О сложностях с паксловидом

[chuka_lis]

Статья, в которой осбуждаются проблемы. Препарат назначают тем, кто болеет умеренно, но в группе риска, начиная с 12 лет. Или госпитализированным. Врачи и ученые отмечают, что порой случается, что после курса лечения, спустя несколько дней, а то и неделю-две,  подтвержденной тестами негативности, человек снова становится позитивным, да и симптомы ковида (по типу ОРЗ) могут возвращатся, хоть и более слабые. Анализ показывает, что это тот же самый  вирус. В чем проблема, имеет смысл разобраться- может нужно изменять курс (начинать позже или лечить дольше), чтоб инфекция не возвращалась (ну или убиралась окончательно).
Кроме того, сложности  с тем, что  препарат ингибирует работу печени (тк он ингибирует ферменты, которые работают и там, не только вирусную протеазу)- что может оборачиваться тем, что в крови принимающих разные лекарства могут быть непредсказуемые количества других фармпрепаратов, которые  тоже нужны для этих групп риска (ведь по здоровью эти люди уже сидят на лекарствах, обычно), что может быть чревато побочками, ну и заморочливо для врачей.
Так же авторы отмечают, что паксловид показывает лучшие результаты, чем молнупиравир, при этом, еще, не лишне разобраться, на сколько он полезен не группам риска.
Кроме того, важно помнить, что препарат не гарантирует того, что человек не заразится (те он не подходит как средство профилактики), и ковид, не смотря на прием лекарства остается "симптоматичным".
Но главная забота- что порой люди после лечения и даже нескольких негативных тестов, уверены, что следующая ОРЗ у них не ковид, и могут даже и не тестироваться, и не изолироваться, а вируса может вырабатыватсья и выделяться достаточно, чтоб  распространять инфекцию (тк он ловится обычным антиегенным тестом).
Under its EUA, nirmatrelvir/ritonavir can be prescribed for mild to moderate COVID-19 in nonhospitalized patients aged 12 years or older who are at high risk of progression to severe disease due to age, obesity, cancer, or chronic diseases such as type 1 or type 2 diabetes. (High-risk patients who have mild to moderate COVID-19 but are hospitalized for other reasons are also eligible.)
A 3-pill dose of Paxlovid consists of 2 nirmatrelvir pills and 1 ritonavir pill, which has no activity against SARS-CoV-2 on its own. Nirmatrelvir is a protease inhibitor that blocks SARS-CoV-2 from replicating, while ritonavir boosts nirmatrelvir by slowing its metabolism in the liver. Ritonavir, which has been used to boost HIV protease inhibitors, also can slow the metabolism of an assortment of other drugs, increasing blood concentrations too much. In many cases, though, drug-drug interactions can be managed by temporarily withholding, adjusting the dose of, or using an alternative to the concomitant medication and by increasing monitoring for potential adverse reactions, according to the National Institutes of Health’s COVID-19 Treatment Guidelines, advice echoed in Infectious Diseases Society of America guidelines published May 6.
However, when compared with a placebo in the clinical trials supporting their EUAs, molnupiravir, a collaboration between Merck and Ridgeback Biotherapeutics, was not as effective as nirmatrelvir/ritonavir in keeping patients out of the hospital. Molnupiravir is authorized for use only by patients for whom alternative FDA-authorized COVID-19 treatments aren’t accessible or clinically appropriate. Also, while nirmatrelvir/ritonavir is authorized for use in children as young as 12 years old, molnupiravir isn’t authorized for use in children younger than 18 years because it may affect bone and cartilage growth. Molnupiravir, which stops SARS-CoV-2 from replicating but via a different pathway than nirmatrelvir/ritonavir, is not recommended for pregnant individuals because animal studies suggest it could cause fetal harm.
The US government has purchased 3.1 million courses of molnupiravir and 20 million courses of nirmatrelvir/ritonavir, to be delivered this year. The Office of the Assistant Secretary for Preparedness and Response, part of the US Department of Health and Human Services, maintains a web-based site locator for drugstores and other facilities that have received an order of nirmatrelvir/ritonavir or molnupiravir in the previous 2 months or reported their availability within the previous 2 weeks. In addition, a constantly updated website enables people to search specifically for SARS-CoV-2 treatments in their community.
Although nirmatrelvir/ritonavir protects against severe COVID-19 in symptomatic people who’ve tested positive for SARS-CoV-2 infection, it doesn’t prevent individuals from becoming positive and symptomatic, according to an April 29 Pfizer press release about the findings of a randomized, placebo-controlled clinical trial among adults who had been exposed to SARS-CoV-2 through a household contact.
Rebound isn’t even mentioned in the article that in April reported results from the EPIC-HR (Evaluation of Protease Inhibition for COVID-19 in High-Risk Patients) trial, which was the basis of Paxlovid’s EUA. Omicron isn’t mentioned either because trial participants, none of whom were vaccinated, contracted COVID-19 before Omicron burst onto the scene.A clinical trial among unvaccinated people that predates Omicron, which now accounts for 100% of circulating SARS-CoV-2 in the US, “holds little clinical relevance” today, Emory University School of Medicine and Grady Health System infectious disease specialist Carlos del Rio, MD, said in an interview. Even unvaccinated people today are different from unvaccinated people pre-Omicron because they’re more likely to have had at least 1 previous COVID-19 infection, Cohen pointed out.
A study posted online May 26 but not peer-reviewed is one of the first to explore real-world effectiveness of nirmatrelvir/ritonavir and molnupiravir in vaccinated as well as unvaccinated patients infected with Omicron, according to its authors.
Conducted in Hong Kong, the retrospective cohort study focused on nearly 1.1 million nonhospitalized patients territory wide with confirmed SARS-CoV-2 infection during the Omicron BA.2.2 wave between February 26 and May 3, 2022. Among them, 5257 took molnupiravir and 5663 took nirmatrelvir/ritonavir.
Both antivirals were associated with lower all-cause mortality risk—a 39% reduction for molnupiravir, 75% for nirmatrelvir/ritonavir—compared with no antiviral use. Both also were associated with a lower risk of inhospital disease progression—36% for molnupiravir and 53% for nirmatrelvir/ritonavir—compared with no antiviral use. Nirmatrelvir/ritonavir was associated with a 31% lower risk of hospitalization, while the hospitalization risk in patients who took molnupiravir was comparable with that of patients who didn’t take an antiviral.
Neither drug was associated with as high a level of protection among the Hong Kong patients infected with Omicron as was seen in its clinical trial among unvaccinated patients infected by the Delta variant. (In its trial, molnupiravir reduced hospitalization risk by 30% compared with placebo, while nirmatrelvir/ritonavir reduced it by 88%.)
In the Hong Kong study, nirmatrelvir/ritonavir use was associated with greater and more consistent protection than molnupiravir use, and the protective effects of nirmatrelvir/ritonavir were similar regardless of vaccination status and age. However, the apparent superiority of nirmatrelvir/ritonavir to molnupiravir in the study could have been due in part to a higher proportion of patients older than 65 years and a lower proportion of fully vaccinated patients among those who received the latter drug, the authors noted.
Pfizer is currently enrolling an estimated 1980 adults in a trial comparing Paxlovid with placebo, similar to EPIC-HR. But in the newer trial, participants have only a standard risk, not a high risk, of progressing from mild or moderate COVID-19 to severe disease. Another major difference between EPIC-HR and EPIC-SR (standard risk) is that all the participants are likely to have been infected with Omicron, not Delta, given the timing of the trial. Anyone who received any COVID-19 vaccine within 12 months of screening is ineligible to enroll in EPIC-SR, which means participants could have received their primary vaccine doses but not boosters.In an email, Pfizer spokeswoman Jerica Pitts echoed the CDC and FDA. “We believe the return of elevated detected nasal viral RNA [is] uncommon and not uniquely associated with treatment,” she wrote.
Ho, coauthor of a study posted May 23 about 10 people—he is the second case described in the report—who rebounded after taking nirmatrelvir/ritonavir, disagrees. When asked whether he thought the rebound could be part of the natural course of SARS-CoV-2 infection, he replied “absolutely not.”
As evidence, he and his coauthors pointed to the experience of the National Basketball Association (NBA), which tests personnel daily. From December 14, 2021, to March 1, 2022, a period during which Omicron was dominant, rebounds occurred only on the basketball court—not among the nearly 1000 NBA personnel who were diagnosed with COVID-19 but not treated with nirmatrelvir/ritonavir, according to Ho and his coauthors. Their study had not undergone peer review. However, Johns Hopkins breast cancer specialist Tatiana Prowell, MD, recently tweeted that she’s heard from physicians who’ve had patients with COVID-19 rebound or test positive on rapid antigen tests for up to 3 weeks, even though they never took nirmatrelvir/ritonavir or any other treatment. Perhaps, she speculated, Omicron and its subvariants take longer to peak or to clear than earlier SARS-CoV-2 variants. (Prowell had recently tweeted about how a household member’s symptoms disappeared and rapid antigen test results turned negative after completion of a course of nirmatrelvir/ritonavir. A week later, though, the symptoms returned, as did positive rapid antigen test results.) The fact that few EPIC-HR participants experienced a rebound “gives me less confidence in all of the findings,” said Wachter, chair of the University of California, San Francisco, Department of Medicine.No one yet knows how common rebound is among people who’ve taken Paxlovid. “You need some very objective evaluation of it,” Lane said.
Ho dismisses Pfizer’s contention that rebound is uncommon. He and his coauthors noted that 5 of the 10 relapses described in their report occurred within 2 families—2 in his family and 3 in another—suggesting it isn’t rare.
That’s concerning, Ho said, because it appears that people who experience a relapse can infect others. Among the 10 cases in the report he coauthored, viral load during the relapse was comparable to levels during the initial infection. During their relapse, 1 symptomatic and 1 presymptomatic patient transmitted SARS-CoV-2 to family members, Ho and his coauthors wrote.