Molecular profile of human immunodeficiency virus type 1 infection in symptomless patients and in patients with AIDS

Abstract

Recent molecular evidence indicates that active human immunodeficiency virus type 1 (HIV-1) infection is detectable in both symptomless and symptomatic infected patients. For this main reason, it has been pointed out that precise quantitative analysis of viral activity in vivo is necessary, firstly, for the pathogenetic investigation of the steps relevant to infection progression and, secondly, for better clinical management of HIV-1-infected patients. In this study, the presence of HIV-1 genomic RNA in plasma samples, specific HIV-1 transcripts in peripheral blood mononuclear cells, and proviral DNA sequences were assayed for 33 HIV-1-infected patients (including symptomless and symptomatic subjects) by using a competitive polymerase chain reaction method that allows quantitation of the RNA/DNA target sequences. The quantitative results obtained confirm that transcription of HIV-1 structural genes and complete viral replication occur in all the HIV-1-infected patients independently of the clinical stage. However, although sharp individual differences were detected, a high degree of correlation of the molecular parameters studied with both disease progression and a decrease in the number of CD4+ T lymphocytes was documented. Interestingly, despite the increasing viremia level associated with infection progression, the mean transcriptional activity of individual infected cells was found to be only moderately greater in AIDS patients than in asymptomatic infected subjects. In addition, it was noted that quantitation of HIV-1 genomic RNA in plasma samples and quantitation of specific HIV-1 transcripts in peripheral blood mononuclear cells appear to be more reliable and sensitive markers of viral activity than quantitative analysis of proviral HIV-1 sequences in peripheral lymphocytes.