OUTLINE OF PROTOCOL 401

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 become infected.

Study Design: Volunteers with evidence of acute HIV-1 infection will be enrolled to confirm infection with HIV-1, evaluated for the evolution of virologic, immunologic, and clinical parameters. If infected they will terminate their original study protocol. If the volunteer is shown not to be HIV-infected they will return to their original vaccine protocol.

Time Period: Follow-up of enrolled subjects for a minimum of 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 vaccines for AIDS

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

INCLUSION CRITERIA

• Volunteers (whether placebo or vaccine recipient) from any preventive vaccine study who 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.
• Volunteers (whether placebo or vaccine recipient) from any preventive vaccine study who:
  • Report a clinical syndrome compatible with acute retroviral infection
  • Have an unexplained drop in the CD4+ lymphocyte count (>200/mm³ or >20%)
  • Found to be incidentally infected in routine screening assays
• The person(s) identified as the probable transmitter who contacts the study site and presents themselves for evaluation.

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 antiretroviral or immunomodulatory therapy will not be excluded.
• Tests will be repeated to confirm or refute the diagnosis of HIV-1 infection. If the diagnosis of HIV-1 infection has not been confirmed in 2 weeks, the volunteer will terminate Protocol 401, and continue with the original vaccine protocol until its completion. Sera collected during the Protocol 401 screening should then be used to cover missed visits in the original protocol.

STUDY GOALS

The purpose of the study is to provide for the intensive evaluation of the immunologic, virologic, and clinical course of vaccinated subjects or placebo recipients who become HIV-infected after enrollment in AVEG or other AIDS vaccine clinical trials. The protocol will provide a template for the combined resources and expertise of a group of investigators to systematically analyze responses of immunized volunteers infected with HIV-1. After a volunteer has undergone definitive testing to establish the diagnosis of HIV-1 infection the additional following questions will be addressed:

• How does the genotype, serotype, and phenotype of HIV in the vaccinee compare to that of the vaccine strain, the strain isolated from transmitter blood and genital secretions, and strains from placebo recipients and nonvaccinees in the same geographic region?
• How does viral load in cells and plasma compare to that in placebo recipients and other nonvaccinated HIV-infected persons during the acute infection and long-term follow-up?
• How do the kinetics, quality, magnitude, and specificity of the HIV-specific cellular and humoral immune response compare to those in placebo recipients and other nonvaccinated HIV-infected persons?
• How do the clinical features of acute HIV-1 infection (including degree of CD4 decline) compare to those in placebo recipients and other nonvaccinated HIV-infected persons?
• How does disease progression (including rate of CD4 decline) compare to that in placebo recipients and other nonvaccinated HIV-infected persons?

REFERENCE

Graham BS, McElrath MJ, Connor RI, Schwartz DH, Gorse GJ, Keefer MC, Mulligan MJ, Matthews TJ, Wolinsky SM, Montefiori DC, Vermund SH, Lambert JS, Corey L, Belshe RB, Dolin R, Wright PF, Korber BT, Wolff MC, Fast PE, AIDS Vaccine Evaluation Group, Correlates of HIV Immune Protection Group. Analysis of intercurrent human immunodeficiency virus type 1 infections in Phase I and II trials of candidate AIDS vaccines. J Infect Dis. 1998;177:310-319.