OUTLINE OF PROTOCOL 402

Subjects: Volunteers enrolled in Phase I and II clinical trials of candidate HIV vaccines who have had a subsequent high-risk exposure to HIV-1 and who are suspected of being infected and/or have become infected. The identified partner(s) will also be evaluated if possible.

Study Design: Volunteers who present with evidence of acute or recent HIV-1 infection and are confirmed to be infected with HIV-1 will be enrolled. Enrollees will be evaluated for evolution of virologic, immunologic, and clinical parameters. Once HIV-1 infection is documented and the subject consents to enrollment in Protocol 402, participation in the original study protocol will be terminated.

Time Period: Follow-up of enrolled subjects for at least 5 years

Clinical Sites: Johns Hopkins University, Saint Louis University, University of Alabama, University of Rochester, University of Washington, Vanderbilt University, and study sites outside the AVEG involved in trials of candidate AIDS vaccines or natural history studies

Study Chairs: Barney Graham, Vanderbilt University; Julie McElrath, University of Washington

INCLUSION CRITERIA

• Volunteers (whether vaccine or placebo recipient) participating in AVEG preventive studies that have protocol-specific diagnostic algorithms for detection of HIV infection are enrolled in Protocol 402 if HIV-infection is confirmed or if HIV-infection status remains ambiguous after completion of the diagnostic algorithm.
• Volunteers (whether placebo or vaccine recipient) from any preventive vaccine study that does not have a specific algorithm for detection of HIV infection who meet one or more of the following criteria:
  • Report a clinical syndrome compatible with acute retroviral infection
  • Have an unexplained drop in the CD4+ lymphocyte count (>300/mm³ or >30%) or have an absolute CD4 count of <400/mm³
  • Have test results in routine screening assays consistent with incident of HIV infection
  • Report an unprotected high-risk exposure (sharing of blood or bodily fluids) with a person known to be HIV-1-infected or an anonymous partner and who are clinically suspected of being infected with HIV-1 and subsequently shown to have laboratory evidence of HIV-1 infection. AND, after evaluation per protocol-specific procedures and the Algorithm for Determination of HIV Infection in AVEG Trials, are confirmed to be infected or whose infection status remains ambiguous.
• Person(s) identified as an infected volunteer's partner who contact the study site and agree to be evaluated in Protocol 402.

EXCLUSION CRITERIA

• None

NOTES:

• Pregnant or lactating women unable to tolerate the requirements of the study and those with poor venous access will have modifications of the blood draw requirements to allow them to participate safely.
• Subjects on anti-retroviral or immunomodulatory therapy will not be excluded.

STUDY GOALS

The purpose of the study is to provide for the intensive long-term evaluation of the immunologic, virologic and clinical parameters of candidate vaccine or placebo recipients who become HIV-1 infected after enrollment in AVEG or other AIDS vaccine clinical trials. After a volunteer has undergone definitive testing to establish the diagnosis of HIV-1 infection, the following questions will be addressed:

• What is the viral load pattern in cells and plasma of infected vaccinees and placebo recipients during the acute infection and long-term follow-up?
• How does the genotype, serotype and phenotype of HIV in the vaccinee compare to that of the vaccine strain, the strain(s) isolated from blood and genital secretions of the volunteer's partner, and strains from any infected placebo recipients?
• How do the immune responses generated by the infected volunteers prior to infection compare to those of non-infected volunteers receiving the same treatment on the same immunization schedule?
• What are the kinetics, quality, magnitude, and specificity of the HIV-specific cellular and humoral immune response of infected vaccinees and placebo recipients during the acute infection and long-term follow-up?
• What are the clinical features of acute HIV-1 infection (including nadir of CD4 count) in infected vaccinees and placebo recipients?
• What are the characteristics of disease progression (including rate of CD4 decline) in infected vaccinees and placebo recipients?
• If appropriate non-vaccinated, infected case controls can be identified, how do their immunological, virological and clinical parameters compare to those of infected vaccinees and placebo recipients in acute infection and long-term follow-up?