individuals than with those infected with HCV only. The
mechanisms by which HIV increases the rate of progression of HCV liver
disease are not understood and further research is needed to understand
the mechanisms by which HIV modulates host immune responses to HCV in
drug abusers. Research is also needed on the effects of HCV/HIV
co-infection on other health outcomes. For example, recent studies have
shown that HCV augments cognitive deficits associated with HIV infection
and methamphetamine abuse. Studies are needed on the effects on liver
function of combined pharmacotherapies for drug abuse, HIV, and HCV and
how best to integrate drug abuse treatment, HIV treatment, and HCV
treatment. Given that a large proportion of co-infected individuals are
minority members, the Minority SIC code is M40%

E\) Cardiovascular Effects Including Sub-clinical Atherosclerosis

Human studies have demonstrated that cocaine and HIV are associated with
clinical cardiovascular disease. Studies in animal models of HIV have
confirmed additive effects of cocaine and viral infection on cardiac
function. Studies in young, African-American cocaine abusers have shown
that HIV infection, cocaine use, or both contribute to sub-clinical
atherosclerosis as measured by coronary artery calcification. Further
research is needed to understand the pathogenesis of cardiovascular
dysfunction in HIV infected cocaine abusers. Studies are also needed to
determine whether gender, race or ethnicity are associated with
increased cardiovascular disease in HIV infected drug abusers. In light
of the high prevalence of drug abuse and cardio vascular diseases among
African Americans, the Minority SIC code for this priority area id M40%.

**F) NeuroAIDS:** In the era of HAART, the incidence of neurological
complications of HIV infection has been reduced somewhat, but their
prevalence remains high. The nature of the neurological effects
associated with HIV infection has also changed somewhat; a milder form
of CNS dysfunction, minor cognitive motor disorder (MCMD), is now seen
more frequently. The incidence of HIV-associated dementia (HAD) has been
reduced, but its prevalence has increased because more people are living
longer with HIV. In the era of HAART, the pattern of HAD is much more
variable in severity and clinical features and in -temporal progression.
Drug abusers are a significant proportion of those infected with HIV,
and studies have demonstrated that drug abuse can exacerbate neuroAIDS.
In Edinburgh, a higher prevalence of HIV encephalitis was found in IDUs
(polydrug users who abused opiates) compared to homosexuals, and greater
microglial activation was found in the brains of drug users with HIV
encephalitis compared to non-drug users. Chronic methamphetamine use has
been demonstrated to exacerbate cognitive deficits seen in HIV-infected
persons and to produce enhanced neurotoxicity. Relevant issues include
effects of drug abuse on HIV entry into the brain, viral replication and
spread within the brain, initiation of immune and inflammatory
responses, and the interaction of viral and cellular proteins within
brain-resident cells. A combination of in vitro, animal and human
neuroscience and neuroimmunology research is needed to explore the
underlying basic mechanisms of chronic HIV-associated neurological
diseases in the context of drug abuse, particularly with respect to
neuroinflammation, changes in blood brain barrier permeability, glial
activation or dysfunction, neurotoxicology, neuroprotection, and
drug-drug interactions**.** Further research is needed to: understand
how drugs of abuse and medications to treat addiction affect blood-brain
barrier integrity and cell phenotype, leukocyte trafficking, HIV/SIV
neuroinvasion, viral replication, and/or progression of neurologic
disease. Studies using structural, functional and/or neurochemical
imaging studies, or other types of clinical or basic neuroscience
studies, are needed to identify brain regions and systems that exhibit
relatively greater or lesser sensitivity to HIV infection as well as to
assess the impact of co-occurring substance abuse on disease
progression, including neuropsychological or cognitive impairment,
and/or response to antiviral treatment of HIV in the context of drug
abuse.

G\) Resistance to Antiretroviral Drug Therapy: It is critically
important to understand how drugs of abuse or medications to treat drug
abuse, or their withdrawal, affect the outcome of antiretroviral
therapy. For example, there are data that indicate that continued
methamphetamine use decreases the effectiveness of HAART therapy leading
to increased viral loads. This could potentially lead to the development
of antiretroviral drug resistance. To stimulate research in this area,
NIDA has encouraged virologists, immunologists, and infectious disease
specialists to partner with researchers conducting epidemiology studies.

**National Institute on Drug Abuse**

**FY08 Priorities**

**Title of Project: Training, Infrastructure, and Capacity Building**

**Area of Emphasis: 6**

**Plan Objective(s): 6A, 6B**

**SIC: M10%**

**Mechanism: Training**

New or Expansion: CR

**Co-funding: NIAID, NIMH, NIAAA**

**Roadmap area: multi- and interdisciplinary research teams**

**A) Institutional Research Training in the areas of Drug Abuse and
Infections:** Drug abuse and related co-infections are associated with a
significant morbidity/mortality among drug abusers. Much research is
needed to determine underlying pathophysiology of
medical/clinical/health consequences of substance abuse and infections
and how these may vary with population subgroups (e.g., women, youth,
and minorities). However, it is apparent that there remains a
substantial need for clinicians/researchers trained, for example, in the
fields of cardiology, endocrinology, hepatology, neurology, and others,
to be able to work with drug addicts and carry out research on various
aspects of drug addiction and HIV/AIDS and other infections, including
sexually transmitted infections.

This program will support research efforts through institutional
training research grants (T32), pre-doctoral (F31), post-doctoral (F32)
and short-term training grants to train clinician/researchers from the
biomedical and clinical fields to conduct research on drug abuse and
co-occurring viral and bacterial infections such as HIV, hepatitis C,
TB, STDs and other bacterial infections. The program will support
eligible institutions of higher learning to develop or enhance research
training opportunities for individuals, selected by the institution, who
are training for careers in specified areas of biomedical, behavioral,
and clinical research, specific/relevant to drug abuse and infections.
The purpose of this program is to help ensure that a diverse and highly
trained workforce is available to assume leadership roles related to the
Nation\'s biomedical and behavioral research agenda in the areas of
substance abuse and infections. Accordingly, this program will support
predoctoral, postdoctoral, and short-term research training experiences.
This training program will be used as the primary means of supporting
graduate and postdoctoral research training in the area of substance
abuse and infections. It will use a combination of institutional
training grants and individual fellowships to ensure a continuing supply
of well-trained scientists prepared to conduct cutting-edge
health-related research on drug abuse and infections at institutions of
higher learning. The program will support the following types of
training: predoctoral training will lead to a Ph.D. degree or a
comparable research doctoral degree and that it will emphasize
fundamental training in areas of biomedical and behavioral sciences;
postdoctoral research training will be for individuals who have received
a Ph.D., D.V.M, D.D.S., M.D., or a comparable doctoral degree from an
accredited domestic or foreign institution. Research training at the
postdoctoral level will emphasize specialized training to meet national
research priorities in the biomedical, behavioral, or clinical sciences.
In addition, short-term (8-12 weeks) research training for
health-professional students will include short-term predoctoral
positions reserved specifically to provide full-time, health-related
research training experiences during the summer or other \"off-quarter\"
periods. Such positions will be limited to medical students, dental
students, students in other health-professional programs to provide such
students with opportunities to participate in biomedical and/or
behavioral research in an effort to attract them into the fields of
substance abuse and infections. This priority area will sustain the same
level of support for minority applicants as it has in the past. That is,
the SIC Minority Code is M15%.

**B) A/START** To facilitate the entry of early career investigators
into the area of AIDS research, NIDA is focusing on newly independent
investigators who have not previously been supported by an R01 grant who
are ready to launch their careers.  The challenge for early career
scientists is to obtain preliminary data related to the intersection of
HIV/AIDS and drug abuse. This program will support feasibility studies
to facilitate the entry of new investigators into the areas of clinical
and basic neuroscience, pathogenesis, epidemiology, treatment, and
prevention related to drug abuse and AIDS research.  In this way it is
anticipated that new careers in HIV/AIDS research in drug abuse will be
established. It is hoped that this process will facilitate and encourage
the development of appropriate and fundable R01 grant applications by
early career investigators subsequent to generating preliminary data
supported by an A-START grant.  Funding would be limited to direct costs
for one-two years of up to \$175,000 and would be non-renewable.

**C) Infrastructure Development**

The global HIV epidemic continues to expand.  UNAIDS estimates that
during 2004 nearly 5 million adults and children became infected with
HIV worldwide -- about 14,000 new infections each day.  The epidemic is
driven primarily by behaviors: heterosexual intercourse is the
predominant mode of transmission in most countries while intravenous
drug use is important in Asia, South East Asia, Central Europe and
Eastern Europe.   Prevention efforts are of critical importance for
slowing the epidemic, and the availability of local behavioral and
social scientists are of critical importance for successful prevention
efforts. In order to increase capacity and capability of those counties
most affected by HIV through drug abuse NIDA plans to collaborate with
NICHD, NIMH, FIC, and NCCAM to encourage partnerships between skilled
foreign investigators and U.S. This collaborative initiative would use
the R24 grant mechanism to support proposed projects. Moreover, NIDA
intends to continue collaborating with NIAID's HIV Networks to
facilitate strengthening the research infrastructure of foreign research
institutions.

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