Cell breakthrough!

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iNature's high-efficiency antiretroviral therapy (HAART) using multiple drugs can effectively inhibit the replication of HIV in the infected person, thereby significantly reducing the incidence and mortality of AIDS
.

However, HAART cannot eradicate HIV from the cell bank of quiescent but replication-competent viruses and therefore requires life-long treatment, which may lead to cumulative toxicity and drug resistance
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On December 16, 2021, He Yuxian from the Institute of Pathogenic Biology, Chinese Academy of Medical Sciences and Xue Jing, a researcher from the Institute of Medical Experimental Animals, Chinese Academy of Medical Sciences, jointly published an online publication entitled "Efficient treatment and pre-exposure prophylaxis in rhesus macaques by an HIV" in Cell fusion-inhibitory lipopeptide" research paper, this study designed two HIV fusion-inhibitory lipopeptide (LP-97 and LP-98), with high-efficiency and long-lasting antiviral activity
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Monotherapy with low-dose LP-98 significantly reduced viral load and maintained long-term viral suppression in 21 Rhesus monkeys infected with SIVSF162P3
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The study found that five treated monkeys achieved potential post-treatment control (PTC) efficacy and had lower viral DNA in deep lymph nodes, while monkeys with stable viral rebound had higher viral DNA in superficial lymph nodes
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The tissues of PTC monkeys showed significantly reduced quantitative virus growth and fewer PD-1+ central memory CD4+ T cells, and CD8+ T cells contributed to the virological control effect
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In addition, LP-98 was administered as a pre-exposure prophylaxis (PrEP), which provided complete protection against SIVSF162P3 and SIVmac239 infections in 51 monkeys through intrarectal, intravaginal or intravenous stimulation
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In conclusion, the lipopeptide studied in this study shows great potential as an effective HIV treatment or prevention strategy
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Due to the lack of preventive vaccines, extensive and effective treatment for human immunodeficiency virus positive (HIV+) individuals plays an important role in controlling the AIDS epidemic
.

High-efficiency antiretroviral therapy (HAART) using a variety of drugs can effectively inhibit HIV replication in infected persons, thereby significantly reducing the incidence and mortality of AIDS
.

However, HAART cannot eradicate HIV from the cell bank of quiescent but replication-competent viruses and therefore requires life-long treatment, which may lead to cumulative toxicity and drug resistance
.

Although there are numerous challenges to overcome in the development of HIV cures or functional HIV cures, two antiviral strategies have shed light on potential treatments
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First, the cases of "Berlin patients" and "London patients" show that the infusion of HIV-resistant cells, whether produced naturally or through gene editing, may provide a viable treatment
.

Second, stopping HAART will lead to rapid viral rebound and disease progression, but continuous control of HIV replication (defined as post-treatment control (PTC)) occurs in a portion of individuals receiving treatment
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Although latent HIV cannot be completely eliminated, cases of PTC have shown that effective treatment can suppress HIV without drugs
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It is important to characterize the potential HIV reservoir, the virological and immunological relevance of viral rebound, and the mechanism of maintaining viremia control after treatment interruption, because therapeutic interventions that use these characteristics can lead to sustained drug-free HIV remission, which is HIV One of the top tasks in the field
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HIV infection requires fusion between the viral envelope (Env) and the host cell membrane, which is mediated by Env glycoproteins gp120 and gp41
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The surface subunit gp120 is responsible for binding to the cell receptor CD4 and co-receptors (CCR5 or CXCR4), while the transmembrane subunit gp41 mediates membrane fusion; both proteins have undergone huge conformational changes
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The peptides derived from the C-terminal heptad repeat (CHR) of gp41 can form a six-helix bundle (6HB)-like assembly with the extended N-terminal heptad repeat (NHR), thereby preventing virus 6-HB from refolding
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The peptide drug Enfuvirtide (T-20) is the only viral membrane fusion inhibitor approved by the U.
S.
Food and Drug Administration.
It has been used in HIV-1 combination therapy, but its antiviral activity is low and genetic barriers exist.
Induce resistance
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Article pattern (picture from Cell) In the past ten years, researchers have devoted a lot of research work to discovering HIV fusion inhibitors with improved drug properties, and thus developed a set of lipopeptides with high-efficiency and long-lasting anti-HIV activity
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In this study, two lipopeptides, LP-97 and LP-98, were characterized, which were modified by cholesterol and showed extremely effective anti-HIV effects in vitro, in vitro and in vivo
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Low-dose LP-98 monotherapy effectively inhibited the replication of rhesus monkey/human immunodeficiency chimeric virus (SHIV) strain SIVSF162P3 in rhesus monkeys, and achieved potential PTC efficacy in a group of treated monkeys
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The virological and immunological relevance related to LP-98 treatment was further studied, and major discoveries were made
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In addition, this study demonstrated that a single dose of LP-98 can potentially protect rhesus monkeys from SIVSF162P3 or Simian Immunodeficiency Virus (SIV) SIVmac239 strains through the rectum, vagina, or intravenous infection
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