The acute infection and early disease research program. (Government Research).

The Division of AIDS (DAIDS) of the National Institute of Allergy and Infectious Diseases (NIAID) sponsors pathogenesis and clinical research of primary (acute) HIV infection through the Acute Infection and Early Disease Research Program (AIEDRP). AIEDRP performs innovative, integrated, investigator-initiated pathogenesis and clinical research on acute and early HIV-1 infection. The program was established in 1997 and now consists of 9 participating research units. In addition to conducting research in the United States, some of the AIEDRP units have international research sites, such as Zambia and Brazil.

To date, investigators at each AIEDRP unit have largely conducted their research independently of the other units. In-depth pathogenesis studies are being done to expand current knowledge about viral dynamics, viral reservoirs and resistance, and immune reconstitution. Clinical trials being conducted include a variety of therapies and strategies, such as emtricitabine, interleukin-2, vaccines, and structured treatment interruption.

A database has been established to collect common data from the AIEDRP units, including demographics, transmission information, virologic and immunologic parameters, treatment information, and HIV-associated events. This has provided a large pool of data that can be used for cross-study analyses.

Through the development of extensive screening mechanisms, AIEDRP investigators have helped to identify HIV-positive individuals whose HIV status had been previously unknown. While most did not meet the established definition of acute HIV infection, the investigators are able to refer these people for further follow-up.

The initial work conducted by the AIEDRP investigators, largely basic science research, has resulted in numerous publications, both from the individual units and from shared data available through the AIEDRP common database.

The AIEDRP units and principal investigators currently include

[right arrow] Aaron Diamond AIDS Research Center
              (David Ho),

[right arrow] Johns Hopkins University
             (Joseph Margolick),

[right arrow] University of Alabama at Birmingham
             (George Shaw),

[right arrow] University of California San Diego
              (Douglas Richman),

[right arrow] University of California San Francisco
              (Jay Levy),

[right arrow] University of Colorado Health Sciences
              Center (Robert Schooley), and

[right arrow] University of Washington
              (Lawrence Corey).

Two additional AIEDRP units funded through a separate grant mechanism are in Boston (Bruce Walker) and Vancouver (Brian Conway).

At present, the AIEDRP 5-year funding cycle is drawing to a close. New applications for the next funding cycle were due to the NIH in the fall of 2001. It is anticipated that funding awards will be made in the summer of 2002. AIEDRP units may be added or removed during the next funding cycle. The new AIEDRP, while continuing pathogenesis and clinical trials conducted at each individual site, will also emphasize larger-scale collaborative clinical trials of therapies for acute HIV infection.

Additional information about AIEDRP can be obtained at the AIEDRP Web site (aiedrp.fhcrc.org).

The following research summaries describe what types of work are being conducted at each AIEDRP unit.

* Aaron Diamond AIDS Research Center (ADARC). Studies from these sites (ADARC and Miriam Hospital) have focused on 1) evaluation of the safety and effectiveness of aggressive HAART regimens used during acute and early HIV infection to improve the chance of HIV eradication; 2) use of viral dynamics to document greater antiviral potency of an anti-HIV regimen; 3) virologic and immunologic characterization during treatment and after treatment interruption in subjects with acute and early HIV infection; 4) determination of the prevalence of drug-resistant HIV variants in newly infected individuals; and 5) evaluation of the safety and effects of therapeutic immunization in individuals receiving drug treatment during early HIV infection.

* Johns Hopkins University. This site is conducting a clinical trial to determine if the immune system is improved when IL-2 is given with HAART (as defined by the Panel on the Use of Antiretroviral Agents in Adults and Adolescents). Subjects will receive 2 cycles of therapy; in one cycle, they will receive HAART plus IL-2, followed by a period of IL-2 alone; in the other, they will receive HAART alone, followed by a period of no therapy (this is done in a randomized fashion, so they may receive IL-2 in either cycle 1 or cycle 2).

* University of Alabama at Birmingham. This group is studying the virus and a variety of host factors, including immunogenetic markers, during acute and early HIV infection. They are looking at the dynamics of the establishment of HIV infection in various anatomic compartments in the body, the host response to contain the infection via neutralizing antibodies and cytotoxic lymphocyte attack, and the mechanisms by which HIV seeks to evade this immune response. The researchers have developed a quantitative dynamic understanding of HIV immune control and escape.

* University of California San Diego. Studies from this site and The University of Texas Southwestern Medical Center cover areas such as: 1) evaluation of immune responses to HIV during acute infection, which may help with design of future HIV vaccines; 2) assessment of thymic function and T cell turnover during acute HIV infection, which has implications for future anti-HIV treatments; and 3) assessment of transmission and prevalence of HIV resistance among treatment-naive subjects.

* University of California San Francisco. Researchers are conducting a clinical trial to evaluate whether IL-2 enhances the ability of combination anti-HIV therapy to improve immunologic measures and maintain suppression of the virus below detectable levels.

* University of Colorado Health Sciences Center. Researchers at this site are exploring whether combinations of certain approved and experimental anti-HIV drugs will reduce HIV replication to undetectable levels.

* University of Washington. Researchers are evaluating the safety and efficacy, and immunologic and virologic responses, of quadruple-combination anti-HIV therapy in acutely infected subjects.

* Massachusetts General Hospital (Boston). Studies from this site have focused on 1) evaluation of whether or not early treatment intervention can enhance immune control of HIV after treatment interruption and 2) pathogenesis studies in treated and untreated HIV-infected individuals identified during acute or early infection to assess what may be required of an immune intervention to control HIV infection.

* University of British Columbia. This site is conducting a study that will evaluate the safety and efficacy of HAART in the acutely infected population, as well as the ability of IL-2, following an initial response to HAART, to purge latent viral stores.

Special thanks to Marjorie Dehlinger for preparing this article.