Cell, 2022-01, Vol.185 (1), p.131-144.e18
2022
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- Autor(en) / Beteiligte
- Titel
- Efficient treatment and pre-exposure prophylaxis in rhesus macaques by an HIV fusion-inhibitory lipopeptide
- Ist Teil von
- Cell, 2022-01, Vol.185 (1), p.131-144.e18
- Ort / Verlag
- United States: Elsevier Inc
- Erscheinungsjahr
- 2022
- Quelle
- Free E-Journal (出版社公開部分のみ）
- Beschreibungen/Notizen
- Two HIV fusion-inhibitory lipopeptides (LP-97 and LP-98) were designed with highly potent, long-acting antiviral activity. Monotherapy using a low dose of LP-98 sharply reduced viral loads and maintained long-term viral suppression in 21 SHIVSF162P3-infected rhesus macaques. We found that five treated monkeys achieved potential posttreatment control (PTC) efficacy and had lower viral DNA in deep lymph nodes, whereas monkeys with a stable viral rebound had higher viral DNA in superficial lymph nodes. The tissues of PTC monkeys exhibited significantly decreased quantitative viral outgrowth and fewer PD-1+ central memory CD4+ T cells, and CD8+ T cells contributed to virologic control efficacy. Moreover, LP-98 administrated as a pre-exposure prophylaxis (PrEP) provided complete protection against SHIVSF162P3 and SIVmac239 infections in 51 monkeys via intrarectal, intravaginal, or intravenous challenge. In conclusion, our lipopeptides exhibit high potential as an efficient HIV treatment or prevention strategy. [Display omitted] •LP-98 shows highly potent in vitro, ex vivo, and in vivo anti-HIV activities•Monkeys with stable virus control have lower viral reservoirs in deep lymph nodes•CD8+ T cells critically contribute to posttreatment control efficacy in monkeys•LP-98 can provide efficient pre-exposure prophylaxis against SHIV or SIV infections An HIV fusion-inhibitory lipopeptide shows pre-exposure prophylaxis protection as well as broad and long-lasting antiviral activity in chimeric simian/human- or simian-immunodeficiency-virus-infected rhesus macaques, where the plasma virus of a subset of treated macaques remains undetectable after treatment cessation.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0092-8674eISSN: 1097-4172DOI: 10.1016/j.cell.2021.11.032Titel-ID: cdi_proquest_miscellaneous_2611666688
- Format
- –
- Schlagworte
- Animals, CD8+ T cells, CD8-Positive T-Lymphocytes - drug effects, CD8-Positive T-Lymphocytes - immunology, Female, fusion inhibitor, HEK293 Cells, HIV, HIV Fusion Inhibitors - administration & dosage, Humans, lipopeptide, Lipopeptides - administration & dosage, Macaca mulatta, Male, membrane fusion, posttreatment control, pre-exposure prophylaxis, Pre-Exposure Prophylaxis - methods, PrEP, PTC, Simian Acquired Immunodeficiency Syndrome - drug therapy, Simian Acquired Immunodeficiency Syndrome - immunology, Simian Acquired Immunodeficiency Syndrome - prevention & control, Simian Acquired Immunodeficiency Syndrome - virology, Simian Immunodeficiency Virus, Sustained Virologic Response, U937 Cells, Viral Load - drug effects, viral reservoir