select one of the following sections:

OPTIMIZATION OF ANTIRETROVIRAL THERAPY (OPART) COMMITTEE

Scientific Agenda of the Optimization Of Antiretroviral Therapy (OPART) Committee

The accomplishments of the Optimization Of Antiretroviral Therapy (OPART) Committee relate to the five major scientific objectives and its overall scientific agenda.

1. Develop new strategies for using antiretroviral therapy that provide optimal initial and subsequent treatment regimens, and study new antiretroviral agents as they are developed.
2. Identify factors related to the failure of treatments and develop treatment strategies for patients whose previous treatment(s) have failed.
3. Determine the impact of HIV drug resistance on therapeutic success.
4. Study the impact of factors related to HIV and HIV-infected persons, and treatment strategies, on long-term clinical, virologic, and immunologic outcome.
5. Support ACTG international research by collaborating with non-U.S. investigators and sites and other DAIDS-sponsored programs.

TRANSLATIONAL RESEARCH AND DRUG DEVELOPMENT (TRADD) COMMITTEE

Scientific Agenda of the Translational Research and Drug Development (TRADD) Committee

The major scientific objectives of the Translational Research and Drug Development (TRADD) Committee are as follows:

1. Perform phase I/II proof of concept studies of new therapies with potential activity against HIV.
2. Perform phase I pharmacokinetic studies of new anti-HIV agents.
3. Perform studies of potential drug interactions among HIV drugs and other agenda of importance to HIV-infected subjects.
4. Perform studies of the influence of age, gender, and race on the pharmacokinetics of HIV medications.
5. Define the role of HIV-specific immune responses in regulating HIV and use this to enhance control of HIV.
6. Assess immune-based therapies to improve CD4+ T-lymphocyte recovery and general immune function.
7. Evaluate potential therapies intended to reduce the pathogenic consequences of acute and chronic HIV infection.
8. Conduct studies of strategies to determine the feasibility of promoting clearance of HIV from the latent cell reservoir.
9. Develop, validate, standardize, and quality assure virologic and immunologic assays to be used in ACTG studies.
10. Conduct studies to determine the pathologic and clinical implications of drug resistance mutations and changes in replicative capacity of the virus.
11. Evaluate genetic and other host factors that may influence the course of HIV infection and response to antiretroviral therapy and immune based therapies.

The TRADD Committee was created in 2006 in order to foster the collaborative efforts among virologists, immunologists, pharmacologists, and other HIV clinical researchers in the design of exploratory proof-of-concept clinical studies of new HIV therapeutics, clinically-relevant pharmacology studies, and translational studies of HIV pathogenesis. It has focused on the development of new antiretroviral drugs, both in the existing classes of compounds and in new classes targeting novel steps in the HIV life cycle. Studies of methods of enhancing HIV-specific immunity, with the ultimate goal of reducing the need for antiretrovirals, remain a high priority. Efforts to improve CD4+ lymphocyte recovery and general immune function continue to be a focus, as well as potential therapies to reduce the pathogenic consequences of HIV infection. In addition to phase l and ll pharmacology trials, it performs studies of potential drug interactions among HIV drugs and between HIV drugs and other agents of importance to HIV-infected patients, as well as studies of the influence of age and gender on the pharmacokinetics of HIV medications. Finally, the TRADD Committee is conducting studies of strategies that probe the latent cell reservoir of HIV, in order to answer pathogenesis questions about the maintenance of this compartment and determine the ultimate feasibility of promoting clearance of HIV from the reservoir.

OPTIMIZATION OF CO-INFECTION & CO-MORBIDITY MANAGEMEMT (OPMAN) COMM

Scientific Agenda of the Optimization Of Co-Infection & Co-Morbidity Management (OPMAN) Committee

The Optimization of Co-Infection and Co-Morbidity Management (OpMAN) Committee is responsible for development, implementation, and oversight of the ACTG research agenda related to optimizing the management of co-infections and co-morbidities associated with HIV infection, both in domestic and international settings. The OpMAN Committee has five major areas of scientific focus:

• Diagnosis, prevention, treatment, and pathogenesis of opportunistic diseases, with a particular emphasis on tuberculosis.
• Treatment, prevention, and pathogenesis of neurological complications of HIV infection, especially peripheral neuropathy and HIV-associated cognitive impairment.
• Treatment, prevention and pathogenesis of AIDS-related malignancies, particularly those that result from co-infection with human papilloma virus (HPV) and Kaposi’s Sarcoma Herpesvirus (KSHV or HHV-8).
• Evaluation of vaccines to prevent co-infections in persons with HIV, including HPV and varicella zoster virus (VZV).
• Diagnosis, prevention, treatment, and pathogenesis of oral complications of HIV infection.

Development and implementation of the OpMAN research agenda is facilitated by two affiliated groups: the Neurology Subcommittee and the Oral HIV/AIDS Research Alliance (OHARA) Subcommittee. These groups draft guidelines for treatment, develop concept proposals for high-priority scientific questions, and monitor and advise the OpMAN Committee on the most recent scientific data in their respective areas of scientific expertise.

HEPATITIS COMMITTEE

The Hepatitis Committee (HEP) is composed of national experts from different areas of research and governmental agencies. The Committee will focus on treatment and management, viral dynamics, immunology, and genomic questions of the HIV/HCV and HIV/HBV coinfections and HCV and HBV monoinfections.

The initial emphasis is on the development of drugs for strategies for the optimal timing and treatment of each virus and for the treatment of drug resistance and salvage therapy. The determination of the natural history and epidemiology of HIV/HCV is being investigated as well as non-invasive markers of fibrosis. The impact of HBV genotypes on the natural history, drug response, and resistance internationally is recognized as being equally important. The HEP Committee will also be looking at non-hepatitis steatosis, hepatoxicity, fatty liver disease, and drug interactions particularly with antiretrovirals or other drugs used in the treatment of AIDS.

The HEP Committee members are charged with developing protocols that are compliant with the scientific research agenda and answer the scientific questions. They will assist in writing grants for appropriate outside funding and will identify pharmaceutical support for early drug studies. Members will be in contact with the local ACTG sites to increase awareness of the HEP Committee scientific agenda and to encourage enrollment into the HEP Committee sponsored studies.

WOMEN'S HEALTH

Women's Studies Protocol Status Report

The overall focus of the WHC scientific agenda is to develop optimal strategies for the prevention and treatment of HIV-1 disease and related complications among women, and to determine the pathogenesis of manifestations unique to women. The two highest priority scientific objectives for the Women's Health Committee (WHC) in the past year have been

1. To examine the impact of contraception, hormonal interventions, and pregnancy on the health of HIV-1-infected women
2. To examine interactions between sex, body-mass index, pharmacokinetic parameters, and antiretroviral drug (ARV) toxicity

The WHC scientific agenda also includes items related to each RAC and to the International scientific agenda.

WHC considers efforts to increase the enrollment of women into ACTG trials as important as the highest-priority research objectives outlined above, since we must enroll a substantial proportion of women to learn about the course of HIV disease and optimal therapy for women. WHC advisory, training, and liaison activities help to support our efforts to optimize the enrollment of women into ACTG trials.

• Increase the recruitment and retention of HIV-1-infected women into ACTG trials.
• Provide education and advice regarding the appropriate use of contraception and fertility regulation policy in the context of clinical trials.
• Train ACTG staff in techniques needed for women-focused protocols.
• Provide a liaison with other groups conducting research in the health of HIV-1-infected women.

LABORATORY RESOURCES

The ACTG provides access to laboratories with state-of-the-art expertise in specialized assay development and application. The ACTG funds these core Specialty Laboratories and through them centralizes the virology, immunology, and pharmacology research specimen analysis.

The core laboratory approach affords uniformity of data, efficiency with reduced cost, streamlined specimen tracking, quality assurance, and rapid incorporation of novel techniques. In addition to routine laboratory testing, the Specialty Laboratories develop of innovative assays and , methodologies for future application to ACTG clinical trials.

Virology Specialty Laboratories (VSL): The primary focus of the Virology Scientific Agenda is HIV pathogenesis as it relates to antiretroviral therapy. The agenda is divided into the following areas: HIV drug resistance, reservoirs for HIV replication, HIV replication fitness, human genetic predictors of antiretroviral treatment response, international virology training and technology transfer. VSLs perform HIV-1 RNA quantitation, DNA-PCR, SI phenotyping, neutralizing antibody assays and phenotypic and genotypic resistance susceptibility testing.

Immunology Specialty Laboratories: The Immunology Laboratory Scientific Agenda includes development and validation of HIV-specific immune function assays, development and validation of hepatitis C-specific immune assays, immunology laboratory performance analysis and cost containment, and quality assurance. The international agenda includes alternate methods for CD4 T-cell enumeration and the identification of appropriate assays to assess pathogen-specific immune responses.

Pharmacology Specialty Laboratories perform accepted clinical pharmacology parameters as well as bioavailability, drug-drug interaction, and gender specific analyses.

INTERNATIONAL AGENDA

The investigators of the ACTG are strongly supportive of the international effort to accelerate access to HIV care in resource-limited settings. The overall goals of the ACTG's international program include clinical, translational and operational research, transfer of technology and enhancement of access to medical care.

The ACTG Executive and Scientific Committees have developed a mechanism by which international investigators will be incorporated within the scientific leadership of the ACTG and with whom they will develop and prioritize an international research agenda. The research will be conducted in the context of a series of clinical protocols that will be developed from this agenda and that will attempt to synergize with in country prevention and vaccine development efforts.

Current status: Working in collaboration with international investigators and with the HIV Prevention Trials Network, two protocols have been developed that can be implemented in the next 6 - 9 months. One study (HPTN 052) seeks to evaluate whether antiretroviral therapy can decrease sexual transmission from HIV seropositive individuals to their partners. The other (ACTG 5175), which was primarily designed by in country investigators, seeks to define the optimal reverse transcripase-based regimens for these settings.