Maternal HIV Drug Resistance Is Associated with Mother-to-Child Transmission

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Antiretroviral therapy of pregnant women and antiretroviral treatment of infants have greatly reduced the rate of mother-to-child HIV transmission, also referred to as vertical transmission. Nevertheless, although these improved rates have occurred in some countries, vertical transmission rates remain relatively high in others. This may be due to multiple factors, including access to testing, care and antiretroviral therapy, adherence to antiretroviral therapy during pregnancy and breastfeeding, and potential HIV drug resistance. In order to evaluate the factors that result in vertical transmission, researchers compared variables that resulted in HIV outcomes in infants from pregnant and breastfeeding mothers from 14 sites in 7 countries.

The researchers analyzed plasma from mothers and their infants at or near the time of infant HIV diagnosis to determine whether their infections were resistant to currently used drugs. Additionally, the researchers did long-term analysis of the HIV genetic structure in the infants so that they could analyze possible drug resistance later on. Their findings showed that maternal HIV drug resistance was not associated with in utero vertical transmission. However, both maternal viral load and HIV drug resistance were associated with vertical transmission during breastfeeding. These findings support efforts to reduce and eliminate HIV reproduction during pregnancy and have implications for re-evaluating appropriate antiretroviral treatment for breastfeeding infants.

Reference: Boyce et al.  Maternal Human Immunodeficiency Virus (HIV) Drug Resistance Is Associated With Vertical Transmission and Is Prevalent in Infected InfantsClinical Infectious Diseases, 2021; ciab744.

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HIV Research Update from CROI 2022 with NIH’s Dr. Carl Dieffenbach—Cancer Prevention, Aging, and the Future of HIV Prevention & Treatment

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Cross-posted from HIV.gov

As the 2022 virtual Conference on Retroviruses and Opportunistic Infections (CROI 2022) came to a close, NIH’s Dr. Carl Dieffenbach joined HIV.gov for a video conversation on February 24 to discuss important findings on cancer prevention in people with HIV, research on HIV and aging, and the future of HIV prevention and treatment. Dr. Dieffenbach is the Director of the Division of AIDS at NIH’s National Institute of Allergy and Infectious Diseases (NIAID). Watch the conversation with Dr. Dieffenbach:

 

 

 

 

 

Here are some highlights from Dr. Dieffenbach’s conversation with HIV.gov:

Anal Cancer Prevention for People with HIV

Dr. Dieffenbach first discussed findings from the ANCHOR study, a large-scale study to investigate whether screening people with HIV for precancerous growths in the anus called high-grade squamous interepithelial lesions (HSIL) and treating them early can prevent anal cancer. Researchers have known for many years that screening and treating HSIL in the cervix can successfully prevent cervical cancer, but they did not know whether similar methods could help prevent anal cancer. While anal cancer is rare, people with HIV are much more likely to develop it than the general population.

In the Anal Cancer/HSIL Outcomes Research (ANCHOR) study, presented at CROI by Dr. Joel Palefsky of the University of California San Francisco, more than 10,000 people with HIV over the age of 35 were screened for HSIL at 25 U.S. sites. Of 4,446 participants found to have HSIL, half were randomly assigned to receive treatment and half to receive active monitoring, but no treatment. The researchers found that treatment of HSIL, primarily with office-based electrocautery in which an electric current was targeted directly to areas of the HSIL to remove them, led to a significant reduction in anal cancer incidence and was well-tolerated. Further, anal cancer incidence was higher than expected among ANCHOR study participants who did not receive treatment. Dr. Dieffenbach observed that these study findings suggest that routine screening for and early treatment of anal HSIL may become a new standard of care for people with HIV so that more cases of anal cancer can be prevented. He also noted the importance of training more healthcare providers to conduct anal HSIL screening and treatment so there is sufficient capacity to do the procedures. The ANCHOR study was supported by NIH’s National Cancer Institute. Jump directly to this part of the conversation in the video.  View the ANCHOR Study abstract on the CROI website.

HIV and Aging

Aging and HIV was a cross-cutting theme of this year’s CROI. As Dr. Dieffenbach explained, this large and growing area of HIV research is the result of highly effective antiretroviral therapy (ART) that has enabled many people with HIV to live long lives. Researchers are now examining what it means to age with HIV and how the consequences of the virus, ART, or both affect the overall health of people with HIV. Scientists are also investigating which interventions effectively prevent or reduce the comorbidities, cancers, and other consequences of the long-term immune activation and inflammation caused by living with HIV for many years. One example of such research that Dr. Dieffenbach pointed to is the NIH-supported REPRIEVE clinical trial, which is studying whether a statin medication could help reduce heart disease among people with HIV.

Findings from research related to aging with HIV must move into practice in health care and other settings, Dr. Dieffenbach observed. He highlighted one way this is happening: recent funding opportunities from HRSA to support Ryan White HIV/AIDS Program sites to identify, refine, evaluate, and disseminate emerging strategies to comprehensively screen and manage comorbidities, geriatric conditions, behavioral health, and psychosocial concerns of people ages 50 years and older with HIV. He also highlighted that the new National HIV/AIDS Strategy focuses on engaging both federal and nonfederal partners in multisectoral approaches to support healthy aging with HIV. Jump directly to this discussion in the video

Future HIV Prevention and Treatment Options

Dr. Dieffenbach then discussed the future of HIV prevention and treatment, which he characterized as “a very active area of research” as evidenced by numerous presentations at the conference. An overarching goal of all the research, he explained, is to make medication adherence as easy as possible, thereby increasing the chances that the HIV treatment or prevention strategy will be successful. One way to foster adherence that researchers are investigating is long-acting or sustained-release drug formulations that easily and safely increase the time between doses. Among the options being studied are a once-weekly pill, as well as long-acting injections and sustained-release implants that provide coverage for a month or more. (Dr. Dieffenbach discussed the latest findings on the one FDA-approved long-acting injectable form of PrEP in a video conversation last week.) Ultimately, Dr. Dieffenbach explained, the hope is to have a suite of choices available for people who need either HIV prevention or HIV treatment so each person can choose the option that works best them. Jump directly to the discussion of this topic in the video

About CROI

CROI is an annual scientific meeting that brings together top researchers from around the world to present and discuss the latest studies that can help accelerate global progress in the response to HIV/AIDS and other infectious diseases, including COVID-19. More than 3,000 HIV and infectious disease researchers gathered virtually this year over two weeks for this forum. Among the studies presented were many that had been conducted or supported by NIH and CDC.

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NIH’s Dr. Carl Dieffenbach Discusses Highlights of HIV Cure, Treatment and Prevention Research from CROI 2022

NIAID Now |

(Cross-posted from HIV.gov)

In an HIV.gov video conversation on February 16, NIH’s Dr. Carl Dieffenbach discussed some of the pivotal HIV research advances presented this week at the 2022 virtual Conference on Retroviruses and Opportunistic Infections (CROI 2022). Dr. Dieffenbach, Director of the Division of AIDS at NIH’s National Institute of Allergy and Infectious Diseases (NIAID), covered developments in HIV cure research, HIV treatment and HIV prevention. Watch the conversation with Dr. Dieffenbach:

Here are some highlights from Dr. Dieffenbach’s conversation with HIV.gov:

HIV Cure Research

Dr. Dieffenbach first discussed a person whose HIV is in remission as the result of a stem cell transplant with an HIV-resistant mutation. The case was presented at CROI by Dr. Yvonne Bryson of the University of California, Los Angeles. This is only the third such case of HIV remission and the first in a woman and a person of mixed-race ancestry. The woman was diagnosed with leukemia after having been on treatment for HIV for several years. When she needed a stem cell transplant to treat the cancer, doctors used a combination of cord blood with the HIV-resistant mutation and stem cells from a close relative. About 37 months after the transplant, the woman stopped taking antiretroviral therapy (ART). No HIV has been detected in the woman for 14 months since cessation of ART. Dr. Dieffenbach reflected on the importance of this case, what it might mean for the future, and when and why the terms remission and cure are used. Read the NIAID news release about this study. Read the study abstract on the CROI website.

Very Early Treatment in Infants and the Promise of HIV Remission

Another study Dr. Dieffenbach discussed explored the effects of early intensive ART on achieving HIV remission in infants. The study, presented by Dr. Deborah Persaud of Johns Hopkins University, is following two small cohorts of children who acquired HIV in the womb and began receiving ART within 48 hours of birth. She presented virologic outcomes indicating that most the infants had achieved viral suppression, defined as HIV RNA less than 200 copies/mL, at six months of age. She also presented data on the amount of HIV DNA detected in the children’s cells, which reflected the size of their viral reservoir. Most of the children had no HIV DNA at two years of age. Having a smaller reservoir may make it possible for these children to stop taking ART and still maintain viral suppression. To evaluate this, in the next stage of the study, children who meet strict criteria will stop taking ART and have their HIV RNA levels closely monitored. Dr. Dieffenbach shared why that’s important and why he thinks pediatric studies are critical for HIV cure research. Read the study abstract on the CROI website. View more information on the study on the IMPAACT Network website.

Antibodies: A Possible Treatment Option for Very Young Children with HIV

Reflecting on future directions in HIV treatment, Dr. Dieffenbach discussed a proof-of-concept study on using broadly neutralizing antibodies (bNAbs) to treat HIV in children in Botswana. These powerful anti-HIV antibodies can stop a wide variety of HIV strains from infecting human cells in the laboratory. In the study, presented by Dr. Roger Shapiro of the Harvard T.H. Chan School of Public Health, 25 children with HIV between ages 2 and 5 years who had begun ART less than 7 days after birth and had undetectable viral loads were given monthly infusions of two bNAbs. The bNAbs were delivered first in combination with ART, and then later, if the children’s HIV remained undetectable, without ART. Eleven (44%) of the children maintained viral suppression through 24 weeks of bNAb-only treatment, and 14 (56%) had viral rebound before 24 weeks. The infusions were safe and well-tolerated. As Dr. Dieffenbach explained, parents found the bNAb infusions acceptable, with many preferring them to daily ART. He also discussed why he thinks bNAbs will be an important tool in future HIV treatment, prevention, and cure research.  View the abstract on the CROI website.

Additional Data on Long-acting, Injectable Cabotegravir for PrEP

Finally, Dr. Dieffenbach highlighted a study providing additional data about long-acting injectable cabotegravir PrEP. Dr. Raphael Landovitz of the University of California Los Angeles reported data from one year of unblinded follow-up in the HIV Prevention Trials Network (HPTN) Study 083 among cisgender men and transgender women who have sex with men. This Phase 2b/3 randomized controlled trial previously demonstrated that a long-acting form of the HIV drug cabotegravir (CAB-LA) injected once every 8 weeks was more effective than daily oral Truvada at preventing HIV acquisition in the study population. At CROI, Dr. Landovitz reported that during the unblinded phase of the trial, the reduction in the risk of HIV acquisition from taking CAB-LA versus daily oral Truvada remained the same as during the blinded phase. Dr. Dieffenbach observed that scaling up available forms of PrEP and other HIV prevention tools will be key factors in achieving the goals of the National HIV/AIDS Strategy and the Ending the HIV Epidemic in the U.S. initiative. View the study abstract on the CROI website.

About CROI

CROI is an annual scientific meeting that brings together top researchers from around the world to present and discuss the latest studies that can help accelerate global progress in the response to HIV/AIDS and other infectious diseases, including COVID-19. More than 3,000 HIV and infectious disease researchers are gathering virtually this year over two weeks for this forum for translating laboratory and clinical research into progress against these diseases. Among the studies being presented are many that have been conducted or supported by NIH and CDC.

Join us again for another conversation with Dr. Dieffenbach at the conclusion of CROI 2022 next Thursday, February 24, 2022, at 5:15 PM (ET).

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