Women with HIV on dolutegravir-based antiretroviral therapy (ART) protocols had higher weights through 18 months of the postpartum period than women on efavirenz-based therapy, according to a recent study. However, women taking dolutegravir had similar postpartum weights to women who did not have HIV infection.

The results were shared by Jennifer Jao, MD, MPH, of Northwestern University, Chicago, in a video presentation of the research during the Conference on Retroviruses & Opportunistic Infections, which was presented online this year. CROI organizers chose to hold a virtual meeting because of concerns about the spread of COVID-19.

Dr. Jao, an internal medicine physician and pediatrician, and colleagues looked at the association between dolutegravir and postpartum weight for women with HIV, compared with women with HIV who were taking efavirenz-based ART and women who did not have HIV infection.

Though there was no significant difference among the three groups for body mass index at 4 weeks post partum (all were between 24 and 26 kg/m²), postpartum weight for the dolutegravir group was significantly higher.

Using a mixed models statistical approach that adjusted for potentially confounding variables, Dr. Jao and associates found that women on a dolutegravir-based regiment weighed an average of 5 kg more postpartum than women on an efavirenz-based regiment. (P less than .01).

Further adjustment that included CD4 count, viral load, and ART status at conception didn’t change the results from the original approach that included such variables as age, breastfeeding duration , gestational diabetes status, and second and third trimester weight gain (P = .04).

The study was a secondary analysis of the Tshilo Dikotla study conducted in Botswana. Dr. Jao said that the study addressed the known association of dolutegravir-based ART with higher weight gain than other ART regimens. Seeing how postpartum weight varies by regimen is important because “postpartum weight retention impacts cardiometabolic risk,” added Dr. Jao.

Of a total of 406 women, 170 were on dolutegravir-based therapy, 114 were on efavirenz-based therapy, and 122 weren’t HIV infected. Overall, the women on efavirenz-based therapy were older, with a median age of 33 years, compared with 28.5 and 25 years for the dolutegravir group and those without HIV, respectively. This and all other between-group differences were statistically significant at P less than .01.

Women without HIV had lower gravidity, with a median one pregnancy, compared with three in the other two groups. Other significant differences included a higher rate of weight gain in the second and third trimesters for the non–HIV-infected group, who gained at a rate of 0.3 kg/week, compared with 0.1 and 0.2 kg/week for the efavirenz and dolutegravir groups, respectively. Breastfeeding duration was longer in the non–HIV-infected group as well.

Finally, 86% of women on efavirenz-based therapy were on ART at the time of conception, compared with just 35.3% of women on dolutegravir-based treatment.

“Further studies to assess mechanisms of postpartum weight retention are needed,” said Dr. Jao.

The study was supported by the National Institutes of Health. Dr. Jao reported no relevant conflicts of interest.

[email protected]

SOURCE: Jao J et al. CROI 2020, Poster 00772.

Women with HIV on dolutegravir-based antiretroviral therapy (ART) protocols had higher weights through 18 months of the postpartum period than women on efavirenz-based therapy, according to a recent study. However, women taking dolutegravir had similar postpartum weights to women who did not have HIV infection.

The results were shared by Jennifer Jao, MD, MPH, of Northwestern University, Chicago, in a video presentation of the research during the Conference on Retroviruses & Opportunistic Infections, which was presented online this year. CROI organizers chose to hold a virtual meeting because of concerns about the spread of COVID-19.

Dr. Jao, an internal medicine physician and pediatrician, and colleagues looked at the association between dolutegravir and postpartum weight for women with HIV, compared with women with HIV who were taking efavirenz-based ART and women who did not have HIV infection.

Though there was no significant difference among the three groups for body mass index at 4 weeks post partum (all were between 24 and 26 kg/m²), postpartum weight for the dolutegravir group was significantly higher.

Using a mixed models statistical approach that adjusted for potentially confounding variables, Dr. Jao and associates found that women on a dolutegravir-based regiment weighed an average of 5 kg more postpartum than women on an efavirenz-based regiment. (P less than .01).

Further adjustment that included CD4 count, viral load, and ART status at conception didn’t change the results from the original approach that included such variables as age, breastfeeding duration , gestational diabetes status, and second and third trimester weight gain (P = .04).

The study was a secondary analysis of the Tshilo Dikotla study conducted in Botswana. Dr. Jao said that the study addressed the known association of dolutegravir-based ART with higher weight gain than other ART regimens. Seeing how postpartum weight varies by regimen is important because “postpartum weight retention impacts cardiometabolic risk,” added Dr. Jao.

Of a total of 406 women, 170 were on dolutegravir-based therapy, 114 were on efavirenz-based therapy, and 122 weren’t HIV infected. Overall, the women on efavirenz-based therapy were older, with a median age of 33 years, compared with 28.5 and 25 years for the dolutegravir group and those without HIV, respectively. This and all other between-group differences were statistically significant at P less than .01.

Women without HIV had lower gravidity, with a median one pregnancy, compared with three in the other two groups. Other significant differences included a higher rate of weight gain in the second and third trimesters for the non–HIV-infected group, who gained at a rate of 0.3 kg/week, compared with 0.1 and 0.2 kg/week for the efavirenz and dolutegravir groups, respectively. Breastfeeding duration was longer in the non–HIV-infected group as well.

Finally, 86% of women on efavirenz-based therapy were on ART at the time of conception, compared with just 35.3% of women on dolutegravir-based treatment.

“Further studies to assess mechanisms of postpartum weight retention are needed,” said Dr. Jao.

The study was supported by the National Institutes of Health. Dr. Jao reported no relevant conflicts of interest.

[email protected]

SOURCE: Jao J et al. CROI 2020, Poster 00772.

Women with HIV on dolutegravir-based antiretroviral therapy (ART) protocols had higher weights through 18 months of the postpartum period than women on efavirenz-based therapy, according to a recent study. However, women taking dolutegravir had similar postpartum weights to women who did not have HIV infection.

The results were shared by Jennifer Jao, MD, MPH, of Northwestern University, Chicago, in a video presentation of the research during the Conference on Retroviruses & Opportunistic Infections, which was presented online this year. CROI organizers chose to hold a virtual meeting because of concerns about the spread of COVID-19.

Dr. Jao, an internal medicine physician and pediatrician, and colleagues looked at the association between dolutegravir and postpartum weight for women with HIV, compared with women with HIV who were taking efavirenz-based ART and women who did not have HIV infection.

Though there was no significant difference among the three groups for body mass index at 4 weeks post partum (all were between 24 and 26 kg/m²), postpartum weight for the dolutegravir group was significantly higher.

Using a mixed models statistical approach that adjusted for potentially confounding variables, Dr. Jao and associates found that women on a dolutegravir-based regiment weighed an average of 5 kg more postpartum than women on an efavirenz-based regiment. (P less than .01).

Further adjustment that included CD4 count, viral load, and ART status at conception didn’t change the results from the original approach that included such variables as age, breastfeeding duration , gestational diabetes status, and second and third trimester weight gain (P = .04).

The study was a secondary analysis of the Tshilo Dikotla study conducted in Botswana. Dr. Jao said that the study addressed the known association of dolutegravir-based ART with higher weight gain than other ART regimens. Seeing how postpartum weight varies by regimen is important because “postpartum weight retention impacts cardiometabolic risk,” added Dr. Jao.

Of a total of 406 women, 170 were on dolutegravir-based therapy, 114 were on efavirenz-based therapy, and 122 weren’t HIV infected. Overall, the women on efavirenz-based therapy were older, with a median age of 33 years, compared with 28.5 and 25 years for the dolutegravir group and those without HIV, respectively. This and all other between-group differences were statistically significant at P less than .01.

Women without HIV had lower gravidity, with a median one pregnancy, compared with three in the other two groups. Other significant differences included a higher rate of weight gain in the second and third trimesters for the non–HIV-infected group, who gained at a rate of 0.3 kg/week, compared with 0.1 and 0.2 kg/week for the efavirenz and dolutegravir groups, respectively. Breastfeeding duration was longer in the non–HIV-infected group as well.

Finally, 86% of women on efavirenz-based therapy were on ART at the time of conception, compared with just 35.3% of women on dolutegravir-based treatment.

“Further studies to assess mechanisms of postpartum weight retention are needed,” said Dr. Jao.

The study was supported by the National Institutes of Health. Dr. Jao reported no relevant conflicts of interest.

[email protected]

SOURCE: Jao J et al. CROI 2020, Poster 00772.

Editor’s note: Find the latest COVID-19 news and guidance in Medscape’s  Coronavirus Resource Center.

The Endocrine Society has canceled its annual scientific meeting because of concerns about the novel coronavirus.

The conference was scheduled to take place March 28-31 in San Francisco. The announcement comes the same day as the American College of Cardiology/World Congress of Cardiology joint conference, scheduled for March 27-30 in Chicago, was also canceled.

“This is an unprecedented public health emergency that is clearly impacting not only the city of San Francisco, but many nations around the world. As such, it is with a very heavy heart that I am reporting to you that out of an abundance of caution, the board of directors has decided to cancel ENDO 2020,” Endocrine Society president E. Dale Abel, MD, PhD, said in a news release.

The Endocrine Society has canceled its annual meeting only twice before in its 104-year history, both during World War II. This year, more than 9,000 people were expected to attend the meeting. “Like you, ENDO is one of the highlights of my professional life each year, and I am sure that you are just as disappointed as I am to hear this news,” Dr. Abel said.

As recently as last week, the society’s board of directors had still hoped that the meeting could take place, but over the weekend it consulted with the San Francisco Department of Public Health, which has recommended canceling or postponing all nonessential gatherings.

The society also has been following reports from the U.S. Centers for Disease Control and Prevention and the World Health Organization.

Moreover, Dr. Abel said, “To add to our concerns, institutions across the world are restricting travel, making it impossible for many who have registered for ENDO 2020 to attend and enjoy the meeting.”

The concerns extend even further, as attendance could take health care providers away from where they’re needed most during the emergency.

“By holding the meeting, we might not only put attendees at risk, but we may also displace health care workers during a public health crisis. This could occur because of the need to self-quarantine upon your return home or, in a worse scenario, contribute to spreading the virus to our attendees’ hometowns,” he said.

Meeting registrants will be contacted soon with refund information. Dr. Abel gave a “special thank you” to the annual meeting steering committee and staff, “who have poured so much into this meeting.”

The society is currently “exploring ways in which we might be able to deliver to our registrants content from ENDO 2020 in various venues in the coming year.”

This article first appeared on Medscape.com.

Editor’s note: Find the latest COVID-19 news and guidance in Medscape’s  Coronavirus Resource Center.

The Endocrine Society has canceled its annual scientific meeting because of concerns about the novel coronavirus.

The conference was scheduled to take place March 28-31 in San Francisco. The announcement comes the same day as the American College of Cardiology/World Congress of Cardiology joint conference, scheduled for March 27-30 in Chicago, was also canceled.

“This is an unprecedented public health emergency that is clearly impacting not only the city of San Francisco, but many nations around the world. As such, it is with a very heavy heart that I am reporting to you that out of an abundance of caution, the board of directors has decided to cancel ENDO 2020,” Endocrine Society president E. Dale Abel, MD, PhD, said in a news release.

The Endocrine Society has canceled its annual meeting only twice before in its 104-year history, both during World War II. This year, more than 9,000 people were expected to attend the meeting. “Like you, ENDO is one of the highlights of my professional life each year, and I am sure that you are just as disappointed as I am to hear this news,” Dr. Abel said.

As recently as last week, the society’s board of directors had still hoped that the meeting could take place, but over the weekend it consulted with the San Francisco Department of Public Health, which has recommended canceling or postponing all nonessential gatherings.

The society also has been following reports from the U.S. Centers for Disease Control and Prevention and the World Health Organization.

Moreover, Dr. Abel said, “To add to our concerns, institutions across the world are restricting travel, making it impossible for many who have registered for ENDO 2020 to attend and enjoy the meeting.”

The concerns extend even further, as attendance could take health care providers away from where they’re needed most during the emergency.

“By holding the meeting, we might not only put attendees at risk, but we may also displace health care workers during a public health crisis. This could occur because of the need to self-quarantine upon your return home or, in a worse scenario, contribute to spreading the virus to our attendees’ hometowns,” he said.

Meeting registrants will be contacted soon with refund information. Dr. Abel gave a “special thank you” to the annual meeting steering committee and staff, “who have poured so much into this meeting.”

The society is currently “exploring ways in which we might be able to deliver to our registrants content from ENDO 2020 in various venues in the coming year.”

This article first appeared on Medscape.com.

Editor’s note: Find the latest COVID-19 news and guidance in Medscape’s  Coronavirus Resource Center.

The Endocrine Society has canceled its annual scientific meeting because of concerns about the novel coronavirus.

The conference was scheduled to take place March 28-31 in San Francisco. The announcement comes the same day as the American College of Cardiology/World Congress of Cardiology joint conference, scheduled for March 27-30 in Chicago, was also canceled.

“This is an unprecedented public health emergency that is clearly impacting not only the city of San Francisco, but many nations around the world. As such, it is with a very heavy heart that I am reporting to you that out of an abundance of caution, the board of directors has decided to cancel ENDO 2020,” Endocrine Society president E. Dale Abel, MD, PhD, said in a news release.

The Endocrine Society has canceled its annual meeting only twice before in its 104-year history, both during World War II. This year, more than 9,000 people were expected to attend the meeting. “Like you, ENDO is one of the highlights of my professional life each year, and I am sure that you are just as disappointed as I am to hear this news,” Dr. Abel said.

As recently as last week, the society’s board of directors had still hoped that the meeting could take place, but over the weekend it consulted with the San Francisco Department of Public Health, which has recommended canceling or postponing all nonessential gatherings.

The society also has been following reports from the U.S. Centers for Disease Control and Prevention and the World Health Organization.

Moreover, Dr. Abel said, “To add to our concerns, institutions across the world are restricting travel, making it impossible for many who have registered for ENDO 2020 to attend and enjoy the meeting.”

The concerns extend even further, as attendance could take health care providers away from where they’re needed most during the emergency.

“By holding the meeting, we might not only put attendees at risk, but we may also displace health care workers during a public health crisis. This could occur because of the need to self-quarantine upon your return home or, in a worse scenario, contribute to spreading the virus to our attendees’ hometowns,” he said.

Meeting registrants will be contacted soon with refund information. Dr. Abel gave a “special thank you” to the annual meeting steering committee and staff, “who have poured so much into this meeting.”

The society is currently “exploring ways in which we might be able to deliver to our registrants content from ENDO 2020 in various venues in the coming year.”

This article first appeared on Medscape.com.

The American Academy of Dermatology annual meeting is the latest large medical conference to be canceled because of the coronavirus disease 2019 (COVID-19) outbreak.

“After carefully weighing the emerging facts, as well as our duties to the Academy, our members, other meeting attendees, and the local communities we as dermatologists serve, the AAD has made the difficult but necessary decision to cancel the AAD 2020 Annual Meeting in Denver,” AAD President George Hruza, MD, said in an announcement posted on the AAD’s website late on March 9. “We also want to respect our physicians’ need to be available to and healthy for their own patients, communities, and countries,” he added.

Earlier in the day, the American College of Cardiology announced that its annual meeting would be canceled, as did the Society of Gynecologic Oncology.

In his statement, Dr. Hruza said that the AAD is looking into “virtual meeting options” to provide content that was scheduled to be presented at the meeting.

Updates on those plans will be posted on the AAD’s website at www.aad.org.

The American Academy of Dermatology annual meeting is the latest large medical conference to be canceled because of the coronavirus disease 2019 (COVID-19) outbreak.

“After carefully weighing the emerging facts, as well as our duties to the Academy, our members, other meeting attendees, and the local communities we as dermatologists serve, the AAD has made the difficult but necessary decision to cancel the AAD 2020 Annual Meeting in Denver,” AAD President George Hruza, MD, said in an announcement posted on the AAD’s website late on March 9. “We also want to respect our physicians’ need to be available to and healthy for their own patients, communities, and countries,” he added.

Earlier in the day, the American College of Cardiology announced that its annual meeting would be canceled, as did the Society of Gynecologic Oncology.

In his statement, Dr. Hruza said that the AAD is looking into “virtual meeting options” to provide content that was scheduled to be presented at the meeting.

Updates on those plans will be posted on the AAD’s website at www.aad.org.

The American Academy of Dermatology annual meeting is the latest large medical conference to be canceled because of the coronavirus disease 2019 (COVID-19) outbreak.

“After carefully weighing the emerging facts, as well as our duties to the Academy, our members, other meeting attendees, and the local communities we as dermatologists serve, the AAD has made the difficult but necessary decision to cancel the AAD 2020 Annual Meeting in Denver,” AAD President George Hruza, MD, said in an announcement posted on the AAD’s website late on March 9. “We also want to respect our physicians’ need to be available to and healthy for their own patients, communities, and countries,” he added.

Earlier in the day, the American College of Cardiology announced that its annual meeting would be canceled, as did the Society of Gynecologic Oncology.

In his statement, Dr. Hruza said that the AAD is looking into “virtual meeting options” to provide content that was scheduled to be presented at the meeting.

Updates on those plans will be posted on the AAD’s website at www.aad.org.

The British Society for Rheumatology (BSR) has canceled its annual conference that was scheduled to take place April 20-22 in Glasgow.

“After careful monitoring of the COVID-19 (coronavirus) situation ... [and] in light of increasing demands on health services, our Board of Trustees felt it was no longer appropriate to host a large-scale event nor to take medical professionals away from where they may be needed most in the coming weeks,” the organization announced on its website.

The BSR said that it will soon have more information available for people affected, including “details of how we will showcase some of the content that would have been celebrated at the event.”

[email protected]

The British Society for Rheumatology (BSR) has canceled its annual conference that was scheduled to take place April 20-22 in Glasgow.

“After careful monitoring of the COVID-19 (coronavirus) situation ... [and] in light of increasing demands on health services, our Board of Trustees felt it was no longer appropriate to host a large-scale event nor to take medical professionals away from where they may be needed most in the coming weeks,” the organization announced on its website.

The BSR said that it will soon have more information available for people affected, including “details of how we will showcase some of the content that would have been celebrated at the event.”

[email protected]

The British Society for Rheumatology (BSR) has canceled its annual conference that was scheduled to take place April 20-22 in Glasgow.

“After careful monitoring of the COVID-19 (coronavirus) situation ... [and] in light of increasing demands on health services, our Board of Trustees felt it was no longer appropriate to host a large-scale event nor to take medical professionals away from where they may be needed most in the coming weeks,” the organization announced on its website.

The BSR said that it will soon have more information available for people affected, including “details of how we will showcase some of the content that would have been celebrated at the event.”

[email protected]

The U.S. Supreme Court will likely decide by the end of the summer whether a controversial Louisiana abortion law that imposes restrictions on physicians can stand.

AndreyPopov/ThinkStock

Justices heard oral arguments March 4, 2020, in June Medicare Services v. Russo, which centers on a Louisiana law requiring physicians who perform abortions to have admitting privileges at a nearby hospital. Doctors who perform abortions without admitting privileges at a hospital within 30 miles face fines and imprisonment, while clinics that violate the law can have their licenses revoked, according to the state law, originally passed in 2014. In 2016, the Supreme Court in 2016 heard a similar case – Whole Woman’s Health v. Hellerstedt – concerning a comparable law in Texas. In that case, the justices struck down the measure as unconstitutional.

During oral arguments, Julie Rikelman an attorney representing June Medical Services, said that the Louisiana law is identical to the abortion law in Texas, and she argued that justices should reach the same conclusion.

“The district court found this law would leave Louisiana with just one clinic in one state to serve about 10,000 people per year,” Ms. Rikelman said during oral arguments. “That would mean that hundreds of thousands of women would now live more than 150 miles from the closest provider. And the burdens were actually more severe than this court found in Whole Woman’s Health.”

Elizabeth Murrill, solicitor general of Louisiana, argued that the Louisiana law was justified, and that the 5th U.S. Circuit Court of Appeals was correct when it reversed a district court decision and upheld the law.

“The 5th Circuit correctly held that the plaintiffs in this case failed to carry their burden – their heavy burden of proof that is required to facially invalidate a state law,” Ms. Murrill said during oral arguments. “Louisiana’s decision to require abortion providers to have admitting privileges was justified by abundant evidence of life-threatening health and safety violations, malpractice, noncompliance with professional licensing rules, legislative testimony from postabortive women, [and] testimony from doctors who took care of abortion providers’ abandoned patients.”

During arguments, Justice Ruth Bader Ginsburg questioned the reasoning behind the 30-mile privileges rule, expressing doubt at the state’s justification for the requirement. “What sense does the 30-mile limit make, considering that – certainly for medication abortions and for the overwhelming number of other abortions ... if the woman has a problem, it will be her local hospital that ... she will need to go to for the care, not something 30 miles from the clinic.”

Ms. Murrill responded that the Louisiana regulation is consistent with surgery and ambulatory surgery regulations and aligns with the state’s regulatory structure.

“We had evidence in the record of women who did require transfers,” Ms. Murrill said. “[An abortion provider] testified unambiguously that he had to transfer four patients who had punctured uteruses and were hemorrhaging.”

Whether the plaintiffs have standing to sue is a key question. As a general rule, a plaintiff can only sue to protect their own rights, unless the plaintiff has a close relationship with a third party and there are barriers that prevent the third party from suing. Attorneys for Louisiana contend that the plaintiffs – the medical clinic and several physicians – have no right to sue because their rights are not at stake, and that there is no obstacle to patients suing over the law.

Since the Louisiana law is intended to protect women from “unscrupulous and incompetent abortion providers,” the state argues also that there is a conflict of interest between the physicians and the patients on whose behalf they are suing.

During arguments, Justice Samuel Alito Jr. repeatedly questioned Ms. Rikelman on the plaintiffs’ right to sue, conveying doubt that the plaintiffs were on solid legal ground.

“Would you agree with the general proposition that a party should not be able to sue ostensibly to protect the rights of other people, if there is a real conflict of interest between the party who is suing and those whose rights the party claims to be attempting to defend?” Associate Justice Alito asked during oral arguments.

The hearing ended with no clear picture of how some justices were leaning. Justice Clarence Thomas and Justice Neil Gorsuch remained silent during arguments and asked no questions. Chief Justice John Roberts Jr., and Justice Brett Kavanaugh questioned whether all admitting privileges laws were unconstitutional or if a state-by-state analysis is required. Near the end of the hearing, Justice Stephen Breyer stressed that more research and fact-finding is necessary before the court can reach a decision.

“We’re not going to solve this at oral argument,” he said.

A decision by the Supreme Court is expected by August 2020.

[email protected]

The U.S. Supreme Court will likely decide by the end of the summer whether a controversial Louisiana abortion law that imposes restrictions on physicians can stand.

AndreyPopov/ThinkStock

Justices heard oral arguments March 4, 2020, in June Medicare Services v. Russo, which centers on a Louisiana law requiring physicians who perform abortions to have admitting privileges at a nearby hospital. Doctors who perform abortions without admitting privileges at a hospital within 30 miles face fines and imprisonment, while clinics that violate the law can have their licenses revoked, according to the state law, originally passed in 2014. In 2016, the Supreme Court in 2016 heard a similar case – Whole Woman’s Health v. Hellerstedt – concerning a comparable law in Texas. In that case, the justices struck down the measure as unconstitutional.

During oral arguments, Julie Rikelman an attorney representing June Medical Services, said that the Louisiana law is identical to the abortion law in Texas, and she argued that justices should reach the same conclusion.

“The district court found this law would leave Louisiana with just one clinic in one state to serve about 10,000 people per year,” Ms. Rikelman said during oral arguments. “That would mean that hundreds of thousands of women would now live more than 150 miles from the closest provider. And the burdens were actually more severe than this court found in Whole Woman’s Health.”

Elizabeth Murrill, solicitor general of Louisiana, argued that the Louisiana law was justified, and that the 5th U.S. Circuit Court of Appeals was correct when it reversed a district court decision and upheld the law.

“The 5th Circuit correctly held that the plaintiffs in this case failed to carry their burden – their heavy burden of proof that is required to facially invalidate a state law,” Ms. Murrill said during oral arguments. “Louisiana’s decision to require abortion providers to have admitting privileges was justified by abundant evidence of life-threatening health and safety violations, malpractice, noncompliance with professional licensing rules, legislative testimony from postabortive women, [and] testimony from doctors who took care of abortion providers’ abandoned patients.”

During arguments, Justice Ruth Bader Ginsburg questioned the reasoning behind the 30-mile privileges rule, expressing doubt at the state’s justification for the requirement. “What sense does the 30-mile limit make, considering that – certainly for medication abortions and for the overwhelming number of other abortions ... if the woman has a problem, it will be her local hospital that ... she will need to go to for the care, not something 30 miles from the clinic.”

Ms. Murrill responded that the Louisiana regulation is consistent with surgery and ambulatory surgery regulations and aligns with the state’s regulatory structure.

“We had evidence in the record of women who did require transfers,” Ms. Murrill said. “[An abortion provider] testified unambiguously that he had to transfer four patients who had punctured uteruses and were hemorrhaging.”

Whether the plaintiffs have standing to sue is a key question. As a general rule, a plaintiff can only sue to protect their own rights, unless the plaintiff has a close relationship with a third party and there are barriers that prevent the third party from suing. Attorneys for Louisiana contend that the plaintiffs – the medical clinic and several physicians – have no right to sue because their rights are not at stake, and that there is no obstacle to patients suing over the law.

Since the Louisiana law is intended to protect women from “unscrupulous and incompetent abortion providers,” the state argues also that there is a conflict of interest between the physicians and the patients on whose behalf they are suing.

During arguments, Justice Samuel Alito Jr. repeatedly questioned Ms. Rikelman on the plaintiffs’ right to sue, conveying doubt that the plaintiffs were on solid legal ground.

“Would you agree with the general proposition that a party should not be able to sue ostensibly to protect the rights of other people, if there is a real conflict of interest between the party who is suing and those whose rights the party claims to be attempting to defend?” Associate Justice Alito asked during oral arguments.

The hearing ended with no clear picture of how some justices were leaning. Justice Clarence Thomas and Justice Neil Gorsuch remained silent during arguments and asked no questions. Chief Justice John Roberts Jr., and Justice Brett Kavanaugh questioned whether all admitting privileges laws were unconstitutional or if a state-by-state analysis is required. Near the end of the hearing, Justice Stephen Breyer stressed that more research and fact-finding is necessary before the court can reach a decision.

“We’re not going to solve this at oral argument,” he said.

A decision by the Supreme Court is expected by August 2020.

[email protected]

The U.S. Supreme Court will likely decide by the end of the summer whether a controversial Louisiana abortion law that imposes restrictions on physicians can stand.

AndreyPopov/ThinkStock

Justices heard oral arguments March 4, 2020, in June Medicare Services v. Russo, which centers on a Louisiana law requiring physicians who perform abortions to have admitting privileges at a nearby hospital. Doctors who perform abortions without admitting privileges at a hospital within 30 miles face fines and imprisonment, while clinics that violate the law can have their licenses revoked, according to the state law, originally passed in 2014. In 2016, the Supreme Court in 2016 heard a similar case – Whole Woman’s Health v. Hellerstedt – concerning a comparable law in Texas. In that case, the justices struck down the measure as unconstitutional.

During oral arguments, Julie Rikelman an attorney representing June Medical Services, said that the Louisiana law is identical to the abortion law in Texas, and she argued that justices should reach the same conclusion.

“The district court found this law would leave Louisiana with just one clinic in one state to serve about 10,000 people per year,” Ms. Rikelman said during oral arguments. “That would mean that hundreds of thousands of women would now live more than 150 miles from the closest provider. And the burdens were actually more severe than this court found in Whole Woman’s Health.”

Elizabeth Murrill, solicitor general of Louisiana, argued that the Louisiana law was justified, and that the 5th U.S. Circuit Court of Appeals was correct when it reversed a district court decision and upheld the law.

“The 5th Circuit correctly held that the plaintiffs in this case failed to carry their burden – their heavy burden of proof that is required to facially invalidate a state law,” Ms. Murrill said during oral arguments. “Louisiana’s decision to require abortion providers to have admitting privileges was justified by abundant evidence of life-threatening health and safety violations, malpractice, noncompliance with professional licensing rules, legislative testimony from postabortive women, [and] testimony from doctors who took care of abortion providers’ abandoned patients.”

During arguments, Justice Ruth Bader Ginsburg questioned the reasoning behind the 30-mile privileges rule, expressing doubt at the state’s justification for the requirement. “What sense does the 30-mile limit make, considering that – certainly for medication abortions and for the overwhelming number of other abortions ... if the woman has a problem, it will be her local hospital that ... she will need to go to for the care, not something 30 miles from the clinic.”

Ms. Murrill responded that the Louisiana regulation is consistent with surgery and ambulatory surgery regulations and aligns with the state’s regulatory structure.

“We had evidence in the record of women who did require transfers,” Ms. Murrill said. “[An abortion provider] testified unambiguously that he had to transfer four patients who had punctured uteruses and were hemorrhaging.”

Whether the plaintiffs have standing to sue is a key question. As a general rule, a plaintiff can only sue to protect their own rights, unless the plaintiff has a close relationship with a third party and there are barriers that prevent the third party from suing. Attorneys for Louisiana contend that the plaintiffs – the medical clinic and several physicians – have no right to sue because their rights are not at stake, and that there is no obstacle to patients suing over the law.

Since the Louisiana law is intended to protect women from “unscrupulous and incompetent abortion providers,” the state argues also that there is a conflict of interest between the physicians and the patients on whose behalf they are suing.

During arguments, Justice Samuel Alito Jr. repeatedly questioned Ms. Rikelman on the plaintiffs’ right to sue, conveying doubt that the plaintiffs were on solid legal ground.

“Would you agree with the general proposition that a party should not be able to sue ostensibly to protect the rights of other people, if there is a real conflict of interest between the party who is suing and those whose rights the party claims to be attempting to defend?” Associate Justice Alito asked during oral arguments.

The hearing ended with no clear picture of how some justices were leaning. Justice Clarence Thomas and Justice Neil Gorsuch remained silent during arguments and asked no questions. Chief Justice John Roberts Jr., and Justice Brett Kavanaugh questioned whether all admitting privileges laws were unconstitutional or if a state-by-state analysis is required. Near the end of the hearing, Justice Stephen Breyer stressed that more research and fact-finding is necessary before the court can reach a decision.

“We’re not going to solve this at oral argument,” he said.

A decision by the Supreme Court is expected by August 2020.

[email protected]

WEST PALM BEACH, FLA. – Onset of hyperlipidemia tends to occur earlier in patients with multiple sclerosis (MS), compared with matched controls, according to new research. Among females and African Americans, the effect of MS on age of hyperlipidemia onset may be especially pronounced, said Diane Krill, PhD, professor of biological sciences at Point Park University, Pittsburgh, and colleagues.

Ugreen/thinkstockphotos

Many patients with MS have hyperlipidemia, and adverse lipid profiles correlate with physical and cognitive impairment in this population. “There is evidence of endothelial dysfunction and inflammation in both MS and hyperlipidemia, but the timing of onset of hyperlipidemia is not known,” the researchers said at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.

To assess whether patients with MS have hyperlipidemia diagnosed at an earlier age, relative to matched controls, Dr. Krill and colleagues analyzed data from the Cleveland Clinic health system. They included in their analyses patients with at least two hyperlipidemia diagnoses and at least five encounters with a primary care physician. They matched each patient with MS to four patients without MS using variables such as birth year, sex, race, and year of first encounter. In all, the study included 669 patients with MS and 2,676 controls. The investigators examined age of hyperlipidemia onset using multivariable Cox proportional hazard models that adjusted for sex, race, smoking, and body mass index.

Patients with MS had a 20% increased risk for earlier onset of hyperlipidemia, relative to matched controls. The effect was greater among females (hazard ratio, 1.22) and African Americans (HR, 1.42). Patients with MS have earlier onset of hyperlipidemia “irrespective of the relationship with age of MS onset,” Dr. Krill and colleagues noted. “Additional research is warranted to further characterize the temporal relationships between MS and hyperlipidemia, as well as considerations for timing of disease-modifying therapies.”

The researchers had no relevant disclosures.

[email protected]

SOURCE: Krill D et al. ACTRIMS Forum 2020, Abstract P085.

WEST PALM BEACH, FLA. – Onset of hyperlipidemia tends to occur earlier in patients with multiple sclerosis (MS), compared with matched controls, according to new research. Among females and African Americans, the effect of MS on age of hyperlipidemia onset may be especially pronounced, said Diane Krill, PhD, professor of biological sciences at Point Park University, Pittsburgh, and colleagues.

Ugreen/thinkstockphotos

Many patients with MS have hyperlipidemia, and adverse lipid profiles correlate with physical and cognitive impairment in this population. “There is evidence of endothelial dysfunction and inflammation in both MS and hyperlipidemia, but the timing of onset of hyperlipidemia is not known,” the researchers said at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.

To assess whether patients with MS have hyperlipidemia diagnosed at an earlier age, relative to matched controls, Dr. Krill and colleagues analyzed data from the Cleveland Clinic health system. They included in their analyses patients with at least two hyperlipidemia diagnoses and at least five encounters with a primary care physician. They matched each patient with MS to four patients without MS using variables such as birth year, sex, race, and year of first encounter. In all, the study included 669 patients with MS and 2,676 controls. The investigators examined age of hyperlipidemia onset using multivariable Cox proportional hazard models that adjusted for sex, race, smoking, and body mass index.

Patients with MS had a 20% increased risk for earlier onset of hyperlipidemia, relative to matched controls. The effect was greater among females (hazard ratio, 1.22) and African Americans (HR, 1.42). Patients with MS have earlier onset of hyperlipidemia “irrespective of the relationship with age of MS onset,” Dr. Krill and colleagues noted. “Additional research is warranted to further characterize the temporal relationships between MS and hyperlipidemia, as well as considerations for timing of disease-modifying therapies.”

The researchers had no relevant disclosures.

[email protected]

SOURCE: Krill D et al. ACTRIMS Forum 2020, Abstract P085.

WEST PALM BEACH, FLA. – Onset of hyperlipidemia tends to occur earlier in patients with multiple sclerosis (MS), compared with matched controls, according to new research. Among females and African Americans, the effect of MS on age of hyperlipidemia onset may be especially pronounced, said Diane Krill, PhD, professor of biological sciences at Point Park University, Pittsburgh, and colleagues.

Ugreen/thinkstockphotos

Many patients with MS have hyperlipidemia, and adverse lipid profiles correlate with physical and cognitive impairment in this population. “There is evidence of endothelial dysfunction and inflammation in both MS and hyperlipidemia, but the timing of onset of hyperlipidemia is not known,” the researchers said at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.

To assess whether patients with MS have hyperlipidemia diagnosed at an earlier age, relative to matched controls, Dr. Krill and colleagues analyzed data from the Cleveland Clinic health system. They included in their analyses patients with at least two hyperlipidemia diagnoses and at least five encounters with a primary care physician. They matched each patient with MS to four patients without MS using variables such as birth year, sex, race, and year of first encounter. In all, the study included 669 patients with MS and 2,676 controls. The investigators examined age of hyperlipidemia onset using multivariable Cox proportional hazard models that adjusted for sex, race, smoking, and body mass index.

Patients with MS had a 20% increased risk for earlier onset of hyperlipidemia, relative to matched controls. The effect was greater among females (hazard ratio, 1.22) and African Americans (HR, 1.42). Patients with MS have earlier onset of hyperlipidemia “irrespective of the relationship with age of MS onset,” Dr. Krill and colleagues noted. “Additional research is warranted to further characterize the temporal relationships between MS and hyperlipidemia, as well as considerations for timing of disease-modifying therapies.”

The researchers had no relevant disclosures.

[email protected]

SOURCE: Krill D et al. ACTRIMS Forum 2020, Abstract P085.

Treatment with the antifungal agent terbinafine during pregnancy does not appear to increase the risk of major malformations or spontaneous abortions, according to results from a large registry study in Denmark.

digitalskillet/Thinkstock

Physicians have been reluctant to prescribe the drug during pregnancy because of the limited safety data. The drug has not been associated with any signs of fetal toxicity in animal studies, but only one study – in 54 pregnancies – has examined the issue in humans and did not identify an increased fetal risk, according to Niklas Worm Andersson, MD, of the department of clinical pharmacology, Copenhagen University Hospital at Bispebjerg and Frederiksberg, and coauthors.

The retrospective, nationwide cohort study analyzed exposure to oral and tropical terbinafine in a large pregnancy registry and found no increase in the risk of major malformations or spontaneous abortions in exposed versus unexposed pregnancies. The study was published in JAMA Dermatology.

Still, these results fell short of certainty, the authors noted. “Although our results may provide reassurance for pregnancies exposed to oral terbinafine by reporting no overall increased risk of major malformations, we cannot exclude a potential increased risk of a specific malformation,” they wrote.

“To our knowledge, this is by far the largest, most statistically rigorous study in the literature regarding this topic,” Jenny E. Murase, MD, of the department of dermatology at the University of California, San Francisco, and Mary Kathryn Abel, a medical student at UCSF, wrote in an accompanying editorial. They described the study as “a substantial contribution to the nearly absent literature regarding the use of terbinafine during pregnancy. Among the antifungal medications, it is possible that terbinafine is the safest one currently available for use in pregnancy, particularly of the oral formulations.”

However, since asymptomatic onychomycosis “is typically a cosmetic, rather than medical, concern, waiting until after pregnancy to initiate therapy is reasonable. ... It is important to acknowledge the uncertainty in this field and question the appropriateness of treating non–life-threatening diseases during pregnancy and lactation,” they wrote.

The Danish researchers drew from a registry of 1,650,649 pregnancies between 1997 and 2016, which included 891 pregnancies exposed to oral terbinafine, and 3,174 exposed to topical terbinafine. Matched outcome analyses compared the exposed pregnancies with up to 40,650 controls unexposed during pregnancy.

Propensity-matched comparisons showed no increased risk of major malformations for oral terbinafine exposure versus no exposure (odds ratio, 1.01; 95% confidence interval, 0.63-1.62) or topical exposure versus no exposure (OR, 1.08; 95% CI, 0.81-1.44). There was also no difference in oral versus topical exposure (OR, 1.18; 95% CI, 0.61-2.29).

iStock

With respect to spontaneous abortions, there was no significant association with oral terbinafine (hazard ratio, 1.06; 95% CI, 0.86-1.32) or topical terbinafine (HR, 1.04; 95% CI, 0.88-1.21), compared with unexposed pregnancies, or oral over topical terbinafine-exposed pregnancies (HR, 1.19; 95% CI, 0.84-1.70).

The study is limited by the fact that it was conducted in a Danish population, and the data relied on filled prescriptions for determining exposure, which did not account for adherence. Residual confounding is possible because of the retrospective nature of the study, the authors pointed out.

No source of funding was disclosed. One of the authors has received grants and personal fees from Novartis. Dr. Murase has received fees from Sanofi Genzyme, Dermira, UCB, Regeneron, Ferndale, and UpToDate.
 

SOURCES: Andersson NW et al. JAMA Dermatol. 2020 Mar 4. doi: 10.1001/jamadermatol.2020.0142; Murase JE, Abel MK. JAMA Dermatol. 2020 Mar 4. doi: 10.1001/jamadermatol.2019.5036.

Treatment with the antifungal agent terbinafine during pregnancy does not appear to increase the risk of major malformations or spontaneous abortions, according to results from a large registry study in Denmark.

digitalskillet/Thinkstock

Physicians have been reluctant to prescribe the drug during pregnancy because of the limited safety data. The drug has not been associated with any signs of fetal toxicity in animal studies, but only one study – in 54 pregnancies – has examined the issue in humans and did not identify an increased fetal risk, according to Niklas Worm Andersson, MD, of the department of clinical pharmacology, Copenhagen University Hospital at Bispebjerg and Frederiksberg, and coauthors.

The retrospective, nationwide cohort study analyzed exposure to oral and tropical terbinafine in a large pregnancy registry and found no increase in the risk of major malformations or spontaneous abortions in exposed versus unexposed pregnancies. The study was published in JAMA Dermatology.

Still, these results fell short of certainty, the authors noted. “Although our results may provide reassurance for pregnancies exposed to oral terbinafine by reporting no overall increased risk of major malformations, we cannot exclude a potential increased risk of a specific malformation,” they wrote.

“To our knowledge, this is by far the largest, most statistically rigorous study in the literature regarding this topic,” Jenny E. Murase, MD, of the department of dermatology at the University of California, San Francisco, and Mary Kathryn Abel, a medical student at UCSF, wrote in an accompanying editorial. They described the study as “a substantial contribution to the nearly absent literature regarding the use of terbinafine during pregnancy. Among the antifungal medications, it is possible that terbinafine is the safest one currently available for use in pregnancy, particularly of the oral formulations.”

However, since asymptomatic onychomycosis “is typically a cosmetic, rather than medical, concern, waiting until after pregnancy to initiate therapy is reasonable. ... It is important to acknowledge the uncertainty in this field and question the appropriateness of treating non–life-threatening diseases during pregnancy and lactation,” they wrote.

The Danish researchers drew from a registry of 1,650,649 pregnancies between 1997 and 2016, which included 891 pregnancies exposed to oral terbinafine, and 3,174 exposed to topical terbinafine. Matched outcome analyses compared the exposed pregnancies with up to 40,650 controls unexposed during pregnancy.

Propensity-matched comparisons showed no increased risk of major malformations for oral terbinafine exposure versus no exposure (odds ratio, 1.01; 95% confidence interval, 0.63-1.62) or topical exposure versus no exposure (OR, 1.08; 95% CI, 0.81-1.44). There was also no difference in oral versus topical exposure (OR, 1.18; 95% CI, 0.61-2.29).

iStock

With respect to spontaneous abortions, there was no significant association with oral terbinafine (hazard ratio, 1.06; 95% CI, 0.86-1.32) or topical terbinafine (HR, 1.04; 95% CI, 0.88-1.21), compared with unexposed pregnancies, or oral over topical terbinafine-exposed pregnancies (HR, 1.19; 95% CI, 0.84-1.70).

The study is limited by the fact that it was conducted in a Danish population, and the data relied on filled prescriptions for determining exposure, which did not account for adherence. Residual confounding is possible because of the retrospective nature of the study, the authors pointed out.

No source of funding was disclosed. One of the authors has received grants and personal fees from Novartis. Dr. Murase has received fees from Sanofi Genzyme, Dermira, UCB, Regeneron, Ferndale, and UpToDate.
 

SOURCES: Andersson NW et al. JAMA Dermatol. 2020 Mar 4. doi: 10.1001/jamadermatol.2020.0142; Murase JE, Abel MK. JAMA Dermatol. 2020 Mar 4. doi: 10.1001/jamadermatol.2019.5036.

Treatment with the antifungal agent terbinafine during pregnancy does not appear to increase the risk of major malformations or spontaneous abortions, according to results from a large registry study in Denmark.

digitalskillet/Thinkstock

Physicians have been reluctant to prescribe the drug during pregnancy because of the limited safety data. The drug has not been associated with any signs of fetal toxicity in animal studies, but only one study – in 54 pregnancies – has examined the issue in humans and did not identify an increased fetal risk, according to Niklas Worm Andersson, MD, of the department of clinical pharmacology, Copenhagen University Hospital at Bispebjerg and Frederiksberg, and coauthors.

The retrospective, nationwide cohort study analyzed exposure to oral and tropical terbinafine in a large pregnancy registry and found no increase in the risk of major malformations or spontaneous abortions in exposed versus unexposed pregnancies. The study was published in JAMA Dermatology.

Still, these results fell short of certainty, the authors noted. “Although our results may provide reassurance for pregnancies exposed to oral terbinafine by reporting no overall increased risk of major malformations, we cannot exclude a potential increased risk of a specific malformation,” they wrote.

“To our knowledge, this is by far the largest, most statistically rigorous study in the literature regarding this topic,” Jenny E. Murase, MD, of the department of dermatology at the University of California, San Francisco, and Mary Kathryn Abel, a medical student at UCSF, wrote in an accompanying editorial. They described the study as “a substantial contribution to the nearly absent literature regarding the use of terbinafine during pregnancy. Among the antifungal medications, it is possible that terbinafine is the safest one currently available for use in pregnancy, particularly of the oral formulations.”

However, since asymptomatic onychomycosis “is typically a cosmetic, rather than medical, concern, waiting until after pregnancy to initiate therapy is reasonable. ... It is important to acknowledge the uncertainty in this field and question the appropriateness of treating non–life-threatening diseases during pregnancy and lactation,” they wrote.

The Danish researchers drew from a registry of 1,650,649 pregnancies between 1997 and 2016, which included 891 pregnancies exposed to oral terbinafine, and 3,174 exposed to topical terbinafine. Matched outcome analyses compared the exposed pregnancies with up to 40,650 controls unexposed during pregnancy.

Propensity-matched comparisons showed no increased risk of major malformations for oral terbinafine exposure versus no exposure (odds ratio, 1.01; 95% confidence interval, 0.63-1.62) or topical exposure versus no exposure (OR, 1.08; 95% CI, 0.81-1.44). There was also no difference in oral versus topical exposure (OR, 1.18; 95% CI, 0.61-2.29).

iStock

With respect to spontaneous abortions, there was no significant association with oral terbinafine (hazard ratio, 1.06; 95% CI, 0.86-1.32) or topical terbinafine (HR, 1.04; 95% CI, 0.88-1.21), compared with unexposed pregnancies, or oral over topical terbinafine-exposed pregnancies (HR, 1.19; 95% CI, 0.84-1.70).

The study is limited by the fact that it was conducted in a Danish population, and the data relied on filled prescriptions for determining exposure, which did not account for adherence. Residual confounding is possible because of the retrospective nature of the study, the authors pointed out.

No source of funding was disclosed. One of the authors has received grants and personal fees from Novartis. Dr. Murase has received fees from Sanofi Genzyme, Dermira, UCB, Regeneron, Ferndale, and UpToDate.
 

SOURCES: Andersson NW et al. JAMA Dermatol. 2020 Mar 4. doi: 10.1001/jamadermatol.2020.0142; Murase JE, Abel MK. JAMA Dermatol. 2020 Mar 4. doi: 10.1001/jamadermatol.2019.5036.

Molecularly guided treatments may extend survival by more than a year for patients with pancreatic cancer who have actionable molecular alterations, according to a retrospective analysis of almost 2,000 patients in the Know Your Tumor registry.

While patients with actionable alterations remain in the minority, experts suggest the study’s results provide a ray of hope for treating a cancer that has historically been associated with a poor prognosis and disappointing clinical trials.

Patients with actionable molecular alterations who received matched therapies had a median overall survival of 2.58 years, compared with 1.51 years for those who received unmatched therapies, reported lead author Michael J. Pishvaian, MD, PhD, of MD Anderson Cancer Center in Houston, and colleagues.

“Our study provides strong rationale that tumor-based molecular profiling for patients with pancreatic cancer should be routinely performed and encourages prospective clinical trials based on this or similar platforms,” the investigators wrote in Lancet Oncology.

In an accompanying comment, Jörg Kleeff, MD, and Christoph W. Michalski, MD, of Martin-Luther University Halle-Wittenberg in Germany, supported this conclusion, calling the study “an encouraging starting point for a structured investigation of molecularly matched therapies.”

The authors also highlighted the untapped potential the trial uncovered, noting that only 4% of patients received a molecularly matched therapy, even though one-quarter had actionable alterations.

“These findings are important in that they define an estimation of the current number of potentially actionable targets and in that they provide a – rather disappointing – real-world assessment of the number of patients who actually received molecularly targeted treatment,” Dr. Kleeff and Dr. Michalski wrote.

They went on to describe a list of unanswered questions in the field, ranging from ethical dilemmas that may be encountered when choosing between targeted trials and chemotherapy for patients with targetable alterations, to more tangible subjects, such as genome sequencing techniques and therapeutic timing.

Their comment and the related study were published simultaneously with a series of pancreatic cancer articles in Lancet journals, which includes:

• A review outlining current and emerging therapies (Lancet Oncol. 2020 Mar;21[3]:e135-e145).
• A review of information on the metastatic cascade (EBioMedicine. 2020 Feb 28:102662. doi: 10.1016/j.ebiom.2020.102662).
• A review of disease biology (EBioMedicine. 2020 Feb 28:102655. doi: 10.1016/j.ebiom.2020.102655).
• A review of early detection strategies (Lancet Gastroenterol Hepatol. 2020 Mar 2. pii: S2468-1253[19]30416-9).

According to the authors of the therapeutic review, treatments for pancreatic cancer have “a bright future.”

“There is more optimism now than ever before that advances will be made by combining chemotherapy more effectively with agents that target the unique features of pancreatic ductal adenocarcinoma tumors,” the authors wrote. “The next 5-10 years should deliver major improvements in outcomes through the use of novel agents that specifically target pathological signaling pathways and genetic alterations.”

In an interview, Dana B. Cardin, MD, of the Vanderbilt-Ingram Cancer Center in Nashville, Tenn., shared this favorable outlook, which she said is particularly needed for a condition that has generally been left behind by the new era of personalized oncology treatments.

“There’s been a lot of frustration on the part of patients and doctors and everyone in the research community that there have been a lot of other tumor types [in which] learning about genetic changes in cancer cells has really revolutionized how patients are being treated,” Dr. Cardin said. “That is something that has really been elusive in pancreas cancer.”

The retrospective study by Dr. Pishvaian and colleagues serves as proof-of-concept by showing that large-scale genomic testing can also identify personalized treatments for patients with pancreatic cancer, Dr. Cardin said.

“When you do find them, even when it’s a small percentage of patients that may have actionable mutations, it really can make a huge difference in the outcomes for those patients,” she said. “We have to get rid of this sense of futility. If you’re not trying to look for those things, then you’re not ever going to find them.”

Regardless of whether a personalized treatment is available for a particular patient, Dr. Cardin emphasized the importance of a positive and active clinical mindset, as data suggest that existing supportive strategies can have a significant impact on patient health.

“We can make a difference for these patients,” Dr. Cardin said, “but we’re only going to make a difference if we try.”

Dr. Cardin, a National Comprehensive Cancer Network panelist for pancreatic cancer, went on to explain how outcomes in the control arm of pancreatic cancer clinical trials have been improving over the past decade, even though the standard control drug, gemcitabine, has stayed the same.

“It doesn’t mean that gemcitabine is better than it used to be,” Dr. Cardin said. “It probably means that we’re treating more patients, and we’re also doing a better job of supporting those patients.” She identified growth factors, nutritional support, and enzyme supplements as key ancillary treatments for those who need them.

Dr. Pishvaian and colleagues’ study was funded by Pancreatic Cancer Action Network and Perthera. The investigators disclosed relationships with Perthera and other companies. Dr. Kleeff, Dr. Michalski, and Dr. Cardin declared no conflicts of interest.

SOURCES: Pishvaian MJ et al. Lancet Oncol. 2020 Mar 2. doi: 10.1016/S1470-2045(20)30074-7; Kleeff J et al. Lancet Oncol. 2020 Mar 2. doi: 10.1016/S1470-2045(20)30148-0; Christenson ES et al. Lancet Oncol. 2020 Mar 2. doi: 10.1016/S1470-2045(19)30795-8.

Molecularly guided treatments may extend survival by more than a year for patients with pancreatic cancer who have actionable molecular alterations, according to a retrospective analysis of almost 2,000 patients in the Know Your Tumor registry.

While patients with actionable alterations remain in the minority, experts suggest the study’s results provide a ray of hope for treating a cancer that has historically been associated with a poor prognosis and disappointing clinical trials.

Patients with actionable molecular alterations who received matched therapies had a median overall survival of 2.58 years, compared with 1.51 years for those who received unmatched therapies, reported lead author Michael J. Pishvaian, MD, PhD, of MD Anderson Cancer Center in Houston, and colleagues.

“Our study provides strong rationale that tumor-based molecular profiling for patients with pancreatic cancer should be routinely performed and encourages prospective clinical trials based on this or similar platforms,” the investigators wrote in Lancet Oncology.

In an accompanying comment, Jörg Kleeff, MD, and Christoph W. Michalski, MD, of Martin-Luther University Halle-Wittenberg in Germany, supported this conclusion, calling the study “an encouraging starting point for a structured investigation of molecularly matched therapies.”

The authors also highlighted the untapped potential the trial uncovered, noting that only 4% of patients received a molecularly matched therapy, even though one-quarter had actionable alterations.

“These findings are important in that they define an estimation of the current number of potentially actionable targets and in that they provide a – rather disappointing – real-world assessment of the number of patients who actually received molecularly targeted treatment,” Dr. Kleeff and Dr. Michalski wrote.

They went on to describe a list of unanswered questions in the field, ranging from ethical dilemmas that may be encountered when choosing between targeted trials and chemotherapy for patients with targetable alterations, to more tangible subjects, such as genome sequencing techniques and therapeutic timing.

Their comment and the related study were published simultaneously with a series of pancreatic cancer articles in Lancet journals, which includes:

• A review outlining current and emerging therapies (Lancet Oncol. 2020 Mar;21[3]:e135-e145).
• A review of information on the metastatic cascade (EBioMedicine. 2020 Feb 28:102662. doi: 10.1016/j.ebiom.2020.102662).
• A review of disease biology (EBioMedicine. 2020 Feb 28:102655. doi: 10.1016/j.ebiom.2020.102655).
• A review of early detection strategies (Lancet Gastroenterol Hepatol. 2020 Mar 2. pii: S2468-1253[19]30416-9).

According to the authors of the therapeutic review, treatments for pancreatic cancer have “a bright future.”

“There is more optimism now than ever before that advances will be made by combining chemotherapy more effectively with agents that target the unique features of pancreatic ductal adenocarcinoma tumors,” the authors wrote. “The next 5-10 years should deliver major improvements in outcomes through the use of novel agents that specifically target pathological signaling pathways and genetic alterations.”

In an interview, Dana B. Cardin, MD, of the Vanderbilt-Ingram Cancer Center in Nashville, Tenn., shared this favorable outlook, which she said is particularly needed for a condition that has generally been left behind by the new era of personalized oncology treatments.

“There’s been a lot of frustration on the part of patients and doctors and everyone in the research community that there have been a lot of other tumor types [in which] learning about genetic changes in cancer cells has really revolutionized how patients are being treated,” Dr. Cardin said. “That is something that has really been elusive in pancreas cancer.”

The retrospective study by Dr. Pishvaian and colleagues serves as proof-of-concept by showing that large-scale genomic testing can also identify personalized treatments for patients with pancreatic cancer, Dr. Cardin said.

“When you do find them, even when it’s a small percentage of patients that may have actionable mutations, it really can make a huge difference in the outcomes for those patients,” she said. “We have to get rid of this sense of futility. If you’re not trying to look for those things, then you’re not ever going to find them.”

Regardless of whether a personalized treatment is available for a particular patient, Dr. Cardin emphasized the importance of a positive and active clinical mindset, as data suggest that existing supportive strategies can have a significant impact on patient health.

“We can make a difference for these patients,” Dr. Cardin said, “but we’re only going to make a difference if we try.”

Dr. Cardin, a National Comprehensive Cancer Network panelist for pancreatic cancer, went on to explain how outcomes in the control arm of pancreatic cancer clinical trials have been improving over the past decade, even though the standard control drug, gemcitabine, has stayed the same.

“It doesn’t mean that gemcitabine is better than it used to be,” Dr. Cardin said. “It probably means that we’re treating more patients, and we’re also doing a better job of supporting those patients.” She identified growth factors, nutritional support, and enzyme supplements as key ancillary treatments for those who need them.

Dr. Pishvaian and colleagues’ study was funded by Pancreatic Cancer Action Network and Perthera. The investigators disclosed relationships with Perthera and other companies. Dr. Kleeff, Dr. Michalski, and Dr. Cardin declared no conflicts of interest.

SOURCES: Pishvaian MJ et al. Lancet Oncol. 2020 Mar 2. doi: 10.1016/S1470-2045(20)30074-7; Kleeff J et al. Lancet Oncol. 2020 Mar 2. doi: 10.1016/S1470-2045(20)30148-0; Christenson ES et al. Lancet Oncol. 2020 Mar 2. doi: 10.1016/S1470-2045(19)30795-8.

Molecularly guided treatments may extend survival by more than a year for patients with pancreatic cancer who have actionable molecular alterations, according to a retrospective analysis of almost 2,000 patients in the Know Your Tumor registry.

While patients with actionable alterations remain in the minority, experts suggest the study’s results provide a ray of hope for treating a cancer that has historically been associated with a poor prognosis and disappointing clinical trials.

Patients with actionable molecular alterations who received matched therapies had a median overall survival of 2.58 years, compared with 1.51 years for those who received unmatched therapies, reported lead author Michael J. Pishvaian, MD, PhD, of MD Anderson Cancer Center in Houston, and colleagues.

“Our study provides strong rationale that tumor-based molecular profiling for patients with pancreatic cancer should be routinely performed and encourages prospective clinical trials based on this or similar platforms,” the investigators wrote in Lancet Oncology.

In an accompanying comment, Jörg Kleeff, MD, and Christoph W. Michalski, MD, of Martin-Luther University Halle-Wittenberg in Germany, supported this conclusion, calling the study “an encouraging starting point for a structured investigation of molecularly matched therapies.”

The authors also highlighted the untapped potential the trial uncovered, noting that only 4% of patients received a molecularly matched therapy, even though one-quarter had actionable alterations.

“These findings are important in that they define an estimation of the current number of potentially actionable targets and in that they provide a – rather disappointing – real-world assessment of the number of patients who actually received molecularly targeted treatment,” Dr. Kleeff and Dr. Michalski wrote.

They went on to describe a list of unanswered questions in the field, ranging from ethical dilemmas that may be encountered when choosing between targeted trials and chemotherapy for patients with targetable alterations, to more tangible subjects, such as genome sequencing techniques and therapeutic timing.

Their comment and the related study were published simultaneously with a series of pancreatic cancer articles in Lancet journals, which includes:

• A review outlining current and emerging therapies (Lancet Oncol. 2020 Mar;21[3]:e135-e145).
• A review of information on the metastatic cascade (EBioMedicine. 2020 Feb 28:102662. doi: 10.1016/j.ebiom.2020.102662).
• A review of disease biology (EBioMedicine. 2020 Feb 28:102655. doi: 10.1016/j.ebiom.2020.102655).
• A review of early detection strategies (Lancet Gastroenterol Hepatol. 2020 Mar 2. pii: S2468-1253[19]30416-9).

According to the authors of the therapeutic review, treatments for pancreatic cancer have “a bright future.”

“There is more optimism now than ever before that advances will be made by combining chemotherapy more effectively with agents that target the unique features of pancreatic ductal adenocarcinoma tumors,” the authors wrote. “The next 5-10 years should deliver major improvements in outcomes through the use of novel agents that specifically target pathological signaling pathways and genetic alterations.”

In an interview, Dana B. Cardin, MD, of the Vanderbilt-Ingram Cancer Center in Nashville, Tenn., shared this favorable outlook, which she said is particularly needed for a condition that has generally been left behind by the new era of personalized oncology treatments.

“There’s been a lot of frustration on the part of patients and doctors and everyone in the research community that there have been a lot of other tumor types [in which] learning about genetic changes in cancer cells has really revolutionized how patients are being treated,” Dr. Cardin said. “That is something that has really been elusive in pancreas cancer.”

The retrospective study by Dr. Pishvaian and colleagues serves as proof-of-concept by showing that large-scale genomic testing can also identify personalized treatments for patients with pancreatic cancer, Dr. Cardin said.

“When you do find them, even when it’s a small percentage of patients that may have actionable mutations, it really can make a huge difference in the outcomes for those patients,” she said. “We have to get rid of this sense of futility. If you’re not trying to look for those things, then you’re not ever going to find them.”

Regardless of whether a personalized treatment is available for a particular patient, Dr. Cardin emphasized the importance of a positive and active clinical mindset, as data suggest that existing supportive strategies can have a significant impact on patient health.

“We can make a difference for these patients,” Dr. Cardin said, “but we’re only going to make a difference if we try.”

Dr. Cardin, a National Comprehensive Cancer Network panelist for pancreatic cancer, went on to explain how outcomes in the control arm of pancreatic cancer clinical trials have been improving over the past decade, even though the standard control drug, gemcitabine, has stayed the same.

“It doesn’t mean that gemcitabine is better than it used to be,” Dr. Cardin said. “It probably means that we’re treating more patients, and we’re also doing a better job of supporting those patients.” She identified growth factors, nutritional support, and enzyme supplements as key ancillary treatments for those who need them.

Dr. Pishvaian and colleagues’ study was funded by Pancreatic Cancer Action Network and Perthera. The investigators disclosed relationships with Perthera and other companies. Dr. Kleeff, Dr. Michalski, and Dr. Cardin declared no conflicts of interest.

SOURCES: Pishvaian MJ et al. Lancet Oncol. 2020 Mar 2. doi: 10.1016/S1470-2045(20)30074-7; Kleeff J et al. Lancet Oncol. 2020 Mar 2. doi: 10.1016/S1470-2045(20)30148-0; Christenson ES et al. Lancet Oncol. 2020 Mar 2. doi: 10.1016/S1470-2045(19)30795-8.

Coronavirus fever is gripping the world. What I hope to do here is open a discussion of what psychiatrists and other clinicians can do to mitigate the psychological consequences of COVID-19. I am focusing on the right now.

The psychological consequences are fear of the disease, effects of possible quarantine, and the potential effects of the economic slowdown on the world economy.

Fear of the disease is gripping the nation. With invisible diseases, that is not irrational. If you do not know whether you are exposed and/or spreading it to coworkers, children, or aged parents, then the fear of contagion is logical. So I would not “poo-poo” the “worried well.” If you do not know whether you are exposed or contagious, anxiety is a legitimate concern – especially if you have parents in nursing homes.

The quarantine issue is harder. I have long thought that quarantine would be harder to implement in the United States than in nations like China. But self or home quarantine is currently the de facto solution for those who have been exposed. What are some remedies?

For everybody, having an adequate supply of basic supplies at home is essential. As in preparing for a snowstorm or hurricane, adequate food, water, and yes, toilet paper, is important to relieve anxiety.

Psychiatrists can encourage patients to have an adequate supply of their medications. That may mean that we prescribe more pills. If the patient has suicidal tendencies, we can ask other family members to safeguard those medications.

A salient question is how likely people who are addicted to alcohol or opiates are to stay in place if they are withdrawing. In previous presentations, delivered some 20 years ago, I have (facetiously) suggested horse-drawn wagons of beer to avoid people breaking quarantine in search of the substances they are physically dependent on.

For people in methadone clinics who require daily visits that kind of approach may be harder. I do not have a solution, other than to plan for the eventuality of large-scale withdrawal and the behavioral consequences, which, unfortunately, often involve crime. Telemedicine may be a solution, but we are not yet equipped for it.

The longer-term psychological impacts of a major economic slowdown are not yet known. Based on past epidemics and other disasters, they might include unemployment and the related consequences of domestic violence and suicide.

COVID-19 is spreading fast. As clinicians, we must take steps to protect ourselves and our patients. Because this is a new virus, we have a lot to learn about it. We must be agile, because our actions will need to change over time.

Dr. Ritchie is chair of psychiatry at Medstar Washington Hospital Center and professor of psychiatry at Georgetown University, Washington.

Coronavirus fever is gripping the world. What I hope to do here is open a discussion of what psychiatrists and other clinicians can do to mitigate the psychological consequences of COVID-19. I am focusing on the right now.

The psychological consequences are fear of the disease, effects of possible quarantine, and the potential effects of the economic slowdown on the world economy.

Fear of the disease is gripping the nation. With invisible diseases, that is not irrational. If you do not know whether you are exposed and/or spreading it to coworkers, children, or aged parents, then the fear of contagion is logical. So I would not “poo-poo” the “worried well.” If you do not know whether you are exposed or contagious, anxiety is a legitimate concern – especially if you have parents in nursing homes.

The quarantine issue is harder. I have long thought that quarantine would be harder to implement in the United States than in nations like China. But self or home quarantine is currently the de facto solution for those who have been exposed. What are some remedies?

For everybody, having an adequate supply of basic supplies at home is essential. As in preparing for a snowstorm or hurricane, adequate food, water, and yes, toilet paper, is important to relieve anxiety.

Psychiatrists can encourage patients to have an adequate supply of their medications. That may mean that we prescribe more pills. If the patient has suicidal tendencies, we can ask other family members to safeguard those medications.

A salient question is how likely people who are addicted to alcohol or opiates are to stay in place if they are withdrawing. In previous presentations, delivered some 20 years ago, I have (facetiously) suggested horse-drawn wagons of beer to avoid people breaking quarantine in search of the substances they are physically dependent on.

For people in methadone clinics who require daily visits that kind of approach may be harder. I do not have a solution, other than to plan for the eventuality of large-scale withdrawal and the behavioral consequences, which, unfortunately, often involve crime. Telemedicine may be a solution, but we are not yet equipped for it.

The longer-term psychological impacts of a major economic slowdown are not yet known. Based on past epidemics and other disasters, they might include unemployment and the related consequences of domestic violence and suicide.

COVID-19 is spreading fast. As clinicians, we must take steps to protect ourselves and our patients. Because this is a new virus, we have a lot to learn about it. We must be agile, because our actions will need to change over time.

Dr. Ritchie is chair of psychiatry at Medstar Washington Hospital Center and professor of psychiatry at Georgetown University, Washington.

Coronavirus fever is gripping the world. What I hope to do here is open a discussion of what psychiatrists and other clinicians can do to mitigate the psychological consequences of COVID-19. I am focusing on the right now.

The psychological consequences are fear of the disease, effects of possible quarantine, and the potential effects of the economic slowdown on the world economy.

Fear of the disease is gripping the nation. With invisible diseases, that is not irrational. If you do not know whether you are exposed and/or spreading it to coworkers, children, or aged parents, then the fear of contagion is logical. So I would not “poo-poo” the “worried well.” If you do not know whether you are exposed or contagious, anxiety is a legitimate concern – especially if you have parents in nursing homes.

The quarantine issue is harder. I have long thought that quarantine would be harder to implement in the United States than in nations like China. But self or home quarantine is currently the de facto solution for those who have been exposed. What are some remedies?

For everybody, having an adequate supply of basic supplies at home is essential. As in preparing for a snowstorm or hurricane, adequate food, water, and yes, toilet paper, is important to relieve anxiety.

Psychiatrists can encourage patients to have an adequate supply of their medications. That may mean that we prescribe more pills. If the patient has suicidal tendencies, we can ask other family members to safeguard those medications.

A salient question is how likely people who are addicted to alcohol or opiates are to stay in place if they are withdrawing. In previous presentations, delivered some 20 years ago, I have (facetiously) suggested horse-drawn wagons of beer to avoid people breaking quarantine in search of the substances they are physically dependent on.

For people in methadone clinics who require daily visits that kind of approach may be harder. I do not have a solution, other than to plan for the eventuality of large-scale withdrawal and the behavioral consequences, which, unfortunately, often involve crime. Telemedicine may be a solution, but we are not yet equipped for it.

The longer-term psychological impacts of a major economic slowdown are not yet known. Based on past epidemics and other disasters, they might include unemployment and the related consequences of domestic violence and suicide.

COVID-19 is spreading fast. As clinicians, we must take steps to protect ourselves and our patients. Because this is a new virus, we have a lot to learn about it. We must be agile, because our actions will need to change over time.

Dr. Ritchie is chair of psychiatry at Medstar Washington Hospital Center and professor of psychiatry at Georgetown University, Washington.

A patient with HIV remission induced by stem cell transplantation continues to be disease free at the 30-month mark.

The individual, referred to as the London patient, received allogeneic hematopoietic stem cell transplantation (allo-HSCT) for stage IVB Hodgkin lymphoma. The transplant donor was homozygous for the CCR5 delta-32 mutation, which confers immunity to HIV because there’s no point of entry for the virus into immune cells.

After extensive sampling of various tissues, including gut, lymph node, blood, semen, and cerebrospinal fluid (CSF), Ravindra Kumar Gupta, MD, PhD, and colleagues found no detectable virus that was competent to replicate. However, they reported that the testing did detect some “fossilized” remnants of HIV DNA persisting in certain tissues.

The results were shared in a video presentation of the research during the Conference on Retroviruses & Opportunistic Infections, which was presented online this year. CROI organizers chose to hold a virtual meeting because of concerns about the spread of COVID-19.

The London patient’s HIV status had been reported the previous year at CROI 2019, but only blood samples were used in that analysis.

In a commentary accompanying the simultaneously published study in the Lancet, Jennifer Zerbato, PhD, and Sharon Lewin, FRACP, PHD, FAAHMS, asked: “A key question now for the area of HIV cure is how soon can one know if someone has been cured of HIV?

“We will need more than a handful of patients cured of HIV to really understand the duration of follow-up needed and the likelihood of an unexpected late rebound in virus replication,” continued Dr. Zerbato, of the University of Melbourne, and Dr. Lewin, of the Royal Melbourne Hospital and Monash University, also in Melbourne.

In their ongoing analysis of data from the London patient, Dr. Gupta, a virologist at the University of Cambridge (England), and associates constructed a mathematical model that maps the probability for lifetime remission or cure of HIV against several factors, including the degree of chimerism achieved with the stem cell transplant.

In this model, when chimerism reaches 80% in total HIV target cells, the probability of remission for life is 98%; when donor chimerism reaches 90%, the probability of lifetime remission is greater than 99%. Peripheral T-cell chimerism in the London patient has held steady at 99%.

Dr. Gupta and associates obtained some testing opportunistically: A PET-CT scan revealed an axillary lymph node that was biopsied after it was found to have avid radiotracer uptake. Similarly, the CSF sample was obtained in the course of a work-up for some neurologic symptoms that the London patient was having.

In contrast to the first patient who achieved ongoing HIV remission from a pair of stem cell transplants received over 13 years ago – the Berlin patient – the London patient did not receive whole-body radiation, but rather underwent a reduced-intensity conditioning regimen. The London patient experienced a bout of gut graft-versus-host disease (GVHD) about 2 months after his transplant, but has been free of GVHD in the interval. He hasn’t taken cytotoxic agents or any GVHD prophylaxis since 6 months post transplant.

Though there’s no sign of HIV that’s competent to replicate, “the London patient has shown somewhat slow CD4 reconstitution,” said Dr. Gupta and coauthors in discussing the results.

The patient had a reactivation of Epstein-Barr virus (EBV) about 21 months after analytic treatment interruption (ATI) of antiretroviral therapy that was managed without any specific treatment, but he hasn’t experienced any opportunistic infections. However, his CD4 count didn’t rebound to pretransplant levels until 28 months after ATI. At that point, his CD4 count was 430 cells per mcL, or 23.5% of total T cells. The CD4:CD8 ratio was 0.86; normal range is 1.5-2.5.

The researchers used quantitative real-time polymerase chain reaction (rt-PCR) to look for packaging site and envelope (env) DNA fragments, and droplet digital PCR to quantify HIV-1 DNA.

The patient’s HIV-1 plasma load measured at 30 months post ATI on an ultrasensitive assay was below the lower limit of detection (less than 1 copy per mL). Semen viremia measured at 21 months was also below the lower limit of detection, as was CSF measured at 25 months.

Samples were taken from the patient’s rectum, cecum, sigmoid colon, and terminal ileum during a colonoscopy conducted 22 months post ATI; all tested negative for HIV DNA via droplet digital PCR.

The lymph node had large numbers of EBV-positive cells and was positive for HIV-1 env and long-terminal repeat by double-drop PCR, but no integrase DNA was detected. Additionally, no intact proviral DNA was found on assay.

Dr. Gupta and associates speculated that “EBV reactivation could have triggered EBV-specific CD4 and CD8 T-cell responses and proliferation, potentially including CD4 T cells containing HIV-1 DNA.” Supporting this hypothesis, EBV-specific CD8 T-cell responses in peripheral blood were “robust,” and the researchers also saw some CD4 response.

“Similar to the Berlin patient, highly sensitive tests showed very low levels of so-called fossilized HIV-1 DNA in some tissue samples from the London patient. Residual HIV-1 DNA and axillary lymph node tissue could represent a defective clone that expanded during hyperplasia within the lymph note sampled,” noted Dr. Gupta and coauthors.

Responses of CD4 and CD8 T cells to HIV have also remained below the limit of detection, though cytomegalovirus-specific responses persist in the London patient.

As with the Berlin patient, standard enzyme-linked immunosorbent assay (ELISA) testing has remained positive in the London patient. “Standard ELISA testing, therefore, cannot be used as a marker for cure, although more work needs to be done to assess the role of detuned low-avidity antibody assays in defining cure,” noted Dr. Gupta and associates.

The ongoing follow-up plan for the London patient is to obtain viral load testing twice yearly up to 5 years post ATI, and then obtain yearly tests for a total of 10 years. Ongoing testing will confirm the investigators’ belief that “these findings probably represent the second recorded HIV-1 cure after CCR5 delta-32/delta-32 allo-HSCT, with evidence of residual low-level HIV-1 DNA.”

Dr. Zerbato and Dr. Lewin advised cautious optimism and ongoing surveillance: “In view of the many cells sampled in this case, and the absence of any intact virus, is the London patient truly cured? The additional data provided in this follow-up case report is certainly exciting and encouraging but, in the end, only time will tell.”

Dr. Gupta reported being a consultant for ViiV Healthcare and Gilead Sciences; several coauthors also reported financial relationships with pharmaceutical companies. The work was funded by amfAR, the American Foundation for AIDS Research, and the Wellcome Trust. Dr. Lewin reported grants from the National Health and Medical Research Council of Australia, the National Institutes of Health, the American Foundation for AIDS Research, Gilead Sciences, Merck, ViiV Healthcare, Leidos, the Wellcome Trust, the Australian Centre for HIV and Hepatitis Virology Research, and the Melbourne HIV Cure Consortium. Dr. Zerbato reported grants from the Melbourne HIV Cure Consortium,

[email protected]

SOURCE: Gupta R et al. Lancet. 2020 Mar 10. doi: 10.1016/ S2352-3018(20)30069-2.

A patient with HIV remission induced by stem cell transplantation continues to be disease free at the 30-month mark.

The individual, referred to as the London patient, received allogeneic hematopoietic stem cell transplantation (allo-HSCT) for stage IVB Hodgkin lymphoma. The transplant donor was homozygous for the CCR5 delta-32 mutation, which confers immunity to HIV because there’s no point of entry for the virus into immune cells.

After extensive sampling of various tissues, including gut, lymph node, blood, semen, and cerebrospinal fluid (CSF), Ravindra Kumar Gupta, MD, PhD, and colleagues found no detectable virus that was competent to replicate. However, they reported that the testing did detect some “fossilized” remnants of HIV DNA persisting in certain tissues.

The results were shared in a video presentation of the research during the Conference on Retroviruses & Opportunistic Infections, which was presented online this year. CROI organizers chose to hold a virtual meeting because of concerns about the spread of COVID-19.

The London patient’s HIV status had been reported the previous year at CROI 2019, but only blood samples were used in that analysis.

In a commentary accompanying the simultaneously published study in the Lancet, Jennifer Zerbato, PhD, and Sharon Lewin, FRACP, PHD, FAAHMS, asked: “A key question now for the area of HIV cure is how soon can one know if someone has been cured of HIV?

“We will need more than a handful of patients cured of HIV to really understand the duration of follow-up needed and the likelihood of an unexpected late rebound in virus replication,” continued Dr. Zerbato, of the University of Melbourne, and Dr. Lewin, of the Royal Melbourne Hospital and Monash University, also in Melbourne.

In their ongoing analysis of data from the London patient, Dr. Gupta, a virologist at the University of Cambridge (England), and associates constructed a mathematical model that maps the probability for lifetime remission or cure of HIV against several factors, including the degree of chimerism achieved with the stem cell transplant.

In this model, when chimerism reaches 80% in total HIV target cells, the probability of remission for life is 98%; when donor chimerism reaches 90%, the probability of lifetime remission is greater than 99%. Peripheral T-cell chimerism in the London patient has held steady at 99%.

Dr. Gupta and associates obtained some testing opportunistically: A PET-CT scan revealed an axillary lymph node that was biopsied after it was found to have avid radiotracer uptake. Similarly, the CSF sample was obtained in the course of a work-up for some neurologic symptoms that the London patient was having.

In contrast to the first patient who achieved ongoing HIV remission from a pair of stem cell transplants received over 13 years ago – the Berlin patient – the London patient did not receive whole-body radiation, but rather underwent a reduced-intensity conditioning regimen. The London patient experienced a bout of gut graft-versus-host disease (GVHD) about 2 months after his transplant, but has been free of GVHD in the interval. He hasn’t taken cytotoxic agents or any GVHD prophylaxis since 6 months post transplant.

Though there’s no sign of HIV that’s competent to replicate, “the London patient has shown somewhat slow CD4 reconstitution,” said Dr. Gupta and coauthors in discussing the results.

The patient had a reactivation of Epstein-Barr virus (EBV) about 21 months after analytic treatment interruption (ATI) of antiretroviral therapy that was managed without any specific treatment, but he hasn’t experienced any opportunistic infections. However, his CD4 count didn’t rebound to pretransplant levels until 28 months after ATI. At that point, his CD4 count was 430 cells per mcL, or 23.5% of total T cells. The CD4:CD8 ratio was 0.86; normal range is 1.5-2.5.

The researchers used quantitative real-time polymerase chain reaction (rt-PCR) to look for packaging site and envelope (env) DNA fragments, and droplet digital PCR to quantify HIV-1 DNA.

The patient’s HIV-1 plasma load measured at 30 months post ATI on an ultrasensitive assay was below the lower limit of detection (less than 1 copy per mL). Semen viremia measured at 21 months was also below the lower limit of detection, as was CSF measured at 25 months.

Samples were taken from the patient’s rectum, cecum, sigmoid colon, and terminal ileum during a colonoscopy conducted 22 months post ATI; all tested negative for HIV DNA via droplet digital PCR.

The lymph node had large numbers of EBV-positive cells and was positive for HIV-1 env and long-terminal repeat by double-drop PCR, but no integrase DNA was detected. Additionally, no intact proviral DNA was found on assay.

Dr. Gupta and associates speculated that “EBV reactivation could have triggered EBV-specific CD4 and CD8 T-cell responses and proliferation, potentially including CD4 T cells containing HIV-1 DNA.” Supporting this hypothesis, EBV-specific CD8 T-cell responses in peripheral blood were “robust,” and the researchers also saw some CD4 response.

“Similar to the Berlin patient, highly sensitive tests showed very low levels of so-called fossilized HIV-1 DNA in some tissue samples from the London patient. Residual HIV-1 DNA and axillary lymph node tissue could represent a defective clone that expanded during hyperplasia within the lymph note sampled,” noted Dr. Gupta and coauthors.

Responses of CD4 and CD8 T cells to HIV have also remained below the limit of detection, though cytomegalovirus-specific responses persist in the London patient.

As with the Berlin patient, standard enzyme-linked immunosorbent assay (ELISA) testing has remained positive in the London patient. “Standard ELISA testing, therefore, cannot be used as a marker for cure, although more work needs to be done to assess the role of detuned low-avidity antibody assays in defining cure,” noted Dr. Gupta and associates.

The ongoing follow-up plan for the London patient is to obtain viral load testing twice yearly up to 5 years post ATI, and then obtain yearly tests for a total of 10 years. Ongoing testing will confirm the investigators’ belief that “these findings probably represent the second recorded HIV-1 cure after CCR5 delta-32/delta-32 allo-HSCT, with evidence of residual low-level HIV-1 DNA.”

Dr. Zerbato and Dr. Lewin advised cautious optimism and ongoing surveillance: “In view of the many cells sampled in this case, and the absence of any intact virus, is the London patient truly cured? The additional data provided in this follow-up case report is certainly exciting and encouraging but, in the end, only time will tell.”

Dr. Gupta reported being a consultant for ViiV Healthcare and Gilead Sciences; several coauthors also reported financial relationships with pharmaceutical companies. The work was funded by amfAR, the American Foundation for AIDS Research, and the Wellcome Trust. Dr. Lewin reported grants from the National Health and Medical Research Council of Australia, the National Institutes of Health, the American Foundation for AIDS Research, Gilead Sciences, Merck, ViiV Healthcare, Leidos, the Wellcome Trust, the Australian Centre for HIV and Hepatitis Virology Research, and the Melbourne HIV Cure Consortium. Dr. Zerbato reported grants from the Melbourne HIV Cure Consortium,

[email protected]

SOURCE: Gupta R et al. Lancet. 2020 Mar 10. doi: 10.1016/ S2352-3018(20)30069-2.

A patient with HIV remission induced by stem cell transplantation continues to be disease free at the 30-month mark.

The individual, referred to as the London patient, received allogeneic hematopoietic stem cell transplantation (allo-HSCT) for stage IVB Hodgkin lymphoma. The transplant donor was homozygous for the CCR5 delta-32 mutation, which confers immunity to HIV because there’s no point of entry for the virus into immune cells.

After extensive sampling of various tissues, including gut, lymph node, blood, semen, and cerebrospinal fluid (CSF), Ravindra Kumar Gupta, MD, PhD, and colleagues found no detectable virus that was competent to replicate. However, they reported that the testing did detect some “fossilized” remnants of HIV DNA persisting in certain tissues.

The results were shared in a video presentation of the research during the Conference on Retroviruses & Opportunistic Infections, which was presented online this year. CROI organizers chose to hold a virtual meeting because of concerns about the spread of COVID-19.

The London patient’s HIV status had been reported the previous year at CROI 2019, but only blood samples were used in that analysis.

In a commentary accompanying the simultaneously published study in the Lancet, Jennifer Zerbato, PhD, and Sharon Lewin, FRACP, PHD, FAAHMS, asked: “A key question now for the area of HIV cure is how soon can one know if someone has been cured of HIV?

“We will need more than a handful of patients cured of HIV to really understand the duration of follow-up needed and the likelihood of an unexpected late rebound in virus replication,” continued Dr. Zerbato, of the University of Melbourne, and Dr. Lewin, of the Royal Melbourne Hospital and Monash University, also in Melbourne.

In their ongoing analysis of data from the London patient, Dr. Gupta, a virologist at the University of Cambridge (England), and associates constructed a mathematical model that maps the probability for lifetime remission or cure of HIV against several factors, including the degree of chimerism achieved with the stem cell transplant.

In this model, when chimerism reaches 80% in total HIV target cells, the probability of remission for life is 98%; when donor chimerism reaches 90%, the probability of lifetime remission is greater than 99%. Peripheral T-cell chimerism in the London patient has held steady at 99%.

Dr. Gupta and associates obtained some testing opportunistically: A PET-CT scan revealed an axillary lymph node that was biopsied after it was found to have avid radiotracer uptake. Similarly, the CSF sample was obtained in the course of a work-up for some neurologic symptoms that the London patient was having.

In contrast to the first patient who achieved ongoing HIV remission from a pair of stem cell transplants received over 13 years ago – the Berlin patient – the London patient did not receive whole-body radiation, but rather underwent a reduced-intensity conditioning regimen. The London patient experienced a bout of gut graft-versus-host disease (GVHD) about 2 months after his transplant, but has been free of GVHD in the interval. He hasn’t taken cytotoxic agents or any GVHD prophylaxis since 6 months post transplant.

Though there’s no sign of HIV that’s competent to replicate, “the London patient has shown somewhat slow CD4 reconstitution,” said Dr. Gupta and coauthors in discussing the results.

The patient had a reactivation of Epstein-Barr virus (EBV) about 21 months after analytic treatment interruption (ATI) of antiretroviral therapy that was managed without any specific treatment, but he hasn’t experienced any opportunistic infections. However, his CD4 count didn’t rebound to pretransplant levels until 28 months after ATI. At that point, his CD4 count was 430 cells per mcL, or 23.5% of total T cells. The CD4:CD8 ratio was 0.86; normal range is 1.5-2.5.

The researchers used quantitative real-time polymerase chain reaction (rt-PCR) to look for packaging site and envelope (env) DNA fragments, and droplet digital PCR to quantify HIV-1 DNA.

The patient’s HIV-1 plasma load measured at 30 months post ATI on an ultrasensitive assay was below the lower limit of detection (less than 1 copy per mL). Semen viremia measured at 21 months was also below the lower limit of detection, as was CSF measured at 25 months.

Samples were taken from the patient’s rectum, cecum, sigmoid colon, and terminal ileum during a colonoscopy conducted 22 months post ATI; all tested negative for HIV DNA via droplet digital PCR.

The lymph node had large numbers of EBV-positive cells and was positive for HIV-1 env and long-terminal repeat by double-drop PCR, but no integrase DNA was detected. Additionally, no intact proviral DNA was found on assay.

Dr. Gupta and associates speculated that “EBV reactivation could have triggered EBV-specific CD4 and CD8 T-cell responses and proliferation, potentially including CD4 T cells containing HIV-1 DNA.” Supporting this hypothesis, EBV-specific CD8 T-cell responses in peripheral blood were “robust,” and the researchers also saw some CD4 response.

“Similar to the Berlin patient, highly sensitive tests showed very low levels of so-called fossilized HIV-1 DNA in some tissue samples from the London patient. Residual HIV-1 DNA and axillary lymph node tissue could represent a defective clone that expanded during hyperplasia within the lymph note sampled,” noted Dr. Gupta and coauthors.

Responses of CD4 and CD8 T cells to HIV have also remained below the limit of detection, though cytomegalovirus-specific responses persist in the London patient.

As with the Berlin patient, standard enzyme-linked immunosorbent assay (ELISA) testing has remained positive in the London patient. “Standard ELISA testing, therefore, cannot be used as a marker for cure, although more work needs to be done to assess the role of detuned low-avidity antibody assays in defining cure,” noted Dr. Gupta and associates.

The ongoing follow-up plan for the London patient is to obtain viral load testing twice yearly up to 5 years post ATI, and then obtain yearly tests for a total of 10 years. Ongoing testing will confirm the investigators’ belief that “these findings probably represent the second recorded HIV-1 cure after CCR5 delta-32/delta-32 allo-HSCT, with evidence of residual low-level HIV-1 DNA.”

Dr. Zerbato and Dr. Lewin advised cautious optimism and ongoing surveillance: “In view of the many cells sampled in this case, and the absence of any intact virus, is the London patient truly cured? The additional data provided in this follow-up case report is certainly exciting and encouraging but, in the end, only time will tell.”

Dr. Gupta reported being a consultant for ViiV Healthcare and Gilead Sciences; several coauthors also reported financial relationships with pharmaceutical companies. The work was funded by amfAR, the American Foundation for AIDS Research, and the Wellcome Trust. Dr. Lewin reported grants from the National Health and Medical Research Council of Australia, the National Institutes of Health, the American Foundation for AIDS Research, Gilead Sciences, Merck, ViiV Healthcare, Leidos, the Wellcome Trust, the Australian Centre for HIV and Hepatitis Virology Research, and the Melbourne HIV Cure Consortium. Dr. Zerbato reported grants from the Melbourne HIV Cure Consortium,

[email protected]

SOURCE: Gupta R et al. Lancet. 2020 Mar 10. doi: 10.1016/ S2352-3018(20)30069-2.