Combination anti-HIV antibodies provide sustained virological suppression

Sneller, Michael C.; Blažková, Jana; Justement, J. Shawn; Shi, Victoria; Kennedy, Brooke D; Gittens, Kathleen; Tolstenko, Jekaterina; McCormack, Genevieve; Whitehead, Emily J; Schneck, Rachel F; Proschan, Michael A.; Benko, Erika; Kovacs, Colin; Oguz, Cihan; Seaman, Michael S.; Caskey, Marina; Nussenzweig, Michel C.; Fauci, Anthony S.; Moir, Susan; Chun, Tae‐Wook

doi:10.1038/s41586-022-04797-9

Cited by 90 publications

(90 citation statements)

References 49 publications

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“…In addition, more creative and revolutionary ideas and worldwide cooperation efforts among academics, drug developers and governmental funding bodies must be encouraged and promoted, and then provide more drugs to therapy the disease. Although drug therapy of HIV is highly effective, eradication of virus has not been possible to date, future new researches may focus on eradication of the virus by using long-acting antiviral agents, low side effect agents, such as combination anti-HIV antibodies ( Sneller et al, 2022 ), which will help individuals with HIV.…”

Section: Discussionmentioning

confidence: 99%

A study of the top-cited studies on drug therapy for HIV

et al. 2022

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Background Research on drug therapy for HIV remained major hot-spots, but relevant data were not satisfactory. We aimed to assess the status and trends of the most cited studies on drug therapy for HIV by using bibliometric methods.Methods The Web of Science Core Collection database was searched for the drug therapy for HIV studies. The period for retrieval was from the beginning of the database to July 26, 2022. The 100 top cited studies were selected. These general information and bibliometric data were collected and analyzed. VOS viewer software was used for visualization analysis.Results The number of citations for the 100 top cited studies ranged from 451 to 5597 and were published from 1987 to 2017. These studies were published in 29 journals. The top 3 journals in terms of the number of studies were the New England Journal of Medicine (n = 22), Lancet (n = 15), and JAMA (n = 13). The most frequently nominated author was Matthias Eiger from the University of Bern, who has contributed 5 studies. United States, Switzerland, and England contributed most of the highly cited studies. Research hot spots reflected clinical trials, treatment adverse events, basic research, and clinical adherence.Conclusion The majority of 100 top-cited studies have been published in the United States, and primarily focused on treatment adverse events, basic research, and clinical adherence. They provide a basic list of the most important and influential academic contributions to literature of HIV drug treatment for researchers.

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Section: Discussionmentioning

confidence: 99%

A study of the top-cited studies on drug therapy for HIV

et al. 2022

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“…This reservoir persists despite treatment with antiretroviral therapy (ART) and precludes cure [3][4][5][6]. Accurate measurement of the reservoir is critical for evaluating interventions aimed at producing a cure such as the "shock and kill" strategy to eliminate latently infected cells [7][8][9], therapeutic vaccination [8] and broadly neutralizing antibodies [10,11] to prevent viral rebound, and combinations of such interventions [8]. Multiple reservoir assays exist [reviewed in Massanella and Richman, 2016 [12] and Abdel-Mohsen et al, 2020 [13]].…”

Section: Introductionmentioning

confidence: 99%

Measuring the latent reservoir for HIV-1: Quantification bias in near full-length genome sequencing methods

et al. 2022

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Antiretroviral therapy (ART) effectively inhibits HIV-1 replication but is not curative due to the persistence of a latent viral reservoir in resting CD4+ T cells. This reservoir is a major barrier to cure. Sequencing studies have revealed that the population of proviruses persisting in ART-treated individuals is dominated by defective proviruses that cannot give rise to viral rebound due to fatal defects including large deletions and APOBEC3-mediated hypermutation. Near full genome sequencing (nFGS) of individual proviruses is used in reservoir assays to provide an estimate of the fraction of proviruses that are intact. nFGS methods rely on a long-distance outer PCR capturing most (~9 kb) of the genome, followed by nested inner PCRs. The outer PCR is carried out at limit dilution, and interpretation of the results is based on the assumption that all proviruses are quantitatively captured. Here, we evaluate nFGS methods using the intact proviral DNA assay (IPDA), a multiplex digital droplet PCR assay that quantitates intact and defective proviruses with single molecule sensitivity using only short, highly efficient amplicons. We analyzed proviral templates of known sequence to avoid the additional complication of sequence polymorphism. With the IPDA, we quantitated molecular yields at each step of nFGS methods. We demonstrate that nFGS methods are inefficient and miss ~70% of full-length proviruses due to amplification failure at the initial outer PCR step. In contrast, proviruses with large internal deletions encompassing 70% of the genome can be quantitatively amplified under the same conditions. Accurate measurement of the latent reservoir of HIV-1 is essential for evaluating the efficacy of cure strategies, and the bias against full length proviruses in nFGS methods must be considered.

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“…In a separate study, Sneller et al. conducted a randomized, double‐blind, placebo‐controlled trial that enrolled participants who initiated ART during the acute/early phase of HIV infection 18 . The participants in the bNAb arm received up to eight infusions of 3BNC117 (30 mg/kg) and 10–1074 (30 mg/kg) over a period of 24 weeks.…”

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confidence: 99%

“…One of the major disadvantages of bNAbs as a therapeutic option for the treatment of HIV over conventional antiretroviral drugs is that a substantial proportion of infected individuals carry antibody‐resistant, pre‐existing viral reservoirs 14,15 . The two aforementioned long‐term studies did not screen study participants for the presence of 3BNC117‐ and/or 10‐1074‐resistant virus prior to administration of the antibodies and clearly demonstrated that those with resistance to one of the two bNAbs failed to suppress their plasma viremia for prolonged periods of time 17,18 . To maximize long‐term therapeutic potential, it would be necessary to develop reliable, high throughput and clinically relevant screening methodologies to identify individuals with antibody‐resistant, pre‐existing HIV reservoirs prior to study enrollment.…”

mentioning

confidence: 99%

“…17 In a separate study, Sneller et al conducted a randomized, double-blind, placebocontrolled trial that enrolled participants who initiated ART during the acute/early phase of HIV infection. 18 The participants in the bNAb arm received up to eight infusions of 3BNC117 (30 mg/kg) and 10-1074 (30 mg/kg) over a period of 24 weeks. The pre-defined virologic endpoint of this study was the difference between the bNAb and placebo arms in the number of participants who experienced viral rebound and met ART restart criteria before reaching study week 28.…”

mentioning

confidence: 99%

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