Treatment interruption in chronically HIV-infected patients with an ultralow HIV reservoir

Câlin, Ruxandra; Hamimi, Chiraz; Lambert-Niclot, Sidonie; Carcelain, Guislaine; Bellet, Jonathan; Assoumou, Lambert; Tubiana, Roland; Cálvez, Vincent; Dudoit, Yasmine; Costagliola, Dominique; Autran, Brigitte; Katlama, Christine

doi:10.1097/qad.0000000000000987

Cited by 71 publications

(73 citation statements)

References 24 publications

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“…1g–h) (12). In all cases, HIV rebound was observed by 2 weeks after therapy interruption, a time to rebound that is within the range observed for patients (18). Considering the absence of detectable viral RNA and DNA in macrophages isolated from ART-suppressed BLT mice, the rapid rebound observed ostensibly results from virus present in T cells.…”

supporting

confidence: 80%

“…indicate that reductions of 2–3 logs in the number of latently infected cells are needed to delay rebound for the time reported herein for MoM (29). The delay in rebound observed in MoM is greater than that reported for patients initiating ART during the chronic phase of infection (30) and from patients with an ultralow HIV reservoir (18). Our results indicate that HIV-infected tissue macrophages have a short half-life and that ART alone can significantly reduce the levels of infected tissue macrophages, further demonstrating the critical contribution of T cells to the viral reservoir.…”

mentioning

confidence: 62%

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HIV persistence in tissue macrophages of humanized myeloid-only mice during antiretroviral therapy

Honeycutt

Thayer

Baker

et al. 2017

Nat Med

245

224

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Despite years of fully suppressive antiretroviral therapy (ART), HIV persists in the host and is never eradicated. One major barrier to eradication is that multiple different cell types are infected that may individually contribute to HIV persistence. Tissue macrophages are critical contributors to HIV disease (1–3); however, their specific role in HIV persistence during long-term suppressive ART has not been established (4–6). Using humanized myeloid-only mice (MoM), we demonstrate that HIV infection of tissue macrophages is rapidly suppressed by ART, as determined by a rapid drop in plasma viral load and a dramatic drop in the levels of cell-associated viral RNA and DNA. No virus rebound was observed in the plasma of 67% of the ART treated animals at seven weeks post-ART interruption, and no replication competent virus was rescued from the tissue macrophages obtained from these animals. In contrast, in a subset of animals (~33%), a significantly delayed viral rebound was observed that is consistent with the establishment of persistent infection in tissue macrophages. These observations represent the first direct evidence of HIV persistence in tissue macrophages in vivo.

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supporting

confidence: 80%

mentioning

confidence: 62%

HIV persistence in tissue macrophages of humanized myeloid-only mice during antiretroviral therapy

Honeycutt

Thayer

Baker

et al. 2017

Nat Med

245

224

View full text Add to dashboard Cite

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“…Conversely, a TI study comparing initiation of ART during early infection versus CHI found an 8.3% rate of post treatment control at 48 weeks among those who started ART during early infection and no post-treatment control among those who started ART during CHI 7 . Even in a highly preselected group of individuals (based on low cell-associated DNA) who initiated therapy in chronic infection and underwent a TI the rates of PTC were 10% 14 . In a retrospective cohort study of individuals started on ART during CHI, 1.6% of individuals were reported to be PTCs 15 .…”

Section: Introductionmentioning

confidence: 97%

“…The presence of PTCs has been examined in both prospective treatment-interruption (TI) and retrospective cohort studies 2–15 . Reported rates of post treatment control are variable and have ranged from the absence of the phenotype 2–6 to rates ranging from 4–14% 7–14 . This variation is partially explained by differences in baseline characteristics of the populations and the definitions of post treatment control in these studies.…”

Section: Introductionmentioning

confidence: 99%

Brief Report: Prevalence of Posttreatment Controller Phenotype Is Rare in HIV-Infected Persons After Stopping Antiretroviral Therapy

Perkins

Bradley

Lalani

et al. 2017

JAIDS Journal of Acquired Immune Deficiency Syndromes

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Background: Posttreatment control of HIV infection is a rare phenomenon primarily described among those initiating treatment with antiretroviral therapy (ART) during early/acute HIV infection. Methods: We examined a large, well-characterized cohort of HIV-infected Department of Defense beneficiaries for the presence of posttreatment controllers (PTCs) whom we defined as individuals with sustained viral suppression for ≥6 months after discontinuation of ART. We defined those who became viremic within 6 months of discontinuing ART as rapid viremics (RVs) and compared demographic and clinical characteristics, CD4 counts, and viral loads prior, during, and after ART discontinuation between the 2 groups. Results: From a cohort of 6070 patients, we identified 95 who had been treated with ART for 2 years or more who subsequently discontinued ART and had viral load assessments available after discontinuation. Four (4.2%) of these 95 met our definition of PTC. The duration of viral suppression off of ART ranged from 267 to 1058 days with 1 of the 4 restarting ART without having redeveloped a significant viremia. All 4 patients initiated ART during chronic HIV infection. Demographic and clinical characteristics of PTCs were similar to RVs. Conclusions: While posttreatment control has predominantly been described among individuals who initiated ART in early/acute HIV infection, we identified 4 PTCs who started ART during chronic infection suggesting that posttreatment control also occurs among such patients. The rarity of PTCs identified in our cohort is consistent with reports from previous studies.

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“…Other few reported cases of long-term remission in individuals controlling viral replication after ART interruption, also called “post-treatment controllers”, have been documented (9–13). However for most HIV-infected individuals, HIV viral load rebounds at a median time of 14 days after treatment interruption from a large number of HIV variants (14–16). Inducing HIV expression has been proposed as a strategy to eliminate persistently HIV-infected cells that constitute the viral reservoir (17–19).…”

Section: Introductionmentioning

confidence: 99%

Kill

Trautmann

2016

Current Opinion in HIV and AIDS

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Purpose of review Increasing evidences suggest that purging the latent HIV reservoir in virally-suppressed individuals will require both the induction of viral replication from its latent state and the elimination of these reactivated HIV infected cells (“Shock and Kill” strategy). Boosting potent HIV-specific CD8 T cells is a promising way to achieve an HIV cure. Recent findings Recent studies provided the rationale for developing immune interventions to increase the numbers, function and location of HIV-specific CD8 T cells to purge HIV reservoirs. Multiple approaches are being evaluated including very early suppression of HIV replication in acute infection, adoptive cell transfer, therapeutic vaccination or use of immunomodulatory molecules. New assays to measure the killing and antiviral function of induced HIV-specific CD8 T cells have been developed to assess the efficacy of these new approaches. The strategies combining HIV reactivation and immunobased therapies to boost HIV-specific CD8 T cells can be tested in in vivo and in silico models to accelerate the design of new clinical trials. Summary New immunobased strategies are explored to boost HIV-specific CD8 T cells able to purge the HIV-infected cells with the ultimate goal of achieving spontaneous control of viral replication without antiretroviral treatment.

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Treatment interruption in chronically HIV-infected patients with an ultralow HIV reservoir

Cited by 71 publications

References 24 publications

HIV persistence in tissue macrophages of humanized myeloid-only mice during antiretroviral therapy

HIV persistence in tissue macrophages of humanized myeloid-only mice during antiretroviral therapy

Brief Report: Prevalence of Posttreatment Controller Phenotype Is Rare in HIV-Infected Persons After Stopping Antiretroviral Therapy

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