Minimal Levels of HIV-1 Infection

NIAID/NIH RO1, UW Royalty Research Fund , PI:   Tuofu Zhu, MD

This proposal is designed to identify and characterize the frequency, replication state and variability of low-levels of HIV-1 infection by taking advantage of our previous experience in this challenging field with our improved technologies.   We have shown persistence of low levels of HIV-1 infection in a few high-risk Exposed Seronegative (ES) individuals , and parallel evidence for low levels of SIV infection in macaques that were transiently viremic or vaccine-protected by standard assays. Most recently, we have found persistent low levels of HIV-1 infection in four vaccinated persons who were transiently viremic by conventional assays. These findings indicate that minimal levels of HIV-1 infection (MLHI) can be demonstrated in ES and vaccinated persons, only by improved technology with hundreds or thousands of PCR amplifications and sequence analyses on large amounts of cells. The goal of this project is to mechanize the viral detection processes and to assess for MLHI more rigorously among larger cohorts.   These would include ES and vaccine recipients from NIH-funded vaccine trials, mainly the HIV Vaccine Trials Network (HVTN) .   We will characterize the genotype and phenotype of virus in breakthrough MLHI infection. These studies should assist in defining virologic and immunologic characteristics required to attenuate and/or substantially control HIV-1 infection, a critical goal of AIDS vaccine development.

Publications:

• Zhu T , Corey L, Hwangbo Y, Lee J, Learn GH, Mullins JI, &   McElrath MJ.   Evidence for Extraordinarily Low Levels of Genetically Homogeneous Human Immunodeficiency Virus Type 1 Infection in Exposed Seronegative Individuals. J. Virol. In press, 2003.

• Zhu T , Korber BT, Nahmias AJ, Hooper E, Sharp PM, Ho DD. An African HIV-1 sequence from 1959 and implications for the origin of the epidemic. Nature. 391(6667): 594-7, 1998.

• Zhu T , Ho DD. Was HIV present in 1959? Nature. 374(6522): 503-4, 1995.