In 1998, new HIV infections world-wide rose to nearly six million, while AIDS deaths increased to 2.5 million, more than were caused by either malaria or tuberculosis. 95% of AIDS cases occur in the developing world. In Zambia, a country in southern Africa, 25-30% of adults in urban areas are infected. In the US, drug-resistant HIV is observed with increasing frequency, and recent declines in HIV mortality have slowed. The US epidemic is increasingly one of underserved minority communities. In Alabama, more than 70% of new HIV infections in 1998 occurred in African-Americans. Understandably, the development of an effective HIV vaccine for global use has been declared the top priority of the NIH AIDS research program. The broad objective of this proposal is the establishment of an HIV Vaccine Trials Unit (HVTU) with a main site at the University of Alabama at Birmingham (UAB) and an international field site at the Zambia-UAB HIV Research Project (ZUHRP) in Lusaka.
The specific aims of the proposed Alabama-Zambia HVTU are: 1) To perform domestic phase I and II clinical trials of candidate HIV vaccines in Alabama, The application describes: six years of AVEU experience at UAB performing phase I and II trials of HIV vaccines in over 225 vaccinated volunteers; and plans for HVTU volunteer recruitment, screening, enrollment, and retention, as well as safety monitoring, immune response analyses, protocol design, and CAB formation. 2) To perform international phase I and II clinical trials of candidate HIV vaccines in Zambia. Thirteen years of field experience in Rwanda and Zambia performing HIV natural history, intervention, and vaccine preparedness studies are described, as are plans for utilizing an existing ZUHRP cohort of HIV sero-discordant or concordant-negative couples in Lusaka for phase I/II HIV vaccine trials. 3) To prepare for future expansion to phase III clinical trials of candidate HIV vaccines in Zambia and Alabama. The Zambian cohort of > 500 discordant couples has a 9% HIV incidence despite voluntary testing and counseling, making this a powerful cohort for fixture efficacy trials. Recently, the Alabama clinic enrolled 125 higher-risk gay men in <5 months in the first US phase III trial. Plans for utilizing these cohorts and others are described.
| Frey, Sharon E; Peiperl, Laurence; McElrath, M Juliana et al. (2014) Phase I/II randomized trial of safety and immunogenicity of LIPO-5 alone, ALVAC-HIV (vCP1452) alone, and ALVAC-HIV (vCP1452) prime/LIPO-5 boost in healthy, HIV-1-uninfected adult participants. Clin Vaccine Immunol 21:1589-99 |
| Churchyard, Gavin J; Morgan, Cecilia; Adams, Elizabeth et al. (2011) A phase IIA randomized clinical trial of a multiclade HIV-1 DNA prime followed by a multiclade rAd5 HIV-1 vaccine boost in healthy adults (HVTN204). PLoS One 6:e21225 |
| Keefer, Michael C; Frey, Sharon E; Elizaga, Marnie et al. (2011) A phase I trial of preventive HIV vaccination with heterologous poxviral-vectors containing matching HIV-1 inserts in healthy HIV-uninfected subjects. Vaccine 29:1948-58 |
| Goepfert, Paul A; Horton, Helen; McElrath, M Juliana et al. (2005) High-dose recombinant Canarypox vaccine expressing HIV-1 protein, in seronegative human subjects. J Infect Dis 192:1249-59 |
