Day: 01/06/2022

Relatlimab and Nivolumab versus Nivolumab in Untreated Advanced Melanoma

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Abstract

BACKGROUND

Lymphocyte-activation gene 3 (LAG-3) and programmed death 1 (PD-1) are distinct inhibitory immune checkpoints that contribute to T-cell exhaustion. The combination of relatlimab, a LAG-3–blocking antibody, and nivolumab, a PD-1–blocking antibody, has been shown to be safe and to have antitumor activity in patients with previously treated melanoma, but the safety and activity in patients with previously untreated melanoma need investigation.

METHODS

In this phase 2–3, global, double-blind, randomized trial, we evaluated relatlimab and nivolumab as a fixed-dose combination as compared with nivolumab alone when administered intravenously every 4 weeks to patients with previously untreated metastatic or unresectable melanoma. The primary end point was progression-free survival as assessed by blinded independent central review.

RESULTS

The median progression-free survival was 10.1 months (95% confidence interval [CI], 6.4 to 15.7) with relatlimab–nivolumab as compared with 4.6 months (95% CI, 3.4 to 5.6) with nivolumab (hazard ratio for progression or death, 0.75 [95% CI, 0.62 to 0.92]; P=0.006 by the log-rank test). Progression-free survival at 12 months was 47.7% (95% CI, 41.8 to 53.2) with relatlimab–nivolumab as compared with 36.0% (95% CI, 30.5 to 41.6) with nivolumab. Progression-free survival across key subgroups favored relatlimab–nivolumab over nivolumab. Grade 3 or 4 treatment-related adverse events occurred in 18.9% of patients in the relatlimab–nivolumab group and in 9.7% of patients in the nivolumab group.

CONCLUSIONS

The inhibition of two immune checkpoints, LAG-3 and PD-1, provided a greater benefit with regard to progression-free survival than inhibition of PD-1 alone in patients with previously untreated metastatic or unresectable melanoma. Relatlimab and nivolumab in combination showed no new safety signals.

Abortion Safety and Use with Normally Prescribed Mifepristone in Canada

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BACKGROUND

In the United States, mifepristone is available for medical abortion (for use with misoprostol) only with Risk Evaluation and Mitigation Strategy (REMS) restrictions, despite an absence of evidence to support such restrictions. Mifepristone has been available in Canada with a normal prescription since November 2017.

METHODS

Using population-based administrative data from Ontario, Canada, we examined abortion use, safety, and effectiveness using an interrupted time-series analysis comparing trends in incidence before mifepristone was available (January 2012 through December 2016) with trends after its availability without restrictions (November 7, 2017, through March 15, 2020).

RESULTS

A total of 195,183 abortions were performed before mifepristone was available and 84,032 after its availability without restrictions. After the availability of mifepristone with a normal prescription, the abortion rate continued to decline, although more slowly than was expected on the basis of trends before mifepristone had been available (adjusted risk difference in time-series analysis, 1.2 per 1000 female residents between 15 and 49 years of age; 95% confidence interval [CI], 1.1 to 1.4), whereas the percentage of abortions provided as medical procedures increased from 2.2% to 31.4% (adjusted risk difference, 28.8 percentage points; 95% CI, 28.0 to 29.7). There were no material changes between the period before mifepristone was available and the nonrestricted period in the incidence of severe adverse events (0.03% vs. 0.04%; adjusted risk difference, 0.01 percentage points; 95% CI, −0.06 to 0.03), complications (0.74% vs. 0.69%; adjusted risk difference, 0.06 percentage points; 95% CI, −0.07 to 0.18), or ectopic pregnancy detected after abortion (0.15% vs. 0.22%; adjusted risk difference, −0.03 percentage points; 95% CI, −0.19 to 0.09). There was a small increase in ongoing intrauterine pregnancy continuing to delivery (adjusted risk difference, 0.08 percentage points; 95% CI, 0.04 to 0.10).

CONCLUSIONS

After mifepristone became available as a normal prescription, the abortion rate remained relatively stable, the proportion of abortions provided by medication increased rapidly, and adverse events and complications remained stable, as compared with the period when mifepristone was unavailable.

Covid-19’s Devastating Effect on Tuberculosis Care — A Path to Recovery

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The Covid-19 pandemic has had devastating effects on every aspect of global health, but tuberculosis services have been disproportionately affected.1 According to the World Health Organization (WHO) Global Tuberculosis Report 2021, case notifications have plummeted because of pandemic-related disruptions in services.2 For the first time in more than a decade, tuberculosis mortality has increased.2

Even as high-income countries roll out Covid-19 vaccine boosters and stockpile millions of vaccine doses, many low- and middle-income countries are struggling to obtain vaccines. Whereas 76% of people in high-income countries have received at least one Covid-19 vaccine dose, as of the end of December 2021, the rate was only 8% in low-income countries. Because of vaccine inequity, new variants of SARS-CoV-2 (such as omicron) are emerging and particularly affect countries with low vaccine coverage and high rates of poverty and tuberculosis.

The WHO (where two of us work) estimates that nearly 10 million people developed tuberculosis in 2020.2 Only 5.8 million cases were diagnosed and reported, however, which reflects an 18% decrease from 2019. This decrease was concentrated in 16 countries, with Asian countries (especially India, Indonesia, the Philippines, and China) seeing the largest reductions in case reporting.2 These countries all had major Covid-19 outbreaks and health care service disruptions.Global Trends in the Estimated Number of Tuberculosis Deaths and Tuberculosis Mortality, 2000 to 2020.

Tuberculosis deaths have increased because of reduced access to care.2 In 2020, there were roughly 1.5 million tuberculosis deaths worldwide, representing the first year-over-year increase in tuberculosis deaths since 2005 (see figure).2 Other negative pandemic-related effects include a 15% reduction in the number of people treated for drug-resistant tuberculosis, a 21% decrease in people receiving preventive treatment for tuberculosis infection, and a decrease (from $5.8 billion to $5.3 billion) in global tuberculosis spending between 2019 and 2020.2

Given these setbacks, progress toward the 2022 targets established by the United Nations (UN) high-level meeting on tuberculosis is off track. Reductions in tuberculosis incidence have dramatically slowed. This trend is expected to worsen, driven by ongoing Covid-19 surges in low- and middle-income countries.2 India and Indonesia, for example, had delta-variant surges in 2021, with millions of excess deaths and severe disruptions to essential health services. The emergence of the omicron variant poses a new threat, especially to countries in southern Africa that are experiencing massive Covid-19 surges on top of already high tuberculosis and HIV coinfection burdens.

Without an effective tuberculosis vaccine for adults, treatment is the primary form of disease control. Because so many tuberculosis cases have been missed during the past 2 years, increased transmission is expected. WHO modeling suggests that the pandemic’s effects on tuberculosis incidence and mortality in 2020 will be exacerbated in 2021 and beyond, in some cases throughout all 16 countries that were considered.2

These projections don’t account for exacerbations in the social determinants (extreme poverty and malnutrition, for example) that fuel the tuberculosis epidemic. In 2020, the Covid-19 pandemic pushed 100 million people into poverty, and the UN estimates that developing economies will have pandemic-related losses of $12 trillion through 2025. Nearly 20% of global tuberculosis incidence is attributable to undernutrition.2 In countries with high tuberculosis burdens, such as India, the population attributable fraction for undernutrition is higher — more than 50% in many Indian states3 — and malnutrition and poverty could be important tuberculosis drivers in coming years.

The path to recovery will require both immediate, short-term steps and longer-term actions. First, ending the Covid-19 pandemic quickly is critical for rebuilding tuberculosis services and other essential health services. No country can keep new variants in check without high Covid-19 vaccine coverage. Without global vaccination, health care systems in low- and middle-income countries will collapse. We believe people working in the tuberculosis field should support the WHO plan — which was also included in the Group of 20 Rome leaders’ declaration — to vaccinate 70% of all countries’ populations by mid-2022. To achieve this goal, high-income countries will need to immediately redistribute surplus vaccine doses and meet their pledges to the Covid-19 Vaccines Global Access (COVAX) program. Waiving intellectual-property rights and sharing vaccine know-how is essential so that countries can produce their own vaccines. The WHO has created a multilateral mechanism to address regional inequities in vaccine manufacturing, with the first mRNA technology–transfer hub established in South Africa and spokes in many countries.

Second, we need to highlight the worsening tuberculosis epidemic. Real-time Covid-19 dashboards are widely available, and governments respond immediately to new data. Tuberculosis programs can learn from this approach. Investments in digital data systems, connected diagnostics, and digital treatment-support tools could make tuberculosis data more visible and accessible. Communities could use these data to hold governments accountable and advocate for increased funding. During the pandemic, the WHO has published monthly tuberculosis-notification data and offered modeling estimates to guide countries’ recovery efforts. Such rapid reporting should become the new normal, and real-time tuberculosis data should be available everywhere.

Third, improving case detection is an urgent priority.4 Doing so will necessitate leveraging mobile-phone–based apps and digital tools to improve patient education, triage, and referrals and contact screening. Targeted active-case–finding initiatives, guided by precision public health (i.e., predictive analytics and mapping of hotspots), could help identify people with undiagnosed tuberculosis. This approach will require learning from Covid-19 testing experiences by bringing tuberculosis testing closer to where people live and work and engaging communities, private providers, and community-based health workers and civil-society organizations.4

Every country has scaled up its molecular-testing capacity for Covid-19, and this capacity could be used for tuberculosis testing, in combination with validation of simpler, nonsputum samples. Better integration of tuberculosis and Covid-19 testing is also necessary. Because of the need to provide medical care during lockdowns, substantial advances have been made in digital health, remote service provision, ultra-portable digital x-ray systems with artificial-intelligence–based reading software, use of digital technologies for promoting medication adherence, and use of e-pharmacies in combination with home delivery of medicines.4 These systems could be leveraged for tuberculosis on a large scale, including scale-up of preventive therapy for tuberculosis.

In the longer term, only by establishing multisectoral collaborations involving personal, societal, and health system interventions will we end the global tuberculosis epidemic by 2035.1 Achieving this goal will require addressing the social determinants of tuberculosis infection and mortality; reducing stigma and other barriers to seeking care; promoting the use of masks, improved ventilation, and other airborne infection–control measures; and ensuring that health care workers have adequate personal protective equipment.

Another long-term strategy involves increasing investment in the development of new tuberculosis tools, taking advantage of the scientific advances that rapidly produced Covid-19 vaccines, diagnostics, and drugs. Development of a simple, point-of-care tuberculosis test, an improved tuberculosis vaccine, and ultra-short drug regimens is critical.

These efforts will require increased funding. Even as more than $100 billion has been invested in developing Covid-19 vaccines, leading to more than a dozen vaccines being authorized within 1 year after the WHO declaration of Covid-19 as a Public Health Emergency of International Concern, the century-old bacille Calmette–Guérin vaccine is still used for tuberculosis. Investments in new tuberculosis vaccines amount to barely $0.1 billion per year, and overall research and development investments reached only $0.9 billion in 2020, as compared with an estimated need of $2 billion.2 New platforms such as mRNA and viral vectors that have proven successful for Covid-19 vaccines could be leveraged to develop tuberculosis vaccines, and clinical trials must be accelerated.

Tuberculosis should be included in the pandemic preparedness and response agenda, which will probably be the focus of international government attention and increases in health spending moving forward. Investments in social protection and universal health coverage would mitigate the Covid-19 pandemic’s effects and help avert the next crisis. Progress toward the UN’s Sustainable Development Goals (SDGs) would be beneficial for tuberculosis and other poverty-related diseases. Conversely, failure to achieve the SDGs’ tuberculosis-mortality target by 2030 would result in substantial health and economic losses.5

We believe world leaders should commit to vaccinating people globally to help end the Covid-19 pandemic. They should also reaffirm their commitment to ending the tuberculosis epidemic, work harder to mitigate the effects of the pandemic, and address the social, environmental, and economic determinants of tuberculosis infection and mortality.

Eltrombopag Added to Immunosuppression in Severe Aplastic Anemia

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Abstract

BACKGROUND

A single-group, phase 1–2 study indicated that eltrombopag improved the efficacy of standard immunosuppressive therapy that entailed horse antithymocyte globulin (ATG) plus cyclosporine in patients with severe aplastic anemia.

METHODS

In this prospective, investigator-led, open-label, multicenter, randomized, phase 3 trial, we compared the efficacy and safety of horse ATG plus cyclosporine with or without eltrombopag as front-line therapy in previously untreated patients with severe aplastic anemia. The primary end point was a hematologic complete response at 3 months.

RESULTS

Patients were assigned to receive immunosuppressive therapy (Group A, 101 patients) or immunosuppressive therapy plus eltrombopag (Group B, 96 patients). The percentage of patients who had a complete response at 3 months was 10% in Group A and 22% in Group B (odds ratio, 3.2; 95% confidence interval [CI], 1.3 to 7.8; P=0.01). At 6 months, the overall response rate (the percentage of patients who had a complete or partial response) was 41% in Group A and 68% in Group B. The median times to the first response were 8.8 months (Group A) and 3.0 months (Group B). The incidence of severe adverse events was similar in the two groups. With a median follow-up of 24 months, a karyotypic abnormality that was classified as myelodysplastic syndrome developed in 1 patient (Group A) and 2 patients (Group B); event-free survival was 34% and 46%, respectively. Somatic mutations were detected in 29% (Group A) and 31% (Group Β) of the patients at baseline; these percentages increased to 66% and 55%, respectively, at 6 months, without affecting the hematologic response and 2-year outcome.

CONCLUSIONS

The addition of eltrombopag to standard immunosuppressive therapy improved the rate, rapidity, and strength of hematologic response among previously untreated patients with severe aplastic anemia, without additional toxic effects.

Effect of Covid-19 Vaccination on Transmission of Alpha and Delta Variants

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Abstract

BACKGROUND

Before the emergence of the B.1.617.2 (delta) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), vaccination reduced transmission of SARS-CoV-2 from vaccinated persons who became infected, potentially by reducing viral loads. Although vaccination still lowers the risk of infection, similar viral loads in vaccinated and unvaccinated persons who are infected with the delta variant call into question the degree to which vaccination prevents transmission.

METHODS

We used contact-testing data from England to perform a retrospective observational cohort study involving adult contacts of SARS-CoV-2–infected adult index patients. We used multivariable Poisson regression to investigate associations between transmission and the vaccination status of index patients and contacts and to determine how these associations varied with the B.1.1.7 (alpha) and delta variants and time since the second vaccination.

RESULTS

Among 146,243 tested contacts of 108,498 index patients, 54,667 (37%) had positive SARS-CoV-2 polymerase-chain-reaction (PCR) tests. In vaccinated index patients who became infected with the alpha variant, two vaccinations with either BNT162b2 or ChAdOx1 nCoV-19 (also known as AZD1222), as compared with no vaccination, were independently associated with reduced PCR positivity in contacts (adjusted rate ratio with BNT162b2, 0.32; 95% confidence interval [CI], 0.21 to 0.48; and with ChAdOx1 nCoV-19, 0.48; 95% CI, 0.30 to 0.78). Vaccine-associated reductions in transmission of the delta variant were smaller than those with the alpha variant, and reductions in transmission of the delta variant after two BNT162b2 vaccinations were greater (adjusted rate ratio for the comparison with no vaccination, 0.50; 95% CI, 0.39 to 0.65) than after two ChAdOx1 vaccinations (adjusted rate ratio, 0.76; 95% CI, 0.70 to 0.82). Variation in cycle-threshold (Ct) values (indicative of viral load) in index patients explained 7 to 23% of vaccine-associated reductions in transmission of the two variants. The reductions in transmission of the delta variant declined over time after the second vaccination, reaching levels that were similar to those in unvaccinated persons by 12 weeks in index patients who had received ChAdOx1 nCoV-19 and attenuating substantially in those who had received BNT162b2. Protection in contacts also declined in the 3-month period after the second vaccination.

CONCLUSIONS

Vaccination was associated with a smaller reduction in transmission of the delta variant than of the alpha variant, and the effects of vaccination decreased over time. PCR Ct values at diagnosis of the index patient only partially explained decreased transmission.

Discussion

We found that both the BNT162b2 and ChAdOx1 nCoV-19 vaccines were associated with reduced onward transmission of SARS-CoV-2 from index patients who became infected despite vaccination. However, in index patients who were vaccinated with BNT162b2 and probably in those who were vaccinated with ChAdOx1 nCoV-19, reductions in transmission of the delta variant were smaller than reductions in transmission of the alpha variant. In population-based studies, vaccines have continued to provide protection against infection with the delta variant, but to a lesser degree than against infection with the alpha variant.8 Therefore, the delta variant eroded vaccine-associated protection against transmission both by making infection more common and by increasing transmission from infected vaccinated persons.

Vaccines have been hypothesized to reduce onward transmission by reducing viral loads.14,15 In our study, vaccination was associated with higher Ct values (lower viral loads) of the alpha variant and, to a smaller extent, with higher Ct values of the delta variant. Higher Ct values were associated with less transmission (Figure 4B). However, we found that differences in Ct values at diagnosis in the index patient accounted for only 7 to 23% of the effect of vaccination, with most of the effect of vaccination probably occurring through other mechanisms. This finding indicates that Ct values measured in diagnostic testing are not necessarily a surrogate for the effect of vaccination on transmission. Ct values at diagnosis are probably imperfectly representative of viral loads at transmission, despite the relationship observed between Ct values and transmission, because viral loads are dynamic over time.22 Vaccination may also act by facilitating faster clearance of viable infectious virions,17,18 but they may leave damaged ineffective virions behind that still contain PCR-detectable RNA. Studies of this possibility and of how antigen assays perform after vaccination could lead to improvement in diagnostic tests after vaccination.

We found differences between vaccines that may have reflected their differing mechanisms of action. Index patients who were vaccinated with BNT162b2 had contacts who were less likely to have positive PCR tests for the delta variant than those of index patients who had received ChAdOx1 nCoV-19. There was potentially insufficient power to resolve differences between the vaccines with respect to the alpha variant because relatively few persons who were vaccinated twice became infected before the delta variant became the dominant lineage. The incidences of infections with the alpha variant and those with the delta variant were also lower among contacts vaccinated twice with BNT162b2 than among those vaccinated twice with ChAdOx1 nCoV-19.

Protection against onward transmission waned during the 3-month period after the second vaccination. Some protection against the alpha variant remained, but much of the protection against onward transmission of the delta variant was lost, particularly with ChAdOx1 nCoV-19. Waning of protective behaviors may explain some of the change, because the use of measures such as social distancing and mask wearing in vaccinated persons may have decreased. However, reductions in antibody levels23 and vaccine effectiveness8 over time provide support for the importance of biologic explanations. In addition, some of the observed decline in protection may be attributed to a longer period since vaccination in persons who were vaccinated early; these persons may have been clinically vulnerable, with immune systems that were weaker than those of persons who were vaccinated more recently.

Contacts were also more likely to test positive as the time since their second vaccination increased. Although contacts who received BNT162b2 had increased protection throughout the 3-month period after the second vaccination, this protection waned faster with BNT162b2 than with ChAdOx1 nCoV-19, as was also seen with new infections in a representative survey in the United Kingdom.8

Our study has several limitations. In order to minimize bias introduced by differences in testing behavior arising for multiple reasons, including the vaccination status of contacts, we included only contacts who had undergone PCR testing. Therefore, we cannot estimate secondary attack rates according to the vaccination status of patients and contacts, and the absolute protective effects of vaccination on transmission may be underestimated because vaccine-protected, uninfected contacts may not have sought testing. Our approach is also unlikely to eliminate bias, particularly if test-seeking behavior is related to perceived vaccine efficacy, given the nonspecificity of many symptoms of Covid-19.24

Some contacts may have been infected by a source other than the identified “index patient”; this would attenuate associations between index-patient–related variables, including vaccination status, and the outcome. To minimize this effect, we restricted our study to contacts who had undergone testing 1 to 10 days after testing in an index patient, with very similar findings when the analysis was restricted to 2 to 7 days. Better data on symptom onset and the timing of exposures between patients and contacts could improve estimates.

In addition, we did not have sufficient data to account for previous infection status, which is also imperfectly ascertained in national testing programs. Increasing immunity arising from previous infection in the unvaccinated comparator group potentially reduces estimates of vaccine effectiveness over time; however, with adjustment for calendar time, previous infection can be allowed for at a population level, along with changes in test-seeking behavior and the incidence of other infections that cause symptoms that are similar to those of Covid-19.25

We used S-gene target failure and time, rather than sequencing, as a proxy to distinguish infection with the alpha variant from that with the delta variant; thus, some low-viral-load delta variant infections with S-gene target failure may have been misclassified as alpha variant infections. However, we restricted the time period of our data set to minimize this effect. We considered all PCR tests in contacts, including results of assays without an S-gene target, so we could not assess the concordance of patient–contact S-gene target failure as evidence supporting transmission.

Finally, we did not have data to adjust for coexisting conditions in clinically vulnerable persons or for health care workers. Both of these groups were vaccinated earlier in the Covid-19 pandemic and were more likely to have had shorter dosing intervals than those who were vaccinated later. This lack of adjustment may have affected the findings, particularly on waning of vaccine protection over time and differences according to vaccine type; it also precluded analysis of the effect of the dosing interval.8

The delta variant has spread globally and caused resurgences of infection even in areas with high vaccination coverage. Increased onward transmission from persons who become infected despite vaccination is probably an important reason for this spread. Booster vaccination campaigns that are being considered and implemented26 may help to control transmission as well as prevent infections.

Supported by the U.K. Government Department of Health and Social Care; the National Institute for Health Research (NIHR) Health Protection Research Unit in Healthcare Associated Infections and Antimicrobial Resistance, Oxford University, in partnership with Public Health England (NIHR200915); and the NIHR Biomedical Research Centre, Oxford. Dr. Eyre is a Robertson Foundation Fellow and an NIHR Oxford Biomedical Research Centre Senior Fellow; and Dr. Walker is an NIHR Senior Investigator.

The views expressed in this article are those of the authors and not necessarily those of the National Health Service, the National Institute for Health Research, the Department of Health, or Public Health England.

Source: NEJM

Fully vaccinated people still get the #omicron variant. Here’s why.

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Fully vaccinated people still get the omicron variant. Here’s why – Deseret News https://www.deseret.com/coronavirus/2022/1/5/22868312/why-fully-vaccinated-people-get-omicron-variant-symptoms

A maternal truth: some women don’t love their children as society thinks they should | Rhiannon Lucy Cosslett | The Guardian

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A maternal truth: some women don’t love their children as society thinks they should | Rhiannon Lucy Cosslett | The Guardian https://www.theguardian.com/commentisfree/2022/jan/05/the-lost-daughter-elena-ferrante-women-complexity-child-rearing

CDC updates STI treatment guidelines for first time since 2015

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The CDC on Thursday published updated clinical guidelines for the treatment of STIs amid a sustained national increase in cases of chlamydia, gonorrhea and syphilis.

The guidance, updated for the first time since 2015, also includes prevention strategies and diagnostic recommendations.

Source: CDC.gov
The CDC updated treatment guidelines for STIs for the first time since 2015, emphasizing new treatments and diagnostics for gonorrhea. Source: CDC

“There are several important updates, but I would highlight the updates that build upon the adjustments to gonorrhea treatment that were made in December 2020 to ensure effective treatment and minimize the threat of drug resistance,” Kimberly A. Workowski, MD, a medical officer in CDC’s Division of STD Prevention, told Healio. “Effectively treating gonorrhea remains a public health priority.”

Gonorrhea, which has consistently developed resistance against the antibiotics used to treat it, is the second most commonly reported bacterial STD in the United States, with cases increasing 56% from 2015 to 2019 to more than 1 million diagnosed and undiagnosed infections per year, according to Workowski.

The CDC now recommends treating gonorrhea with a single 500 mg injection of ceftriaxone. If chlamydia testing has not been performed, doxycycline 100 mg orally twice a day for 7 days is also recommended.

Workowski noted additional updates to the treatment guidelines regarding gonorrhea, including that a test of cure is not needed for patients who receive a diagnosis of uncomplicated urogenital or rectal gonorrhea unless symptoms persist. A test of cure is recommended for patients with pharyngeal gonorrhea using either culture or nucleic acid amplification tests 7 to 14 days after the initial treatment, regardless of the regimen, Workowski said.

She said patients who have been treated for gonorrhea should be retested 3 months after treatment to ensure reinfection has not occurred. If retesting at 3 months is not possible, patients should be retested within 12 months after initial treatment and providers should facilitate partners’ treatment, Workowski said.

The new guidelines note that there are now FDA-cleared rectal and oral tests to diagnose chlamydia and gonorrhea that have been validated for clinical use — an important development “because infection at these sites is often without symptoms,” Workowski said.

The guidelines also include updates for hepatitis C virus testing and HPV vaccination.

The CDC recommends that all adults aged 18 years or older be screened for HCV at least once in their lifetime, and that all women be screened during pregnancy — recommendations that do not apply in settings where the prevalence of HCV infection is below 0.1%.

The new guidelines align with the latest Advisory Committee on Immunization Practices recommendations for HPV vaccination, which raised the upper age for catch-up vaccination in men to 26 years, matching the recommendation for women, and said unvaccinated patients aged 27 to 45 years should speak with their physicians about receiving the vaccine.

As expected, the guidance now recommends 100 mg of oral doxycycline as first-line treatment for chlamydia at any site, based on studies demonstrating that it is superior to azithromycin.

The guidance updates recommendations for other infections, including trichomoniasis and pelvic inflammatory disease, as well as uncomplicated gonorrhea infection in neonates, children and other clinical situations, including proctitis, epididymitis and cases of sexual assault.

Workowski said that with 26 million new STIs occurring each year, totaling nearly $16 billion in medical costs, “evidence-based prevention, diagnostic, and treatment recommendations are critical to halting continued increases.”

Monoclonal antibody combination reduces COVID-19 hospitalizations, deaths by nearly 80%

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Interim phase 3 data released by Brii Biosciences showed that the company’s monoclonal antibody combination therapy reduced the combined endpoint of COVID-19 hospitalizations and death by 78% in high-risk patients compared with placebo.

According to a press release issued by the company, the combination BRII-196/BRII-198 treatment arm of the ongoing phase 2/3 ACTIV-2 platform trial evaluated 837 patients enrolled within 10 days of COVID-19 symptom onset and at high risk for clinical progression.

Source: Adobe Stock.
Source: Adobe Stock.

Researchers evaluated the participants for the combined primary endpoint of hospitalizations and death relative to placebo in the 28 days following treatment. The trial is sponsored by the National Institute of Allergy and Infectious Diseases.

According to Brii, interim data showed that the combination therapy demonstrated a 78% reduction in the combined endpoint of hospitalization (12 in the therapy group vs. 45 in the placebo group) and death (one in the therapy group vs. nine in the placebo group). Additionally, grade three or higher adverse events were observed less frequently among the combination treatment arm (3.8% active vs. 13.4% placebo), with few events being considered drug related, according to the press release.

“We are thrilled to announce the interim phase 3 results from ACTIV-2, which demonstrate a significant reduction in the endpoint of hospitalizations or death among nonhospitalized people with mild COVID-19 who were treated with BRII-196/BRII-198,” Teresa H. Evering, MD, MS, co-lead investigator on the trial and an assistant professor of medicine at Weill Cornell Medicine, said in the release. “The devastating resurgence in COVID-19 cases over the past several months is a sobering reminder of how desperately we need treatment options.”

Once the ACTIV-2 study is completed, the full analysis dataset will include participants enrolled in the U.S., as well as Brazil, South Africa, Mexico, Argentina and the Philippines between January and July 2021. According to Brii, data on the efficacy of the combination therapy by variant type also will be evaluated.

The FDA has authorized several monoclonal antibodies to treat COVID-19 including the combination of bamlanivimab and etesevimab, which is authorized for patients aged 12 years or older, and sotrovimab, which received an emergency use authorization for mild-to-moderate COVID-19 in patients at risk for progressing to severe disease and Regeneron’s antibody cocktail as a postexposure prophylaxis.

Additionally, the Infectious Diseases Society of America has suggested the use of some neutralizing antibodies to treat patients who are at high risk for progression to severe disease.

ACIP recommends universal hepatitis B vaccination for adults aged 19 to 59 years

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The CDC’s Advisory Committee on Immunization Practices voted unanimously, 15-0, on Wednesday to recommend hepatitis B vaccination for all adults aged 19 to 59 years.

The recommendation says adults in this age group — plus adults aged 60 years or older with risk factors — “should” be vaccinated against HBV. It says adults aged 60 years or older who do not have known risk factors for HBV infection “may” receive an HBV vaccine.

Source: Adobe Stock.

It was one of nine different recommendations made Wednesday by the ACIP, which also supported vaccinating people at occupational risk against orthopoxviruses and Ebola virus, including health care personnel and lab workers.

The votes came 1 day after the same committee unanimously endorsed Pfizer’s pediatric COVID-19 vaccine for children aged 5 to 11 years.

CDC medical officer Mark K. Weng, MD, MSc, FAAP, who leads the ACIP’s hepatitis vaccines work group, presented data on the importance of vaccinating adults against HBV.

“In the U.S. every year, there are 20,700 estimated acute hepatitis B infections, and over $1 billion dollars spent on hepatitis B-related hospitalizations,” Weng said. “There are almost two million people estimated to be living with chronic hepatitis B in the U.S., of whom there’s a [15% to 25%] risk of premature death from cirrhosis or liver cancer.”

According to Weng, a universal vaccine recommendation for adults would serve as a “natural extension” of existing routine childhood recommendations and simplify existing adult risk groups into a single recommendation.

A 2005 recommendation that all newborns should receive their first HBV vaccine dose before hospital discharge resulted in large decreases in new cases among children and adolescents, Weng said. However, adult rates have plateaued in the last decade, he said.

“The past decade has illustrated that risk-based screening among adults has got us as far as it can take us,” Weng said. “Initial decreases in new infections have stagnated. Rates of acute infections are now highest among 30- to 59-year-olds, and rates have actually increased among adults aged 40 years and older, indicating that we’re losing ground. We cannot eliminate hepatitis B in the U.S. without a new approach.”

Weng said the work group reasoned that it would be better for adults to be vaccinated before exposure, and the new recommendation would also promote health equality.

The CDC is currently drafting recommendations for all adults to be screened for HBV at least once in their lifetime, an ACIP member said. The recommendation will not be discussed or voted on until next year.

The ACIP voted unanimously on five different recommendations supporting the use of Jynneos — a vaccine approved by the FDA in 2019 to prevent smallpox and monkeypox disease in adults at a high risk for infection — as an alternative to the ACAM2000 smallpox vaccine, including for booster doses.

Two votes supporting the use of an FDA-approved Ebola vaccine as PrEP for health care personnel involved in the care and transport of suspected or confirmed Ebola cases at special treatment centers, or lab and support staff at facilities that handle Ebola specimens, were not unanimous.

Both recommendations passed 11-4, with dissenting members suggesting they would have preferred the recommendations include language on “shared clinical decision making” — that is, patients and physicians decide for themselves if it is appropriate.

PERSPECTIVE

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Rita K. Kuwahara, MD, MIH

Rita K. Kuwahara

I think that universal adult HBV vaccination is absolutely necessary in order to prevent further outbreaks of HBV, which is a vaccine-preventable disease. We have such safe and highly effective vaccines for HBV that there really shouldn’t be a single new infection in our country. However, there are certain populations that have historically been at much higher risk for contracting HBV, and then other populations that are becoming increasingly affected.

In particular, historically, the Asian American/Pacific Islander American community, as well as the African immigrant community, have seen very high levels of HBV. But we’ve also seen enormous rises in acute HBV among persons who inject drugs, particularly within the opioid epidemic.

Currently, the adult HBV vaccination rate has stood at around 25% to 30%. We currently estimate that up to 2.4 million people in the U.S. are chronically infected with HBV. To note, one in four people with unmanaged chronic HBV will develop liver cancer, liver failure or liver cirrhosis. We really do need to push for universal vaccinations to achieve elimination.Rita K. Kuwahara, MD, MIHPrimary care health policy fellow
Internal medicine physician
Georgetown University