EXPERIMENTAL HUMAN INFECTION WITH HAEMOPHILUS DUCREYI IN PERSONS WHO ARE HIV

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Haemophilus ducreyi is a bacterium that causes chancroid, a genital ulcer disease (GUD) that is common in many developing countries. Chancroid is a public health problem because persons with chancroid acquire the human immunodeficiency virus (HIV) at a rate that is higher than persons who do not have chancroid. Persons who are co-infected with HIV and chancroid have detectable HIV DNA or recoverable HIV in their genital ulcers and may transmit HIV more readily to their partners than persons infected with HIV alone. However, little is known about how the bacterial infection affects HIV replication in co-infected patients. The purpose of this protocol is to evaluate the safety of infecting selected, clinically stable, HIV seropositive individuals with H. ducreyi and to examine how H. ducreyi interacts with HIV. Our hypotheses are that local infection with H. ducreyi to the pustular stage of disease will be safe, and will not affect viral replication or CD4 counts in the systemic compartment, but will recruit latently infected memory CD4 cells and macrophages into the lesions, activate them, and cause them to produce virus locally. These studies will help us understand the biological mechanisms that allow co-infected persons to be more efficient transmitters of HIV than persons infected with HIV alone, establish which latently infected cells produce HIV upon immune stimulation, and provide a compelling scientific rationale to focus public health efforts on chancroid eradication in HIV endemic areas.