A woman with HIV who received a cord blood stem cell transplant to treat acute myeloid leukemia has had no detectable levels of HIV for 14 months despite cessation of antiretroviral therapy (ART), according to a presentation at today’s Conference on Retroviruses and Opportunistic Infections (CROI).
Scanning electron micrograph of an HIV-infected H9 T cell, colorized in Halloween colors.NIAID
This is the third known case of HIV remission in an individual who received a stem cell transplant. The research was conducted by the International Maternal Pediatric Adolescent AIDS Clinical Trial Network (IMPAACT) P1107 observational study led by Yvonne Bryson, M.D., of the University of California Los Angeles, and Deborah Persaud, M.D., of Johns Hopkins University, Baltimore. The IMPAACT network is funded by the National Institutes of Health.
The IMPAACT P1107 study began in 2015 and was a U.S.-based observational study designed to describe the outcomes of up to 25 participants living with HIV who underwent a transplant with CCR5Δ32/Δ32 cord blood stem cells for the treatment of cancer, hematopoietic disease, or other underlying diseases. As a result of the genetic mutation CCR5Δ32/Δ32, missing cells lack CCR5 co-receptors, which is what HIV uses to infect cells. By killing off the cancerous immune cells via chemotherapy and then transplanting stem cells with the CCR5 genetic mutation, scientists theorize that people with HIV then develop an HIV-resistant immune system.
The case described today at the CROI meeting involves a woman of mixed race ancestry who had been on ART for HIV infection for four years at the time of her acute myeloid leukemia diagnosis. She achieved acute myeloid leukemia remission after chemotherapy. Prior to receiving the stem cell transplant, the participant’s HIV was well-controlled but detectable.
In 2017, she received a transplant of CCR5Δ32/Δ32 cord blood stem cells supplemented with adult donor cells from a relative (called haplo cells). After receiving the stem cell transplant, she engrafted with 100% cord blood cells at day 100 and had no detectable HIV. At 37 months post-transplant, the patient ceased ART. According to the study team, no HIV was detected in the participant for 14 months except for a transient detection of trace levels of HIV DNA in the woman’s blood cells at 14 weeks after stopping ART. The haplo cells only transiently engrafted and contributed to rapid recovery.
HIV remission resulting from a stem cell transplant had been previously observed in two cases. The first, known as the “Berlin patient” (a Caucasian male), experienced HIV remission for 12 years and was deemed cured of HIV; he died of leukemia in September 2020. The “London patient” (a Latino male) has been in HIV remission for more than 30 months. This third case of HIV remission suggests that CCRΔ5/Δ32 cord stem cell transplantation should be considered to achieve HIV remission and cure for people living with HIV who require such a transplant for other diseases, according to the study team.
Kidney transplantation from deceased donors with HIV to people living with both HIV and end-stage kidney disease is feasible and safe, investigators supported by the National Institutes of Health have found.
Their study demonstrates that the pool of available kidneys for people with HIV can be expanded by including donors with HIV, making more kidneys available for all who are awaiting a transplant.
The new findings build on research from 2019, when scientists from the University of Cape Town and NIH reported that people living with HIV who received kidney transplants from deceased donors with HIV had high overall survival and kidney graft survival after five years.
People living with HIV have a growing prevalence of end-stage kidney disease and are nearly three times more likely to die while on kidney dialysis than people without HIV. Kidney transplantation extends the lives of people with HIV and end-stage kidney disease, but these individuals face a shortage of donors and limited access to donor kidneys. The HIV Organ Policy Equity (HOPE) Act, passed by the U.S. Congress and signed into law in 2013, allows organ transplants from donors with HIV to recipients with HIV in approved research studies in the United States. Experts concurred that kidney transplantation between people with HIV would expand the pool of available organs and save lives. Consequently, investigators sought to explore the safety of this innovative transplantation practice.
The multicenter study was conducted by the HOPE in Action team led by Christine M. Durand, M.D., associate professor of medicine, and Dorry Segev, M.D., professor of surgery at Johns Hopkins University in Baltimore. NIH’s National Institute of Allergy and Infectious Diseases (NIAID) funded the study with additional support from the National Cancer Institute, also part of NIH.
Between March 2016 and July 2019, investigators at 14 clinical research sites enrolled 75 adults with end-stage kidney disease and HIV whose virus was reliably suppressed by anti-HIV therapy. Twenty-five participants received kidney transplants from deceased donors with HIV, and 50 participants received kidney transplants from deceased donors without HIV. The latter group included 22 donors who had false-positive HIV tests, another new organ source that has been an unexpected benefit of the HOPE Act.
All participants survived transplantation at a median follow-up of 1.4 years for recipients of HIV-positive kidneys and 1.8 years for recipients of HIV-negative kidneys. One year after transplantation, overall graft survival was excellent and comparable between recipients of HIV-positive kidneys (91%) and HIV-negative kidneys (92%). In addition, there were no differences in the rates of infections requiring hospitalization, serious adverse events (1.1 per person year) or HIV-related complications, which were rare.
Dr. Durand also is leading the HOPE in Action Multicenter Kidney Study, a large-scale, NIAID-sponsored clinical trial to further study the safety of kidney transplantation between people with HIV.
A research team led by Univ.-Prof. Dr. Florian Klein of the Institute of Virology of the University Hospital Cologne and the German Center for Infection Research (DZIF) has identified a new highly active antibody targeting HIV.
Whereas the development of viral resistance limits the efficacy of previously described HIV antibodies, the newly identified antibody 1-18 can continuously suppress viral replication.
1-18 therefore has high potential for successful application in the prevention and treatment of HIV infection. An article describing antibody 1-18 has now been published in Cell.
Antiretroviral drugs are the gold standard for the treatment of HIV infection. They are highly effective in suppressing replication of the virus but require lifelong daily application and can be associated with side effects. Due to the high mutability of HIV and its capacity for rapid adaptation, combinations of antiretroviral agents are required to prevent the development of drug resistance and treatment failure.
Broadly neutralizing antibodies are a focus of ongoing research on novel options for the treatment and prevention of HIV infection. Their mode of action substantially differs from regular antiretroviral drugs, as antibodies target the virus through specific binding of HIV surface proteins.
Clinical trials have demonstrated the potential of broadly neutralizing antibodies by reducing the viral load in the blood of HIV-infected individuals. Similar to antiretroviral drugs, however, the effects of single antibodies were only temporary because of the development of viral resistance.
Scientists at the University Hospital Cologne have now identified a novel antibody called 1-18 that targets HIV. This antibody is highly potent and showed activity against 97% of the tested HIV variants. „1-18 is therefore among the best HIV neutralizing antibodies described to date“, says Dr. Philipp Schommers, resident physician at the Department I of Internal Medicine and one of the first authors of the article.
In collaboration with colleagues at the California Institute of Technology (Pasadena, USA), the researchers identified the mode of action of antibody 1-18 in detail. 1-18 binds and inactivates a surface structure of HIV that is particularly relevant because it is essential for viral infection and replication.
The therapeutic efficacy of the newly identified antibody 1-18 was studied using a mouse model that allows recapitulation of HIV infection as it occurs in humans. In this model, other broadly neutralizing antibodies showed only short-term effects because of the rapid development of viral resistance. In contrast, treatment with the antibody 1-18 resulted in suppression of the viral load that was maintained for the duration of therapy. „These results indicate that development of viral resistance against the new antibody 1-18 is restricted when compared to other antibodies“, says Dr. Henning Grüll, resident physician at the Institute of Virology and also first author of the work.
Due to its high potency, the scientists consider 1-18 a promising candidate for HIV immunotherapy. “In addition, 1-18 has great potential for preventing HIV infection by passive immunization“, adds Prof. Dr. Florian Klein, lead and senior author of the study. Clinical trials are now planned to further investigate antibody 1-18.
Efforts to prevent new HIV transmissions in the United States must be accompanied by advances in addressing HIV-associated comorbidities to improve the health of people already living with HIV, National Institutes of Health experts assert in the third of a series of JAMA commentaries.
Assuming the aspirational goals of Ending the HIV Epidemic are achieved, at least one million people in the United States still will be living with the virus. With effective antiretroviral therapy (ART), people with HIV can expect a near-normal lifespan. But even when treated with ART, people living with HIV are at heightened risk for numerous comorbidities, including heart disease, kidney disease, osteoporosis, liver disease, certain cancers and neurocognitive disease.
Successfully addressing HIV-associated comorbidities will require research advances to better understand how these conditions develop, write Anthony S. Fauci, M.D., director of NIH’s National Institute of Allergy and Infectious Diseases (NIAID), and colleagues. Clinical trials to assess treatments for HIV-associated comorbidities and efforts to reduce health care disparities also must be prioritized.
Insight into the mechanisms underlying the chronic immune activation and dysfunction associated with HIV could lead to new therapies to manage numerous HIV-associated comorbidities, including heart disease. In this regard, the REPRIEVE clinical trial is investigating whether a statin medication can reduce the risk of cardiovascular disease among people with HIV. Other factors involved in driving HIV-associated comorbidities include side effects of long-term ART use, such as lowered bone mineral density, and coinfections, such as viral hepatitis. Establishing a better understanding of these comorbidities and how to manage them will be essential to reduce the burden these conditions place on individuals and the health care system, the authors conclude.
Researchers at the National Institutes of Health and their colleagues at Massachusetts General Hospital (MGH) in Boston report that the injectable hormone tesamorelin reduces liver fat and prevents liver fibrosis (scarring) in people living with HIV.
The study was conducted by the National Institute of Allergy and Infectious Diseases (NIAID) and the National Cancer Institute, both parts of NIH. The findings were published online today in The Lancet HIV
A microscopic image of liver tissue affected by non-alcoholic fatty liver disease (NAFLD). The large and small white spots are excess fat droplets filling liver cells (hepatocytes). Dr. David Kleiner, NCI
“Many people living with HIV have overcome significant obstacles to live longer, healthier lives, though many still experience liver disease,” said NIAID Director Anthony S. Fauci, M.D. “It is encouraging that tesamorelin, a drug already approved to treat other complications of HIV, may be effective in addressing non-alcoholic fatty liver disease.”
Non-alcoholic fatty liver disease, or NAFLD, frequently occurs alongside HIV, affecting as many as 25% of people living with HIV in the developed world. However, no effective treatments currently exist to treat the condition, which is a risk factor for progressive liver disease and liver cancer. Investigators led by Colleen M. Hadigan, M.D., senior research physician in NIAID’s Laboratory of Immunoregulation, and Steven K. Grinspoon, M.D., Chief of the Metabolism Unit at MGH, tested whether tesamorelin could decrease liver fat in men and women living with both HIV and NAFLD. Among the participants enrolled, 43% had at least mild fibrosis, and 33% met the diagnostic criteria for a more severe subset of NAFLD called nonalcoholic steatohepatitis (NASH). Thirty-one participants were randomized to receive daily 2-mg injections of tesamorelin, and 30 were randomized to receive identical-looking injections containing a placebo. Researchers provided nutritional counseling to all participants, as well as training in self-administering the daily injections. Researchers then compared measures of liver health in both groups at baseline and 12 months.
After one year, participants receiving tesamorelin had better liver health than those receiving placebo, as defined by reduction in hepatic fat fraction (HFF)—the ratio of fat to other tissue in the liver. The healthy range for HFF is less than 5%. Thirty-five percent of study participants receiving tesamorelin achieved a normal HFF, while only 4% of those on placebo reached that range with nutritional advice alone. Overall, tesamorelin was well-tolerated and reduced participants’ HFF by an absolute difference of 4.1% (corresponding to a 37% relative reduction from the beginning of the study). While nine participants receiving placebo experienced onset or worsening of fibrosis, only two participants in the tesamorelin group experienced the same. Additionally, levels of several blood markers associated with inflammation and liver damage — including the enzyme alanine aminotransferase (ALT) — decreased more among those taking tesamorelin compared to those on a placebo, particularly among those with increased levels at the beginning of the study.
Given these positive results, investigators suggest expanding the indication for tesamorelin to include people living with HIV who have been diagnosed with NAFLD. They also recommend additional research to determine if tesamorelin could contribute to long-term protection against serious liver disease in people without HIV.
“Our hope is that this intervention may help people living with HIV, as well as benefit HIV-negative people with liver abnormalities,” said Dr. Hadigan. “Further research may inform us of the potential long-term benefits of this approach and develop formulations that can benefit everyone with liver disease, regardless of HIV status.”
Egrifta (tesamorelin) was approved in 2010 by the U.S. Food and Drug Administration to reduce excess abdominal fat in HIV patients with lipodystrophy — a complication characterized by an abnormal distribution of body fat initially associated with older classes of HIV medications. The most commonly reported side effects in previous clinical trials evaluating Egrifta included joint pain (arthralgia), skin redness and rash at the injection site (erythema and pruritis), stomach pain, swelling, and muscle pain (myalgia). Worsening blood sugar control occurred more often in trial participants treated with Egrifta than with placebo.
“Because tesamorelin proved effective in treating abnormal fat build-up in the abdomens of people in the context of HIV and related medication use, we hypothesized that the drug might also reduce fat that accrues in the liver and causes damage in a similar population,” said Dr. Grinspoon.
While liver disease is often associated with heavy alcohol use, NAFLD occurs when excess fat builds up in the liver without alcohol as a contributing factor. This condition may progress to liver damage, cirrhosis or cancer that could be life-threatening and necessitate liver transplantation.
Previous studies have found that vitamin E supplements, weight loss and other lifestyle changes can improve outcomes among HIV-negative people with NASH. However, treatment options for NASH and NAFLD are often not tested in people with HIV and none are available for this group. Obesity and type 2 diabetes raise the risk of developing NAFLD regardless of HIV status, and people with HIV are at increased risk of NAFLD because some HIV medications and HIV itself are associated with gaining abdominal fat and may contribute to liver fat build-up.
Infections that can affect the health of the pregnant woman, the pregnancy, and the baby after delivery include (but are not limited to):
Bacterial vaginosis (pronounced vaj-in-NOH-sis) is the most common vaginal infection in women of reproductive age. It increases the risk of contracting sexually transmitted infections (STIs) and may play a role in preterm labor. The condition results from a change in the balance of bacteria that normally live in the vagina. Having unprotected sex and douching can increase the risk of bacterial vaginosis. The Centers for Disease Control and Prevention (CDC) recommends that pregnant women get tested for bacterial vaginosis if they have symptoms and get treated if necessary.
Chlamydia infection during pregnancy is associated with an increased risk of preterm birth and its complications. If the infection is present and untreated at the time of delivery, it can lead to eye infections or pneumonia in the infant. In most hospitals, infants’ eyes are routinely treated with an antibiotic ointment shortly after birth. The ointment can prevent blindness from exposure to chlamydia bacteria during delivery in case the pregnant woman had an undetected infection.
Cytomegalovirus (CMV) (pronounced sahy-toh-meg-uh-loh-VAHY-ruhs) is a common virus present in many body fluids that can be spread through close personal contact, such as kissing or sharing eating utensils, as well as sexual contact. The virus usually does not cause health problems, but once it is in a person’s body, it stays there for life and can reactivate at different times. A pregnant woman may not even know she has the infection, and she may pass the virus on to her fetus, causing congenital CMV infection. Most infants with congenital CMV infection never show signs or have health problems. However, some infants have health problems such as hearing or vision loss, seizures, or intellectual disabilities that are apparent at birth or that develop later during infancy or childhood. Currently, routine screening for CMV during pregnancy is not recommended. Researchers are working on treatments for CMV and vaccines to try to prevent new infections during pregnancy and to reduce the risk of transmission to the infant. Congenital CMV infection can be diagnosed by testing a newborn baby’s saliva, urine, or blood. Treatment with antiviral drugs may decrease the risk of health problems and hearing loss in some infected infants.
Fifth disease is caused by human parvovirus (pronounced PAHR-voh-vahy-ruhs) type B19. The virus causes a common childhood disease that spreads easily from person to person. Children who get it usually have a fever and a red rash on their cheeks. Parvovirus B19 usually does not cause problems for pregnant women or the fetus, but in rare cases, the woman might have a miscarriage or the fetus could develop anemia. There is no vaccine or treatment for fifth disease. You can reduce your chance of being infected with parvovirus B19 or infecting others by avoiding contact with people who have parvovirus B19 and by thoroughly and regularly washing your hands. Sometimes health care providers recommend testing pregnant women to see if they are immune to the virus already.
Untreated gonorrhea infection in pregnancy has been linked to miscarriage, preterm birth and low birth weight, premature rupture of the membranes surrounding the fetus in the uterus, and infection of the fluid that surrounds the fetus during pregnancy. Gonorrhea can also infect an infant during delivery as it passes through the birth canal. If untreated, infants can develop eye infections and blindness. In most hospitals, infants’ eyes are routinely treated with an antibiotic ointment shortly after birth to prevent eye problems from exposure to gonorrhea during delivery, in case the pregnant woman had an undetected infection. Treating gonorrhea as soon as it is detected in pregnant women reduces the risk of transmission.
Group B streptococcus (GBS) can cause serious health problems in infants. But giving antibiotics during labor can prevent the spread of GBS, so it’s important to get tested for the infection during pregnancy. Learn more about GBS and pregnancy.
Pregnant women who get infected with genital herpes late in pregnancy have a high risk of infecting their fetus. The risk of infection is particularly high during delivery. Herpes infections in newborns are serious and potentially life-threatening. Infection with the herpes virus during pregnancy or at the time of delivery can lead to brain damage, blindness, and damage to other organs. Rarely, herpes infection during pregnancy can lead to serious complications in the mother, including severe liver damage and possibly death.
If a pregnant woman has had genital herpes in the past, there are medications that she can take to reduce the chance that she will have an outbreak, which also reduces the risk to her fetus.If a woman has active herpes sores when she goes into labor, the infant can be delivered by cesarean section to reduce the chance that the infant will come in contact with the virus.
If a woman is infected with hepatitis B virus (HBV) during pregnancy, the virus could infect her fetus. The likelihood of transmission depends on when during pregnancy the mother was infected. If the mother gets the infection later in her pregnancy, the risk that the virus will infect her fetus is quite high. If the infection occurs early in pregnancy, the risk of the virus infecting the fetus is much lower. For more information about Hep B during pregnancy, visit the Centers for Disease Control and Prevention (CDC) website. In infants, HBV can be serious and can lead to chronic liver disease or liver cancer later in life. In addition, infected newborns have a very high risk of becoming carriers of HBV and can spread the infection to others.
In some cases, if a woman is exposed to HBV during pregnancy, she may be treated with a special antibody to reduce the likelihood that she will get the infection.All healthy infants should be vaccinated against HBV to give them lifelong protection.Infants born to women with evidence of ongoing HBV infection (HBV surface antigen positive) should also receive hepatitis B hyperimmune globulin as soon as possible after birth. Hepatitis C virus (HCV). CDC offers more information about HCV.
HIV/AIDS. HIV can be passed from mother to infant during pregnancy before birth, at the time of delivery, or after birth during breastfeeding.
Listeria or listeriosis (pronounced li-steer-ee-OH-sis) is a serious infection usually caused by eating food contaminated with a particular type of bacteria. Infection during pregnancy can lead to pregnancy loss, stillbirth, preterm birth, or life-threatening infection of the newborn. Listeriosis is most often associated with eating soft cheeses and raw milk, but recent outbreaks have been associated with fresh and frozen produce. Prevention recommendations include checking food labels to avoid eating unpasteurized cheese (made from raw milk) and other actions. Learn more about preventing listeria during pregnancy.
Getting rubella (sometimes called German measles) during pregnancy can cause problems with the pregnancy as well as birth defects in the infant. Health care providers recommend that women get vaccinated against rubella before they get pregnant. Learn more about rubella and pregnancy.
Syphilis may pass from an infected mother to her fetus during pregnancy. The infection has been linked to preterm birth, stillbirth, and, in some cases, death shortly after birth. Untreated infants who survive tend to develop problems in many organs, including the brain, eyes, ears, heart, skin, teeth, and bones. All pregnant women should be screened for syphilis during their first prenatal visit. Women considered to be high risk should be screened again in the third trimester.1
Toxoplasmosis (pronounced tok-soh-plaz-MOH-sis) is a disease caused by a parasite that can be present in cat feces or used cat litter. Cats get the parasite from eating small animals or birds. In humans, the disease is usually mild, but if the parasite passes from a pregnant woman to the developing fetus, it can cause intellectual disabilities, blindness, or other problems. Women who are trying to become pregnant or are pregnant can take steps to prevent exposure to the parasite, such as having someone else clean or change the cat litter box and wearing rubber gloves to handle cat litter or while gardening.
Trichomoniasis. CDC offers more information about trichomoniasis.
Zikais caused by a virus spread mainly by the bite of a certain type of mosquito, but it is also spread through sexual contact. Although its symptoms are usually mild, Zika infection during pregnancy can cause pregnancy loss and other pregnancy complications, as well as birth defects and other problems for the infant.
Bill & Melinda Gates Foundation said there is need for improved quality of counseling and a range of contraceptive and HIV prevention options, so women can make informed decisions to protect their health and future.
HIV Study underscores urgent need for high-quality counseling prevention options. Photo credit Family Planing 2020
The Evidence for Contraceptive Options and HIV Outcomes (ECHO) trial, funded by the Bill & Melinda Gates Foundation, USAID, SIDA, UNFPA, NICHD and the Medical Research Council of South Africa, compared the relative risk of HIV acquisition among women using one of the following three contraceptive methods: the injectable contraceptive DMPA-IM; the Jadelle LNG-implant; and a copper intrauterine device, or IUD.
USAID and the South African government donated the contraceptives used in the trial.
“We’re encouraged the ECHO trial found no substantial difference in HIV acquisition among the methods tested because millions of women around the world rely on modern contraception to make informed decisions about their health and futures,” said Chris Elias, President of Global Development at the Bill & Melinda Gates Foundation. “Nonetheless, it’s concerning to see persistently high HIV incidence among women seeking contraception in eastern and southern Africa. This study underscores the urgent need to improve integrated care that includes high-quality counseling and a range of contraceptive and HIV prevention options.”
The foundation noted that there has been a longstanding question as to whether an association exists between hormonal contraceptive use and HIV acquisition among women who are at high risk for HIV.
In 2015, the Gates Foundation along with USAID, WHO and other partners launched the Evidence for Contraceptive Options and HIV Outcomes (ECHO) trial to assess the comparative risk of HIV acquisition among women using one of the following three hormonal contraceptive methods: injectable DMPA-IM, LNG implant/Jadelle and copper intrauterine devices (IUDs). The study enrolled 7,830 women across 12 sites in Kenya, South Africa, eSwatini and Zambia, and was the most comprehensive study attempted to date to investigate the question.
The ECHO study did not result in a statistically significant difference in the risk of acquiring HIV among women using any of the three contraceptive methods included in the trial. All contraceptive methods studied were found to be safe, effective and generally well-accepted by the women using them. The high incidence of HIV among women involved in the study, regardless of the contraceptive used, demonstrates the persistent threat women seeking contraception face when living in high HIV prevalence communities or settings.
The results also draw renewed focus to the need for improved quality of counseling and a range of contraceptive and HIV prevention options, so women can make informed decisions to protect their health and future.
The ECHO trial was designed and implemented to high methodological, ethical and regulatory standards. An independent Data and Safety Monitoring Board regularly met to review the trial data to ensure the health and safety of the 7,830 participating women involved in the study were not compromised.
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