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. Co-infection of macaques with SIV and Plasmodium cynomolgi, a parasite that causes vivax-like malaria was used to develop a non-human primate model of HIV-1/malaria in humans. It was hypothesized that malaria may alter the progression of SIV infection by activating lymphocytes which preferentially support the growth of this virus; likewise, the immunosuppression caused by SIV may alter the growth of P. cynomolgi. The four animal groups used were: SIV-only (n = 5), SIV/malaria (n = 5), malaria-only (n = 5), and mock-infected controls (n = 3). All groups have been inoculated with either SIV, P. cynomolgi, or a combination of the 2 with SIV following malaria to mimic the situation experienced in malaria endemic regions where exposure to malaria occurs before HIV. The parameters studied included virus levels, parasite levels, clinical blood counts, lymphocyte subset distributions, antibody levels to SIV and P. cynomolgi antigens, cytokine and chemokine levels in blood and lymph nodes and in situ hybridization of organisms in tissues. Results indicate that parasitemia is worse in monkeys who are co-infected with SIV with an increased incidence of recrudescence(~8-10 per animal) in the SIV/malaria group as compared to what has been observed historically with malaria alone (2-4 relapses). However, this is still under investigation as the control group with malaria alone has only recently been inoculated (Feb 06). However, SIV viral loads have not proven to be significantly different in co-infection compared to SIV alone and no significant differences occurred in the survival curves between the SIV and the SIV/malaria groups. However, CD4+ counts in the SIV/malaria group have decreased more rapidly and to a lower absolute count than that observed with SIV alone and CD8+ counts declined in the SIV/malaria group while increasing in the SIV group. Cytokine and chemokine analysis studies are currently in progress.
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