Genotypes that confer drug resistance were evaluated in human immunodeficiency virus (HIV) proviral DNA obtained from peripheral blood mononuclear cells (PBMC) and lymphoid tissue at baseline and after 8 weeks of therapy with zidovudine alone or in combination with didanosine from 22 patients (8 zidovudine-naive and 14 zidovudine-experienced). There was evidence of zidovudine resistance at codon 215 in 27.3% (6/22) of patients. All 20 patients evaluable for codon 74 (site of didanosine resistance) had virus that remained wild type during the 8-week study period. When HIV proviral DNA from PBMC was compared with that from lymphoid tissue, 94.7% (18/19) of evaluable samples were concordant at codon 215 at baseline, while 85.7% (12/14) were concordant at week 8. Resistance in PBMC (but not in lymphoid tissue) developed in 1 of 8 zidovudine-naive patients; an increased proportion of resistant strains in PBMC (but not in lymphoid tissue) was observed in 2 of 14 zidovudine-experienced patients. These results suggest high concordance for drug resistance mutations in HIV proviral DNA from blood and lymph node tissue.
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http://dx.doi.org/10.1086/517433 | DOI Listing |
Pathogens
December 2024
State Research Center of Virology and Biotechnology "Vector", Koltsovo 630559, Russia.
Human Immunodeficiency Virus (HIV) proviral reservoirs are cells that harbor integrated HIV proviral DNA within their nuclear genomes. These cells form a heterogeneous group, represented by peripheral blood mononuclear cells (PBMCs), tissue-resident lymphoid and monocytic cells, and glial cells of the central nervous system. The importance of studying the properties of proviral reservoirs is connected with the inaccessibility of integrated HIV proviral DNA for modern anti-retroviral therapies (ARTs) that block virus reproduction.
View Article and Find Full Text PDFClin Chem
January 2025
Department of Internal Medicine and Pediatrics, HIV Cure Research Center, Ghent University Hospital, Ghent University Ghent, Belgium.
Background: Persistent latent reservoirs of intact HIV-1 proviruses, capable of rebounding despite suppressive antiretroviral therapy (ART), hinder efforts towards an HIV-1 cure. Hence, assays specifically quantifying intact proviruses are crucial to assess the impact of curative interventions. Two recent assays have been utilized in clinical trials: intact proviral DNA assay (IPDA) and quadruplex quantitative PCR (Q4PCR).
View Article and Find Full Text PDFJ Mol Evol
December 2024
Laboratory of Experimental Virology, Department of Medical Microbiology and Infection Prevention, Amsterdam UMC, Location AMC, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.
The time of integration of germline-targeting Long Terminal Repeat (LTR) retroposons, such as endogenous retroviruses (ERVs), can be estimated by assessing the nucleotide divergence between the LTR sequences flanking the viral genes. Due to the viral replication mechanism, both LTRs are identical at the moment of integration, when the provirus becomes part of the host genome. After that time, proviral sequences evolve within the host DNA.
View Article and Find Full Text PDFJ Virol
December 2024
Department of Biochemistry, Microbiology, and Immunology, College of Medicine, University of Saskatchewan, Saskatoon, Saskatchewan, Canada.
Several APOBEC3 enzymes restrict HIV-1 by deaminating cytosine to form uracil in single-stranded proviral (-)DNA. However, HIV-1 Vif counteracts their activity by inducing their proteasomal degradation. This counteraction by Vif is incomplete, as evidenced by footprints of APOBEC3-mediated mutations within integrated proviral genomes of people living with HIV-1.
View Article and Find Full Text PDFBackground: Identifying risk factors for HIV rebound after treatment interruption is crucial for designing effective remission strategies.
Methods: Peripheral blood mononuclear cells from participants in the Zurich HIV Primary Infection Cohort (ZPHI, N=73) and ACTG study A5345 (N=44) were analyzed before ART interruption. We measured cell-associated HIV RNA, total HIV DNA, and proviral diversity (env gene).
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