Quantitative molecular monitoring of human immunodeficiency virus type 1 activity during therapy with specific antiretroviral compounds

P. Bagnarelli, S. Menzo, A. Valenza, S. Paolucci, S. Petroni, G. Scalise, R. Sampaolesi, A. Manzin, P. E. Varaldo, M. Clementi

Research output: Contribution to journalArticle

Abstract

Methods for the absolute quantitation of nucleic acids present in small amounts in biological samples (competitive PCR and competitive reverse transcription PCR) were applied to the direct monitoring of specific anti- human immunodeficiency virus type 1 (HIV-1) therapy. With these techniques, different parameters of HIV-1 activity (including genomic RNA copy numbers in plasma, proviral and late transcript copy numbers in peripheral blood lymphocytes, and mean transcriptional activity per each HIV-1 provirus) were monitored during therapy with azidothymidine or ddI. In most of these treated patients, a direct response to the antiretroviral compounds employed was detected during the first few weeks of treatment, as documented by a fast decrease of all molecular indexes of HIV-1 activity. However, residual viral replication (albeit at minimal levels) was documented during therapy in all subjects monitored in this study. In a minority of the patients under study (3 of 12), the drug-dependent viral inhibition was maintained throughout the observation time (213 to 791 days), but in 9 patients a rebound in viremia level was detected during therapy with competitive reverse transcription PCR. Sequencing analysis of a portion of the HIV-1 gene pol from cell-free virions showed that circulating viral variants bearing at least two mutations compatible with azidothymidine or ddI resistance were detectable in the patients who exhibited a rebound in cell-free HIV-1 genomic RNA copy numbers in plasma but not in one patient who maintained (for 455 days) lowered levels of viral load during ddI treatment.

Original languageEnglish
Pages (from-to)16-23
Number of pages8
JournalJournal of Clinical Microbiology
Volume33
Issue number1
Publication statusPublished - 1995

Fingerprint

HIV-1
Zidovudine
Polymerase Chain Reaction
Reverse Transcription
Therapeutics
RNA
pol Genes
Proviruses
Viremia
Viral Load
Virion
Nucleic Acids
Observation
Lymphocytes
Mutation
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Microbiology
  • Microbiology (medical)

Cite this

Quantitative molecular monitoring of human immunodeficiency virus type 1 activity during therapy with specific antiretroviral compounds. / Bagnarelli, P.; Menzo, S.; Valenza, A.; Paolucci, S.; Petroni, S.; Scalise, G.; Sampaolesi, R.; Manzin, A.; Varaldo, P. E.; Clementi, M.

In: Journal of Clinical Microbiology, Vol. 33, No. 1, 1995, p. 16-23.

Research output: Contribution to journalArticle

Bagnarelli, P, Menzo, S, Valenza, A, Paolucci, S, Petroni, S, Scalise, G, Sampaolesi, R, Manzin, A, Varaldo, PE & Clementi, M 1995, 'Quantitative molecular monitoring of human immunodeficiency virus type 1 activity during therapy with specific antiretroviral compounds', Journal of Clinical Microbiology, vol. 33, no. 1, pp. 16-23.
Bagnarelli, P. ; Menzo, S. ; Valenza, A. ; Paolucci, S. ; Petroni, S. ; Scalise, G. ; Sampaolesi, R. ; Manzin, A. ; Varaldo, P. E. ; Clementi, M. / Quantitative molecular monitoring of human immunodeficiency virus type 1 activity during therapy with specific antiretroviral compounds. In: Journal of Clinical Microbiology. 1995 ; Vol. 33, No. 1. pp. 16-23.
@article{9531b1d4386b4a019992f66b8f7c247a,
title = "Quantitative molecular monitoring of human immunodeficiency virus type 1 activity during therapy with specific antiretroviral compounds",
abstract = "Methods for the absolute quantitation of nucleic acids present in small amounts in biological samples (competitive PCR and competitive reverse transcription PCR) were applied to the direct monitoring of specific anti- human immunodeficiency virus type 1 (HIV-1) therapy. With these techniques, different parameters of HIV-1 activity (including genomic RNA copy numbers in plasma, proviral and late transcript copy numbers in peripheral blood lymphocytes, and mean transcriptional activity per each HIV-1 provirus) were monitored during therapy with azidothymidine or ddI. In most of these treated patients, a direct response to the antiretroviral compounds employed was detected during the first few weeks of treatment, as documented by a fast decrease of all molecular indexes of HIV-1 activity. However, residual viral replication (albeit at minimal levels) was documented during therapy in all subjects monitored in this study. In a minority of the patients under study (3 of 12), the drug-dependent viral inhibition was maintained throughout the observation time (213 to 791 days), but in 9 patients a rebound in viremia level was detected during therapy with competitive reverse transcription PCR. Sequencing analysis of a portion of the HIV-1 gene pol from cell-free virions showed that circulating viral variants bearing at least two mutations compatible with azidothymidine or ddI resistance were detectable in the patients who exhibited a rebound in cell-free HIV-1 genomic RNA copy numbers in plasma but not in one patient who maintained (for 455 days) lowered levels of viral load during ddI treatment.",
author = "P. Bagnarelli and S. Menzo and A. Valenza and S. Paolucci and S. Petroni and G. Scalise and R. Sampaolesi and A. Manzin and Varaldo, {P. E.} and M. Clementi",
year = "1995",
language = "English",
volume = "33",
pages = "16--23",
journal = "Journal of Clinical Microbiology",
issn = "0095-1137",
publisher = "American Society for Microbiology",
number = "1",

}

TY - JOUR

T1 - Quantitative molecular monitoring of human immunodeficiency virus type 1 activity during therapy with specific antiretroviral compounds

AU - Bagnarelli, P.

AU - Menzo, S.

AU - Valenza, A.

AU - Paolucci, S.

AU - Petroni, S.

AU - Scalise, G.

AU - Sampaolesi, R.

AU - Manzin, A.

AU - Varaldo, P. E.

AU - Clementi, M.

PY - 1995

Y1 - 1995

N2 - Methods for the absolute quantitation of nucleic acids present in small amounts in biological samples (competitive PCR and competitive reverse transcription PCR) were applied to the direct monitoring of specific anti- human immunodeficiency virus type 1 (HIV-1) therapy. With these techniques, different parameters of HIV-1 activity (including genomic RNA copy numbers in plasma, proviral and late transcript copy numbers in peripheral blood lymphocytes, and mean transcriptional activity per each HIV-1 provirus) were monitored during therapy with azidothymidine or ddI. In most of these treated patients, a direct response to the antiretroviral compounds employed was detected during the first few weeks of treatment, as documented by a fast decrease of all molecular indexes of HIV-1 activity. However, residual viral replication (albeit at minimal levels) was documented during therapy in all subjects monitored in this study. In a minority of the patients under study (3 of 12), the drug-dependent viral inhibition was maintained throughout the observation time (213 to 791 days), but in 9 patients a rebound in viremia level was detected during therapy with competitive reverse transcription PCR. Sequencing analysis of a portion of the HIV-1 gene pol from cell-free virions showed that circulating viral variants bearing at least two mutations compatible with azidothymidine or ddI resistance were detectable in the patients who exhibited a rebound in cell-free HIV-1 genomic RNA copy numbers in plasma but not in one patient who maintained (for 455 days) lowered levels of viral load during ddI treatment.

AB - Methods for the absolute quantitation of nucleic acids present in small amounts in biological samples (competitive PCR and competitive reverse transcription PCR) were applied to the direct monitoring of specific anti- human immunodeficiency virus type 1 (HIV-1) therapy. With these techniques, different parameters of HIV-1 activity (including genomic RNA copy numbers in plasma, proviral and late transcript copy numbers in peripheral blood lymphocytes, and mean transcriptional activity per each HIV-1 provirus) were monitored during therapy with azidothymidine or ddI. In most of these treated patients, a direct response to the antiretroviral compounds employed was detected during the first few weeks of treatment, as documented by a fast decrease of all molecular indexes of HIV-1 activity. However, residual viral replication (albeit at minimal levels) was documented during therapy in all subjects monitored in this study. In a minority of the patients under study (3 of 12), the drug-dependent viral inhibition was maintained throughout the observation time (213 to 791 days), but in 9 patients a rebound in viremia level was detected during therapy with competitive reverse transcription PCR. Sequencing analysis of a portion of the HIV-1 gene pol from cell-free virions showed that circulating viral variants bearing at least two mutations compatible with azidothymidine or ddI resistance were detectable in the patients who exhibited a rebound in cell-free HIV-1 genomic RNA copy numbers in plasma but not in one patient who maintained (for 455 days) lowered levels of viral load during ddI treatment.

UR - http://www.scopus.com/inward/record.url?scp=0028936199&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0028936199&partnerID=8YFLogxK

M3 - Article

C2 - 7699034

AN - SCOPUS:0028936199

VL - 33

SP - 16

EP - 23

JO - Journal of Clinical Microbiology

JF - Journal of Clinical Microbiology

SN - 0095-1137

IS - 1

ER -