Effect of intermittent interleukin-2 therapy on CD4+ T-cell counts following antiretroviral cessation in patients with HIV

Lévy, Yves; Thiébaut, Rodolphe; Gougeon, Marie‐Lise; Molina, Jean‐Michel; Weiss, Laurence; Girard, Pierre‐Marie; Venet, Alain; Morlat, Philippe; Poirier, Béatrice; Lascaux, Anne-Sophie; Boucherie, Céline; Séréni, D.; Rouzioux, Christine; Viard, Jean‐Paul; Lane, Cliff; Delfraissy, Jean‐François; Sereti, Irini; Chêne, Geneviève

doi:10.1097/qad.0b013e3283519214

Cited by 20 publications

(18 citation statements)

References 26 publications

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“…Several studies have shown that a lower HIV DNA load during cART is associated with better immune recovery (194,200,201). Similarly, a low HIV DNA load was found to be predictive of better immune restora-tion in children on cART (202) and was associated with CD4 cell count dynamics during cART combined with interleukin-2 (203). In patients with advanced therapeutic failure and AIDS, a larger viral reservoir was associated with poorer CD4 cell recovery during optimized background therapy (197).…”

Section: Total Hiv Dna Load During Cart Is Informative Of Patient Prementioning

confidence: 95%

Total HIV-1 DNA, a Marker of Viral Reservoir Dynamics with Clinical Implications

et al. 2016

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SUMMARYHIV-1 DNA persists in infected cells despite combined antiretroviral therapy (cART), forming viral reservoirs. Recent trials of strategies targeting latent HIV reservoirs have rekindled hopes of curing HIV infection, and reliable markers are thus needed to evaluate viral reservoirs. Total HIV DNA quantification is simple, standardized, sensitive, and reproducible. Total HIV DNA load influences the course of the infection and is therefore clinically relevant. In particular, it is predictive of progression to AIDS and death, independently of HIV RNA load and the CD4 cell count. Baseline total HIV DNA load is predictive of the response to cART. It declines during cART but remains quantifiable, at a level that reflects both the history of infection (HIV RNA zenith, CD4 cell count nadir) and treatment efficacy (residual viremia, cumulative viremia, immune restoration, immune cell activation). Total HIV DNA load in blood is also predictive of the presence and severity of some HIV-1-associated end-organ disorders. It can be useful to guide individual treatment, notably, therapeutic de-escalation. Although it does not distinguish between replication-competent and -defective latent viruses, the total HIV DNA load in blood, tissues, and cells provides insights into HIV pathogenesis, probably because all viral forms participate in host cell activation and HIV pathogenesis. Total HIV DNA is thus a biomarker of HIV reservoirs, which can be defined as all infected cells and tissues containing all forms of HIV persistence that participate in pathogenesis. This participation may occur through the production of new virions, creating new cycles of infection and disseminating infected cells; maintenance or amplification of reservoirs by homeostatic cell proliferation; and viral transcription and synthesis of viral proteins without new virion production. These proteins can induce immune activation, thus participating in the vicious circle of HIV pathogenesis.

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Section: Total Hiv Dna Load During Cart Is Informative Of Patient Prementioning

confidence: 95%

Total HIV-1 DNA, a Marker of Viral Reservoir Dynamics with Clinical Implications

et al. 2016

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“…Resumption of HAART was recommended in case of immunologic failure defined as a drop of CD4 + T-cell count below 350/μL confirmed 2 weeks apart. Safety was assessed through the reporting of adverse events and laboratory abnormalities (ANRS toxicity grading scale [25]). …”

Section: Study Monitoringmentioning

confidence: 99%

Dendritic cell‐based therapeutic vaccine elicits polyfunctional HIV‐specific T‐cell immunity associated with control of viral load

et al. 2014

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Eur. J. Immunol. 2014Immunol. . 44: 2802Immunol. -2810 Clinical immunology 2803 IntroductionTo date, no effective therapeutic or prophylactic HIV vaccines are yet available. Recent encouraging results from the RV 144 trial showed a modest but statistically significant 31% reduction in the rate of HIV infection in vaccinated healthy volunteers receiving a prophylactic vaccine [1]. However, immune responses that would eradicate or control HIV are likely to be different from those needed to prevent primary infection. Indeed, eradication of HIV infection is likely to depend on the establishment of strong cytotoxic T lymphocytes, while prevention of infection will likely depend on the establishment of antibodies neutralizing the virus [2,3]. In both cases, CD4 + T helper cells are necessary for the establishment of robust and long-lasting immunity. Several candidate vaccines are under evaluation including peptides, inactivated virus, viral vectors, and ex vivo-generated DCs [4]. The latter represents an approach to optimize the induction of immune responses [5]. To date, only two studies, in which DCs have been loaded with chemically inactivated autologous virus, have reported a decrease in viral load [6,7]. Another approach using DCs transfected with RNA isolated from autologous virus yielded immune responses without control of viral replication [8]. However, these very promising data with inactivated autologous virus still need to be reproduced. For large scale use of DC vaccination, it would be advantageous to identify an antigenic cargo that could be used without having to isolate and expand the autologous virus which necessitates antiretroviral treatment interruption. We report here the safety and immunogenicity of a new DC platform loaded with five HIV-1-derived lipopeptides (LP) [9] in HIV-1-infected patients treated with highly active antiretroviral treatment (HAART). The study design included a 6-month analytical treatment interruption (ATI), a period which allowed us to evaluate the effects of vaccine-elicited immune responses on viral replication (Fig. 1). Results Patients and study outcomesTwenty patients were screened and 19 were enrolled within 17 months. Baseline characteristics of patients are reported in Table 1. All patients received the four vaccinations with no changes in vaccine dose. All patients but one completed the trial at 48 weeks.The vaccination was well tolerated. Two patients reached a safety endpoint (CD4 + T-cell counts below 500 cells/μL) during the vaccination phase while no safety endpoints were observed during the ATI phase. Systemic or local adverse events were mild or moderate (grade 1 or 2) and resolved in less than 2 days in the majority of cases. All patients stopped HAART at 24 weeks post inclusion except two of them who stopped at 25 and 26 weeks.Through 48 weeks, eight patients reached the immunology endpoint defining a failure of the strategy: at 28 (two patients), 32 (three patients), 36, 40, and 44 weeks. Three of these patients resumed HAART. No clinical events or pro...

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“…We extracted deoxyribonucleic acid (DNA) from the same PBMC obtained for ICS and performed quantitative PCR for the signal-joint (sj)TREC. Results are expressed in sjTREC copies per microgram of PBMC DNA, hereafter abbreviated as TREC cps/μg PBMC DNA 13,19 . We compared the survival experience in those with high (>2000 copies/μg PBMC DNA) versus low (<2000 copies/μg PBMC DNA) TREC levels using Kaplan-Meier survival analysis based on baseline levels and we used the log-rank test to compare survival experiences.…”

Section: Methodsmentioning

confidence: 99%

“…We compared the survival experience in those with high (>2000 copies/μg PBMC DNA) versus low (<2000 copies/μg PBMC DNA) TREC levels using Kaplan-Meier survival analysis based on baseline levels and we used the log-rank test to compare survival experiences. The cut-off TREC level of 2000 copies/μg PBMC DNA has been previously used in thymopoiesis studies 19 . We used Cox proportional hazards regression models to estimate hazard ratios of death, comparing those with high versus low TREC levels at baseline, and we repeated the analysis accounting for all follow-up TREC measurements.…”

Section: Methodsmentioning

confidence: 99%

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Chalkias

Gheuens

Bord

et al. 2015

JAIDS Journal of Acquired Immune Deficiency Syndromes

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The implications of thymopoiesis in acquired immunodeficiency syndrome (AIDS) - related opportunistic infections (OI) remain unexplored. We used progressive multifocal leukoencephalopathy (PML), caused by JC virus, as an OI model and we simultaneously investigated thymic output and T-cell responses against JCV in 22 PML patients treated with combined antiretroviral therapy. Thymic output was significantly associated with JCV-specific CD4+ and CD8+ T-cell responses and improved survival. Our data suggest that patients with AIDS-related PML and impaired thymopoiesis are less likely to develop a robust JCV-specific cellular immune response and consequently are at an increased risk for a poor clinical outcome.

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Effect of intermittent interleukin-2 therapy on CD4+ T-cell counts following antiretroviral cessation in patients with HIV

Abstract: In IL-2-treated patients, CD4(+)CD25(+) T cells persisting despite viral replication allow a longer period of ART interruption.

Cited by 20 publications

References 26 publications

Total HIV-1 DNA, a Marker of Viral Reservoir Dynamics with Clinical Implications

Total HIV-1 DNA, a Marker of Viral Reservoir Dynamics with Clinical Implications

Dendritic cell‐based therapeutic vaccine elicits polyfunctional HIV‐specific T‐cell immunity associated with control of viral load

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