Heritability of the HIV-1 reservoir size and decay under long-term suppressive ART

Wan, Chenjie; Bachmann, Nadine; Mitov, Venelin; Blanquart, François; Posada-Céspedes, Susana; Turk, Teja; Neumann, Katja; Beerenwinkel, Niko; Bogojeska, Jasmina; Röth, Volker; Kusejko, Katharina; Walti, Laura N; Günthard, Huldrych F.; Anagnostopoulos, Alexia; Battegay, Manuel; Bernasconi, Enos; Böni, Jürg; Braun, Dominique L; Bucher, Heiner C.; Calmy, Alexandra; Cavassini, Matthias; Ciuffi, Angela; Dollenmaier, Günter; Egger, Matthias; Elzi, Luigia; Fehr, Jan; Fellay, Jacques; Furrer, Hansjakob; Fux, Christoph A; Günthard, Huldrych F.; Haerry, David; Hasse, Barbara; Hirsch, Hans H.; Hoffmann, Matthias; Hösli, Irène; Huber, Michael; Kahlert, Christian R.; Kaiser, Laurent; Keiser, Olivia; Klimkait, Thomas; Kouyos, Roger D.; Kovari, Helen; Ledergerber, Bruno; Martinetti, Gladys; Tejada, Begoña Martínez de; Marzolini, Catia; Metzner, Karin J.; Müller, Nicolas; Nicca, Dunja; Paioni, Paolo; Pantaleo, G.; Perreau, Matthieu; Rauch, Andri; Rudin, Christoph; Scherrer, Alexandra U.; Schmid, Patrick; Speck, R. Renae; Stöckle, Marcel; Tarr, Philip; Trkola, Alexandra; Vernazza, Pietro; Wandeler, Gilles; Weber, Rainer; Yerly, Sabine

doi:10.1038/s41467-020-19198-7

Cited by 6 publications

(1 citation statement)

References 67 publications

(146 reference statements)

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“…A possible cause for failure of sequencing might therefore be the decay of the viral reservoir and the recovery of the CD4+ T cells to higher numbers over time under long-term successful ART. 38–40 Particularly in untreated patients, the viral genome is not only present in a state of integrated proviral DNA, but also to a substantial extent as non-integrated DNA, which can be amplified by this method, enhancing the yield of the PCR. Further, we observed a significantly lower concentration of isolated DNA from PBMC samples that failed sequence acquisition compared with those that were successful.…”

Section: Discussionmentioning

confidence: 99%

Prevalence of HIV-1 drug resistance mutations in proviral DNA in the Swiss HIV Cohort Study, a retrospective study from 1995 to 2018

Jaha,

Schenkel,

Jörimann

et al. 2023

Journal of Antimicrobial Chemotherapy

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Background Genotypic resistance testing (GRT) is routinely performed upon diagnosis of HIV-1 infection or during virological failure using plasma viral RNA. An alternative source for GRT could be cellular HIV-1 DNA. Objectives A substantial number of participants in the Swiss HIV Cohort Study (SHCS) never received GRT. We applied a method that enables access to the near full-length proviral HIV-1 genome without requiring detectable viraemia. Methods Nine hundred and sixty-two PBMC specimens were received. Our two-step nested PCR protocol was applied to generate two overlapping long-range amplicons of the HIV-1 genome, sequenced by next-generation sequencing (NGS) and analysed by MinVar, a pipeline to detect drug resistance mutations (DRMs). Results Six hundred and eighty-one (70.8%) of the samples were successfully amplified, sequenced and analysed by MinVar. Only partial information of the pol gene was contained in 82/681 (12%), probably due to naturally occurring deletions in the proviral sequence. All common HIV-1 subtypes were successfully sequenced. We detected at least one major DRM at high frequency (≥15%) in 331/599 (55.3%) individuals. Excluding APOBEC-signature (G-to-A mutation) DRMs, 145/599 (24.2%) individuals carried at least one major DRM. RT-inhibitor DRMs were most prevalent. The experienced time on ART was significantly longer in DRM carriers (P = 0.001) independent of inclusion or exclusion of APOBEC-signature DRMs. Conclusions We successfully applied a reliable and efficient method to analyse near full-length HIV-1 proviral DNA and investigated DRMs in individuals with undetectable or low viraemia. Additionally, our data underscore the need for new computational tools to exclude APOBEC-related hypermutated NGS sequence reads for reporting DRMs.

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Section: Discussionmentioning

confidence: 99%

Prevalence of HIV-1 drug resistance mutations in proviral DNA in the Swiss HIV Cohort Study, a retrospective study from 1995 to 2018

Jaha,

Schenkel,

Jörimann

et al. 2023

Journal of Antimicrobial Chemotherapy

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HIV Reservoir: How to Measure It?

Zhang

2023

Curr HIV/AIDS Rep

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The Interplay Between Replication Capacity of HIV-1 and Surrogate Markers of Disease

Rindler

Kusejko

Küster

et al. 2022

The Journal of Infectious Diseases

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Background HIV-1 replication capacity (RC) of transmitted/founder viruses may influence the further course of HIV-1 infection. Methods Replication capacities (RCs) of 355 whole genome primary HIV-1 isolates derived from samples acquired during acute and recent primary HIV-1 infection (PHI) were determined using a novel high throughput infection assay in primary cells. The RCs were used to elucidate potential factors that could be associated with RC during PHI. Results Increased RC was found to be associated with increased set point viral load (VL), and significant differences in RCs among 13 different HIV-1 subtypes were discerned. Notably, we observed an increase in RCs for primary HIV-1 isolates of HIV-1 subtype B over a 17-year period. Associations were not observed between RC and CD4 count at sample date of RC measurement, CD4 recovery after initiation of antiretroviral treatment (ART), CD4 decline in untreated individuals, and acute retroviral syndrome severity scores. Discussion These findings highlight that RCs of primary HIV-1 isolates acquired during the acute and recent phase of infection are more associated with viral factors, i.e., set point VL, than with host factors. Furthermore, we observed a temporal increase in RC for HIV-1 subtype B viruses over a period of 17 years.

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Heritability of the HIV-1 reservoir size and decay under long-term suppressive ART

Cited by 6 publications

References 67 publications

Prevalence of HIV-1 drug resistance mutations in proviral DNA in the Swiss HIV Cohort Study, a retrospective study from 1995 to 2018

Prevalence of HIV-1 drug resistance mutations in proviral DNA in the Swiss HIV Cohort Study, a retrospective study from 1995 to 2018

HIV Reservoir: How to Measure It?

The Interplay Between Replication Capacity of HIV-1 and Surrogate Markers of Disease

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