HIV-1 Latent Reservoir: Size Matters

Hodel, Flavia; Patxot, Marion; Snäkä, Tiia; Ciuffi, Angela

doi:10.2217/fvl-2016-0093

Cited by 23 publications

(27 citation statements)

References 30 publications

(83 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Currently, there is no gold standard method to measure the size of HIV reservoir. 74,75 The quantitative viral outgrowth assay underestimates the size of HIV reservoir, [74][75][76] while the nucleic acid-based measures overestimate it, as only a portion of latently infected cells is able to reactivate and produce replicationcompetent virus. [77][78][79] However, recent reports indicated that levels of HIV DNA and RNA during ART are predictors of viral rebound upon therapy interruption.…”

Section: Levels Of Circulating Anti-inflammatory Glycans Associate Wimentioning

confidence: 99%

Frontline Science: Plasma and immunoglobulin G galactosylation associate with HIV persistence during antiretroviral therapy

Vadrevu

Trbojević‐Akmačić

Kossenkov

et al. 2018

Journal of Leukocyte Biology

View full text Add to dashboard Cite

Global antibody glycosylation is dynamic and plays critical roles in shaping different immunological outcomes and direct antibody functionality during HIV infection. However, the relevance of global antibody or plasma glycosylation patterns to HIV persistence after antiretroviral therapy (ART) has not been characterized. First, we compared glycomes of total plasma and isolated immunoglobulin G (IgG) from HIV+ ART-suppressed, HIV+ viremic, and HIV-negative individuals. Second, in ART-suppressed individuals, we examined the associations between glycomes and (1) levels of cell-associated HIV DNA and RNA in PBMCs and isolated CD4+ T cells, (2) CD4 count and CD4%, and (3) expression of CD4+ T-cell activation markers. HIV infection is associated with persistent alterations in the IgG glycome including decreased levels of disialylated glycans, which is associated with a lower anti-inflammatory activity, and increased levels of fucosylated glycans, which is associated with lower antibody-dependent cell-mediated cytotoxicity (ADCC). We also show that levels of certain mono- and digalactosylated nonfucosylated glycomic traits (A2G1, A2G2, and A2BG2), which have been reported to be associated with higher ADCC and higher anti-inflammatory activities, exhibit significant negative correlations with levels of cell-associated total HIV DNA and HIV RNA in ART-suppressed individuals. Finally, levels of certain circulating anti-inflammatory glycans are associated with higher levels of CD4 T cells and lower levels of T-cell activation. Our findings represent the first proof-of-concept evidence that glycomic alterations, known to be associated with differential states of inflammation and ADCC activities, are also associated with levels of HIV persistence in the setting of ART suppression.

show abstract

Section: Levels Of Circulating Anti-inflammatory Glycans Associate Wimentioning

confidence: 99%

Frontline Science: Plasma and immunoglobulin G galactosylation associate with HIV persistence during antiretroviral therapy

Vadrevu

Trbojević‐Akmačić

Kossenkov

et al. 2018

Journal of Leukocyte Biology

View full text Add to dashboard Cite

show abstract

“…Despite extensive studies in humans (5,(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18), much remains unclear about HIV reservoirs that persist during ART (19)(20)(21)(22)(23). In part, this is because of technical limitations and limited access to appropriately collected tissues for such studies.…”

Section: Introductionmentioning

confidence: 99%

HIV persists throughout deep tissues with repopulation from multiple anatomical sources

Chaillon¹,

Gianella²,

Dellicour³

et al. 2020

Journal of Clinical Investigation

167

154

View full text Add to dashboard Cite

BACKGROUND. Understanding HIV dynamics across the human body is important for cure efforts. This goal has been hampered by technical difficulties and the challenge of obtaining fresh tissues. METHODS. This observational study evaluated 6 individuals with HIV (n = 4 with viral suppression using antiretroviral [ART] therapy; n = 2 with rebound viremia after stopping ART), who provided serial blood samples before death and their bodies for rapid autopsy. HIV reservoirs were characterized by digital droplet PCR, single-genome amplification, and sequencing of fulllength (FL) envelope HIV. Phylogeographic methods were used to reconstruct HIV spread, and generalized linear models were tested for viral factors associated with dispersal. RESULTS. Across participants, HIV DNA levels varied from approximately 0 to 659 copies/10 6 cells (IQR: 22.9-126.5). A total of 605 intact FL env sequences were recovered in antemortem blood cells and across 28 tissues (IQR: 5-9). Sequence analysis showed (a) the emergence of large, identical, intact HIV RNA populations in blood after cessation of therapy, which repopulated tissues throughout the body; (b) that multiple sites acted as hubs for HIV dissemination but that blood and lymphoid tissues were the main source; (c) that viral exchanges occurred within brain areas and across the blood-brain barrier; and (d) that migration was associated with low HIV divergence between sites and greater diversity at the recipient site. CONCLUSION. HIV reservoirs persisted in all deep tissues, and blood was the main source of dispersal. This may explain why eliminating HIV susceptibility in circulating T cells via bone marrow transplants allowed some individuals with HIV to experience therapy-free remission, even though deeper tissue reservoirs were not targeted. TRIAL REGISTRATION. Not applicable.

show abstract

“…9 The viral reservoir is measurable through different methods, including viral outgrowth assay and intracellular HIV-1 DNA quantification. 10,11 Currently, there is no consensus on the best HIV-1 reservoir biomarker. Viral outgrowth assays only measure replication-competent proviruses and have therefore been considered to be the gold standard to measure the latent reservoir.…”

Section: Introductionmentioning

confidence: 99%

Host Genomics of the HIV-1 Reservoir Size and Its Decay Rate During Suppressive Antiretroviral Treatment

Thorball

Borghesi

Bachmann

et al. 2020

JAIDS Journal of Acquired Immune Deficiency Syndromes

View full text Add to dashboard Cite

Background. The primary hurdle for the eradication of HIV-1 is the establishment of a latent viral reservoir early after primary infection. Here we investigated the potential influence of human genetic variation on the HIV-1 reservoir size and its decay rate during suppressive antiretroviral treatment (ART). Setting. Genome-wide association study and exome sequencing study to look for host genetic determinants of HIV-1 reservoir measurements in patients enrolled in the Swiss HIV Cohort Study (SHCS), a nationwide prospective observational study. Methods. We measured total HIV-1 DNA in peripheral blood mononuclear cells from study participants, as a proxy for the reservoir size, at three time points over a median of 5.4 years, and searched for associations between human genetic variation and two phenotypic readouts: the reservoir size at the first time point and its decay rate over the study period. We assessed the contribution of common genetic variants using genome-wide genotyping data from 797 patients with European ancestry enrolled in the Swiss HIV Cohort Study and searched for a potential impact of rare variants and exonic copy number variants using exome sequencing data generated in a subset of 194 study participants. Results. Genome-and exome-wide analyses did not reveal any significant association with the size of the HIV-1 reservoir or its decay rate on suppressive ART. Conclusions. Our results point to a limited influence of human genetics on the size of the HIV-1 reservoir and its long-term dynamics in successfully treated individuals.

show abstract

HIV-1 Latent Reservoir: Size Matters

Cited by 23 publications

References 30 publications

Frontline Science: Plasma and immunoglobulin G galactosylation associate with HIV persistence during antiretroviral therapy

Frontline Science: Plasma and immunoglobulin G galactosylation associate with HIV persistence during antiretroviral therapy

HIV persists throughout deep tissues with repopulation from multiple anatomical sources

Host Genomics of the HIV-1 Reservoir Size and Its Decay Rate During Suppressive Antiretroviral Treatment

Contact Info

Product

Resources

About