HIV THERAPY FOR DRUG USERS:  ACCESS, ADHERENCE, EFFECTIVENESS

Release Date:  December 20, 1999

RFA:  DA-00-007

National Institute on Drug Abuse

Letter of Intent Receipt Date:  February 28, 2000
Application Receipt Date:       March 29, 2000

THIS REQUEST FOR APPLICATIONS (RFA) USES THE “MODULAR GRANT” AND “JUST-IN-
TIME” CONCEPTS.  IT INCLUDES DETAILED MODIFICATIONS TO STANDARD APPLICATION 
INSTRUCTIONS THAT MUST BE USED WHEN PREPARING APPLICATIONS IN RESPONSE TO THIS 
RFA.

PURPOSE 

The National Institute on Drug Abuse (NIDA) invites applications for research 
on access, adherence and effectiveness relevant to the treatment of drug users 
with HIV. Treatment and management of HIV/AIDS in drug users is complicated by 
social, behavioral, clinical and pharmacological factors which may alter the 
long-term effectiveness of HIV therapies. Poorer access to health care and the 
difficulties in managing and sustaining complex treatment regimens for HIV, 
have limited the numbers of drug users who are on combination antiretroviral 
therapy. While engagement of drug users into HIV care through accessible 
programs, such as primary care linked with methadone treatment, has 
demonstrated reduced morbidity and improved survival, providers may consider 
drug users as high-risk for developing drug resistant HIV infection due to a 
perceived inability to adhere to complex medical regimens.  As a result, drug 
users may not be considered good candidates for anti-retroviral therapy or to 
receive the clinical support necessary to take chronic medications correctly. 
 Further understanding of the factors influencing adherence and development of 
effective interventions are critical for improved clinical outcomes and 
prevention of development of resistance to antiretroviral medications. 
Determining patterns of use of therapies and the impact of episodic or 
intermittent patterns of adherence, as well as the impact of ongoing 
injection, are important to understanding selection of drug-resistant strains 
of HIV.  Due to an underrepresentation of drug users in clinical studies of 
HIV therapies, there is a lack of data on potential risks of drug interactions 
and toxicity.  Interactions between illicit drugs and HIV therapies, as well 
as pharmacotherapies for substance abuse, mental health conditions, and for 
other diseases common in drug users, may cause morbidity, influence adherence, 
and reduce the effectiveness of HIV treatment.

HEALTHY PEOPLE 2000

The Public Health Service (PHS) is committed to achieving the health promotion 
and disease prevention objectives of “Healthy People 2000,” a PHS-led national 
activity for setting priority areas.  This RFA, “HIV Therapy for Drug Users:  
Access, Adherence, Effectiveness,” is related to the priority areas of alcohol 
and other drugs, HIV infection, and sexually transmitted diseases. Potential 
applicants may obtain a copy of “Healthy People 2000” at 
http://odphp.osophs.dhhs.gov/pubs/hp2000.

ELIGIBILITY REQUIREMENTS

Applications may be submitted by domestic and foreign for-profit and non-
profit organizations, public and private, such as universities, colleges, 
hospitals, laboratories, units of State and local governments, and eligible 
agencies of the federal government.  Racial/ethnic minority individuals, 
women, and persons with disabilities are encouraged to apply as Principal 
Investigators.  

MECHANISM OF SUPPORT

The mechanism of support for this RFA will be the investigator-initiated 
research project grant (R01). Applicants are advised to contact NIDA program 
staff listed under INQUIRIES for additional information.  Responsibility for 
the planning, direction, and execution of the proposed project will be solely 
that of the applicant.  Specific information on individual research mechanisms 
can be obtained from the NIDA home page at 
http://www.nida.nih.gov/Funding.html.

Support may be requested for a period of up to 5 years for R01 grants.  
Modular budgeting procedures apply for grants up to $250,000.  See 
http://grants.nih.gov/grants/funding/modular/modular.htm for further 
information about modular budgets. 

FUNDS AVAILABLE

NIDA intends to commit approximately $3,000,000 in FY 2000 to fund 
approximately seven new grants in response to this RFA. An applicant may 
request a project period of up to 5 years.  Because the nature and scope of 
the research proposed may vary, it is anticipated that the size of each award 
will also vary. Although the financial plans of NIDA provide support for this 
program, awards pursuant to this RFA are contingent upon the availability of 
funds and the receipt of a sufficient number of applications of outstanding 
scientific and technical merit.

RESEARCH OBJECTIVES

Background

The advent of combined antiretroviral therapy has resulted in dramatic 
reductions in both morbidity and mortality due to HIV/AIDS. Benefits for drug 
users from these potent combination therapies have lagged behind those of 
other populations.  While data from selected samples demonstrate improvement 
in the numbers of drug users receiving combination therapy, deaths due to 
HIV/AIDS among drug users have declined at a significantly lower rate compared 
with other risk groups. Limited access to care, an important predictor of 
inconsistent medical care and poorer survival, remains a significant problem 
for drug users.  Studies have shown that injection drug users tend to seek 
medical care later in their disease course and are less likely than other 
groups to receive HIV-related therapy.  Psychiatric co-morbidity, common among 
drug users, as well as ongoing substance abuse, have been shown to be 
associated with poorer levels of adherence.  Drug users have high rates of co-
morbid medical conditions, including renal, hepatic, and neurologic disease, 
as well as bacterial pneumonia, tuberculosis, and hepatitis B and C. These 
prevalent conditions complicate the medical management of HIV-infected drug 
users and increase the risk of toxicities and drug-drug interactions from use 
of multiple therapies and ongoing substance use.  Drug users co-infected with 
hepatitis C and HIV who are being treated with protease inhibitors may be at 
particular risk for hepatotoxicity or acute hepatitis. Recent data have shown 
that chronic methadone treatment increases plasma levels of AZT, that protease 
inhibitors can inhibit metabolism of both methadone and buprenorphine, and 
that nevirapine can induce opiate withdrawal in patients on methadone. Further 
understanding of the complex components of treating HIV-infected drug users is 
important to the development of improved clinical management approaches. 
. 
Areas of Research Focus
 
This initiative will support research on a broad range of HIV care-related 
issues, including, 
1) access issues related to receipt of HIV-related treatment and outreach 
strategies to improve access; 2) factors influencing initiation of HIV 
treatment and long-term adherence to HIV treatment regimens; 3) the 
development of intervention strategies to improve use of and adherence to 
complex medical regimens in a variety of settings; 4) the development and 
testing of behavioral treatments as an integral component of comprehensive 
approaches designed to reduce risk behaviors, prevent transmission of 
infection, and enhance adherence with medications and care, 5) the occurrence 
of beneficial and deleterious behavior risk changes as a result of HIV 
therapy, 6) factors influencing long-term therapeutic effectiveness, 
development of viral resistance, disease progression, and medical outcomes, 7) 
consequences of the use of therapies in drug users--including toxicities and 
pharmacologic interactions of antiretrovirals with drug abuse treatment 
medications (methadone, LAAM, buprenorphine), illicit substances,  medications 
for dual diagnosis patients and for other diseases common in drug-users--and 
with alternative/complimentary therapies for drug users with HIV infection; 8) 
clinical management approaches for drug users on multiple medical therapies 
for HIV and associated infectious and non-infectious conditions associated 
with drug use; and 9) bioethical considerations involving availability of 
care, provider attitudes, and clinical management approaches. 

INCLUSION OF WOMEN AND MINORITIES IN RESEARCH INVOLVING HUMAN SUBJECTS

It is the policy of the NIH that women and members of minority groups and 
their subpopulations must be included in all NIH supported biomedical and 
behavioral research projects involving human subjects, unless a clear and 
compelling rationale or justification is provided that inclusion is 
inappropriate with respect to the health of the subjects or the purpose of the 
research.  This new policy results from the NIH Revitalization Act of 1993 
(Section 492B of Public Law
103-43).

All investigators proposing research involving human subjects should read the 
“NIH Guidelines for Inclusion of Women and Minorities as Subjects in Clinical 
Research,” published in the Federal Register on March 28, 1994 (FR 59 14508-
14513) and in the NIH Guide for Grants and Contracts, Volume 23, Number 11, 
March 18, 1994, available on the web at:  
http://grants.nih.gov/grants/guide/notice-files/not94-100.html.


NIH POLICY AND GUIDELINES ON THE INCLUSION OF CHILDREN AS PARTICIPANTS IN 
RESEARCH INVOLVING HUMAN SUBJECTS:

It is the policy of NIH that children (i.e., individuals under the age of 21) 
must be included in all human subjects research, conducted or supported by the 
NIH, unless there are scientific and ethical reasons not to include them.  
This policy applies to all initial (Type 1) applications  submitted for 
receipt dates after October 1, 1998.

All investigators proposing research involving human subjects should read the 
“NIH Policy and Guidelines on the Inclusion of Children as Participants in 
Research Involving Human Subjects” that was published in the NIH Guide for 
Grants and Contracts, March 6, 1998, and is available at the following URL 
address:   http://grants.nih.gov/grants/guide/notice-files/not98-024.html.

Investigators also may obtain copies of these policies from the program staff 
listed under INQUIRIES.  Program staff may also provide additional relevant 
information concerning these policies.

NATIONAL ADVISORY COUNCIL ON DRUG ABUSE RECOMMENDED GUIDELINES FOR THE 
ADMINISTRATION OF DRUGS TO HUMAN SUBJECTS

The National Advisory Council on Drug Abuse recognizes the importance of 
research involving the administration of drugs to human subjects and has 
developed guidelines relevant to such research.   Potential applicants are 
encouraged to obtain and review these recommendations of Council before 
submitting an application that will administer compounds to human subjects.  
The guidelines are available on NIDA’s home page at 
www.nida.nih.gov/HSGuide.html or may be obtained by calling (301) 443-2755.

LETTER OF INTENT

Prospective applicants are asked to submit by February 28, 2000, a letter of 
intent that includes a descriptive title of the proposed research; the name, 
address, telephone number, and institution of the Principal Investigator; 
names of other key investigators and their respective institutions (if 
applicable); and the title and number of this RFA in response to which the 
application will be submitted.  Although a letter of intent is not required, 
it is not binding and is not a factor in the peer review of the application.  
The information it contains is helpful, however, in planning for the review of 
applications because it allows NIDA staff to estimate the potential review 
workload and avoid conflict of interest in the review. 

The letter of intent is to be sent to:

Director, Office of Extramural Program Review
National Institute on Drug Abuse
6001 Executive Boulevard, Room 3158, MSC 9547
Bethesda, MD  20892-9547
Telephone:  (301) 443-2755
FAX:  (301) 443-0538

APPLICATION PROCEDURES

The research grant application form PHS 398 (rev. 4/98) is to be used in 
applying for these grants.  Application kits are available at most 
institutional offices of sponsored research and may be obtained from the 
Division of Extramural Outreach and Information Resources, National Institutes 
of Health, 6701 Rockledge Drive, MSC 7910, Bethesda, MD 20892-7910, telephone 
(301) 435-0714,  E-mail:  GrantsInfo@nih.gov.  

SPECIFIC APPLICATION INSTRUCTIONS FOR MODULAR GRANTS

The modular grant concept establishes specific modules in which direct costs 
may be requested, as well as a maximum level for requested budgets.  Only 
limited budgetary information is required under this approach.  The 
just-in-time concept allows applicants to submit certain information only when 
there is a possibility for an award.  It is anticipated that these changes 
will reduce the administrative burden for the applicants, reviewers, and 
Institute staff.  The research grant application form PHS 398 (rev. 4/98) is 
to be used in applying for these grants, with the modifications noted below.

BUDGET INSTRUCTIONS

Modular Grant applications will request direct costs in $25,000 modules, up to 
a total direct cost request of $250,000 per year.  (Applications that request 
more than $250,000 direct costs in any year must follow the traditional PHS 
398 application instructions.)  The total direct costs must be requested in 
accordance with the program guidelines and the modifications made to the 
standard  PHS 398 application instructions described below:

PHS 398

FACE PAGE - Items 7a and 7b should be completed, indicating Direct Costs (in 
$25,000 increments up to a maximum of $250,000) and Total Costs [Modular Total 
Direct plus Facilities and Administrative (F&A) costs] for the initial budget 
period. Items 8a and 8b should be completed indicating the Direct and Total 
Costs for the entire proposed period of support.

DETAILED BUDGET FOR THE INITIAL BUDGET PERIOD - Do not complete Form Page 4 of 
the PHS 398.  It is not required and will not be accepted with the 
application.

BUDGET FOR THE ENTIRE PROPOSED PERIOD OF SUPPORT - Do not complete the 
categorical budget table on Form Page 5 of the PHS 398.  It is not required 
and will not be accepted with the application.

NARRATIVE BUDGET JUSTIFICATION - Prepare a Modular Grant Budget Narrative page 
(see http://grants.nih.gov/grants/funding/modular/modular.htm for sample 
pages).  At the top of the page, enter the total Direct Costs requested for 
each year.  This is not a Form page.

Under Personnel, list key project personnel, including their names, percent of 
effort, and roles on the project.  No individual salary information should be 
provided.  However, the applicant should use the NIH appropriation language 
salary cap and the NIH policy for graduate student compensation in developing 
the budget request.

For Consortium/Contractual costs, provide an estimate of total costs (Direct 
plus F&A) for each year, each rounded to the nearest $1,000.  List the 
individuals/organizations with whom consortium or contractual arrangements 
have been made, the percent effort of key personnel, and the role on the 
project.  Indicate whether the collaborating institution is foreign or 
domestic.  The total cost for a consortium/contractual arrangement is included 
in the overall requested Modular Direct Cost amount.  Include the letter of 
intent to establish a consortium.

Provide an additional narrative budget justification for any variation in the 
number of modules requested.

BIOGRAPHICAL SKETCH - The Biographical Sketch provides information used by 
reviewers in the assessment of each individual's qualifications for a specific 
role in the proposed project, as well as to evaluate the overall 
qualifications of the research team.  A biographical sketch is required for 
all key personnel, following the instructions below.  No more than three pages 
may be used for each person.  A sample biographical sketch may be viewed at:  
http://grants.nih.gov/grants/funding/modular/modular.htm.

- Complete the educational block at the top of the Form page;
- List position(s) and any honors;
- Provide information, including overall goals and responsibilities, on 
research projects ongoing or completed during the last three years; and
- List selected peer-reviewed publications, with full citations.

CHECKLIST - This page should be completed and submitted with the application. 
 If the F&A rate agreement has been established, indicate the type of 
agreement and the date.  All appropriate exclusions must be applied in the 
calculation of the F&A costs for the initial budget period and all future 
budget years.

The applicant should provide the name and phone number of the individual to 
contact concerning fiscal and administrative issues if additional information 
is necessary following the initial review. 

The RFA label available in the PHS 398 (rev. 4/98) application form must be 
affixed to the bottom of the face page of the application.  Failure to use 
this label could result in delayed processing of the application such that it 
may not reach the review committee in time for review.
In addition, the title and number of this RFA must be typed in Item 2 on the 
face page of the application form, and the YES box must be marked.  The RFA 
number must be typed on the label as well.

The sample RFA label is available at: 
http://grants.nih.gov/grants/funding/phs398/label-bk.pdf has been modified to 
allow for this change.  Please note this is in pdf format.

Submit a signed, typewritten original of the application, including the 
Checklist, and three signed photocopies in one package to:

CENTER FOR SCIENTIFIC REVIEW
NATIONAL INSTITUTES OF HEALTH
6701 ROCKLEDGE DRIVE, ROOM 1040 - MSC 7710
BETHESDA, MD  20892-7710
BETHESDA, MD  20817 (for express/courier service)

At the time of submission, two additional copies of the application must be 
sent to:

Director, Office of Extramural Program Review
National Institute on Drug Abuse
6001 Executive Boulevard, Room 3158, MSC 9547
Bethesda, MD  20892-9547
Rockville, MD  20852 (for express/courier service)

Applications must be received by March 29, 2000.  If an application is 
received after that date, it will be returned to the applicant without review. 
 The Center for Scientific Research (CSR) will not accept any application in 
response to this RFA that is essentially the same as one currently pending 
initial review, unless the applicant withdraws the pending application.  The 
CSR will not accept any application that is essentially the same as one 
already reviewed.  This does not preclude the submission of substantial 
revisions of applications already reviewed, but such applications must include 
an introduction addressing the previous critique.

REVIEW CONSIDERATIONS

Upon receipt, applications will be reviewed for completeness by the CSR and 
for responsiveness by NIDA.  Incomplete and/or non-responsive applications 
will be returned to the applicant without further consideration.

Applications that are complete and responsive to the RFA will be evaluated for 
scientific and technical merit by an appropriate peer review group convened by 
NIDA in accordance with the review criteria stated below.  As part of the 
initial merit review, a process will be used by the initial review group in 
which applications receive a written critique and undergo a process in which 
only those applications deemed to have the highest scientific merit, generally 
the top half of the applications under review, will be discussed, assigned a 
priority score, and receive a second level review by the NIDA National 
Advisory Council.

REVIEW CRITERIA

The goals of NIH-supported research are to advance the understanding of 
biological systems, improve the control of disease, and enhance health.  In 
the written comments, reviewers will be asked to discuss the following aspects 
of the application in order to judge the likelihood that the proposed research 
will have a substantial impact on the pursuit of these goals.  Each of these 
criteria will be addressed and considered in assigning the overall score, 
weighting them as appropriate for each application.  Note that the application 
does not need to be strong in all categories to be judged likely to have major 
scientific impact and thus deserve a high priority score.

(1)  Significance:   Are the goals and objectives of this application relevant 
to this RFA?  Does this study address an important problem?  If the aims of 
the application are achieved, how will scientific knowledge be advanced?  What 
will be the effect of these studies on the concepts or methods that drive this 
field?  

(2)  Approach:  Are the conceptual framework, design, methods, and analyses 
adequately developed, well-integrated, and appropriate to the aims of the 
project?  Does the applicant acknowledge potential problem areas and consider 
alternative tactics?  

(3)  Innovation:  Does the project employ novel concepts, approaches, or 
method? Are the aims original and innovative?  Does the project challenge 
existing paradigms or develop new methodologies or technologies?  

(4)  Investigator:  Is the investigator appropriately trained and well suited 
to carry out this work?  Is the work proposed appropriate to the experience 
level of the principal investigator and other researchers (if any)?

(5)  Environment:  Does the scientific environment in which the work will be 
done contribute to the probability of success?  Do the proposed experiments 
take advantage of unique features of the scientific environment or employ 
useful collaborative arrangements?  Is there evidence of institutional 
support?

In addition to the above criteria, in accordance with NIH policy, all 
applications will also be reviewed with respect to the following:

The adequacy of plans to include both genders, minorities, and their 
subgroups, as appropriate for the scientific goals of the research.  Plans for 
the recruitment and retention of subjects will also be evaluated. 

The adequacy of plans to make data available to other investigators in a 
timely fashion.

The reasonableness of the proposed budget and duration in relation to the 
proposed research.

The adequacy of the proposed protection for humans, animals, or the 
environment, to the extent they may be adversely affected by the project 
proposed in the application.

The adequacy of plans for including children as appropriate for the scientific 
goals of the research.

Schedule:
Letter of Intent:          February 28, 2000		
Application Receipt Date:  March 29, 2000
Special Review Meeting:    Summer 2000
Council Review:            September 2000			
Earliest Start Date:       September 29, 2000		

AWARD CRITERIA

Award criteria that will be used to make award decisions include:  scientific 
merit as determined by peer review, availability of funds, and programmatic 
priorities.

INQUIRIES

Inquiries concerning this RFA are strongly encouraged.  The opportunity to 
clarify issues or questions from potential applicants is welcome.

Direct inquiries regarding programmatic issues to:

Elizabeth Lambert, M.S.
Center on AIDS and Other Medical Consequences of Drug Abuse
National Institute on Drug Abuse
6001 Executive Boulevard, Room.5198, MSC 9593
Bethesda, MD 20892-9593
Telephone:  (301) 402-1933
FAX:  (301) 443-4100
E-mail: el46i@nih.gov  

Direct inquiries regarding fiscal matters to:

Gary Fleming, J.D., M.A.
Grants Management Branch
National Institute on Drug Abuse
6001 Executive Boulevard, Room 3131, MSC 9541
Bethesda, MD  20892-9541
Telephone:  (301) 443-6710
FAX :  (301) 594-6847
E-mail: gf6s@nih.gov

Direct inquiries regarding review matters to:

Teresa Levitin, Ph.D.
Director, Office of Extramural Program Review
National Institute on Drug Abuse
6001 Executive Boulevard, Room 3158, MSC 9547
Bethesda, MD  20892-9547
Telephone :  (301) 443-2755
FAX:  (301) 443-0538
E-mail:  tl25u@nih.gov

AUTHORITY AND REGULATIONS

This program is described in the Catalog of Federal Domestic Assistance No. 
93.279.  Awards are made under authorization of the Public Health Service Act, 
Title IV, Part A (Public Law
78-410, as amended by Public Law 99-158, 42 USC 241 and 285) and are 
administered under PHS grants policies and Federal Regulations 42 CFR 52 and 
45 CFR Part 74.  This program is not subject to the intergovernmental review 
requirements of Executive Order 12372 or Health Systems Agency review.

The PHS strongly encourages all grant recipients to provide a smoke-free 
workplace and promote the non-use of all tobacco products.  In addition, 
Public Law 103-227, the Pro-Children Act of 1994, prohibits smoking in certain 
facilities (or in some cases, any portion of a facility) in which regular or 
routine education, library, day care, health care or early childhood 
development services are provided to children.  This is consistent with the 
PHS mission to protect and advance the physical and mental health of the 
American people.


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