This Program Announcement expires on May 2, 2004, unless reissued.


Release Date:  June 28, 2001

PA NUMBER:  PA-01-113 (see replacement PA-04-157)
                      (see NOT-AI-04-014 and NOT-AI-04-010)

National Institute of Allergy and Infectious Diseases
National Cancer Institute
National Institute of Dental and Craniofacial Research

Application Receipt Dates:  January 2, May 1, September 1


The purpose of this Program Announcement (PA) is to encourage research grant 
applications aimed at novel approaches to discovery and preclinical 
development of therapeutic agents against opportunistic infections (OIs) and 
malignancies in people with AIDS.  The intent of this PA is to seek 
investigator-initiated grant applications that involve creative and original 
preclinical research utilizing state-of-the-art technologies necessary to 
propel advances in new or improved therapies.  No clinical trials will be 
supported under this PA.

This PA is being issued by NIAID, and co-sponsored by the National Cancer 
Institute (NCI) and the National Institute of Dental and Craniofacial 
Research (NIDCR).  The National Heart, Lung, and Blood Institute (NHLBI), and 
the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) 
also have an interest in and support research on opportunistic infections 
associated with AIDS.  Applicants may wish to contact these NIH components 
listed under INQUIRIES to find out about other funding opportunities.
Applicants for Small Business Innovation Research (SBIR) projects on 
investigational areas included in this PA should consider applying through 
NIAID PAR 00-126, published in the NIH Guide for Grants and Contracts on July 
26, 2000, which is available on the World Wide Web at:


The Public Health Service (PHS) is committed to achieving the health 
promotion and disease prevention objectives of "Healthy People 2010," a PHS 
led national activity for setting priority areas.  This Program Announcement 
(PA), Therapeutics Research on AIDS-Associated Opportunistic Infections, is 
related to one or more of the priority areas.  Potential applicants may 
obtain a copy of "Healthy People 2010" at


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 


This PA will use the National Institutes of Health (NIH) individual research 
project grant (R01) and the exploratory/developmental grant (R21) mechanism.  
A sound rationale and a well-designed research plan with limited preliminary 
data are required for a R21.  The R01 supports more advanced projects.  
Responsibility for the planning, direction, and execution of the proposed 
research for all applicable mechanisms of support will be solely that of the 

Specific application instructions have been modified to reflect "MODULAR 
GRANT" and "JUST-IN-TIME" streamlining efforts being examined by the NIH. 
Complete and detailed instructions and information on Modular Grant 
applications can be found at

A notice of modification and update (OD-00-046) regarding modular grants was 
released on 7/24/00 and can be found at

SBIR applicants should refer to NIAID PAR-00-126 cited above.

Applicants for R01 grants will request direct costs in $25,000 modules, up to 
a total direct cost request of $250,000 per year. This applies only up to 
$250,000. Applications that request more than $250,000 direct costs in any 
year must follow the traditional PHS 398 application instructions.  A typical 
modular grant application will request the same number of modules in each 
year. Applications for R01 grants may request a maximum five years of 

Applicants for the R21 grant mechanism may request up to $150,000 (6- $25,000 
modules) direct costs per year and support may not exceed two years.  This 
mechanism provides short-duration support for preliminary studies of a highly 
speculative nature, which are expected to yield sufficient information upon 
which to base a well-planned and rigorous series of further investigations.  
The R21 grants are non-renewable and competitive continuation of projects 
developed under this grant mechanism will be through the R01 research grant 
mechanism.  Funds and time requested should be appropriate for the research 


AIDS-Associated Opportunistic Infections

The most notable advance in AIDS-associated opportunistic infections (OIs) 
has been the decline in their incidence, which is a result of the effect of 
potent antiretroviral therapy.  Recent findings also suggest that although 
the natural history of OIs in patients with HIV infection is changing, OIs 
are still an important clinical and pathophysiological manifestation of HIV 
disease.  For example, HIV-infected patients have an elevated risk of primary 
or reactivated tuberculosis, and such active infectious processes may enhance 
HIV replication and increase risk of death.

The long-term effectiveness of antiretroviral therapy in developed countries 
remains unknown, and it is unclear whether the reduced rates of OIs are 
temporary or permanent.  HIV/AIDS continues at an epidemic rate in developing 
countries where antiretroviral therapy remains unavailable.

Significant pathological consequences associated with OIs in AIDS include 
tuberculosis (Mycobacterium tuberculosis), pneumonia (Pneumocystis carinii), 
protracted diarrhea (Cryptosporidium parvum, Enterocytozoon bieneusi) and 
painful oral ulcerative lesions.

Limitations of currently available drugs for treatment and prevention of OIs 
include the static nature of most agents, toxicity, and emergence of 
resistance.  The discovery of more potent and less toxic compounds would 
provide improved medical management of these AIDS-associated complications.  
Furthermore, no standard treatments exist for opportunistic pathogens such as 
C. parvum, and E. bieneusi.

AIDS-Associated Malignancies

As HIV-infected individuals survive longer, the number of cases of AIDS-
associated malignancies (AAMs) continues to increase.  While the incidence of 
Kaposi’s sarcoma and primary CNS lymphomas in HIV-infected individuals has 
been reduced since the widespread use of potent antiretroviral therapy, there 
has been no substantial change in the incidence of non-Hodgkin’s lymphomas, 
cervical cancer and anogenital cancers.  Many of these malignancies are 
associated with viral infections such as Kaposi’s sarcoma herpesvirus (KSHV) 
with Kaposi’s sarcoma, Epstein-Barr virus (EBV) with certain lymphomas, and 
human papillomavirus (HPV) with cervical and anogenital cancers.  Therapies 
developed for cancers in the non-immunocompromised setting have not always 
proven to be effective in patients with HIV/AIDS.  Oral cancers may in fact 
remain the same or increase following potent antiretroviral treatment.  The 
discovery of new therapies for AAMs remains an unmet need.

Research Objectives and Experimental Approaches

The goal of this PA is the development of agents for treatment of AIDS-
associated OIs and malignancies.  Given present advances in molecular 
biology, the principal objectives of the PA are to stimulate original and 
innovative preclinical research to (1) identify and characterize new, 
pathogen-specific or malignancy-specific molecular targets and (2) develop 
promising therapeutic approaches.  Applications directly linking disease 
pathogenesis to molecular target identification are encouraged.

AIDS-associated opportunistic pathogens emphasized by this PA are: 
Mycobacterium tuberculosis, Pneumocystis carinii, Cryptosporidium parvum, and 
the microsporidia.

AIDS-associated malignancies emphasized by this PA are: Kaposi’s sarcoma, 
lymphomas, cervical cancer, oral warts and cancers, and anogenital cancers.

Areas of study may include but are not restricted to the following examples:

o  discovery and development of efficacious new therapeutic agents for 
treatment of AIDS-associated OIs and malignancies,

o  validation of molecular targets for therapeutic agents utilizing state-of-
the-art molecular genetic technology,

o  discovery and evaluation of novel, selective chemical entities generated 
by combinatorial chemistry or combinatorial genomics methodologies,

o  development of improved delivery systems for therapeutic agents (improved 
bioavailability, pharmacokinetics), and

o  development of improved assays, in vitro (cell culture) and in vivo 
(animal model) systems for drug evaluations.


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 and justification is provided that inclusion is 
inappropriate with respect to the health of the subjects or the purpose of 
the research. This 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," which have been published in the Federal Register of March 28, 
1994 (FR 59 14508-14513) and in the NIH Guide for Grants and Contracts, Vol. 
23, No. 11, March 18, 1994 available on the web at the following URL address:


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 

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


All applications and proposals for NIH funding must be self-contained within 
specified page limitations.  Unless otherwise specified in an NIH 
solicitation, internet addresses (URLs) should not be used to provide 
information necessary to the review because reviewers are under no obligation 
to view the Internet sites.  Reviewers are cautioned that their anonymity may 
be compromised when they directly access an Internet site.


The Office of Management and Budget (OMB) Circular A-110 has been revised to 
provide public access to research data through the Freedom of Information Act 
(FOIA) under some circumstances.  Data that are (1) first produced in a 
project that is supported in whole or in part with Federal funds and (2) 
cited publicly and officially by a Federal agency in support of an action 
that has the force and effect of law (i.e., a regulation) may be accessed 
through FOIA.  It is important for applicants to understand the basic scope 
of this amendment.  NIH has provided guidance at:

Applicants may wish to place data collected under this PA in a public 
archive, which can provide protections for the data and manage the 
distribution for an indefinite period of time.  If so, the application should 
include a description of the archiving plan in the study design and include 
information about this in the budget justification section of the 
application. In addition, applicants should think about how to structure 
informed consent statements and other human subjects procedures given the 
potential for wider use of data collected under this award.

Applications are to be submitted on the grant application form PHS 398 (rev. 
4/98) at and will be accepted at the 
standard application deadlines ( as 
indicated in the application kit. Application kits are also 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 301/710-0267, email:

Applicants planning to submit an investigator-initiated new (type 1), 
competing continuation (type 2), competing supplement, or any amended/revised 
version of the preceding grant application types requesting $500,000 or more 
in direct costs for any year are advised that he or she must contact the 
Institute or Center (IC) program staff before submitting the application, 
i.e., as plans for the study are being developed. Furthermore, the 
application must obtain agreement from the IC staff that the IC will accept 
the application for consideration for award. Finally, the applicant must 
identify, in a cover letter sent with the application, the staff member and 
Institute or Center who agreed to accept assignment of the application. 

This policy requires an applicant to obtain agreement for acceptance of both 
any such application and any such subsequent amendment. Refer to the NIH 
Guide for Grants and Contracts, March 20, 1998 at



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

o 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.

of the PHS 398. It is not required and will not be accepted with the 

categorical budget table on Form Page 5 of the PHS 398. It is not required 
and will not be accepted with the application.

o NARRATIVE BUDGET JUSTIFICATION - Prepare a Modular Grant Budget Narrative 
page. (See for 
sample pages.) At the top of the page, enter the total direct costs requested 
for each year.  This is not a Form page.

o Under Personnel, List all 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 facilities and administrative) 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 all 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.

o 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:

- 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.
- List selected peer-reviewed publications, with full citations,

o 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.

o 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 title and number of the program announcement must be typed on line 2 of 
the face page of the application form and the YES box must be marked.

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

BETHESDA, MD 20892-7710
BETHESDA, MD 20817 (for express/courier service)


Review Procedures

Applications will be assigned on the basis of established NIH referral 
guidelines. Applications will be evaluated for scientific and technical merit 
by an appropriate scientific review group convened in accordance with the 
standard NIH peer review procedures. As part of the initial merit review, all 
applications will 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 applications under review, will be discussed, 
assigned a priority score, and receive a second level review by the 
appropriate national advisory council or board.

Review Criteria

The goals of NIH-supported research are to advance our understanding of 
biological systems, improve the control of disease, and enhance health.  The 
reviewers will comment on the following aspects of the application in their 
written critiques 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 by the reviewers 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 a major scientific impact and thus deserve a high priority 
score.  For example, an investigator may propose to carry out important work 
that by its nature is not innovative but is essential to move a field 

1) Significance. 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 

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

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

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

o 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.


Applications will compete for available funds with all other recommended 
applications. The following will be considered in making funding decisions: 

o scientific merit (as determined by peer review)
o availability of funds
o programmatic priorities.


Written and telephone inquiries are encouraged.  The opportunity to clarify 
any issues or questions from potential applicants is welcome.

The National Institute of Allergy and Infectious Diseases has an interest in 
the validation of novel molecular targets for drug development programs and 
the evaluation of new and novel therapies against AIDS-associated 
opportunistic infections.  Inquiries regarding programmatic issues may be 
directed to:

Chris Lambros, Ph.D.
Division of AIDS
National Institute of Allergy and Infectious Diseases
6700B Rockledge Drive, Room 5227, MSC 7624
Bethesda, MD  20892-7624
Telephone:  301-435-3769
FAX:  301-402-3171

The National Cancer Institute (NCI) has an interest in the discovery and 
validation of novel molecular targets for drug discovery programs and the 
evaluation of new and novel therapies against AIDS-associated malignancies.  
Therefore, applications of  interest on AIDS-associated malignancies are 
likely to be given primary assignment to NCI in accordance with the NIH 
referral guidelines.  Inquiries regarding NCI programmatic issues may be 
directed to:

Kenneth Cremer, PhD
Division of Cancer Biology
National Cancer Institute
Room 5016
6130 Executive Boulevard, MSC 7398
Bethesda, MD  20892-7398
Telephone:  301-496-6085
FAX:  301-496-2025

The National Institute of Dental and Craniofacial Research (NIDCR) has an 
interest in opportunistic infections in the oral cavity.  Therefore, 
applications of interest will be assigned to NIDCR in accordance with the NIH 
referral guidelines.  Inquiries regarding NIDCR programmatic issues may be 
directed to:

Dennis F. Mangan, Ph.D.
Division of Extramural Research
National Institute of Dental and Craniofacial Research
Building 45, Room 4AN-32F, MSC 6402
Bethesda, MD  20892-6402
Telephone:  301-594-2421
FAX:  301-480-8318

The National Heart, Lung, and Blood Institute (NHLBI) has an interest in
supporting research on the pulmonary, cardiovascular and hematologic aspects 
of opportunistic infections associated with HIV infection.  Therefore, 
applications of interest are likely to be given a may be primary or secondary  
assignment to NHLBI in accordance with the NIH referral guidelines.  
Inquiries regarding NHLBI programmatic issues may be directed to:

Hannah H. Peavy, M.D.
Division of Lung Diseases
National Heart, Lung, and Blood Institute
6701 Rockledge Drive, Suite 10018, MSC 7952
Bethesda, MD  20892-7952
Telephone:  301-435-0222
FAX:  301-480-3557

The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) 
has an interest in supporting research on the influence of opportunistic 
pathogens on the enterocytes in the gastrointestinal tract as well as the 
hepatocytes in the liver in liver disease expression.  Therefore, 
applications of interest are likely to be given a may be primary or secondary 
assignment to NIDDK in accordance with the NIH referral guidelines.  
Inquiries regarding NIDDK programmatic issues may be directed to:

Frank A. Hamilton, M.D., Ph.D.
Chief, Digestive Diseases Program Branch
Room 6AN12B
Natcher Building 45
45 Center Drive, MSC 6600
Bethesda, MD  20892-6600
Telephone:  301-594-8877
FAX:  301-480-8300

Direct inquiries regarding fiscal matters to:

Ms. Linda Shaw
Division of Extramural Activities
National Institute of Allergy and Infectious Diseases
Room 2125
6700B Rockledge Drive, MSC 7614
Bethesda, MD  20892-7614
Telephone:  301-402-6611
FAX:  301-480-3780

Mr. Bill Wells
Grants Administration Branch
National Cancer Institute
Executive Plaza South, Room 243
6120 Executive Boulevard, MSC 7150
Bethesda, MD  20892-7150
Telephone:  301-496-8796
FAX:  301-496-8601

Mr. Martin R. Rubinstein
Grants Management Branch
Division of Extramural Research
National Institute of Dental Research
Natcher Building, Room 4AN-44A
Bethesda, MD  20892-6402
Telephone:  301-594-4800
FAX:  301-480-8301


This program is supported under authorization of the Public Health Service 
Act, Sec. 301 (c), Public Law 78-410, as amended.  The Catalogue of Federal 
Domestic Assistance Citations are Sec. 93.856, Microbiology and Infectious 
Diseases Research, No. 93.855 - Immunology, Allergy, and Transplantation 
Research, and 93.121, Oral Diseases and Disorders Research Awards.  Awards 
will be administered under PHS grants policies and Federal Regulations 42 CFR 
Part 52 and 45 CFR Part 74.  This program is not subject to the 
intergovernmental review requirements of Executive Order 12372 or Health 
Systems review.

The PHS strongly encourages all grant and contract 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.

Weekly TOC for this Announcement
NIH Funding Opportunities and Notices

Office of Extramural Research (OER) - Home Page Office of Extramural
Research (OER)
  National Institutes of Health (NIH) - Home Page National Institutes of Health (NIH)
9000 Rockville Pike
Bethesda, Maryland 20892
  Department of Health and Human Services (HHS) - Home Page Department of Health
and Human Services (HHS) - Government Made Easy

Note: For help accessing PDF, RTF, MS Word, Excel, PowerPoint, Audio or Video files, see Help Downloading Files.