The effects various therapeutic modalities have on the molecular pathogenesis of human immunodeficiency virus type 1 (HIV-1), in vivo has only begun to be evaluated. As the antiretroviral therapies and therapies for the opportunistic infections which develop in patients with the Acquired Immune Deficiency Syndrome (AIDS) increase in numbers and complexity, sensitive and specific techniques to investigate alterations in HIV-1 replication are critically needed. The changes in the total numbers of HIV-1-infected unfractionated peripheral blood lymphocytes (PBL) and CD4-positive lymphocytes, in patients undergoing various therapeutic protocols, will be evaluated using a novel new technique, In Situ Polymerase Chain Reaction (PCR). This technique, which allows amplification of portions of the HIV-1 genome within intact cells has been demonstrated to be extraordinarily sensitive in detecting cells containing the HIV-1 provirus. A quantitative HIV-1 RNA (Reverse Transcriptase) PCR technique will, as well, be utilized to directly investigate HIV-1 transcriptional alterations in the settings of various therapies. Total levels of HIV-1-specific RNA species in PBL and in serum or plasma will be measured. Alterations in the patterns of HIV-1-specific unspliced and multiply-spliced RNAs, associated with a proposed model of HIV-1 proviral latency, shall also be evaluated. Utilizing these techniques, a more precise picture will be gained, regarding the interrelationships of the therapeutic modalities, soon to become available to HIV-1-infected individuals, and the molecular events occurring in vivo. As well, HIV-1 proviral load and replication patterns in treated individuals will be correlated with levels of immunosuppression, CDC-classification of HIV-1 infection and with other, commonly utilized, markers of viral replication in vivo.
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