Virus World

This report describes the prevention and treatment of monkeypox in people with HIV infection. 

What is already known about this topic?

 A multinational monkeypox outbreak disproportionately affecting men who have sex with men, including persons with HIV infection, is ongoing worldwide.

What is added by this report?

 CDC has developed clinical considerations for prevention and treatment of monkeypox in persons with HIV infection, including pre-exposure and post-exposure prophylaxis with JYNNEOS vaccine, treatment with tecovirimat, and infection control.

What are the implications for public health practice?

 Persons with advanced HIV might be at increased risk for severe monkeypox. Post-exposure prophylaxis and antiviral treatments are available for persons with HIV infection. Prompt diagnosis and treatment and enhanced prevention efforts might reduce the risk for severe outcomes....

For the first time in Southern California, surgeons at UC San Diego Health have transplanted the kidney of a deceased donor with HIV into a recipient with a pre-existing HIV infection. The procedure is part of an unprecedented multi-site national clinical trial.

The procedure occurred earlier this month. The patient is expected to make a full recovery. In 2013, Congress passed the HIV Organ Policy Equity (HOPE) Act, an effort to alleviate a chronic shortage of donor organs, which hits patients with HIV particularly hard, resulting in extremely long wait times and a greater likelihood of dying before a donor organ becomes available. Though organ transplants between donors and recipients with HIV have been successfully conducted in South Africa since 2008, such transplants were illegal in the U.S. until passage of the HOPE Act, which permits transplants of kidneys and livers from donors with HIV to qualified recipients with well-controlled HIV and end-stage organ failure, under approved research protocols. The kidney clinical trial launched last year. The transplantation of organs from donors with HIV to recipients without HIV remains prohibited.

The shortage of donor organs is universal and persistent, with more than 113,000 Americans currently needing a transplant (with almost 75,000 on active waiting lists), according to the United Network for Organ Sharing. The kidney was the first human organ to be successfully transplanted in 1954 and is, by far, the organ most often transplanted. The use of donor organs infected with HIV or hepatitis B and C viruses has become more viable in recent years. In 2016, Saima Aslam, MBBS, associate professor of medicine at UC San Diego School of Medicine and director of the Solid Organ Transplant Infectious Diseases Service at UC San Diego Health, and colleagues in the organ transplant programs launched a clinical practice protocol to use organs from donors actively infected with the hepatitis C virus, which is now curable. The change has resulted in a significant expansion of the organ donor pool and a reduction in wait list time. Persons with HIV are at higher risk of requiring a kidney (or liver) transplant due to organ damage caused by the virus and by common, associated co-infections and conditions, such as hepatitis B and C, hypertension and diabetes.

UC San Diego is also participating in a second, similar clinical trial involving HIV-to-HIV liver transplants. That first-ever trial launched earlier this year at UC San Diego; it is actively recruiting patients as well.

A single viral factor released from HIV-infected cells may wreak havoc on the body and lead to the development of chronic and potentially deadly diseases like heart disease, diabetes and dementia, according to a new study by scientists at the Baker Heart and Diabetes Institute in Melbourne.

Studies show that not only are people living with HIV at increased risk of these chronic diseases, they are occurring at an earlier age and progress faster. These co-morbidities persist even after successful application of antiretroviral therapy, when no virus is found in the blood. Scientists have been intrigued as to what is going on in the small number of infected cells, believing that HIV-infected cells instead of the virus release a toxic substance that kills cells around them.

Baker Institute scientists showed that the HIV protein, Nef, released from infected cells in specialised vesicles, is taken up by uninfected 'bystander' cells, impairing cholesterol metabolism in these cells. This impairment triggers inflammation, contributing to the development of diseases including dementia,  heart disease and diabetes.

Head of Lipoproteins and Atherosclerosis at the Baker Institute, Professor Dmitri Sviridov says the study demonstrates how a single viral molecule released from infected cells into circulation may contribute to a range of pathogenic responses. "The good news is that there are many drugs on the market and in development to tackle impaired cholesterol metabolism which could be repurposed for this specific population to effectively treat these diseases," says Professor Sviridov.

The findings were published in PLOS Pathogens (Open Access):

https://doi.org/10.1371/journal.ppat.1007907

Children born to women on HIV therapy containing the drug efavirenz were 2 to 2.5 times more likely to have microcephaly, or small head size, compared to children born to women on regimens of other antiretroviral drugs, according to an analysis funded by the National Institutes of Health. The children with microcephaly also had a higher risk for developmental delays, compared to children with normal head size. The study was conducted by Paige L. Williams, Ph.D., of the Harvard T.H. Chan School of Public Health, and colleagues. It appears in The Lancet.

"Our findings underlie the importance of having alternatives to combination therapy with efavirenz for pregnant women  with HIV," said study author Rohan Hazra, M.D., chief of the Maternal and Pediatric Infectious Disease Branch of NIH's Eunice Kennedy Shriver National Institute of Child Health and Human Development, which provided funding for the study.

Researchers analyzed data from a follow-up study of more than 3,000 infants born to women on HIV therapy during pregnancy. In this earlier study, the children's head circumferences were measured periodically from 6 months of age through 5 to 7 years of age. For the current study, investigators used two classification systems to rank the children's head growth. The first classification system combined standards developed by the U.S. Centers for Disease Control and Prevention for children under 3 years of age with Nellhaus Charts, an older set of standards for children over 3 years of age. For the second classification system, the researchers consulted Nellhaus Charts from birth to age 18. 

Based on Nellhaus standards, children whose mothers were on regimens containing the drug efavirenz were more than twice as likely to have microcephaly, compared to children whose mothers were on other regimens. According to the combined Nellhaus-CDC standards, children exposed to efavirenz in the womb were around 2.5 times as likely to have microcephaly. Children with microcephaly according to Nellhaus standards also scored lower on standardized tests of child development at ages 1 and 5 years. Of the 141 children exposed to efavirenz in the womb, 14 (9.9%) had microcephaly, compared to 142 of 2,842 who were not exposed to efavirenz (5%). The researchers noted that exposure to all other types of HIV therapies was not associated with a higher risk of microcephaly.

Published in The Lancet (November 15, 2019):

https://doi.org/10.1016/S2352-3018(19)30340-6

Michelle Moorhouse, MB BCh, from Wits Reproductive Health and HIVInstitute, like many other physicians, started to notice that the numbers on the scale kept going up for her patients who were taking integrase inhibitors. Speaking from the podium here at the International AIDS Society (IAS) 2019 Conference on HIV Science, Moorhouse explained that "a real flurry" of reports started coming in about tenofovir alafenamide and dolutegravir being associated with weight gain.

Dolutegravir and tenofovir alafenamide can lead to weight gain, especially in women, according to new data that are changing the way researchers look at their study populations.  So the ADVANCE team worked with researchers from the New Antiretroviral and Monitoring Strategies in HIV Infected Adults in Low-income countries (NAMSAL) trial NCT02777229) to pull together all the weight-gain data accrued from their combined cohort of 1666 participants.  And they found a consistent story.

In the NAMSAL trial, weight gain was higher in the dolutegravir group than in the efavirenz group (5 kg vs 3 kg; P ≤ .001), and the mean increase in body mass index was greater in the dolutegravir group (1.7 vs 1.2 kg/m2; P ≤ .001). In the ADVANCE trial, weight gain was even more pronounced, but the pattern was the same: participants in the dolutegravir plus Descovy group gained more weight over 96 weeks than those in the dolutegravir plus Truvada group (8 kg vs 5 kg).