BIOMEDICA CRO’s Post

Rapid Emergence and Evolution of SARS-CoV-2 Variants in Advanced HIV Infection. Abstract Previous studies have linked the evolution of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) genetic variants to persistent infections in people with immunocompromising conditions, but the evolutionary processes underlying these observations are incompletely understood. Here we used high-throughput, single-genome amplification and sequencing (HT-SGS) to obtain up to ~103 SARS-CoV-2 spike gene sequences in each of 184 respiratory samples from 22 people with HIV (PWH) and 25 people without HIV (PWOH). Twelve of 22 PWH had advanced HIV infection, defined by peripheral blood CD4 T cell counts (i.e., CD4 counts) <200 cells/μL. In PWOH and PWH with CD4 counts ≥200 cells/μL, most single-genome spike sequences in each person matched one haplotype that predominated throughout the infection. By contrast, people with advanced HIV showed elevated intra-host spike diversity with a median of 46 haplotypes per person (IQR 14-114). Higher intra-host spike diversity immediately after COVID-19 symptom onset predicted longer SARS-CoV-2 RNA shedding among PWH, and intra-host spike diversity at this timepoint was significantly higher in people with advanced HIV than in PWOH. Composition of spike sequence populations in people with advanced HIV fluctuated rapidly over time, with founder sequences often replaced by groups of new haplotypes. These population-level changes were associated with a high total burden of intra-host mutations and positive selection at functionally important residues. In several cases, delayed emergence of detectable serum binding to spike was associated with positive selection for presumptive antibody-escape mutations. Taken together, our findings show remarkable intra-host genetic diversity of SARS-CoV-2 in advanced HIV infection and suggest that adaptive intra-host SARS-CoV-2 evolution in this setting may contribute to the emergence of new variants of concern (VOCs). Dr Neil Bodie Juan Lama https://lnkd.in/eNXkFhPW

Interesting preprint... High levels of intra-host genetic diversity of the SARS-CoV-2 spike protein in individuals with advanced, poorly controlled HIV infection A group of scientists from the United States, South Africa and Canada developed a high-throughput, single-genome amplification and sequencing (HT-SGS) methodology to obtain up to ~103 gene sequences of the SARS-CoV-2 spike protein in two cohorts, with and without the human immunodeficiency virus (HIV). In individuals infected with HIV who had CD4 counts ≥200 cells/μL and individuals who were not infected with HIV, the majority of single-genome spike sequences in each individual matched one haplotype that predominated throughout the infection. By contrast, individuals with advanced HIV infection exhibited intra-host spike diversity, with a median of 46 haplotypes per person. Higher intra-host spike diversity immediately after the onset of COVID-19 symptoms predicted longer SARS-CoV-2 RNA shedding among individuals with HIV. In individuals with advanced HIV, the composition of spike sequences fluctuated rapidly over time, with founder sequences frequently being replaced by groups of new haplotypes. These population-level changes were associated with a high total burden of intra-host mutations and positive selection at functionally significant residues. The authors concluded that evolution of SARS-CoV-2 in these individuals is not only a product of random diversification through unchecked replication, but also of intra-host adaptation. High levels of SARS-CoV-2 spike genetic diversity in individuals with advanced, poorly controlled HIV infection markedly increase the risk for the emergence of new variants of concern (VOCs) in these individuals. Etc. A link to the original article is included in the text. https://lnkd.in/dHSpC6MT

Metformin, a drug used to treat type 2 diabetes, could help deplete and eliminate the viral reservoir in people living with HIV who receive antiretroviral therapy. University of Montreal CRCHUM. 11 September 2024. Excerpt: In 2021, a team led by immunologist Petronela Ancuta of Université de Montréal’s affiliated hospital research centre, the CRCHUM, showed metformin, when taken for three months, improved patients’ immunity and reduced chronic inflammation usually associated with complications such as cardiovascular disease. Note: One reason the benefits are effective is that metformin inhibits activity of mTOR (mechanistic target of rapamycin) molecule, which in turn slows down HIV replication in the cells of patients infected with virus. In the journal iScience, Ancuta's student Augustine Fert, the study’s first author, a recent Ph.D, studied the mechanisms of action of metformin on HIV replication in CD4 T lymphocytes, immune system cells that provide shelter for the virus. In these reservoirs, HIV keeps on replicating, which contributes to the chronic inflammation by constantly activating the immune system. “The results of our in vitro tests on cells from people living with HIV and treated with antiretroviral therapy caught us off guard,” said Ancuta. “They were surprising. We discovered netformin had a proviral and an antiviral effect. The drug helped boost the number of HIV-infected cells, while also stopping the virus from escaping the cell.” Another benefit of metformin is that it overexpresses BST2 protein, which acts as a kind of glue to keep virions clinging to the surface of HIV-infected cells. The immune system can target them with antibodies. “Together with my colleague Andrés Finzi, we tested the ability of several broad-spectrum neutralizing anti-HIV antibodies to recognize viral reservoir cells after metformin exposure in vitro,” said Ancuta. “Some of them recognized the virus very well, suggesting their ability to attract and trigger the destruction of infected cells by NK cells through a process of cellular cytotoxicity.” “In people living with HIV and treated with antiretroviral therapy, we could use metformin to reactivate reservoir cells responsible for viral replication upon treatment interruption, in combination with antibodies that are already used clinically and well tolerated. These antibodies can then detect the rare infected cells and eliminate them.” In the next phase of research, Ancuta plans to launch a clinical trial to validate her in vitro research results, in collaboration with Finzi and their CRCHUM colleague Nicolas Chomont, and Jean-Pierre Routy of McGill University Health Centre Research Institute. Link to published research accessible in enclosed announcement.

A new collaboration between The Wistar Institute’s Lieberman Lab and the Collman Lab at @Penn’s Perelman School of Medicine reveals a surprising ally of chronic HIV: RSAD2/Viperin, a gene typically associated with antiviral activity. In their new paper from The Journal of Virology, the researchers show how targeting RSAD2/Viperin reduces HIV’s activity in one of the most common HIV reservoirs — a key target in the search for a cure. “Looking closely at RSAD2/Viperin in these HIV-infected MDMs, we’ve identified yet another paradox of HIV infection,” said Dr. Paul Lieberman. “Our data show that while, yes, this is an antiviral gene that can come to the body’s defense against the virus at first, it also seems to maintain HIV’s ability to persist as a chronic infection. That makes RSAD2/Viperin a compelling candidate for further research and possible targeting of HIV reservoirs — which is critical to future cure research.” https://bit.ly/4dzObtg

Tuberculosis (TB) remains the leading cause of death among people living with HIV (PLHIV). In 2019, TB accounted for an estimated 30% of the 690 000 AIDS-related deaths in the world. These 208 000 deaths represented approximately 15% of the 1.4 million TB deaths that year. According to the 2020 Global TB Report, PLHIV are 18 (15–21) times more likely to develop active TB disease than people without HIV. In 2019, of the estimated 10 million (range, 8.9–11.0 million) people who developed TB worldwide, 8.2% were PLHIV. Even when on antiretroviral therapy (ART), PLHIV are 3 times more likely to die during TB treatment, and continue to suffer disproportionately from this preventable and curable disease. In addition to early access to ART, high quality TB screening and expanded use of TB preventive treatment are critical interventions to ensure that people with HIV receive timely treatment for TB disease or TB infection. The new WHO guidelines on systematic TB screening provide TB and HIV programmes with a range of new TB screening tools to enhance the early detection of TB among people with HIV. TB preventive treatment and ART have been proven to reduce TB incidence and mortality. However, only 50% of PLHIV initiating ART received TB preventive treatment in 2019 (from the subset of countries that reported) and only 41% of PLHIV estimated to have TB are receiving ART. HIV programmes must take measures to address these TB, diagnosis, prevention and treatment gaps among PLHIV, in order to reduce preventable TB incidence and mortality.

🌎 Diagnostic Speech: HIV virus 🇺🇲 Discourse Language: English ★ Global Health Management (Hospitals & Clínics) ★ Dr. Worldwide PCP - Emergency & Consultations ★ Massachusetts General Hospital MGH ★ Address: 55 fruit street Boston, MA 02114 ★ United States of America VPN: Working HIV stands for Human Immunodeficiency Virus. It's a virus that attacks the body's immune system, specifically targeting CD4 cells, which are crucial for fighting off infections. Certainly, here are some key characteristics of HIV: 1. **Retrovirus**: HIV belongs to the retrovirus family, meaning it carries its genetic material in the form of RNA rather than DNA. It replicates by converting its RNA into DNA using an enzyme called reverse transcriptase. 2. **Target Cells**: HIV primarily targets CD4+ T cells, which are a type of white blood cell crucial for the immune system's proper functioning. It also infects other cells, including macrophages and dendritic cells. 3. **Transmission**: HIV can be transmitted through certain bodily fluids, including blood, semen, vaginal fluids, and breast milk. Common modes of transmission include unprotected sexual intercourse, sharing contaminated needles, and from mother to child during childbirth or breastfeeding. 4. **Progression to AIDS**: If left untreated, HIV infection can progress to Acquired Immunodeficiency Syndrome (AIDS), which is characterized by a severely weakened immune system and increased susceptibility to opportunistic infections and certain cancers. There are numerous ways HIV can be proven to exist and cause AIDS: 1. **Laboratory Tests**: HIV can be detected through various laboratory tests, including ELISA, Western blot, and PCR tests. 2. **Genetic Sequencing**: The genetic sequence of HIV has been extensively studied and is well-documented. 3. **Clinical Observations**: The progression of HIV infection to AIDS has been observed in countless patients, with characteristic symptoms and immune system decline. Dr. Worldwide Networks: Requests: Dr.worldwide.telehealth@hotmail.com WhatsApp (+57) 3025140175 YouTube: https://lnkd.in/eUYQmhFV Instagram: https://lnkd.in/e-6wV8vG Facebook Fanpage: https://lnkd.in/eXmpPHwT Pinterest: https://pin.it/5c16QqcQL Harvard University Spotify Podcast: https://lnkd.in/eAe9dwjy LinkedIn: https://lnkd.in/e89Y6-HG Tiktok: https://lnkd.in/eHynj5B5 tags: #disease #health #sickness #treatment #doctors #patients #employment #greens #jobposting #remotework #humans #ops #illness #prevention #reels #youtuber #doctor #ambulances #manager #leadership

N-803 Combined with Natural Killer Cells Showed Potential to Reduce HIV Viral Load in HIV Positive Subjects; Part of HIV Cure Study All participants in the Phase 1 pilot study experienced a marked decrease in the burden of infection, and the procedures were found to be safe and well tolerated N-803 is being studied in three other HIV cure-related clinical trials CULVER CITY, Calif., March 5, 2024 — ImmunityBio (NASDAQ: IBRX), a clinical-stage immunotherapy company, today announced data from a Phase 1 pilot study showed N-803 combined with natural killer cells could have the potential to reduce viral load in people living with HIV. Published in The Journal of Infectious Diseases, researchers at the University of Minnesota Medical School gave six HIV-positive individuals infusions of healthy NK cells from close relatives, along with N-803 to boost NK cell activity. All participants in this Phase 1 study experienced significant reduction in infection levels following treatment with N-803. The approach was well tolerated with no unexpected adverse events. Tim Schacker, MD, senior author of this paper, and colleagues at the University of Minnesota Medical School are planning a follow-on study in additional participants to further investigate these immunotherapies in HIV infected individuals. https://lnkd.in/gzSDxZxf

SEVENTH PATIENT ‘CURED’ OF HIV: WHY SCIENTISTS ARE EXCITED A 60-year-old man in Germany has become at least the seventh person with HIV to be announced free of the virus after receiving a stem-cell transplant1. But the man, who has been virus-free for close to six years, is only the second person to receive stem cells that are not resistant to the virus. “I am quite surprised that it worked,” says Ravindra Gupta, a microbiologist at the University of Cambridge, UK, who led a team that treated one of the other people who is now free of HIV2,3. “It’s a big deal.” The first person found to be HIV-free after a bone-marrow transplant to treat blood cancer4 was Timothy Ray Brown, who is known as the Berlin patient. Brown and a handful of others received special donor stem cells2,3. These carried a mutation in the gene that encodes a receptor called CCR5, which is used by most HIV virus strains to enter immune cells. To many scientists, these cases suggested that CCR5 was the best target for an HIV cure. The latest case — presented at the 25th International AIDS Conference in Munich, Germany, this week — turns that on its head. The patient, referred to as the next Berlin patient, received stem cells from a donor who only had one copy of the mutated gene, which means their cells do express CCR5, but at lower levels than usual.... #HIVRemission #StemCellTransplant #CCR5Gene #BerlinPatient #HIVCure #AIDSConference #GeneEditing #HIVResearch #AntiretroviralTherapy #Leukemia #HIVTreatment #MedicalBreakthrough #CRISPRCas9 #HIVScience #StemCellTherapy https://lnkd.in/dvH_DVzn

I researched HIV for 8 years - so I’m thrilled 👏 That a new Phase 3 trial of an anti-HIV drug 💉 Showed protection of 💯%! “Lenacapavir, a twice-yearly injectable HIV-1 capsid inhibitor, has shown 100% efficacy in preventing HIV in women at a high risk for infection, according to an interim analysis of the phase 3 PURPOSE 1 trial. The results were so promising that the independent data monitoring committee recommended that Gilead Sciences stop the blinded phase of the trial & offer open-label lenacapavir to all participants. The results were both unexpected & exciting. "I've been in the HIV field for a really long time, and there's no other phase 3 PrEP trial that found zero infections," said Moupali Das, MD, PhD, executive director of clinical development at Gilead Sciences, Foster City, California. PURPOSE 1 is evaluating the safety and efficacy of two regimens — twice-yearly subcutaneous lenacapavir for preexposure prophylaxis and once-daily oral Descovy (emtricitabine 200 mg and tenofovir alafenamide 25 mg) — in women and girls aged 16-25 years. The two drugs are being compared with the standard once-daily oral Truvada (emtricitabine 200 mg and tenofovir disoproxil fumarate 300 mg). There were no cases of HIV infection among the more than 2000 women in the lenacapavir group; in contrast, the incidence of HIV in the Descovy group was 2.02 per 100 person-years and in the Truvada group was 1.69 per 100 person-years. The background incidence of HIV, one of the primary endpoints of the trial, was 2.41 per 100 person-years with lenacapavir. All drugs were found safe and well tolerated, and the full interim data from the trial will be released at an upcoming conference, according to Das. The medical community is "thrilled" with the results so far, said Monica Gandhi, director of the University of California, San Francisco-Gladstone Institutes Center for AIDS Research. "We have to wait for the full data, but so far, it has been 100% effective and far superior to other treatments." Gandhi said she is waiting to see more details on side effects and tolerability, as well as discontinuation rates in the trial and the reasons people dropped out. For example, lenacapavir tends to cause nodules to form under the skin, which are the depots from which the drug is released over the course of 6 months. Gandhi said she is interested in whether any participants found them bothersome enough to discontinue the treatment. The global HIV epidemic is still ongoing, with 1.3 million new infections in 2022, and existing oral PrEP options, and even the long-acting injectable cabotegravir, have so far failed to make as much of a dent in infection rates as hoped, said Gandhi. "We've been waiting for another option." The twice-yearly shot is easy and convenient to administer compared with oral PrEP. Many people find it difficult to remember to take the pills every day." #clinicaltrials #HIV #HIVPrep Thanks to Brian Owens, for Medscape - link in the comments!