» Articles » PMID: 29879542

Associations Between HIV-1 DNA Copy Number, Proviral Transcriptional Activity, and Plasma Viremia in Individuals off or on Suppressive Antiretroviral Therapy

Overview
Journal Virology
Specialty Microbiology
Date 2018 Jun 8
PMID 29879542
Citations 17
Authors
Affiliations
Soon will be listed here.
Abstract

The relationships between HIV-1 DNA copy number, proviral transcriptional activity, and residual plasma viremia in individuals off and on ART are not well defined. To address this, we performed a cross-sectional study of 12 viremic donors and 23 ART-treated virologically suppressed (plasma HIV-1 RNA<20 copies/ml) donors. We report a strong association between HIV-1 DNA copy number and HIV-1 transcriptional activity in blood that persists on suppressive ART, but not between transcriptional activity and the levels of persistent viremia on ART. The latter finding contrasts with that in viremic donors and suggests that most HIV transcription in donors on suppressive ART does not result in virion production. This uncoupling of proviral transcription and viremia warrants closer investigation.

Citing Articles

HIV-1 control in vivo is related to the number but not the fraction of infected cells with viral unspliced RNA.

Capoferri A, Wiegand A, Hong F, Jacobs J, Spindler J, Musick A Proc Natl Acad Sci U S A. 2024; 121(36):e2405210121.

PMID: 39190360 PMC: 11388345. DOI: 10.1073/pnas.2405210121.


Evaluation of HIV-1 DNA levels among adolescents living with perinatally acquired HIV-1 in Yaounde, Cameroon: A contribution to paediatric HIV cure research in Sub-Saharan Africa.

Kae A, Santoro M, Duca L, Ambe Chenwi C, Ngoufack Jagni Semengue E, Nka A J Virus Erad. 2024; 10(1):100367.

PMID: 38601701 PMC: 11004643. DOI: 10.1016/j.jve.2024.100367.


Low unspliced cell-associated HIV RNA in early treated adolescents living with HIV on long suppressive ART.

Gartner K, Dominguez-Rodriguez S, Heaney J, Gkouleli T, Grant P, Dorgham K Front Immunol. 2024; 15:1334236.

PMID: 38444847 PMC: 10912947. DOI: 10.3389/fimmu.2024.1334236.


Challenges in HIV-1 Latent Reservoir and Target Cell Quantification in CAR-T Cell and Other Lentiviral Gene Modifying HIV Cure Strategies.

Buck A, Deveau T, Henrich T, Deitchman A Viruses. 2023; 15(5).

PMID: 37243212 PMC: 10222761. DOI: 10.3390/v15051126.


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.


References
1.
Wiegand A, Spindler J, Hong F, Shao W, Cyktor J, Cillo A . Single-cell analysis of HIV-1 transcriptional activity reveals expression of proviruses in expanded clones during ART. Proc Natl Acad Sci U S A. 2017; 114(18):E3659-E3668. PMC: 5422779. DOI: 10.1073/pnas.1617961114. View

2.
Imamichi H, Dewar R, Adelsberger J, Rehm C, ODoherty U, Paxinos E . Defective HIV-1 proviruses produce novel protein-coding RNA species in HIV-infected patients on combination antiretroviral therapy. Proc Natl Acad Sci U S A. 2016; 113(31):8783-8. PMC: 4978246. DOI: 10.1073/pnas.1609057113. View

3.
Bruner K, Murray A, Pollack R, Soliman M, Laskey S, Capoferri A . Defective proviruses rapidly accumulate during acute HIV-1 infection. Nat Med. 2016; 22(9):1043-9. PMC: 5014606. DOI: 10.1038/nm.4156. View

4.
Rasmussen T, Tolstrup M, Brinkmann C, Olesen R, Erikstrup C, Solomon A . Panobinostat, a histone deacetylase inhibitor, for latent-virus reactivation in HIV-infected patients on suppressive antiretroviral therapy: a phase 1/2, single group, clinical trial. Lancet HIV. 2015; 1(1):e13-21. DOI: 10.1016/S2352-3018(14)70014-1. View

5.
Furtado M, Callaway D, Phair J, Kunstman K, Stanton J, Macken C . Persistence of HIV-1 transcription in peripheral-blood mononuclear cells in patients receiving potent antiretroviral therapy. N Engl J Med. 1999; 340(21):1614-22. DOI: 10.1056/NEJM199905273402102. View