» Articles » PMID: 20970154

Patients on HAART Often Have an Excess of Unintegrated HIV DNA: Implications for Monitoring Reservoirs

Overview
Journal Virology
Specialty Microbiology
Date 2010 Oct 26
PMID 20970154
Citations 22
Authors
Affiliations
Soon will be listed here.
Abstract

HIV establishes a latent reservoir early in infection that is resistant to anti-retroviral therapy and has a slow rate of decay. It is thought that the majority of HIV DNA in treated patients is integrated since unintegrated HIV DNA appears to be unstable. Thus, to monitor the HIV latent reservoir, total HIV DNA is commonly measured in PBMC from infected individuals. We investigated how often total approaches integrated HIV DNA in treated patients. To do this, we first assessed how accurate our integration assay is and determined the error in our measurements of total and integrated HIV DNA. We demonstrated an excess of total over integrated HIV DNA was present in a subset of patients, suggesting that measurements of total HIV DNA do not always correlate to the level of integration. Determining the cause of this excess and its frequency may have important implications for understanding HIV latent reservoir maintenance.

Citing Articles

Primary HIV infection features colonic damage and neutrophil inflammation yet containment of microbial translocation.

Tincati C, Bono V, Cannizzo E, Tosi D, Savi F, Falcinella C AIDS. 2023; 38(5):623-632.

PMID: 38016163 PMC: 10942218. DOI: 10.1097/QAD.0000000000003799.


Quantification of Total HIV DNA as a Marker to Measure Viral Reservoir: Methods and Potential Implications for Clinical Practice.

Belmonti S, Di Giambenedetto S, Lombardi F Diagnostics (Basel). 2022; 12(1).

PMID: 35054206 PMC: 8774405. DOI: 10.3390/diagnostics12010039.


Ex Vivo Differentiation of Resting CD4+ T Lymphocytes Enhances Detection of Replication Competent HIV-1 in Viral Outgrowth Assays.

Wonderlich E, Reece M, Kulpa D Methods Mol Biol. 2022; 2407:315-331.

PMID: 34985673 DOI: 10.1007/978-1-0716-1871-4_21.


A comparative analysis of unintegrated HIV-1 DNA measurement as a potential biomarker of the cellular reservoir in the blood of patients controlling and non-controlling viral replication.

Orlandi C, Canovari B, Bozzano F, Marras F, Pasquini Z, Barchiesi F J Transl Med. 2020; 18(1):204.

PMID: 32429953 PMC: 7236182. DOI: 10.1186/s12967-020-02368-y.


Effector memory differentiation increases detection of replication-competent HIV-l in resting CD4+ T cells from virally suppressed individuals.

Wonderlich E, Subramanian K, Cox B, Wiegand A, Lackman-Smith C, Bale M PLoS Pathog. 2019; 15(10):e1008074.

PMID: 31609991 PMC: 6812841. DOI: 10.1371/journal.ppat.1008074.


References
1.
Ibanez A, Puig T, Elias J, Clotet B, Ruiz L, Martinez M . Quantification of integrated and total HIV-1 DNA after long-term highly active antiretroviral therapy in HIV-1-infected patients. AIDS. 1999; 13(9):1045-9. DOI: 10.1097/00002030-199906180-00007. View

2.
Wiskerchen M, Muesing M . Identification and characterization of a temperature-sensitive mutant of human immunodeficiency virus type 1 by alanine scanning mutagenesis of the integrase gene. J Virol. 1995; 69(1):597-601. PMC: 188617. DOI: 10.1128/JVI.69.1.597-601.1995. View

3.
Tobin N, Learn G, Holte S, Wang Y, Melvin A, McKernan J . Evidence that low-level viremias during effective highly active antiretroviral therapy result from two processes: expression of archival virus and replication of virus. J Virol. 2005; 79(15):9625-34. PMC: 1181593. DOI: 10.1128/JVI.79.15.9625-9634.2005. View

4.
Jelinek W, Schmid C . Repetitive sequences in eukaryotic DNA and their expression. Annu Rev Biochem. 1982; 51:813-44. DOI: 10.1146/annurev.bi.51.070182.004121. View

5.
Butler S, Johnson E, Bushman F . Human immunodeficiency virus cDNA metabolism: notable stability of two-long terminal repeat circles. J Virol. 2002; 76(8):3739-47. PMC: 136088. DOI: 10.1128/jvi.76.8.3739-3747.2002. View