Infectious Diseases

It’s not necessary to completely eradicate all Clostridioides difficile to successfully treat recurrent C. difficile infections with fecal microbiota transplant (FMT), according to a study presented online July 12 at the European Congress of Clinical Microbiology & Infectious Diseases.

C. difficile colonization persisted for 3 weeks after FMT in about one-quarter of patients, but it’s not clear whether this is a persistent infection, a newly acquired infection, or partial persistence of a mixed infection, said Elisabeth Terveer, MD, a medical microbiologist at Leiden (the Netherlands) University Medical Center. In addition, “82% of patients with detectable C. diff do not relapse, so it’s absolutely not necessary for a cure,” she said.

Several mechanisms explain why FMT is a highly effective therapy for recurrent C. difficile infections, including restoration of bacterial metabolism in the gut, immune modulation, and direct competition between bacteria, Dr. Terveer said, but it’s less clear whether eradication of C. difficile spores is among these mechanisms. 

Between May 2016 and April 2020, the researchers analyzed fecal samples from 84 patients who took vancomycin for at least 4 days before undergoing FMT. The researchers took fecal samples from patients before FMT and 3 weeks after FMT to culture them and the donor samples for presence of C. difficile, and they assessed clinical outcomes at 3 weeks and 6 months after FMT.

After antibiotic treatment but prior to FMT, 19% of patients (n = 16) still had a toxigenic C. difficile culture while the other 81% had a negative culture. None of the donor samples had a positive C. difficile culture. After FMT treatment, five patients who had a positive pre-FMT culture remained positive, and the other 11 were negative. Among the 81% of patients (n = 68) who had a negative culture just before FMT, 22 had a positive culture and 46 had a negative culture after FMT. Overall, 26% of patients post FMT had a positive C. difficile culture, a finding that was 10-fold higher than another study that assessed C. difficile with PCR testing, Dr. Terveer said.

The clinical cure rate after FMT was 94%, and five patients had relapses within 2 months of their FMT. These relapses were more prevalent in patients with a positive C. difficile culture prior to FMT (odds ratio [OR], 7.6; P = .045) and a positive C. difficile culture after FMT (OR, 13.6; P = .016). Still, 82% of patients who had a positive C. difficile culture post FMT remained clinically cured 2 months later.

It’s unclear why 19% of patients had a positive culture after their antibiotic pretreatment prior to FMT, Dr. Terveer said, but it may be because the pretreatment was of such a short duration.

“I think the advice should be: Give a full anti–C. diff antibiotic course to treat the C. diff infection, and then give FMT afterward to restore the microbiota and prevent further relapses,” Dr. Terveer told attendees.

Dimitri Drekonja, MD, chief of the Minneapolis VA Infectious Disease Section, said the findings were not necessarily surprising, but it would have been interesting for the researchers to have conducted DNA sequencing of the patients’ fecal samples post FMT to see what the biological diversity looked like.

“One school of thought has been that you have to repopulate the normal diverse microbiota of the colon” with FMT, and the other “is that you need to get rid of the C. diff that›s there,” Dr. Drekonja, who was not involved in the study, said in an interview. “I think more people think it’s the diverse microbiota because if it’s just getting rid of C. diff, we can get do that with antibiotics – but that gets rid of the other organisms.”

As long as you have a diverse microbiota post FMT, Dr. Drekonja said, then “having a few residual organisms, even if they get magnified in the culture process, is probably not that big a deal.”

But there’s a third school of thought that Dr. Drekonja said he himself falls into: “I don’t really care how it works, just that in well-done trials, it does work.” As long as large, robust, well-blinded trials show that FMT works, “I’m open to all sorts of ideas of what the mechanism is,” he said. “The main thing is that it does or doesn’t work.”

These findings basically reinforce current guidance not to test patients’ stools if they are asymptomatic, Dr. Drekonja said. In the past, clinicians sometimes tested patients’ stool after therapy to ensure the C. difficile was eradicated, regardless of whether the patient had symptoms of infection, he said.

“We’ve since become much more attuned that there are lots of people who have detectable C. diff in their stool without any symptoms,” whether detectable by culture or PCR, Dr. Drekonja said. “Generally, if you’re doing well and you’re not having diarrhea, don’t test, and if someone does test and finds it, pretend you didn’t see the test,” he advised. “This is a big part of diagnostic stewardship, which is: You don’t go testing people who are doing well.”

The Netherlands Donor Feces Bank used in the research is funded by a grant from Vedanta Biosciences. Dr. Drekonja had no disclosures.

A version of this article first appeared on Medscape.com.

It’s not necessary to completely eradicate all Clostridioides difficile to successfully treat recurrent C. difficile infections with fecal microbiota transplant (FMT), according to a study presented online July 12 at the European Congress of Clinical Microbiology & Infectious Diseases.

C. difficile colonization persisted for 3 weeks after FMT in about one-quarter of patients, but it’s not clear whether this is a persistent infection, a newly acquired infection, or partial persistence of a mixed infection, said Elisabeth Terveer, MD, a medical microbiologist at Leiden (the Netherlands) University Medical Center. In addition, “82% of patients with detectable C. diff do not relapse, so it’s absolutely not necessary for a cure,” she said.

Several mechanisms explain why FMT is a highly effective therapy for recurrent C. difficile infections, including restoration of bacterial metabolism in the gut, immune modulation, and direct competition between bacteria, Dr. Terveer said, but it’s less clear whether eradication of C. difficile spores is among these mechanisms. 

Between May 2016 and April 2020, the researchers analyzed fecal samples from 84 patients who took vancomycin for at least 4 days before undergoing FMT. The researchers took fecal samples from patients before FMT and 3 weeks after FMT to culture them and the donor samples for presence of C. difficile, and they assessed clinical outcomes at 3 weeks and 6 months after FMT.

After antibiotic treatment but prior to FMT, 19% of patients (n = 16) still had a toxigenic C. difficile culture while the other 81% had a negative culture. None of the donor samples had a positive C. difficile culture. After FMT treatment, five patients who had a positive pre-FMT culture remained positive, and the other 11 were negative. Among the 81% of patients (n = 68) who had a negative culture just before FMT, 22 had a positive culture and 46 had a negative culture after FMT. Overall, 26% of patients post FMT had a positive C. difficile culture, a finding that was 10-fold higher than another study that assessed C. difficile with PCR testing, Dr. Terveer said.

The clinical cure rate after FMT was 94%, and five patients had relapses within 2 months of their FMT. These relapses were more prevalent in patients with a positive C. difficile culture prior to FMT (odds ratio [OR], 7.6; P = .045) and a positive C. difficile culture after FMT (OR, 13.6; P = .016). Still, 82% of patients who had a positive C. difficile culture post FMT remained clinically cured 2 months later.

It’s unclear why 19% of patients had a positive culture after their antibiotic pretreatment prior to FMT, Dr. Terveer said, but it may be because the pretreatment was of such a short duration.

“I think the advice should be: Give a full anti–C. diff antibiotic course to treat the C. diff infection, and then give FMT afterward to restore the microbiota and prevent further relapses,” Dr. Terveer told attendees.

Dimitri Drekonja, MD, chief of the Minneapolis VA Infectious Disease Section, said the findings were not necessarily surprising, but it would have been interesting for the researchers to have conducted DNA sequencing of the patients’ fecal samples post FMT to see what the biological diversity looked like.

“One school of thought has been that you have to repopulate the normal diverse microbiota of the colon” with FMT, and the other “is that you need to get rid of the C. diff that›s there,” Dr. Drekonja, who was not involved in the study, said in an interview. “I think more people think it’s the diverse microbiota because if it’s just getting rid of C. diff, we can get do that with antibiotics – but that gets rid of the other organisms.”

As long as you have a diverse microbiota post FMT, Dr. Drekonja said, then “having a few residual organisms, even if they get magnified in the culture process, is probably not that big a deal.”

But there’s a third school of thought that Dr. Drekonja said he himself falls into: “I don’t really care how it works, just that in well-done trials, it does work.” As long as large, robust, well-blinded trials show that FMT works, “I’m open to all sorts of ideas of what the mechanism is,” he said. “The main thing is that it does or doesn’t work.”

These findings basically reinforce current guidance not to test patients’ stools if they are asymptomatic, Dr. Drekonja said. In the past, clinicians sometimes tested patients’ stool after therapy to ensure the C. difficile was eradicated, regardless of whether the patient had symptoms of infection, he said.

“We’ve since become much more attuned that there are lots of people who have detectable C. diff in their stool without any symptoms,” whether detectable by culture or PCR, Dr. Drekonja said. “Generally, if you’re doing well and you’re not having diarrhea, don’t test, and if someone does test and finds it, pretend you didn’t see the test,” he advised. “This is a big part of diagnostic stewardship, which is: You don’t go testing people who are doing well.”

The Netherlands Donor Feces Bank used in the research is funded by a grant from Vedanta Biosciences. Dr. Drekonja had no disclosures.

A version of this article first appeared on Medscape.com.

It’s not necessary to completely eradicate all Clostridioides difficile to successfully treat recurrent C. difficile infections with fecal microbiota transplant (FMT), according to a study presented online July 12 at the European Congress of Clinical Microbiology & Infectious Diseases.

C. difficile colonization persisted for 3 weeks after FMT in about one-quarter of patients, but it’s not clear whether this is a persistent infection, a newly acquired infection, or partial persistence of a mixed infection, said Elisabeth Terveer, MD, a medical microbiologist at Leiden (the Netherlands) University Medical Center. In addition, “82% of patients with detectable C. diff do not relapse, so it’s absolutely not necessary for a cure,” she said.

Several mechanisms explain why FMT is a highly effective therapy for recurrent C. difficile infections, including restoration of bacterial metabolism in the gut, immune modulation, and direct competition between bacteria, Dr. Terveer said, but it’s less clear whether eradication of C. difficile spores is among these mechanisms. 

Between May 2016 and April 2020, the researchers analyzed fecal samples from 84 patients who took vancomycin for at least 4 days before undergoing FMT. The researchers took fecal samples from patients before FMT and 3 weeks after FMT to culture them and the donor samples for presence of C. difficile, and they assessed clinical outcomes at 3 weeks and 6 months after FMT.

After antibiotic treatment but prior to FMT, 19% of patients (n = 16) still had a toxigenic C. difficile culture while the other 81% had a negative culture. None of the donor samples had a positive C. difficile culture. After FMT treatment, five patients who had a positive pre-FMT culture remained positive, and the other 11 were negative. Among the 81% of patients (n = 68) who had a negative culture just before FMT, 22 had a positive culture and 46 had a negative culture after FMT. Overall, 26% of patients post FMT had a positive C. difficile culture, a finding that was 10-fold higher than another study that assessed C. difficile with PCR testing, Dr. Terveer said.

The clinical cure rate after FMT was 94%, and five patients had relapses within 2 months of their FMT. These relapses were more prevalent in patients with a positive C. difficile culture prior to FMT (odds ratio [OR], 7.6; P = .045) and a positive C. difficile culture after FMT (OR, 13.6; P = .016). Still, 82% of patients who had a positive C. difficile culture post FMT remained clinically cured 2 months later.

It’s unclear why 19% of patients had a positive culture after their antibiotic pretreatment prior to FMT, Dr. Terveer said, but it may be because the pretreatment was of such a short duration.

“I think the advice should be: Give a full anti–C. diff antibiotic course to treat the C. diff infection, and then give FMT afterward to restore the microbiota and prevent further relapses,” Dr. Terveer told attendees.

Dimitri Drekonja, MD, chief of the Minneapolis VA Infectious Disease Section, said the findings were not necessarily surprising, but it would have been interesting for the researchers to have conducted DNA sequencing of the patients’ fecal samples post FMT to see what the biological diversity looked like.

“One school of thought has been that you have to repopulate the normal diverse microbiota of the colon” with FMT, and the other “is that you need to get rid of the C. diff that›s there,” Dr. Drekonja, who was not involved in the study, said in an interview. “I think more people think it’s the diverse microbiota because if it’s just getting rid of C. diff, we can get do that with antibiotics – but that gets rid of the other organisms.”

As long as you have a diverse microbiota post FMT, Dr. Drekonja said, then “having a few residual organisms, even if they get magnified in the culture process, is probably not that big a deal.”

But there’s a third school of thought that Dr. Drekonja said he himself falls into: “I don’t really care how it works, just that in well-done trials, it does work.” As long as large, robust, well-blinded trials show that FMT works, “I’m open to all sorts of ideas of what the mechanism is,” he said. “The main thing is that it does or doesn’t work.”

These findings basically reinforce current guidance not to test patients’ stools if they are asymptomatic, Dr. Drekonja said. In the past, clinicians sometimes tested patients’ stool after therapy to ensure the C. difficile was eradicated, regardless of whether the patient had symptoms of infection, he said.

“We’ve since become much more attuned that there are lots of people who have detectable C. diff in their stool without any symptoms,” whether detectable by culture or PCR, Dr. Drekonja said. “Generally, if you’re doing well and you’re not having diarrhea, don’t test, and if someone does test and finds it, pretend you didn’t see the test,” he advised. “This is a big part of diagnostic stewardship, which is: You don’t go testing people who are doing well.”

The Netherlands Donor Feces Bank used in the research is funded by a grant from Vedanta Biosciences. Dr. Drekonja had no disclosures.

A version of this article first appeared on Medscape.com.

For the first time, an HIV prevention trial that was limited to adolescent girls and young women found that, given sufficient support, girls will use either daily oral pre-exposure prophylaxis (PrEP) or the vaginal dapivirine ring to protect themselves from HIV.

The secret, said Gonasagrie Nair, MBChB, faculty of medicine and health sciences at Stellenbosch University, Zimbabwe, is offering intensive wraparound services to support teenagers – a lesson that may be useful as adolescent and family medicine professionals in the United States begin to roll out HIV prevention in their clinics.

This is important in the United States because cisgender Black women make up 60% of all new HIV cases in the United States while accounting for just 14% of the overall U.S. population. The Centers for Disease Control and Prevention has found that only about 1% of Black Americans who could benefit from PrEP have access to it.

“Younger women and adolescent girls in particular face a number of cultural and social challenges that impact their ability to make decisions related to their own health,” said Dr. Nair, who presented the data at the International AIDS Society (IAS) Conference 2021. “The adherence support provided by this study empowered them to make choices and stick to these choices,” she said.

In total, 247 women and girls aged 16 to 21 who were without HIV were enrolled in the Reversing the Epidemic in Africa with Choices in HIV Prevention (REACH) trial in two sites in South Africa and one each in Uganda and Zimbabwe beginning in February 2019. One-third of the participants were minors; the average age was 18.2 years.

The women were good candidates for PrEP. More than 1 in 3 of the women started the study with a sexually transmitted infection (STI), the most prevalent of which was chlamydia. This is often a good marker for condomless sex. Of the participants, 89% had a primary sex partner; a quarter of those thought their partner was having sex with other people. Only 7% of participants reported being very worried about acquiring HIV. More than 1 in 3 (39%) weren’t worried about HIV at all. This conforms to previous data suggesting that those who could most benefit from PrEP often don’t perceive their own vulnerability.

In the study, the women were randomly assigned two groups. In one group, the participants used the dapivirine ring for 6 months; in the other, participants used oral PrEP for 6 months. The participants then swapped prevention methods and used the alternative method for 6 more months. After a year of trying both methods, the women will be asked to choose one of the two prevention method or to stop PrEP altogether. At the IAS conference, the researchers reported interim data from the first year of the study, before the girls had the opportunity to choose for themselves.

During that first year, girls received intensive adherence support, including daily or weekly text check-ins, phone check-ins, peer buddy support, additional onsite counseling visits, access to adherence support groups, participation in online support groups via apps such as WhatsApp, and in-person social events designed to empower young women and to teach them skills. Support included discussion of adherence, contraceptives, and STIs. In addition, when girls came in for study visits, staff provided feedback on how adherent the girls had been, as determined on the basis of residual levels of dapivirine in the rings or, with regard to oral pills, drug levels as determined with blood spots.

Girls were considered to have had high adherence if they were found to have oral PrEP concentrations equivalent to four or more doses per week or if residual levels of dapivirine in their rings were 0.1071 mg/d. Moderate adherence was the equivalent of one to three doses of oral PrEP a week or dapivirine levels between 0.0321 mg/d and 0.1071 mg/d.

In total, 95.6% of ring users showed some adherence to the ring. Of those, adherence was high for 50.2%; 49.8% used the ring perfectly. For oral PrEP, 98.5% showed some level of PrEP use; for 58.6%, lab results suggested adherence high enough to provide protection from HIV, and 22% took their pills at least six times a week. Between the two arms, 54.3% of all participants used the medication sufficiently to be protected from HIV.

One person acquired HIV during the study. Dr. Nair did not say which study arm that participant was in or how adherent that person has been to their prevention method.

That level of adherence is on par with studies in the United States, which have found 56% adherence to PrEP among adolescent and young men who have sex with men. But the level of adherence is far higher than has been found in other studies that tested oral PrEP among women who did not have a partner with HIV. In particular, the VOICE and FEM-PrEP trials were both stopped early for lack of adherence. In those placebo-controlled oral-PrEP trials, fewer than 25% of participants used the oral prevention pills. Although adherence to the vaginal ring was estimated to be 61% for women older than 25 in the ASPIRE trial, it was effectively zero among women aged 18 to 21 years. Adherence has been the “bugaboo of efficacy for PrEP in young women,” said Judith Auerbach, PhD, independent science and policy consultant and professor of medicine at the University of California, San Francisco. But health care professionals have a long way to go to support young people in general in using PrEP.

“Yes, this shows improvement compared to previous studies,” Dr. Auerbach told this news organization. “But is it sufficient to have an epidemiological impact at the population level?”

Medical Advocacy and Outreach (MAO) is an HIV clinic and services program in Montgomery, Alabama, that offers a clinic specifically for some of their 144 clients to receive oral PrEP. In addition to in-person testing, MAO offers home HIV testing and lab work and televisits to support the college students they serve in taking PrEP whether they’re at school or at home on break. Currently, MAO provides a series of support groups and other social support programs for their clients living with HIV, but there are none for those receiving PrEP. The organization is in the process of hiring a social worker for the PrEP side of the clinic.

Until that person is on board, “I’m their support system in an unofficial capacity,” Shericka Williams, MPH, told this news organization. She runs education programs at MAO and handles all the phone calls from PrEP clients. “My title changes a lot, but the one I like to go with most often is the PrEP navigator,” she said.

She said she was intrigued by the dapivirine ring and oral PrEP data but said that currently, the women they serve are still learning that PrEP is for them, too. The women report that all the ads and all the information they receive is aimed at gay or bisexual men or transgender women. It takes a while for them to recognize that they could benefit, so a lot of the work that Ms. Williams does is focused on explaining the benefit of PrEP.

In MAO, the number of women receiving PrEP fluctuates more than for men. Mostly, women start PrEP because of they are in a relationship with someone who receives HIV care from MAO’s other wing – women who potentially would experience less vulnerability to HIV if their partners had undetectable viral loads. The other reason women take it is because they suspect that their partner is cheating or because they are in abusive relationships in which they want their partner to use a condom but the partner won’t. As in the PrEP trials, they often see women discontinue PrEP when they leave those relationships. In part, her job is to educate women regarding all the ways PrEP could serve them.

“Most of the time, they’re just no longer in that relationship, and they’re just taking some time for themselves,” she said in an interview. “We definitely try to bring up other reasons to stay on PrEP, but we don’t want to seem like we’re bullying someone to stay on it.”

Dr. Nair, Dr. Auerbach, and Ms. Williams report no relevant financial relationships.

A version of this article first appeared on Medscape.com.

For the first time, an HIV prevention trial that was limited to adolescent girls and young women found that, given sufficient support, girls will use either daily oral pre-exposure prophylaxis (PrEP) or the vaginal dapivirine ring to protect themselves from HIV.

The secret, said Gonasagrie Nair, MBChB, faculty of medicine and health sciences at Stellenbosch University, Zimbabwe, is offering intensive wraparound services to support teenagers – a lesson that may be useful as adolescent and family medicine professionals in the United States begin to roll out HIV prevention in their clinics.

This is important in the United States because cisgender Black women make up 60% of all new HIV cases in the United States while accounting for just 14% of the overall U.S. population. The Centers for Disease Control and Prevention has found that only about 1% of Black Americans who could benefit from PrEP have access to it.

“Younger women and adolescent girls in particular face a number of cultural and social challenges that impact their ability to make decisions related to their own health,” said Dr. Nair, who presented the data at the International AIDS Society (IAS) Conference 2021. “The adherence support provided by this study empowered them to make choices and stick to these choices,” she said.

In total, 247 women and girls aged 16 to 21 who were without HIV were enrolled in the Reversing the Epidemic in Africa with Choices in HIV Prevention (REACH) trial in two sites in South Africa and one each in Uganda and Zimbabwe beginning in February 2019. One-third of the participants were minors; the average age was 18.2 years.

The women were good candidates for PrEP. More than 1 in 3 of the women started the study with a sexually transmitted infection (STI), the most prevalent of which was chlamydia. This is often a good marker for condomless sex. Of the participants, 89% had a primary sex partner; a quarter of those thought their partner was having sex with other people. Only 7% of participants reported being very worried about acquiring HIV. More than 1 in 3 (39%) weren’t worried about HIV at all. This conforms to previous data suggesting that those who could most benefit from PrEP often don’t perceive their own vulnerability.

In the study, the women were randomly assigned two groups. In one group, the participants used the dapivirine ring for 6 months; in the other, participants used oral PrEP for 6 months. The participants then swapped prevention methods and used the alternative method for 6 more months. After a year of trying both methods, the women will be asked to choose one of the two prevention method or to stop PrEP altogether. At the IAS conference, the researchers reported interim data from the first year of the study, before the girls had the opportunity to choose for themselves.

During that first year, girls received intensive adherence support, including daily or weekly text check-ins, phone check-ins, peer buddy support, additional onsite counseling visits, access to adherence support groups, participation in online support groups via apps such as WhatsApp, and in-person social events designed to empower young women and to teach them skills. Support included discussion of adherence, contraceptives, and STIs. In addition, when girls came in for study visits, staff provided feedback on how adherent the girls had been, as determined on the basis of residual levels of dapivirine in the rings or, with regard to oral pills, drug levels as determined with blood spots.

Girls were considered to have had high adherence if they were found to have oral PrEP concentrations equivalent to four or more doses per week or if residual levels of dapivirine in their rings were 0.1071 mg/d. Moderate adherence was the equivalent of one to three doses of oral PrEP a week or dapivirine levels between 0.0321 mg/d and 0.1071 mg/d.

In total, 95.6% of ring users showed some adherence to the ring. Of those, adherence was high for 50.2%; 49.8% used the ring perfectly. For oral PrEP, 98.5% showed some level of PrEP use; for 58.6%, lab results suggested adherence high enough to provide protection from HIV, and 22% took their pills at least six times a week. Between the two arms, 54.3% of all participants used the medication sufficiently to be protected from HIV.

One person acquired HIV during the study. Dr. Nair did not say which study arm that participant was in or how adherent that person has been to their prevention method.

That level of adherence is on par with studies in the United States, which have found 56% adherence to PrEP among adolescent and young men who have sex with men. But the level of adherence is far higher than has been found in other studies that tested oral PrEP among women who did not have a partner with HIV. In particular, the VOICE and FEM-PrEP trials were both stopped early for lack of adherence. In those placebo-controlled oral-PrEP trials, fewer than 25% of participants used the oral prevention pills. Although adherence to the vaginal ring was estimated to be 61% for women older than 25 in the ASPIRE trial, it was effectively zero among women aged 18 to 21 years. Adherence has been the “bugaboo of efficacy for PrEP in young women,” said Judith Auerbach, PhD, independent science and policy consultant and professor of medicine at the University of California, San Francisco. But health care professionals have a long way to go to support young people in general in using PrEP.

“Yes, this shows improvement compared to previous studies,” Dr. Auerbach told this news organization. “But is it sufficient to have an epidemiological impact at the population level?”

Medical Advocacy and Outreach (MAO) is an HIV clinic and services program in Montgomery, Alabama, that offers a clinic specifically for some of their 144 clients to receive oral PrEP. In addition to in-person testing, MAO offers home HIV testing and lab work and televisits to support the college students they serve in taking PrEP whether they’re at school or at home on break. Currently, MAO provides a series of support groups and other social support programs for their clients living with HIV, but there are none for those receiving PrEP. The organization is in the process of hiring a social worker for the PrEP side of the clinic.

Until that person is on board, “I’m their support system in an unofficial capacity,” Shericka Williams, MPH, told this news organization. She runs education programs at MAO and handles all the phone calls from PrEP clients. “My title changes a lot, but the one I like to go with most often is the PrEP navigator,” she said.

She said she was intrigued by the dapivirine ring and oral PrEP data but said that currently, the women they serve are still learning that PrEP is for them, too. The women report that all the ads and all the information they receive is aimed at gay or bisexual men or transgender women. It takes a while for them to recognize that they could benefit, so a lot of the work that Ms. Williams does is focused on explaining the benefit of PrEP.

In MAO, the number of women receiving PrEP fluctuates more than for men. Mostly, women start PrEP because of they are in a relationship with someone who receives HIV care from MAO’s other wing – women who potentially would experience less vulnerability to HIV if their partners had undetectable viral loads. The other reason women take it is because they suspect that their partner is cheating or because they are in abusive relationships in which they want their partner to use a condom but the partner won’t. As in the PrEP trials, they often see women discontinue PrEP when they leave those relationships. In part, her job is to educate women regarding all the ways PrEP could serve them.

“Most of the time, they’re just no longer in that relationship, and they’re just taking some time for themselves,” she said in an interview. “We definitely try to bring up other reasons to stay on PrEP, but we don’t want to seem like we’re bullying someone to stay on it.”

Dr. Nair, Dr. Auerbach, and Ms. Williams report no relevant financial relationships.

A version of this article first appeared on Medscape.com.

For the first time, an HIV prevention trial that was limited to adolescent girls and young women found that, given sufficient support, girls will use either daily oral pre-exposure prophylaxis (PrEP) or the vaginal dapivirine ring to protect themselves from HIV.

The secret, said Gonasagrie Nair, MBChB, faculty of medicine and health sciences at Stellenbosch University, Zimbabwe, is offering intensive wraparound services to support teenagers – a lesson that may be useful as adolescent and family medicine professionals in the United States begin to roll out HIV prevention in their clinics.

This is important in the United States because cisgender Black women make up 60% of all new HIV cases in the United States while accounting for just 14% of the overall U.S. population. The Centers for Disease Control and Prevention has found that only about 1% of Black Americans who could benefit from PrEP have access to it.

“Younger women and adolescent girls in particular face a number of cultural and social challenges that impact their ability to make decisions related to their own health,” said Dr. Nair, who presented the data at the International AIDS Society (IAS) Conference 2021. “The adherence support provided by this study empowered them to make choices and stick to these choices,” she said.

In total, 247 women and girls aged 16 to 21 who were without HIV were enrolled in the Reversing the Epidemic in Africa with Choices in HIV Prevention (REACH) trial in two sites in South Africa and one each in Uganda and Zimbabwe beginning in February 2019. One-third of the participants were minors; the average age was 18.2 years.

The women were good candidates for PrEP. More than 1 in 3 of the women started the study with a sexually transmitted infection (STI), the most prevalent of which was chlamydia. This is often a good marker for condomless sex. Of the participants, 89% had a primary sex partner; a quarter of those thought their partner was having sex with other people. Only 7% of participants reported being very worried about acquiring HIV. More than 1 in 3 (39%) weren’t worried about HIV at all. This conforms to previous data suggesting that those who could most benefit from PrEP often don’t perceive their own vulnerability.

In the study, the women were randomly assigned two groups. In one group, the participants used the dapivirine ring for 6 months; in the other, participants used oral PrEP for 6 months. The participants then swapped prevention methods and used the alternative method for 6 more months. After a year of trying both methods, the women will be asked to choose one of the two prevention method or to stop PrEP altogether. At the IAS conference, the researchers reported interim data from the first year of the study, before the girls had the opportunity to choose for themselves.

During that first year, girls received intensive adherence support, including daily or weekly text check-ins, phone check-ins, peer buddy support, additional onsite counseling visits, access to adherence support groups, participation in online support groups via apps such as WhatsApp, and in-person social events designed to empower young women and to teach them skills. Support included discussion of adherence, contraceptives, and STIs. In addition, when girls came in for study visits, staff provided feedback on how adherent the girls had been, as determined on the basis of residual levels of dapivirine in the rings or, with regard to oral pills, drug levels as determined with blood spots.

Girls were considered to have had high adherence if they were found to have oral PrEP concentrations equivalent to four or more doses per week or if residual levels of dapivirine in their rings were 0.1071 mg/d. Moderate adherence was the equivalent of one to three doses of oral PrEP a week or dapivirine levels between 0.0321 mg/d and 0.1071 mg/d.

In total, 95.6% of ring users showed some adherence to the ring. Of those, adherence was high for 50.2%; 49.8% used the ring perfectly. For oral PrEP, 98.5% showed some level of PrEP use; for 58.6%, lab results suggested adherence high enough to provide protection from HIV, and 22% took their pills at least six times a week. Between the two arms, 54.3% of all participants used the medication sufficiently to be protected from HIV.

One person acquired HIV during the study. Dr. Nair did not say which study arm that participant was in or how adherent that person has been to their prevention method.

That level of adherence is on par with studies in the United States, which have found 56% adherence to PrEP among adolescent and young men who have sex with men. But the level of adherence is far higher than has been found in other studies that tested oral PrEP among women who did not have a partner with HIV. In particular, the VOICE and FEM-PrEP trials were both stopped early for lack of adherence. In those placebo-controlled oral-PrEP trials, fewer than 25% of participants used the oral prevention pills. Although adherence to the vaginal ring was estimated to be 61% for women older than 25 in the ASPIRE trial, it was effectively zero among women aged 18 to 21 years. Adherence has been the “bugaboo of efficacy for PrEP in young women,” said Judith Auerbach, PhD, independent science and policy consultant and professor of medicine at the University of California, San Francisco. But health care professionals have a long way to go to support young people in general in using PrEP.

“Yes, this shows improvement compared to previous studies,” Dr. Auerbach told this news organization. “But is it sufficient to have an epidemiological impact at the population level?”

Medical Advocacy and Outreach (MAO) is an HIV clinic and services program in Montgomery, Alabama, that offers a clinic specifically for some of their 144 clients to receive oral PrEP. In addition to in-person testing, MAO offers home HIV testing and lab work and televisits to support the college students they serve in taking PrEP whether they’re at school or at home on break. Currently, MAO provides a series of support groups and other social support programs for their clients living with HIV, but there are none for those receiving PrEP. The organization is in the process of hiring a social worker for the PrEP side of the clinic.

Until that person is on board, “I’m their support system in an unofficial capacity,” Shericka Williams, MPH, told this news organization. She runs education programs at MAO and handles all the phone calls from PrEP clients. “My title changes a lot, but the one I like to go with most often is the PrEP navigator,” she said.

She said she was intrigued by the dapivirine ring and oral PrEP data but said that currently, the women they serve are still learning that PrEP is for them, too. The women report that all the ads and all the information they receive is aimed at gay or bisexual men or transgender women. It takes a while for them to recognize that they could benefit, so a lot of the work that Ms. Williams does is focused on explaining the benefit of PrEP.

In MAO, the number of women receiving PrEP fluctuates more than for men. Mostly, women start PrEP because of they are in a relationship with someone who receives HIV care from MAO’s other wing – women who potentially would experience less vulnerability to HIV if their partners had undetectable viral loads. The other reason women take it is because they suspect that their partner is cheating or because they are in abusive relationships in which they want their partner to use a condom but the partner won’t. As in the PrEP trials, they often see women discontinue PrEP when they leave those relationships. In part, her job is to educate women regarding all the ways PrEP could serve them.

“Most of the time, they’re just no longer in that relationship, and they’re just taking some time for themselves,” she said in an interview. “We definitely try to bring up other reasons to stay on PrEP, but we don’t want to seem like we’re bullying someone to stay on it.”

Dr. Nair, Dr. Auerbach, and Ms. Williams report no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Background: Spontaneous bacterial peritonitis is common and is associated with significant short-term mortality. Antibiotic prophylaxis is the mainstay preventive treatment, but there is concern about development of drug resistance and other adverse events. There is uncertainty regarding relative efficacy and optimal combination of the different available prophylactic treatments.

Dr. Millard is assistant professor of medicine, section of hospital medicine, at the University of Virginia School of Medicine, Charlottesville.

Background: Spontaneous bacterial peritonitis is common and is associated with significant short-term mortality. Antibiotic prophylaxis is the mainstay preventive treatment, but there is concern about development of drug resistance and other adverse events. There is uncertainty regarding relative efficacy and optimal combination of the different available prophylactic treatments.

Dr. Millard is assistant professor of medicine, section of hospital medicine, at the University of Virginia School of Medicine, Charlottesville.

Background: Spontaneous bacterial peritonitis is common and is associated with significant short-term mortality. Antibiotic prophylaxis is the mainstay preventive treatment, but there is concern about development of drug resistance and other adverse events. There is uncertainty regarding relative efficacy and optimal combination of the different available prophylactic treatments.

Dr. Millard is assistant professor of medicine, section of hospital medicine, at the University of Virginia School of Medicine, Charlottesville.

People age 40 and younger living with HIV have a higher risk for heart disease than even their over-40 peers living with HIV – and that risk was 54% higher than the general public.

And this was among people without traditional heart disease risks, such as smoking and obesity.

“What’s surprising is that not only do we see that, yes, they do have increased risk, but this is after controlling for all of that – which means the mechanism underlying this risk,” said Tiffany Gooden, MPH and a PhD candidate at the University of Birmingham, England, who presented the data at the 11th International AIDS Society Conference on HIV Science (IAS 2021).

“If we’re using a non–HIV-validated assessment tool, you should always know that there could be a risk that you are under-recognizing,” she added.

Right now, there’s not a lot to aid clinicians in ferreting out this increased risk. Traditional cardiovascular risk assessment tools, like Framingham risk scores and atherosclerotic cardiovascular disease risk score from the American College of Cardiology, have been found to overlook the real risk of cardiovascular disease in people living with HIV. Plus, most guidelines, including those from the British HIV Medical Association and the American College of Cardiology, primarily focus screening on people 40 or older.

Ms. Gooden’s study drew data from The Health Improvement Network (THIN) database, which combines data from 800 primary care practices in the United Kingdom. Looking at data between January 2000 and January 2020, the investigators compared each person living with HIV with four peers not living with HIV, matched for age, gender, and practice. In total, 9,233 people living with HIV and 35,721 people without HIV were included in the analysis. Median age of participants was 41 years in people living with HIV and 40.4 years in people without HIV. About 35% of participants in both arms were women, and a greater proportion of participants living with HIV were Black, accounting for 22.5% of people living with HIV, versus 3.8% of the general population. Fewer people living with HIV were overweight or obese compared to people without HIV.

Researchers then tracked participants over time to identify the incidence of heart attack, stroke, peripheral vascular disease, and heart failure, as well as common risk factors for heart problems, such as high blood pressure, type 2 diabetes, chronic kidney disease, atrial fibrillation, and use of a lipid-lowering drug such as a statin.

The investigators then sectioned the data on heart disease risk by decade – 2000-2009 and 2010-2019 – in order to separate the potential impact of antiretroviral treatment (ART) drugs, from early combinations that have been associated with cardiovascular disease, to current drugs that are less likely to have that effect.

Overall risk for any kind of cardiovascular disease was 54% higher among people living with HIV of any age, compared to their age- and risk-matched peers. And when they broke the data down by age, they found that people younger than 40 had nearly twice the risk for any heart disease as their HIV-negative peers, which was a numerically higher risk than for people older than 40 – though not significantly so.

People living with HIV also had a 49% increased risk for stroke and a 59% increased risk for ischemic heart disease but no increased risk for peripheral vascular disease, heart failure, or heart attack. But the confidence intervals here were wide, “which may indicate lack of power and therefore not be conclusive,” Ms. Gooden said.

People living with HIV also had a 37% increased risk for hypertension, were 96% more likely to be prescribed lipid-lowering drugs, 2.4-times more likely to have chronic kidney disease, and 2.68-times more likely to experience all-cause mortality. The study couldn’t account for the type of HIV medications people living with the virus used, their viral load, or their CD4 counts – all of which have been found in previous studies to contribute to heart disease in people with HIV.

“That was the biggest limitation of our study,” Ms. Gooden said in an interview. “The fact that the risk of cardiovascular disease remains the same in the [first decade] and the later decade goes to show that even if antiretroviral therapies contributed to that … now or 20 years ago, it’s still not the entire reason for the risk.”

Steven Grinspoon, MD, of Harvard Medical School, Boston, is the lead author on the REPRIEVE trial, now testing statins as a treatment for people like those in this study. He told this news organization that this large analysis had one of the youngest cohorts of people living with HIV he’d seen to explore these issues. Additionally, it backs up what the team recently reported in the Journal of the American Medical Association – that plaque was present in 49% of 755 people living with HIV, despite having risk scores for cardiovascular disease in the normal range. This was as true for people younger than 40 as those older than 40.

For primary care clinicians, the message is that even relatively young people with HIV should be counseled early and often about amending traditional risk factors, while we wait for the results of REPRIEVE to say whether statins improve outcomes for people living with HIV, Dr. Grinspoon said in an interview.

“Sometimes physicians and primary care providers say, ‘Well I’ll focus my hypertension efforts on older people, who are closer to having heart attacks,’” Dr. Grinspoon said. “But this data suggests we should pay attention even in young people … and pay particular attention to women who wouldn’t have traditional risk scores that were very high at all, largely because they are women.”

The study was funded by Merck. Ms. Gooden has disclosed no relevant financial relationships. Dr. Grinspoon reports receiving personal and consulting fees from Theratechnologies and ViiV Healthcare.

A version of this article first appeared on Medscape.com.

People age 40 and younger living with HIV have a higher risk for heart disease than even their over-40 peers living with HIV – and that risk was 54% higher than the general public.

And this was among people without traditional heart disease risks, such as smoking and obesity.

“What’s surprising is that not only do we see that, yes, they do have increased risk, but this is after controlling for all of that – which means the mechanism underlying this risk,” said Tiffany Gooden, MPH and a PhD candidate at the University of Birmingham, England, who presented the data at the 11th International AIDS Society Conference on HIV Science (IAS 2021).

“If we’re using a non–HIV-validated assessment tool, you should always know that there could be a risk that you are under-recognizing,” she added.

Right now, there’s not a lot to aid clinicians in ferreting out this increased risk. Traditional cardiovascular risk assessment tools, like Framingham risk scores and atherosclerotic cardiovascular disease risk score from the American College of Cardiology, have been found to overlook the real risk of cardiovascular disease in people living with HIV. Plus, most guidelines, including those from the British HIV Medical Association and the American College of Cardiology, primarily focus screening on people 40 or older.

Ms. Gooden’s study drew data from The Health Improvement Network (THIN) database, which combines data from 800 primary care practices in the United Kingdom. Looking at data between January 2000 and January 2020, the investigators compared each person living with HIV with four peers not living with HIV, matched for age, gender, and practice. In total, 9,233 people living with HIV and 35,721 people without HIV were included in the analysis. Median age of participants was 41 years in people living with HIV and 40.4 years in people without HIV. About 35% of participants in both arms were women, and a greater proportion of participants living with HIV were Black, accounting for 22.5% of people living with HIV, versus 3.8% of the general population. Fewer people living with HIV were overweight or obese compared to people without HIV.

Researchers then tracked participants over time to identify the incidence of heart attack, stroke, peripheral vascular disease, and heart failure, as well as common risk factors for heart problems, such as high blood pressure, type 2 diabetes, chronic kidney disease, atrial fibrillation, and use of a lipid-lowering drug such as a statin.

The investigators then sectioned the data on heart disease risk by decade – 2000-2009 and 2010-2019 – in order to separate the potential impact of antiretroviral treatment (ART) drugs, from early combinations that have been associated with cardiovascular disease, to current drugs that are less likely to have that effect.

Overall risk for any kind of cardiovascular disease was 54% higher among people living with HIV of any age, compared to their age- and risk-matched peers. And when they broke the data down by age, they found that people younger than 40 had nearly twice the risk for any heart disease as their HIV-negative peers, which was a numerically higher risk than for people older than 40 – though not significantly so.

People living with HIV also had a 49% increased risk for stroke and a 59% increased risk for ischemic heart disease but no increased risk for peripheral vascular disease, heart failure, or heart attack. But the confidence intervals here were wide, “which may indicate lack of power and therefore not be conclusive,” Ms. Gooden said.

People living with HIV also had a 37% increased risk for hypertension, were 96% more likely to be prescribed lipid-lowering drugs, 2.4-times more likely to have chronic kidney disease, and 2.68-times more likely to experience all-cause mortality. The study couldn’t account for the type of HIV medications people living with the virus used, their viral load, or their CD4 counts – all of which have been found in previous studies to contribute to heart disease in people with HIV.

“That was the biggest limitation of our study,” Ms. Gooden said in an interview. “The fact that the risk of cardiovascular disease remains the same in the [first decade] and the later decade goes to show that even if antiretroviral therapies contributed to that … now or 20 years ago, it’s still not the entire reason for the risk.”

Steven Grinspoon, MD, of Harvard Medical School, Boston, is the lead author on the REPRIEVE trial, now testing statins as a treatment for people like those in this study. He told this news organization that this large analysis had one of the youngest cohorts of people living with HIV he’d seen to explore these issues. Additionally, it backs up what the team recently reported in the Journal of the American Medical Association – that plaque was present in 49% of 755 people living with HIV, despite having risk scores for cardiovascular disease in the normal range. This was as true for people younger than 40 as those older than 40.

For primary care clinicians, the message is that even relatively young people with HIV should be counseled early and often about amending traditional risk factors, while we wait for the results of REPRIEVE to say whether statins improve outcomes for people living with HIV, Dr. Grinspoon said in an interview.

“Sometimes physicians and primary care providers say, ‘Well I’ll focus my hypertension efforts on older people, who are closer to having heart attacks,’” Dr. Grinspoon said. “But this data suggests we should pay attention even in young people … and pay particular attention to women who wouldn’t have traditional risk scores that were very high at all, largely because they are women.”

The study was funded by Merck. Ms. Gooden has disclosed no relevant financial relationships. Dr. Grinspoon reports receiving personal and consulting fees from Theratechnologies and ViiV Healthcare.

A version of this article first appeared on Medscape.com.

People age 40 and younger living with HIV have a higher risk for heart disease than even their over-40 peers living with HIV – and that risk was 54% higher than the general public.

And this was among people without traditional heart disease risks, such as smoking and obesity.

“What’s surprising is that not only do we see that, yes, they do have increased risk, but this is after controlling for all of that – which means the mechanism underlying this risk,” said Tiffany Gooden, MPH and a PhD candidate at the University of Birmingham, England, who presented the data at the 11th International AIDS Society Conference on HIV Science (IAS 2021).

“If we’re using a non–HIV-validated assessment tool, you should always know that there could be a risk that you are under-recognizing,” she added.

Right now, there’s not a lot to aid clinicians in ferreting out this increased risk. Traditional cardiovascular risk assessment tools, like Framingham risk scores and atherosclerotic cardiovascular disease risk score from the American College of Cardiology, have been found to overlook the real risk of cardiovascular disease in people living with HIV. Plus, most guidelines, including those from the British HIV Medical Association and the American College of Cardiology, primarily focus screening on people 40 or older.

Ms. Gooden’s study drew data from The Health Improvement Network (THIN) database, which combines data from 800 primary care practices in the United Kingdom. Looking at data between January 2000 and January 2020, the investigators compared each person living with HIV with four peers not living with HIV, matched for age, gender, and practice. In total, 9,233 people living with HIV and 35,721 people without HIV were included in the analysis. Median age of participants was 41 years in people living with HIV and 40.4 years in people without HIV. About 35% of participants in both arms were women, and a greater proportion of participants living with HIV were Black, accounting for 22.5% of people living with HIV, versus 3.8% of the general population. Fewer people living with HIV were overweight or obese compared to people without HIV.

Researchers then tracked participants over time to identify the incidence of heart attack, stroke, peripheral vascular disease, and heart failure, as well as common risk factors for heart problems, such as high blood pressure, type 2 diabetes, chronic kidney disease, atrial fibrillation, and use of a lipid-lowering drug such as a statin.

The investigators then sectioned the data on heart disease risk by decade – 2000-2009 and 2010-2019 – in order to separate the potential impact of antiretroviral treatment (ART) drugs, from early combinations that have been associated with cardiovascular disease, to current drugs that are less likely to have that effect.

Overall risk for any kind of cardiovascular disease was 54% higher among people living with HIV of any age, compared to their age- and risk-matched peers. And when they broke the data down by age, they found that people younger than 40 had nearly twice the risk for any heart disease as their HIV-negative peers, which was a numerically higher risk than for people older than 40 – though not significantly so.

People living with HIV also had a 49% increased risk for stroke and a 59% increased risk for ischemic heart disease but no increased risk for peripheral vascular disease, heart failure, or heart attack. But the confidence intervals here were wide, “which may indicate lack of power and therefore not be conclusive,” Ms. Gooden said.

People living with HIV also had a 37% increased risk for hypertension, were 96% more likely to be prescribed lipid-lowering drugs, 2.4-times more likely to have chronic kidney disease, and 2.68-times more likely to experience all-cause mortality. The study couldn’t account for the type of HIV medications people living with the virus used, their viral load, or their CD4 counts – all of which have been found in previous studies to contribute to heart disease in people with HIV.

“That was the biggest limitation of our study,” Ms. Gooden said in an interview. “The fact that the risk of cardiovascular disease remains the same in the [first decade] and the later decade goes to show that even if antiretroviral therapies contributed to that … now or 20 years ago, it’s still not the entire reason for the risk.”

Steven Grinspoon, MD, of Harvard Medical School, Boston, is the lead author on the REPRIEVE trial, now testing statins as a treatment for people like those in this study. He told this news organization that this large analysis had one of the youngest cohorts of people living with HIV he’d seen to explore these issues. Additionally, it backs up what the team recently reported in the Journal of the American Medical Association – that plaque was present in 49% of 755 people living with HIV, despite having risk scores for cardiovascular disease in the normal range. This was as true for people younger than 40 as those older than 40.

For primary care clinicians, the message is that even relatively young people with HIV should be counseled early and often about amending traditional risk factors, while we wait for the results of REPRIEVE to say whether statins improve outcomes for people living with HIV, Dr. Grinspoon said in an interview.

“Sometimes physicians and primary care providers say, ‘Well I’ll focus my hypertension efforts on older people, who are closer to having heart attacks,’” Dr. Grinspoon said. “But this data suggests we should pay attention even in young people … and pay particular attention to women who wouldn’t have traditional risk scores that were very high at all, largely because they are women.”

The study was funded by Merck. Ms. Gooden has disclosed no relevant financial relationships. Dr. Grinspoon reports receiving personal and consulting fees from Theratechnologies and ViiV Healthcare.

A version of this article first appeared on Medscape.com.

On July 22, the Centers for Disease Control and Prevention released updated sexually transmitted infection treatment guidelines to reflect current screening, testing, and treatment recommendations. The guidelines were last updated in 2015.

The new recommendations come at a pivotal moment in the field’s history, Kimberly Workowski, MD, a medical officer at the CDC’s Division of STD Prevention, told this news organization in an email. “The COVID-19 pandemic has caused decreased clinic capacity and drug and diagnostic test kit shortages,” she says. Many of these shortages have been resolved, she added, and it is important that health care professionals use the most current evidence-based recommendations for screening and management of STIs.

Updates to these guidelines were necessary to reflect “continued advances in research in the prevention of STIs, new interventions in terms of STI prevention, and thirdly, changing epidemiology,” Jeffrey Klausner, MD, MPH, an STI specialist with the Keck School of Medicine at the University of Southern California, Los Angeles, said in an interview. “There’s been increased concern about antimicrobial resistance, and that’s really driven some of the key changes in these new STI treatment guidelines.”

Notable updates to the guidelines include the following:

• Updated treatment recommendations for gonorrhea, chlamydia, , and 
• Two-step testing for diagnosing genital  virus
• Expanded risk factors for  testing in pregnant women
• Information on FDA-cleared rectal and oral tests to diagnose chlamydia and gonorrhea
• A recommendation that universal  screening be conducted at least once in a lifetime for adults aged 18 years and older

Dr. Workowski emphasized updates to gonorrhea treatment that built on the recommendation published in December 2020 in Morbidity and Mortality Weekly Report. The CDC now recommends that gonorrhea be treated with a single 500-mg injection of ceftriaxone, and if chlamydial infection is not ruled out, treating with a regimen of 100 mg of oral doxycycline taken twice daily for 7 days. Other gonorrhea treatment recommendations include retesting patients 3 months after treatment and that a test of cure be conducted for people with pharyngeal gonorrhea 1 to 2 weeks after treatment, using either culture or nucleic-acid amplification tests.

“Effectively treating gonorrhea remains a public health priority,” Dr. Workowski said. “Gonorrhea can rapidly develop antibiotic resistance and is the second most commonly reported bacterial STI in the U.S., increasing 56% from 2015 to 2019.”

The updates to syphilis screening for pregnant women are also important, added Dr. Klausner. “We’ve seen a dramatic and shameful rise in congenital syphilis,” he said. In addition to screening all pregnant women at the first prenatal visit, the CDC recommends retesting for syphilis at 28 weeks’ gestation and at delivery if the mother lives in an area where the prevalence of syphilis is high or if she is at risk of acquiring syphilis during pregnancy. An expectant mother is at higher risk if she has multiple sex partners, has an STI during pregnancy, has a partner with an STI, has a new sex partner, or misuses drugs, the recommendations state.

Dr. Klausner also noted that the updates provide more robust guidelines for treating transgender individuals and incarcerated people.

The treatment guidelines are available online along with a wall chart and a pocket guide that summarizes these updates. The mobile app with the 2015 guidelines will be retired at the end of July 2021, Dr. Workowski said. An app with these updated treatment recommendations is in development and will be available later this year.

A version of this article first appeared on Medscape.com.

On July 22, the Centers for Disease Control and Prevention released updated sexually transmitted infection treatment guidelines to reflect current screening, testing, and treatment recommendations. The guidelines were last updated in 2015.

The new recommendations come at a pivotal moment in the field’s history, Kimberly Workowski, MD, a medical officer at the CDC’s Division of STD Prevention, told this news organization in an email. “The COVID-19 pandemic has caused decreased clinic capacity and drug and diagnostic test kit shortages,” she says. Many of these shortages have been resolved, she added, and it is important that health care professionals use the most current evidence-based recommendations for screening and management of STIs.

Updates to these guidelines were necessary to reflect “continued advances in research in the prevention of STIs, new interventions in terms of STI prevention, and thirdly, changing epidemiology,” Jeffrey Klausner, MD, MPH, an STI specialist with the Keck School of Medicine at the University of Southern California, Los Angeles, said in an interview. “There’s been increased concern about antimicrobial resistance, and that’s really driven some of the key changes in these new STI treatment guidelines.”

Notable updates to the guidelines include the following:

• Updated treatment recommendations for gonorrhea, chlamydia, , and 
• Two-step testing for diagnosing genital  virus
• Expanded risk factors for  testing in pregnant women
• Information on FDA-cleared rectal and oral tests to diagnose chlamydia and gonorrhea
• A recommendation that universal  screening be conducted at least once in a lifetime for adults aged 18 years and older

Dr. Workowski emphasized updates to gonorrhea treatment that built on the recommendation published in December 2020 in Morbidity and Mortality Weekly Report. The CDC now recommends that gonorrhea be treated with a single 500-mg injection of ceftriaxone, and if chlamydial infection is not ruled out, treating with a regimen of 100 mg of oral doxycycline taken twice daily for 7 days. Other gonorrhea treatment recommendations include retesting patients 3 months after treatment and that a test of cure be conducted for people with pharyngeal gonorrhea 1 to 2 weeks after treatment, using either culture or nucleic-acid amplification tests.

“Effectively treating gonorrhea remains a public health priority,” Dr. Workowski said. “Gonorrhea can rapidly develop antibiotic resistance and is the second most commonly reported bacterial STI in the U.S., increasing 56% from 2015 to 2019.”

The updates to syphilis screening for pregnant women are also important, added Dr. Klausner. “We’ve seen a dramatic and shameful rise in congenital syphilis,” he said. In addition to screening all pregnant women at the first prenatal visit, the CDC recommends retesting for syphilis at 28 weeks’ gestation and at delivery if the mother lives in an area where the prevalence of syphilis is high or if she is at risk of acquiring syphilis during pregnancy. An expectant mother is at higher risk if she has multiple sex partners, has an STI during pregnancy, has a partner with an STI, has a new sex partner, or misuses drugs, the recommendations state.

Dr. Klausner also noted that the updates provide more robust guidelines for treating transgender individuals and incarcerated people.

The treatment guidelines are available online along with a wall chart and a pocket guide that summarizes these updates. The mobile app with the 2015 guidelines will be retired at the end of July 2021, Dr. Workowski said. An app with these updated treatment recommendations is in development and will be available later this year.

A version of this article first appeared on Medscape.com.

On July 22, the Centers for Disease Control and Prevention released updated sexually transmitted infection treatment guidelines to reflect current screening, testing, and treatment recommendations. The guidelines were last updated in 2015.

The new recommendations come at a pivotal moment in the field’s history, Kimberly Workowski, MD, a medical officer at the CDC’s Division of STD Prevention, told this news organization in an email. “The COVID-19 pandemic has caused decreased clinic capacity and drug and diagnostic test kit shortages,” she says. Many of these shortages have been resolved, she added, and it is important that health care professionals use the most current evidence-based recommendations for screening and management of STIs.

Updates to these guidelines were necessary to reflect “continued advances in research in the prevention of STIs, new interventions in terms of STI prevention, and thirdly, changing epidemiology,” Jeffrey Klausner, MD, MPH, an STI specialist with the Keck School of Medicine at the University of Southern California, Los Angeles, said in an interview. “There’s been increased concern about antimicrobial resistance, and that’s really driven some of the key changes in these new STI treatment guidelines.”

Notable updates to the guidelines include the following:

• Updated treatment recommendations for gonorrhea, chlamydia, , and 
• Two-step testing for diagnosing genital  virus
• Expanded risk factors for  testing in pregnant women
• Information on FDA-cleared rectal and oral tests to diagnose chlamydia and gonorrhea
• A recommendation that universal  screening be conducted at least once in a lifetime for adults aged 18 years and older

Dr. Workowski emphasized updates to gonorrhea treatment that built on the recommendation published in December 2020 in Morbidity and Mortality Weekly Report. The CDC now recommends that gonorrhea be treated with a single 500-mg injection of ceftriaxone, and if chlamydial infection is not ruled out, treating with a regimen of 100 mg of oral doxycycline taken twice daily for 7 days. Other gonorrhea treatment recommendations include retesting patients 3 months after treatment and that a test of cure be conducted for people with pharyngeal gonorrhea 1 to 2 weeks after treatment, using either culture or nucleic-acid amplification tests.

“Effectively treating gonorrhea remains a public health priority,” Dr. Workowski said. “Gonorrhea can rapidly develop antibiotic resistance and is the second most commonly reported bacterial STI in the U.S., increasing 56% from 2015 to 2019.”

The updates to syphilis screening for pregnant women are also important, added Dr. Klausner. “We’ve seen a dramatic and shameful rise in congenital syphilis,” he said. In addition to screening all pregnant women at the first prenatal visit, the CDC recommends retesting for syphilis at 28 weeks’ gestation and at delivery if the mother lives in an area where the prevalence of syphilis is high or if she is at risk of acquiring syphilis during pregnancy. An expectant mother is at higher risk if she has multiple sex partners, has an STI during pregnancy, has a partner with an STI, has a new sex partner, or misuses drugs, the recommendations state.

Dr. Klausner also noted that the updates provide more robust guidelines for treating transgender individuals and incarcerated people.

The treatment guidelines are available online along with a wall chart and a pocket guide that summarizes these updates. The mobile app with the 2015 guidelines will be retired at the end of July 2021, Dr. Workowski said. An app with these updated treatment recommendations is in development and will be available later this year.

A version of this article first appeared on Medscape.com.

A two-drug fixed-dose tablet therapy of dolutegravir/lamivudine (Dovato, ViiV Healthcare; DTG/3TC) shows noninferiority in viral suppression among people with HIV-1 who switch from any type of three- or four-drug antiretroviral (ART) regimens. But, DTG/3TC also shows feasibility as a first-line regimen in a test-and-treat setting, according to two studies presented at the virtual meeting of the International AIDS Society.

The results on the switch to DTG/3TC are from the phase 3 SALSA trial, which compared patients with HIV-1 who either remained on any current three- or four-drug ART regimen or who switched to the two-drug dolutegravir option.

For the primary endpoint, rates of virologic failure at 48 weeks were noninferior in the DTG/3TC group versus the three- or four-drug regimen (.4% vs. 1.2; adjusted difference: –.8% [95% confidence interval, –2.4%, .8%]).

In addition, rates of virologic suppression at week 48 were noninferior, with 94.3% of patients achieving HIV-1 RNA < 50 c/mL in the DTG/3TC group versus 92.7% in the three- or four-drug regimen (adjusted difference: 1.6% [95% CI, –2.8%, 5.9%).

“These data build upon the previous TANGO study and support DTG/3TC as a robust switch option with high levels of efficacy, good safety and tolerability, and a high barrier of resistance,” first author Josep M. Llibre, MD, PhD, consultant, infectious diseases department, Germans Trias i Pujol University Hospital, Barcelona, said in presenting the findings.

The two-drug dolutegravir-based regimen had previously been shown in the phase 3 GEMINI-1 and GEMINI-2 trials to have virologic noninferiority and safety compared with three- or four-drug DTG plus tenofovir/emtricitabine (TDF/FTC) ART regimens in treatment-naive individuals, and, in the subsequent TANGO trial, the regimen was also noninferior versus tenofovir alafenamide–based regimens among treatment-experienced patients, at 144 weeks in both studies.


 

Trial details

The new SALSA trial, designed to broaden the comparison to treatment with any current three- or four-drug ART regimen, involved 493 patients at 120 study sites in 17 countries.

All patients were initially on a three- or four-drug regimen, with HIV-1 RNA of less than 50 c/mL for more than 6 months, and without prior virologic failure or nucleoside reverse transcriptase inhibitors or dolutegravir resistance-associated mutations.

The participants were randomized 1:1 to remain on their current regimen (n = 247) or to switch to the once-daily, fixed-dose tablet two-drug combination of dolutegravir 50 mg/lamivudine 300 mg (n = 246) for 52 weeks.

In addition to the noninferior virologic outcomes, there were no serious drug-related adverse events, no confirmed virologic withdrawals, and no resistance mutations in either group.

Of note, weight increase was higher in the DTG/3TC group (8%; n = 20) versus the current ART arm (2%; n = 5), as has been observed in previous studies. The adjusted mean change in weight from baseline to week 48 in the DTG arm was 2.1 kg versus 0.6 kg in the current ART arm.

Dr. Llibre pointed out that many of the participants who switched were discontinuing regimens such as TDF and efavirenz that are associated with weight loss, “so discontinuation could be more related to weight gain than the introduction of dolutegravir, but this deserves further study,” he noted.

There were no significant differences in changes in eGFR and fasting lipids, or in changes in inflammatory biomarkers between the groups.

Bone and renal biomarkers were more favorable in the dolutegravir two-drug arm, suggesting that bone and renal function was either maintained or even improved with the drug switch, Dr. Llibre noted.

STAT trial: Feasibility of two-drug DTG/3TC as first-line treatment

In further findings presented at the meeting on the STAT trial, researchers evaluated the feasibility not of switching to, but of initiating patients on, the two-drug DTG treatment as a first-line therapy, within 14 days of HIV-1 diagnosis.

The “test-and-treat” approach counters common belief that the regimen should be started only after the traditional three-drug regimens, because of the potential of transmitted resistance and baseline hepatitis B virus coinfection.

In the study of 131 patients, at week 48, 82% (107/131) of all participants and 97% (107/110) of those with available data achieved HIV-1 RNA levels of < 50 c/mL.

While two participants had confirmed virologic failure in the study, there were no treatment-emergent resistance-associated mutations, and neither patient discontinued the two-drug DTG treatment. There were low rates of drug-related adverse events (8%) and they were not serious.

A two-drug fixed-dose tablet therapy of dolutegravir/lamivudine (Dovato, ViiV Healthcare; DTG/3TC) shows noninferiority in viral suppression among people with HIV-1 who switch from any type of three- or four-drug antiretroviral (ART) regimens. But, DTG/3TC also shows feasibility as a first-line regimen in a test-and-treat setting, according to two studies presented at the virtual meeting of the International AIDS Society.

The results on the switch to DTG/3TC are from the phase 3 SALSA trial, which compared patients with HIV-1 who either remained on any current three- or four-drug ART regimen or who switched to the two-drug dolutegravir option.

For the primary endpoint, rates of virologic failure at 48 weeks were noninferior in the DTG/3TC group versus the three- or four-drug regimen (.4% vs. 1.2; adjusted difference: –.8% [95% confidence interval, –2.4%, .8%]).

In addition, rates of virologic suppression at week 48 were noninferior, with 94.3% of patients achieving HIV-1 RNA < 50 c/mL in the DTG/3TC group versus 92.7% in the three- or four-drug regimen (adjusted difference: 1.6% [95% CI, –2.8%, 5.9%).

“These data build upon the previous TANGO study and support DTG/3TC as a robust switch option with high levels of efficacy, good safety and tolerability, and a high barrier of resistance,” first author Josep M. Llibre, MD, PhD, consultant, infectious diseases department, Germans Trias i Pujol University Hospital, Barcelona, said in presenting the findings.

The two-drug dolutegravir-based regimen had previously been shown in the phase 3 GEMINI-1 and GEMINI-2 trials to have virologic noninferiority and safety compared with three- or four-drug DTG plus tenofovir/emtricitabine (TDF/FTC) ART regimens in treatment-naive individuals, and, in the subsequent TANGO trial, the regimen was also noninferior versus tenofovir alafenamide–based regimens among treatment-experienced patients, at 144 weeks in both studies.


 

Trial details

The new SALSA trial, designed to broaden the comparison to treatment with any current three- or four-drug ART regimen, involved 493 patients at 120 study sites in 17 countries.

All patients were initially on a three- or four-drug regimen, with HIV-1 RNA of less than 50 c/mL for more than 6 months, and without prior virologic failure or nucleoside reverse transcriptase inhibitors or dolutegravir resistance-associated mutations.

The participants were randomized 1:1 to remain on their current regimen (n = 247) or to switch to the once-daily, fixed-dose tablet two-drug combination of dolutegravir 50 mg/lamivudine 300 mg (n = 246) for 52 weeks.

In addition to the noninferior virologic outcomes, there were no serious drug-related adverse events, no confirmed virologic withdrawals, and no resistance mutations in either group.

Of note, weight increase was higher in the DTG/3TC group (8%; n = 20) versus the current ART arm (2%; n = 5), as has been observed in previous studies. The adjusted mean change in weight from baseline to week 48 in the DTG arm was 2.1 kg versus 0.6 kg in the current ART arm.

Dr. Llibre pointed out that many of the participants who switched were discontinuing regimens such as TDF and efavirenz that are associated with weight loss, “so discontinuation could be more related to weight gain than the introduction of dolutegravir, but this deserves further study,” he noted.

There were no significant differences in changes in eGFR and fasting lipids, or in changes in inflammatory biomarkers between the groups.

Bone and renal biomarkers were more favorable in the dolutegravir two-drug arm, suggesting that bone and renal function was either maintained or even improved with the drug switch, Dr. Llibre noted.

STAT trial: Feasibility of two-drug DTG/3TC as first-line treatment

In further findings presented at the meeting on the STAT trial, researchers evaluated the feasibility not of switching to, but of initiating patients on, the two-drug DTG treatment as a first-line therapy, within 14 days of HIV-1 diagnosis.

The “test-and-treat” approach counters common belief that the regimen should be started only after the traditional three-drug regimens, because of the potential of transmitted resistance and baseline hepatitis B virus coinfection.

In the study of 131 patients, at week 48, 82% (107/131) of all participants and 97% (107/110) of those with available data achieved HIV-1 RNA levels of < 50 c/mL.

While two participants had confirmed virologic failure in the study, there were no treatment-emergent resistance-associated mutations, and neither patient discontinued the two-drug DTG treatment. There were low rates of drug-related adverse events (8%) and they were not serious.

A two-drug fixed-dose tablet therapy of dolutegravir/lamivudine (Dovato, ViiV Healthcare; DTG/3TC) shows noninferiority in viral suppression among people with HIV-1 who switch from any type of three- or four-drug antiretroviral (ART) regimens. But, DTG/3TC also shows feasibility as a first-line regimen in a test-and-treat setting, according to two studies presented at the virtual meeting of the International AIDS Society.

The results on the switch to DTG/3TC are from the phase 3 SALSA trial, which compared patients with HIV-1 who either remained on any current three- or four-drug ART regimen or who switched to the two-drug dolutegravir option.

For the primary endpoint, rates of virologic failure at 48 weeks were noninferior in the DTG/3TC group versus the three- or four-drug regimen (.4% vs. 1.2; adjusted difference: –.8% [95% confidence interval, –2.4%, .8%]).

In addition, rates of virologic suppression at week 48 were noninferior, with 94.3% of patients achieving HIV-1 RNA < 50 c/mL in the DTG/3TC group versus 92.7% in the three- or four-drug regimen (adjusted difference: 1.6% [95% CI, –2.8%, 5.9%).

“These data build upon the previous TANGO study and support DTG/3TC as a robust switch option with high levels of efficacy, good safety and tolerability, and a high barrier of resistance,” first author Josep M. Llibre, MD, PhD, consultant, infectious diseases department, Germans Trias i Pujol University Hospital, Barcelona, said in presenting the findings.

The two-drug dolutegravir-based regimen had previously been shown in the phase 3 GEMINI-1 and GEMINI-2 trials to have virologic noninferiority and safety compared with three- or four-drug DTG plus tenofovir/emtricitabine (TDF/FTC) ART regimens in treatment-naive individuals, and, in the subsequent TANGO trial, the regimen was also noninferior versus tenofovir alafenamide–based regimens among treatment-experienced patients, at 144 weeks in both studies.


 

Trial details

The new SALSA trial, designed to broaden the comparison to treatment with any current three- or four-drug ART regimen, involved 493 patients at 120 study sites in 17 countries.

All patients were initially on a three- or four-drug regimen, with HIV-1 RNA of less than 50 c/mL for more than 6 months, and without prior virologic failure or nucleoside reverse transcriptase inhibitors or dolutegravir resistance-associated mutations.

The participants were randomized 1:1 to remain on their current regimen (n = 247) or to switch to the once-daily, fixed-dose tablet two-drug combination of dolutegravir 50 mg/lamivudine 300 mg (n = 246) for 52 weeks.

In addition to the noninferior virologic outcomes, there were no serious drug-related adverse events, no confirmed virologic withdrawals, and no resistance mutations in either group.

Of note, weight increase was higher in the DTG/3TC group (8%; n = 20) versus the current ART arm (2%; n = 5), as has been observed in previous studies. The adjusted mean change in weight from baseline to week 48 in the DTG arm was 2.1 kg versus 0.6 kg in the current ART arm.

Dr. Llibre pointed out that many of the participants who switched were discontinuing regimens such as TDF and efavirenz that are associated with weight loss, “so discontinuation could be more related to weight gain than the introduction of dolutegravir, but this deserves further study,” he noted.

There were no significant differences in changes in eGFR and fasting lipids, or in changes in inflammatory biomarkers between the groups.

Bone and renal biomarkers were more favorable in the dolutegravir two-drug arm, suggesting that bone and renal function was either maintained or even improved with the drug switch, Dr. Llibre noted.

STAT trial: Feasibility of two-drug DTG/3TC as first-line treatment

In further findings presented at the meeting on the STAT trial, researchers evaluated the feasibility not of switching to, but of initiating patients on, the two-drug DTG treatment as a first-line therapy, within 14 days of HIV-1 diagnosis.

The “test-and-treat” approach counters common belief that the regimen should be started only after the traditional three-drug regimens, because of the potential of transmitted resistance and baseline hepatitis B virus coinfection.

In the study of 131 patients, at week 48, 82% (107/131) of all participants and 97% (107/110) of those with available data achieved HIV-1 RNA levels of < 50 c/mL.

While two participants had confirmed virologic failure in the study, there were no treatment-emergent resistance-associated mutations, and neither patient discontinued the two-drug DTG treatment. There were low rates of drug-related adverse events (8%) and they were not serious.

CDC Director Rochelle Walensky, MD, called the COVID-19 Delta variant “one of the most infectious respiratory viruses we know of” and reported more cases and hospitalizations.

“Today, I want to speak about our need to come together against a common enemy. SARS-CoV-2 and the Delta variant is spreading with incredible efficiency, and now represents more than 83% of the virus circulating in the U.S.,” Dr. Walensky said at a news briefing July 22. “It is one of the most infectious respiratory viruses we know of and that I have seen in my 20-year career.”

Dr. Walensky said there were 46,318 cases of COVID-19 reported July 21, with a 7-day average of 37,700 cases per day -- up 53% from the previous week. Hospital admissions average about 3,500 per day, an increase of 32%. The 7-day average of deaths is 237 -- a 19% increase from the previous week.

Meanwhile, there are now 162 million Americans who are fully vaccinated against COVID-19.

Areas with low vaccination coverage continue to have the highest case numbers, she reported, with unvaccinated people accounting for 97% of hospitalizations and deaths.

But there may be early signs of progress. The four states with the highest case rates -- Arkansas, Florida, Louisiana, and Nevada -- had a higher rate of new vaccinations, compared with the national average over the past week, White House COVID-19 Response Coordinator Jeff Zients said.

He also announced that the administration will send $100 million to nearly 2,000 rural health clinics to support vaccine education and outreach efforts.

Dr. Walensky said despite the rising numbers, the CDC mask guidance remains the same, but she encouraged vaccinated people to wear masks if they choose.

“Whether you are vaccinated or not, please know we together are not out of the woods yet,” she said. “We are yet at another pivotal moment in this pandemic, with cases rising again and hospitals reaching their capacity in some areas.”

A version of this article first appeared on WebMD.com.

CDC Director Rochelle Walensky, MD, called the COVID-19 Delta variant “one of the most infectious respiratory viruses we know of” and reported more cases and hospitalizations.

“Today, I want to speak about our need to come together against a common enemy. SARS-CoV-2 and the Delta variant is spreading with incredible efficiency, and now represents more than 83% of the virus circulating in the U.S.,” Dr. Walensky said at a news briefing July 22. “It is one of the most infectious respiratory viruses we know of and that I have seen in my 20-year career.”

Dr. Walensky said there were 46,318 cases of COVID-19 reported July 21, with a 7-day average of 37,700 cases per day -- up 53% from the previous week. Hospital admissions average about 3,500 per day, an increase of 32%. The 7-day average of deaths is 237 -- a 19% increase from the previous week.

Meanwhile, there are now 162 million Americans who are fully vaccinated against COVID-19.

Areas with low vaccination coverage continue to have the highest case numbers, she reported, with unvaccinated people accounting for 97% of hospitalizations and deaths.

But there may be early signs of progress. The four states with the highest case rates -- Arkansas, Florida, Louisiana, and Nevada -- had a higher rate of new vaccinations, compared with the national average over the past week, White House COVID-19 Response Coordinator Jeff Zients said.

He also announced that the administration will send $100 million to nearly 2,000 rural health clinics to support vaccine education and outreach efforts.

Dr. Walensky said despite the rising numbers, the CDC mask guidance remains the same, but she encouraged vaccinated people to wear masks if they choose.

“Whether you are vaccinated or not, please know we together are not out of the woods yet,” she said. “We are yet at another pivotal moment in this pandemic, with cases rising again and hospitals reaching their capacity in some areas.”

A version of this article first appeared on WebMD.com.

CDC Director Rochelle Walensky, MD, called the COVID-19 Delta variant “one of the most infectious respiratory viruses we know of” and reported more cases and hospitalizations.

“Today, I want to speak about our need to come together against a common enemy. SARS-CoV-2 and the Delta variant is spreading with incredible efficiency, and now represents more than 83% of the virus circulating in the U.S.,” Dr. Walensky said at a news briefing July 22. “It is one of the most infectious respiratory viruses we know of and that I have seen in my 20-year career.”

Dr. Walensky said there were 46,318 cases of COVID-19 reported July 21, with a 7-day average of 37,700 cases per day -- up 53% from the previous week. Hospital admissions average about 3,500 per day, an increase of 32%. The 7-day average of deaths is 237 -- a 19% increase from the previous week.

Meanwhile, there are now 162 million Americans who are fully vaccinated against COVID-19.

Areas with low vaccination coverage continue to have the highest case numbers, she reported, with unvaccinated people accounting for 97% of hospitalizations and deaths.

But there may be early signs of progress. The four states with the highest case rates -- Arkansas, Florida, Louisiana, and Nevada -- had a higher rate of new vaccinations, compared with the national average over the past week, White House COVID-19 Response Coordinator Jeff Zients said.

He also announced that the administration will send $100 million to nearly 2,000 rural health clinics to support vaccine education and outreach efforts.

Dr. Walensky said despite the rising numbers, the CDC mask guidance remains the same, but she encouraged vaccinated people to wear masks if they choose.

“Whether you are vaccinated or not, please know we together are not out of the woods yet,” she said. “We are yet at another pivotal moment in this pandemic, with cases rising again and hospitals reaching their capacity in some areas.”

A version of this article first appeared on WebMD.com.

Background: Acid suppressants inhibit gastric acid secretion and disrupt the intestinal microbiome, but whether that facilitates colonization and infection with MDROs is unclear.

Dr. Li is assistant professor of medicine, section of hospital medicine, at the University of Virginia School of Medicine, Charlottesville.

Background: Acid suppressants inhibit gastric acid secretion and disrupt the intestinal microbiome, but whether that facilitates colonization and infection with MDROs is unclear.

Dr. Li is assistant professor of medicine, section of hospital medicine, at the University of Virginia School of Medicine, Charlottesville.

Background: Acid suppressants inhibit gastric acid secretion and disrupt the intestinal microbiome, but whether that facilitates colonization and infection with MDROs is unclear.

Dr. Li is assistant professor of medicine, section of hospital medicine, at the University of Virginia School of Medicine, Charlottesville.

A single high dose of the antifungal agent liposomal amphotericin B (L-AmB; AmBisome, Gilead Sciences), with a background regimen of flucytosine and fluconazole, is non-inferior and significantly safer in preventing mortality in HIV-associated cryptococcal meningitis than a conventional seven-day regimen that is the current standard of care, according to a new study.

The much-anticipated results suggest an important alternative amid controversy over the drug’s cost and availability.

“The results of this phase 3 [AMBITION-cm] trial make it clear that this approach is just as good as the current World Health Organization-recommended first-line treatment in preventing death,” first author David S. Lawrence, MD, AMBITION study lead clinician, of the London School of Hygiene and Tropical Medicine, United Kingdom, said in an interview.

“The fact that this was the largest ever trial [on HIV-associated cryptococcal meningitis] conducted to date… gives us a high level of confidence in these results,” he said of the study, which was presented at the virtual annual meeting of the International AIDS Society.

“We believe that this should become the WHO-recommended first-line regimen,” he emphasized.

In commenting on the study, Meg Doherty, MD, PhD, director of global HIV, hepatitis, and STI programs at WHO, agreed that a shorter regimen could be vital, particularly in settings with limited resources.

“The results from the AMBITION trial are important for low- and middle-income countries, where the cost and complexity of implementing the current standard seven-day course of L-ambisome or cryptococcal meningitis treatment can put this out of reach for many,” she told this news organization.

“Simplification that maintains the highest quality of care is an important component of the public health approach for HIV treatment and care,” she added.

Dr. Doherty could not comment on any possible changes to WHO recommendations, which are formulated by an independent guideline development group, but a spokesperson said that “WHO is preparing an updated review of the evidence for treating cryptococcal disease as a first step towards updating guidance.”

Conventional treatment toxicities

Cryptococcal meningitis is a leading cause of death in HIV, and the conventional treatment of amphotericin B deoxycholate, though less expensive than L-AmB, is more toxic, causing anemia, renal impairment, and electrolyte abnormalities, Dr. Lawrence explained

Having previously shown a single 10 mg/kg dose of L-AmB to be as effective as the longer regimen of 14 daily doses in terms of clearing cryptococcus from the cerebrospinal fluid, Dr. Lawrence and his colleagues conducted the phase 3 AMBITION-Cm trial to evaluate the effect on mortality, enrolling 844 patients in Botswana, Malawi, South Africa, Uganda, and Zimbabwe who were HIV-positive and had a first episode of cryptococcal meningitis.

Participants in the study were randomized to treatment either with single, high-dose L-AmB (10 mg/kg), combined with 14 days of flucytosine 100 mg/kg/day and fluconazole 1,200 mg/day or to a control group receiving 7 daily doses of AmB deoxycholate (1 mg/kg) plus 7 days of flucytosine 100 mg/kg/day, followed by 7 days of fluconazole 1,200 mg/day.

All patients were also provided with consolidation therapy of fluconazole 800 mg/day for eight weeks. Of the patients, 60.2% were male, their median age was 37, and their median CD4 count was 27 cells/mm³.

For the primary endpoint in the intention-to-treat analysis of 814 patients, the 10-week mortality rate in the single-dose L-AmB group was 24.82% (101 of 407) and 28.75% (117 of 407) in the control arm, for a difference (-3.93%) that was well within the pre-specified non-inferiority margin of 10%.

As expected, the safety measures were significantly improved with the single-dose of L-AmB: Rates of grade 3 or 4 adverse events within the initial 21 days of treatment in the single-dose L-AmB group were 50% versus 62.3% in the control group, and severe anemia occurred in just 13% of single-dose L-AmB participants, compared with 41% in the AmB deoxycholate control arm (both P < .001), Dr. Lawrence reported.

Furthermore, the average decline in hemoglobin over the first week was 0.3 g/dL in the single-dose L-AmB arm and 1.9 g/dL in the control arm, resulting in the need for more blood transfusions in the control arm (P < .001).

The impact on kidney function was also worse in the higher dose arm, with an average increase in creatinine over the first week of 20.2% in the L-AmB group versus 49.7% in the control group, while hypokalemia and thrombophlebitis were also more common with the higher dose group, Dr. Lawrence noted.

In the adjusted analysis, the single-dose L-AmB measures were in fact superior after adjusting for factors including research site, age, sex, baseline Glasgow Coma Scale, CD4 count, CSF cryptococcal colony-forming units/mL, antiretroviral therapy status, hemoglobin, and CSF opening pressure.

Mortality rate still high – but significantly reduced

The mortality rate of about 25% in the study after the treatment is still significantly higher than typically seen in high-income countries such as the United States, where HIV-associated cryptococcal meningitis is less common and associated with a mortality of roughly 10-15%, Dr. Lawrence noted.

The rate is nevertheless among the lowest mortality rates ever reported within a clinical trial conducted in resource-limited settings, he explained.

“These results are a step in the right direction and a significant improvement on the rates of 40% to 45% reported with two-week L-AmB-based regimens in African settings,” Dr. Lawrence underscored.

Higher cost — but potentially more cost-effective

With a higher cost than AmB deoxycholate, L-AmB’s utilization in resource-limited settings has been a challenge: A single vial of L-AmB ranges from $80 to $200, according to some reports, and while 14-day dosing requires as many as 42 vials of L-AmB, even a 7-day regimen still requires 21 vials.

In comparison, the single-dose L-AmB regimen only requires an average of 10 to 11 vials per patient, but the regimen’s higher safety could translate to far greater cost savings, Dr. Lawrence explained.

“While the AmBisome regimen is technically more expensive in terms of drugs, we expect it to be cost-effective or possibly cost-saving when taking into account that there is less toxicity, fewer blood tests, less transfusions, etc., and possibly shorter duration of hospital admission,” he said.

Cost, supply controversy: ‘Black fungus’-related demand

The drug’s cost — as well as supply issues — have meanwhile become even more of a problem as L-AmB has unexpectedly also become urgently needed in the treatment of mucormycosis in India and Nepal, where the otherwise rare fungal disease, commonly known as “black fungus,” has been increasingly affecting COVID-19 patients and survivors.

Gilead had previously announced in 2018 its intention to make L-AmB more widely available at a price of $16.25 per vial, but “implementation of this has been slow,” Dr. Lawrence said.

As a result, Gilead is facing heightened pressure to implement the lower prices – and also improve substantial supply issues, with Médecins Sans Frontières (Doctors Without Borders) and dozens of other global organizations issuing an open letter to Gilead and partner Viatris in June calling for immediate action to implement the lower price and improve supply of L-AmB.

In a company statement, Gilead responded, detailing its “commit[ment] to the non-profit pricing for the treatment of cryptococcal meningitis” and to efforts to improve the public health crisis in India.

For their part, Dr. Lawrence and his colleagues are working on producing more research on the issue.

“We hope that the conclusive results of the AMBITION trial will give a much needed push to implement this program,” he said.

“We are also currently completing the cost-effectiveness analysis of the study, which we hope will provide additional evidence to support widespread implementation of this regimen and highlight further the urgent need to broaden access to AmBisome and flucytosine,” he said.

The trial was supported by a grant through the European Developing Countries Clinical Trials Partnership (EDCTP), the Swedish International Development Cooperation Agency (SIDA) (TRIA2015-1092), and the Wellcome Trust / Medical Research Council (UK)/UKAID Joint Global Health Trials (MR/P006922/1. The AmBisome was donated by Gilead Sciences. Dr. Lawrence had no disclosures to report.

A single high dose of the antifungal agent liposomal amphotericin B (L-AmB; AmBisome, Gilead Sciences), with a background regimen of flucytosine and fluconazole, is non-inferior and significantly safer in preventing mortality in HIV-associated cryptococcal meningitis than a conventional seven-day regimen that is the current standard of care, according to a new study.

The much-anticipated results suggest an important alternative amid controversy over the drug’s cost and availability.

“The results of this phase 3 [AMBITION-cm] trial make it clear that this approach is just as good as the current World Health Organization-recommended first-line treatment in preventing death,” first author David S. Lawrence, MD, AMBITION study lead clinician, of the London School of Hygiene and Tropical Medicine, United Kingdom, said in an interview.

“The fact that this was the largest ever trial [on HIV-associated cryptococcal meningitis] conducted to date… gives us a high level of confidence in these results,” he said of the study, which was presented at the virtual annual meeting of the International AIDS Society.

“We believe that this should become the WHO-recommended first-line regimen,” he emphasized.

In commenting on the study, Meg Doherty, MD, PhD, director of global HIV, hepatitis, and STI programs at WHO, agreed that a shorter regimen could be vital, particularly in settings with limited resources.

“The results from the AMBITION trial are important for low- and middle-income countries, where the cost and complexity of implementing the current standard seven-day course of L-ambisome or cryptococcal meningitis treatment can put this out of reach for many,” she told this news organization.

“Simplification that maintains the highest quality of care is an important component of the public health approach for HIV treatment and care,” she added.

Dr. Doherty could not comment on any possible changes to WHO recommendations, which are formulated by an independent guideline development group, but a spokesperson said that “WHO is preparing an updated review of the evidence for treating cryptococcal disease as a first step towards updating guidance.”

Conventional treatment toxicities

Cryptococcal meningitis is a leading cause of death in HIV, and the conventional treatment of amphotericin B deoxycholate, though less expensive than L-AmB, is more toxic, causing anemia, renal impairment, and electrolyte abnormalities, Dr. Lawrence explained

Having previously shown a single 10 mg/kg dose of L-AmB to be as effective as the longer regimen of 14 daily doses in terms of clearing cryptococcus from the cerebrospinal fluid, Dr. Lawrence and his colleagues conducted the phase 3 AMBITION-Cm trial to evaluate the effect on mortality, enrolling 844 patients in Botswana, Malawi, South Africa, Uganda, and Zimbabwe who were HIV-positive and had a first episode of cryptococcal meningitis.

Participants in the study were randomized to treatment either with single, high-dose L-AmB (10 mg/kg), combined with 14 days of flucytosine 100 mg/kg/day and fluconazole 1,200 mg/day or to a control group receiving 7 daily doses of AmB deoxycholate (1 mg/kg) plus 7 days of flucytosine 100 mg/kg/day, followed by 7 days of fluconazole 1,200 mg/day.

All patients were also provided with consolidation therapy of fluconazole 800 mg/day for eight weeks. Of the patients, 60.2% were male, their median age was 37, and their median CD4 count was 27 cells/mm³.

For the primary endpoint in the intention-to-treat analysis of 814 patients, the 10-week mortality rate in the single-dose L-AmB group was 24.82% (101 of 407) and 28.75% (117 of 407) in the control arm, for a difference (-3.93%) that was well within the pre-specified non-inferiority margin of 10%.

As expected, the safety measures were significantly improved with the single-dose of L-AmB: Rates of grade 3 or 4 adverse events within the initial 21 days of treatment in the single-dose L-AmB group were 50% versus 62.3% in the control group, and severe anemia occurred in just 13% of single-dose L-AmB participants, compared with 41% in the AmB deoxycholate control arm (both P < .001), Dr. Lawrence reported.

Furthermore, the average decline in hemoglobin over the first week was 0.3 g/dL in the single-dose L-AmB arm and 1.9 g/dL in the control arm, resulting in the need for more blood transfusions in the control arm (P < .001).

The impact on kidney function was also worse in the higher dose arm, with an average increase in creatinine over the first week of 20.2% in the L-AmB group versus 49.7% in the control group, while hypokalemia and thrombophlebitis were also more common with the higher dose group, Dr. Lawrence noted.

In the adjusted analysis, the single-dose L-AmB measures were in fact superior after adjusting for factors including research site, age, sex, baseline Glasgow Coma Scale, CD4 count, CSF cryptococcal colony-forming units/mL, antiretroviral therapy status, hemoglobin, and CSF opening pressure.

Mortality rate still high – but significantly reduced

The mortality rate of about 25% in the study after the treatment is still significantly higher than typically seen in high-income countries such as the United States, where HIV-associated cryptococcal meningitis is less common and associated with a mortality of roughly 10-15%, Dr. Lawrence noted.

The rate is nevertheless among the lowest mortality rates ever reported within a clinical trial conducted in resource-limited settings, he explained.

“These results are a step in the right direction and a significant improvement on the rates of 40% to 45% reported with two-week L-AmB-based regimens in African settings,” Dr. Lawrence underscored.

Higher cost — but potentially more cost-effective

With a higher cost than AmB deoxycholate, L-AmB’s utilization in resource-limited settings has been a challenge: A single vial of L-AmB ranges from $80 to $200, according to some reports, and while 14-day dosing requires as many as 42 vials of L-AmB, even a 7-day regimen still requires 21 vials.

In comparison, the single-dose L-AmB regimen only requires an average of 10 to 11 vials per patient, but the regimen’s higher safety could translate to far greater cost savings, Dr. Lawrence explained.

“While the AmBisome regimen is technically more expensive in terms of drugs, we expect it to be cost-effective or possibly cost-saving when taking into account that there is less toxicity, fewer blood tests, less transfusions, etc., and possibly shorter duration of hospital admission,” he said.

Cost, supply controversy: ‘Black fungus’-related demand

The drug’s cost — as well as supply issues — have meanwhile become even more of a problem as L-AmB has unexpectedly also become urgently needed in the treatment of mucormycosis in India and Nepal, where the otherwise rare fungal disease, commonly known as “black fungus,” has been increasingly affecting COVID-19 patients and survivors.

Gilead had previously announced in 2018 its intention to make L-AmB more widely available at a price of $16.25 per vial, but “implementation of this has been slow,” Dr. Lawrence said.

As a result, Gilead is facing heightened pressure to implement the lower prices – and also improve substantial supply issues, with Médecins Sans Frontières (Doctors Without Borders) and dozens of other global organizations issuing an open letter to Gilead and partner Viatris in June calling for immediate action to implement the lower price and improve supply of L-AmB.

In a company statement, Gilead responded, detailing its “commit[ment] to the non-profit pricing for the treatment of cryptococcal meningitis” and to efforts to improve the public health crisis in India.

For their part, Dr. Lawrence and his colleagues are working on producing more research on the issue.

“We hope that the conclusive results of the AMBITION trial will give a much needed push to implement this program,” he said.

“We are also currently completing the cost-effectiveness analysis of the study, which we hope will provide additional evidence to support widespread implementation of this regimen and highlight further the urgent need to broaden access to AmBisome and flucytosine,” he said.

The trial was supported by a grant through the European Developing Countries Clinical Trials Partnership (EDCTP), the Swedish International Development Cooperation Agency (SIDA) (TRIA2015-1092), and the Wellcome Trust / Medical Research Council (UK)/UKAID Joint Global Health Trials (MR/P006922/1. The AmBisome was donated by Gilead Sciences. Dr. Lawrence had no disclosures to report.

A single high dose of the antifungal agent liposomal amphotericin B (L-AmB; AmBisome, Gilead Sciences), with a background regimen of flucytosine and fluconazole, is non-inferior and significantly safer in preventing mortality in HIV-associated cryptococcal meningitis than a conventional seven-day regimen that is the current standard of care, according to a new study.

The much-anticipated results suggest an important alternative amid controversy over the drug’s cost and availability.

“The results of this phase 3 [AMBITION-cm] trial make it clear that this approach is just as good as the current World Health Organization-recommended first-line treatment in preventing death,” first author David S. Lawrence, MD, AMBITION study lead clinician, of the London School of Hygiene and Tropical Medicine, United Kingdom, said in an interview.

“The fact that this was the largest ever trial [on HIV-associated cryptococcal meningitis] conducted to date… gives us a high level of confidence in these results,” he said of the study, which was presented at the virtual annual meeting of the International AIDS Society.

“We believe that this should become the WHO-recommended first-line regimen,” he emphasized.

In commenting on the study, Meg Doherty, MD, PhD, director of global HIV, hepatitis, and STI programs at WHO, agreed that a shorter regimen could be vital, particularly in settings with limited resources.

“The results from the AMBITION trial are important for low- and middle-income countries, where the cost and complexity of implementing the current standard seven-day course of L-ambisome or cryptococcal meningitis treatment can put this out of reach for many,” she told this news organization.

“Simplification that maintains the highest quality of care is an important component of the public health approach for HIV treatment and care,” she added.

Dr. Doherty could not comment on any possible changes to WHO recommendations, which are formulated by an independent guideline development group, but a spokesperson said that “WHO is preparing an updated review of the evidence for treating cryptococcal disease as a first step towards updating guidance.”

Conventional treatment toxicities

Cryptococcal meningitis is a leading cause of death in HIV, and the conventional treatment of amphotericin B deoxycholate, though less expensive than L-AmB, is more toxic, causing anemia, renal impairment, and electrolyte abnormalities, Dr. Lawrence explained

Having previously shown a single 10 mg/kg dose of L-AmB to be as effective as the longer regimen of 14 daily doses in terms of clearing cryptococcus from the cerebrospinal fluid, Dr. Lawrence and his colleagues conducted the phase 3 AMBITION-Cm trial to evaluate the effect on mortality, enrolling 844 patients in Botswana, Malawi, South Africa, Uganda, and Zimbabwe who were HIV-positive and had a first episode of cryptococcal meningitis.

Participants in the study were randomized to treatment either with single, high-dose L-AmB (10 mg/kg), combined with 14 days of flucytosine 100 mg/kg/day and fluconazole 1,200 mg/day or to a control group receiving 7 daily doses of AmB deoxycholate (1 mg/kg) plus 7 days of flucytosine 100 mg/kg/day, followed by 7 days of fluconazole 1,200 mg/day.

All patients were also provided with consolidation therapy of fluconazole 800 mg/day for eight weeks. Of the patients, 60.2% were male, their median age was 37, and their median CD4 count was 27 cells/mm³.

For the primary endpoint in the intention-to-treat analysis of 814 patients, the 10-week mortality rate in the single-dose L-AmB group was 24.82% (101 of 407) and 28.75% (117 of 407) in the control arm, for a difference (-3.93%) that was well within the pre-specified non-inferiority margin of 10%.

As expected, the safety measures were significantly improved with the single-dose of L-AmB: Rates of grade 3 or 4 adverse events within the initial 21 days of treatment in the single-dose L-AmB group were 50% versus 62.3% in the control group, and severe anemia occurred in just 13% of single-dose L-AmB participants, compared with 41% in the AmB deoxycholate control arm (both P < .001), Dr. Lawrence reported.

Furthermore, the average decline in hemoglobin over the first week was 0.3 g/dL in the single-dose L-AmB arm and 1.9 g/dL in the control arm, resulting in the need for more blood transfusions in the control arm (P < .001).

The impact on kidney function was also worse in the higher dose arm, with an average increase in creatinine over the first week of 20.2% in the L-AmB group versus 49.7% in the control group, while hypokalemia and thrombophlebitis were also more common with the higher dose group, Dr. Lawrence noted.

In the adjusted analysis, the single-dose L-AmB measures were in fact superior after adjusting for factors including research site, age, sex, baseline Glasgow Coma Scale, CD4 count, CSF cryptococcal colony-forming units/mL, antiretroviral therapy status, hemoglobin, and CSF opening pressure.

Mortality rate still high – but significantly reduced

The mortality rate of about 25% in the study after the treatment is still significantly higher than typically seen in high-income countries such as the United States, where HIV-associated cryptococcal meningitis is less common and associated with a mortality of roughly 10-15%, Dr. Lawrence noted.

The rate is nevertheless among the lowest mortality rates ever reported within a clinical trial conducted in resource-limited settings, he explained.

“These results are a step in the right direction and a significant improvement on the rates of 40% to 45% reported with two-week L-AmB-based regimens in African settings,” Dr. Lawrence underscored.

Higher cost — but potentially more cost-effective

With a higher cost than AmB deoxycholate, L-AmB’s utilization in resource-limited settings has been a challenge: A single vial of L-AmB ranges from $80 to $200, according to some reports, and while 14-day dosing requires as many as 42 vials of L-AmB, even a 7-day regimen still requires 21 vials.

In comparison, the single-dose L-AmB regimen only requires an average of 10 to 11 vials per patient, but the regimen’s higher safety could translate to far greater cost savings, Dr. Lawrence explained.

“While the AmBisome regimen is technically more expensive in terms of drugs, we expect it to be cost-effective or possibly cost-saving when taking into account that there is less toxicity, fewer blood tests, less transfusions, etc., and possibly shorter duration of hospital admission,” he said.

Cost, supply controversy: ‘Black fungus’-related demand

The drug’s cost — as well as supply issues — have meanwhile become even more of a problem as L-AmB has unexpectedly also become urgently needed in the treatment of mucormycosis in India and Nepal, where the otherwise rare fungal disease, commonly known as “black fungus,” has been increasingly affecting COVID-19 patients and survivors.

Gilead had previously announced in 2018 its intention to make L-AmB more widely available at a price of $16.25 per vial, but “implementation of this has been slow,” Dr. Lawrence said.

As a result, Gilead is facing heightened pressure to implement the lower prices – and also improve substantial supply issues, with Médecins Sans Frontières (Doctors Without Borders) and dozens of other global organizations issuing an open letter to Gilead and partner Viatris in June calling for immediate action to implement the lower price and improve supply of L-AmB.

In a company statement, Gilead responded, detailing its “commit[ment] to the non-profit pricing for the treatment of cryptococcal meningitis” and to efforts to improve the public health crisis in India.

For their part, Dr. Lawrence and his colleagues are working on producing more research on the issue.

“We hope that the conclusive results of the AMBITION trial will give a much needed push to implement this program,” he said.

“We are also currently completing the cost-effectiveness analysis of the study, which we hope will provide additional evidence to support widespread implementation of this regimen and highlight further the urgent need to broaden access to AmBisome and flucytosine,” he said.

The trial was supported by a grant through the European Developing Countries Clinical Trials Partnership (EDCTP), the Swedish International Development Cooperation Agency (SIDA) (TRIA2015-1092), and the Wellcome Trust / Medical Research Council (UK)/UKAID Joint Global Health Trials (MR/P006922/1. The AmBisome was donated by Gilead Sciences. Dr. Lawrence had no disclosures to report.

Background: Empirical broad-spectrum antibiotics including anti-MRSA therapy are often selected because of concerns for resistant organisms. However, the outcomes of empirical anti-MRSA therapy among patients with pneumonia are unknown.

Dr. Li is assistant professor of medicine, section of hospital medicine, at the University of Virginia School of Medicine, Charlottesville.

Background: Empirical broad-spectrum antibiotics including anti-MRSA therapy are often selected because of concerns for resistant organisms. However, the outcomes of empirical anti-MRSA therapy among patients with pneumonia are unknown.

Dr. Li is assistant professor of medicine, section of hospital medicine, at the University of Virginia School of Medicine, Charlottesville.

Background: Empirical broad-spectrum antibiotics including anti-MRSA therapy are often selected because of concerns for resistant organisms. However, the outcomes of empirical anti-MRSA therapy among patients with pneumonia are unknown.

Dr. Li is assistant professor of medicine, section of hospital medicine, at the University of Virginia School of Medicine, Charlottesville.