Zambia is a sub-sahara African nation that is located in the HIV belt where there is a very high incidence of HIV infection.. In the general population, it is estimated that both 30 to 40% may be infected by HIV. Our preliminary study with at randomized cohort of pregnant women, delivering at the University of Zambia Teaching Hospital in Lusaka, Zambia, showed an HIV seroprevalence rate of about 32%. It is expected that many of the babies born to these women will also be infected by HIV. The HIV isolated from this region of the world are the non-major subgroup, such as subgroup Clade C. Thus, there is an urgent need to develop inexpensive and effective means to prevent perinatal transmission of Clade C viruses. This program project proposes to test a combination of active and passive immunoprophylaxis treatments on newborns to prevent vertical transmission, focusing on the Clade C virus, using the SHIV virus to test in the macaque model. This core will make use of an ongoing study in Zambia to study the transmission of Kaposi's sarcoma associated herpesviruses, KSHV, or human herpesvirus-8, HHV-8. Using the developed infrastructure at the University Teaching Hospital in Zambia, its ongoing recruitment of mother-infant pairs at delivery, as well as follow-up studies to collect matched mother-infant pairs, Clade C or non-Clade B local viral isolates to support the program project.
The specific aims are: 1) To recruit mother/infant pairs into this study; to identify those that have transmitted HIV vertically. 2) To isolated both the mother/infant viral pairs. 3) To PCR amplify, clone, and determine the viral Clade subgroup by sequence analysis. 4) To clone and express the HIV env genes, and to determine whether the cloned env genes are functional by pseudotyping. 5) To provider the cloned functional env genes from the infants' HIV isolates, the paired Clade C or local HIV Clade strains, as well as whole blood from Clade C infected individuals to the Projects 1 and 2, as well as Cores of this program project.
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