International AIDS Society global scientific strategy: towards an HIV cure 2016

Deeks, Steven G.; Lewin, Sharon R.; Ross, Anna Laura; Ananworanich, Jintanat; Benkirane, Monsef; Cannon, Paula M.; Chomont, Nicolas; Douek, Daniel C.; Lifson, Jeffrey D.; Lo, Ying-Ru; Kuritzkes, Daniel R.; Margolis, David M.; Mellors, John W.; Persaud, Deborah; Tucker, Joseph D.; Barré‐Sinoussi, Françoise; Alter, Galit; Auerbach, Judith D.; Autran, Brigitte; Barouch, Dan H.; Behrens, Georg M. N.; Cavazzana, Marina; Chen, Zhiwei; Cohen, Éric A.; Corbelli, Giulio Maria; Eholié, Serge; Eyal, Nir; Fidler, Sarah; Garcia, Laurindo; Grossman, Cynthia; Henderson, Gail E.; Henrich, Timothy J.; Jefferys, Richard; Kiem, Hans–Peter; McCune, Joseph M.; Moodley, Keymanthri; Newman, Peter A.; Nijhuis, Monique; Nsubuga, Moses Supercharger; Ott, Mélanie; Palmer, Sarah; Richman, Douglas D.; Sáez‐Cirión, Asier; Sharp, Michael; Siliciano, Janet D.; Silvestri, Guido; Singh, Jerome Amir; Spire, Bruno; Taylor, Jeffrey; Tolstrup, Martin; Valente, Susana T.; Lunzen, Jan van; Walensky, Rochelle P.; Wilson, Ira B.; Zack, Jerome A.

doi:10.1038/nm.4108

Cited by 385 publications

(341 citation statements)

References 123 publications

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“…6,7 Thus, the need for ART is lifelong and the cost is substantial 8,9 and may be difficult to sustain economically. 10 Although ART is highly efficacious in preventing transmission in the setting of mother to child transmission, 11 in sexual transmission through the treatment of infected partners in serodiscordant relationships, 12 through pre-exposure, 4,13,14 or post-exposure prophylaxis 15 scale-up difficulties and costs may make widespread implementation challenging. Furthermore, adherence is critical to the efficacy of biomedical preventive interventions but has been varied across study populations.…”

Section: Introductionmentioning

confidence: 99%

Progress in HIV vaccine development

Hsu

O’Connell

2017

Human Vaccines & Immunotherapeutics

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Section: Introductionmentioning

confidence: 99%

Progress in HIV vaccine development

Hsu

O’Connell

2017

Human Vaccines & Immunotherapeutics

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“…Changes in HIV transcription have been demonstrated in all trials by showing an increase in the level of cell-associated HIV RNA (CA RNA) in total and resting CD4 ϩ T cells (21). Synthesis of unspliced (US) HIV RNA is the first step in virus transcription, and multiple subsequent steps, including splicing, cytoplasmic export, synthesis of the regulatory proteins tat and rev, maturation, and budding, are subsequently required for virion release (22), but US HIV RNA is a marker that HIV transcription has been initiated (18).…”

mentioning

confidence: 99%

Relationship between Measures of HIV Reactivation and Decline of the Latent Reservoir under Latency-Reversing Agents

Petravic

Rasmussen

Lewin

et al. 2017

J Virol

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Antiretroviral-free HIV remission requires substantial reduction of the number of latently infected cells and enhanced immune control of viremia. Latencyreversing agents (LRAs) aim to eliminate latently infected cells by increasing the rate of reactivation of HIV transcription, which exposes these cells to killing by the immune system. As LRAs are explored in clinical trials, it becomes increasingly important to assess the effect of an increased HIV reactivation rate on the decline of latently infected cells and to estimate LRA efficacy in increasing virus reactivation. However, whether the extent of HIV reactivation is a good predictor of the rate of decline of the number of latently infected cells is dependent on a number of factors. Our modeling shows that the mechanisms of maintenance and clearance of the reservoir, the life span of cells with reactivated HIV, and other factors may significantly impact the relationship between measures of HIV reactivation and the decline in the number of latently infected cells. The usual measures of HIV reactivation are the increase in cell-associated HIV RNA (CA RNA) and/or plasma HIV RNA soon after administration. We analyze two recent studies where CA RNA was used to estimate the impact of two novel LRAs, panobinostat and romidepsin. Both drugs increased the CA RNA level 3-to 4-fold in clinical trials. However, cells with panobinostat-reactivated HIV appeared long-lived (half-life Ͼ 1 month), suggesting that the HIV reactivation rate increased by approximately 8%. With romidepsin, the life span of cells that reactivated HIV was short (2 days), suggesting that the HIV reactivation rate may have doubled under treatment.IMPORTANCE Long-lived latently infected cells that persist on antiretroviral treatment (ART) are thought to be the source of viral rebound soon after ART interruption. The elimination of latently infected cells is an important step in achieving antiretroviral-free HIV remission. Latency-reversing agents (LRAs) aim to activate HIV expression in latently infected cells, which could lead to their death. Here, we discuss the possible impact of the LRAs on the reduction of the number of latently infected cells, depending on the mechanisms of their loss and self-renewal and on the life span of the cells that have HIV transcription activated by the LRAs.KEYWORDS latency, reactivation, human immunodeficiency virus C ombination antiretroviral therapy (ART) suppresses plasma HIV RNA below the detection limit of laboratory assays and restores the immune systems of infected patients by preventing new rounds of productive infection. However, ART cannot eradicate the infection, and virus replication starts again within weeks of ART cessation

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“…Steve Deeks (University of California, San Francisco, CA) presented the final talk of the introductory session. Providing a basic science overview of the CD4 + T cell reservoir, he discussed: (1) the size and stability of the reservoir, (2) T cell subsets that comprise the reservoir, (3) the source of virus production, (4) the source of viral persistence, (5) the timing of reservoir establishment, and (6) current thoughts about macrophages as a reservoir, and prevention of infection and latency reversal in this population [6][7][8][9][10]. Currently, sampling issues limit the study of the human reservoir, and in addition to blood, gut, and lymph nodes, more tissues will need to be sampled to achieve improved coverage.…”

Section: Introductory Sessionmentioning

confidence: 99%

HIV Infection of Macrophages: Implications for Pathogenesis and Cure

Clayton

García

Clements

et al. 2017

PAI

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Although CD4+ T cells represent the major reservoir of persistent HIV and SIV infection, accumulating evidence suggests that macrophages also contribute. However, investigations of the role of macrophages are often underrepresented at HIV pathogenesis and cure meetings. This was the impetus for a scientific workshop dedicated to this area of study, held in Cambridge, MA in January 2017. The workshop brought together experts in the fields of HIV/SIV immunology/virology, macrophage biology and immunology, and animal models of HIV/SIV infection to facilitate discussions regarding the role of macrophages as a physiologically relevant viral reservoir, and the implications of macrophage infection for HIV pathogenesis and cure strategies. An emerging consensus that infected macrophages likely persist in the setting of combination antiretroviral therapy, driving persistent inflammation and contributing to the viral reservoir, indicate the importance of addressing macrophages as well as CD4+ T cells with future therapeutic strategies.

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International AIDS Society global scientific strategy: towards an HIV cure 2016

Cited by 385 publications

References 123 publications

Progress in HIV vaccine development

Progress in HIV vaccine development

Relationship between Measures of HIV Reactivation and Decline of the Latent Reservoir under Latency-Reversing Agents

HIV Infection of Macrophages: Implications for Pathogenesis and Cure

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