Friday, October 25, 2013

Child 'Cured' of HIV Remains Free of Virus



A 3-year-old Mississippi girl apparently cured of HIV infection by aggressive treatment right after her birth remains free of the virus, her doctors report.

Early treatment with a combination of potent antiretroviral drugs appears to have kept the virus from successfully establishing a reservoir in the child's system, said immunologist Dr. Katherine Luzuriaga, of the University of Massachusetts Medical School, who is part of the research team tracking the case.

Doctors are hesitant to declare the child fully cured, but they said that no actively replicating HIV has been found in her system by even the most sensitive tests available. The girl stopped taking HIV medication when she was 18 months old.

A couple of tests have found very low-level indications of HIV in the girl's blood, but doctors cannot tell if they are false positives or simply remnants of the eradicated virus.

"If they are remnants, the question is whether they are capable of reigniting," Luzuriaga said. "For that reason, we are calling this a remission because we want to follow the baby over a longer period of time to see if the child continues to control the virus without rebound."

The girl's pediatrician, Dr. Hannah Gay, of the University of Mississippi Medical Center, launched HIV treatment just 30 hours following her birth. Doctors normally put HIV-positive mothers on two antiretroviral medications prior to birth as a way of preventing transmission of the virus to their unborn children, Luzuriaga said. After delivery, doctors test the newborns for HIV and continue treatment if the virus appears.

But in this girl's case, no one knew the mother was HIV-positive before delivery and the girl was born infected. This led Gay to put the newborn on antiretroviral treatment immediately, and that timing appears to have made a difference. Gay also chose to employ a combination of three antiretroviral drugs, all at doses commonly used to treat HIV-infected infants, and kept the girl on the medications until she was 18 months old. This prevented the virus from mounting any drug resistance before it could be wiped clean from her body, Luzuriaga said.

Tests showed progressively diminishing HIV levels in the infant's blood, until it reached undetectable levels 29 days after birth. The child remained on antiretrovirals until 18 months of age, at which point doctors said they lost track of her and she stopped treatment. Doctors next saw her about 10 months after her treatment ceased. The child underwent repeated standard HIV tests, which detected no virus in her blood.

The two factors -- timing and medication -- appear to have prevented HIV from gaining a foothold in the girl's immune system. The virus was unable to create a reservoir in her body in which dormant HIV can hide and later reignite when drug therapy is suspended.

"What studies in other babies have shown us is if you treat very early, you're not only able to treat the viral replication but also able to limit the number of cells in which HIV integrates itself into the host genes," Luzuriaga said. "Basically, HIV makes copies of DNA and that DNA integrates itself into host genes. That's the barrier to cure. As long as you have those white blood cells floating around the body that have HIV stitched into the host DNA, the patient is not cured."

A key point is that the child exhibits none of the immune characteristics seen in "elite controllers," the tiny percentage of HIV-infected people whose immune systems are so active that they can keep the virus in check without treatment, the researchers said. The absence of these characteristics indicates that early therapy -- rather than natural immune mechanisms -- led to the child's remission.

Based on this girl's case, a federally funded study set to begin in early 2014 will test the early treatment method to determine whether the approach could be used in all HIV-infected newborns.

This method could cure newborns infected with HIV but is unlikely to help adults, given that they rarely learn of their infection until months or years after transmission, said Dr. Rowena Johnston, vice president of research at the Foundation for AIDS Research (amfAR).

"If there is something key to treating HIV within the first couple of days of transmission, it's going to be incredibly difficult to treat adults in this manner," Johnston said. "But this case really opens up the possibility that there may be different HIV cures for different populations, depending on what the circumstances are."

Dr. Michael Horberg, director of HIV/AIDS treatment and research for Kaiser Permanente, agreed that the infant's case is very encouraging, but said it's not an indication of a potential cure for all people with HIV.

"This is a very unique situation, but it does show that very early treatment is very successful," Horberg said. "We can envision potential future pathways with correct medication and vigilance where there might be a percentage of patients who could be successfully treated."

Only one other instance of an HIV cure has been documented, in the so-called "Berlin patient." An American man living in Germany received a bone marrow transplant for leukemia, with cells from a donor who had a rare genetic mutation that increases immunity against HIV. This patient has remained HIV-free after discontinuing drug therapy.

Thursday, October 17, 2013

Breast milk found to kill HIV


Is it possible that breast milk contains the magic potion which kills the virus that causes AIDS? According to new research, that's a distinct possibility.

A recent study, which was conducted by researchers from the University of North Carolina School of Medicine, found that mice did not contract HIV after ingesting virus-tainted breast milk.

Moreover, the researchers found, the breast milk actually killed the virus.

The mice used in the study had previously been injected with human cells to reconstitute their bodies, the CBS affiliate in Charlotte reported. Other reports said the mice were injected with human bone marrow, liver and thymus tissues so they would have fully functional human immune systems and be nearly as susceptible to the HIV virus.

It's the first study to examine the effect of breast milk on HIV in a mammalian model. Prior research has only been done in test tubes.

"The results of these experiments highlight the potent HIV inhibitory activity of normal human breast milk and demonstrate that the in vitro HIV inhibitory activity of human breast milk is also capable of efficiently preventing oral transmission of cell-free HIV," the study said.

Breast milk serves a 'protective role'

Researchers who conducted the study hope it demonstrates that it's safe for an HIV-positive woman who is taking anti-retrovirals to breastfeed her children, even though for years they have been told not to do so if infected.

"Our results highlight the protective role of human breast milk against HIV transmission and suggest that components in both the skim milk and lipid fractions may contribute to its HIV inhibitory activity," the study said.

Dr. Viktor Garcia, the study's senior author, said in a press release that this study will help "close this important door to the spread of AIDS."

"No child should ever be infected with HIV because it is breastfed. Breastfeeding provides critical nutrition and protection from other infections, especially where clean water for infant formula is scarce," he said in a press release to the university. "Understanding how HIV is transmitted to infants and children despite the protective effects of milk will help us close this important door to the spread of AIDS."

Study results provide the path ahead

Angela Wahl, a post-doctoral researcher at UNC School of Medicine and lead author of the paper, said, "These results are highly significant because they show that breast milk can completely block oral transmission of both forms of HIV that are found in the breast milk of HIV-infected mothers: virus particles and virus-infected cells.

Wahl added: "This refutes the 'Trojan horse' hypothesis which says that HIV in cells is more stubborn against the body's own innate defenses than HIV in virus particles."

Despite the encouraging study, it's not a certainty that mothers with HIV who breastfeed their children won't pass the virus along. But Wahl said the research is, essentially, a good starting point for further study because it lays the foundation for the next step - figuring out what component of breast milk actually provides the protection. To do that, researchers will now have to study breast milk from mothers who did pass along the virus and the milk of mothers who did not, to find the difference.

"What we have shown is that breast milk is indeed a protective agent, so it should not be denied even to children of HIV-infected women," "What we know is that infants who acquire HIV during breastfeeding weren't infected at the time of birth, and when you look at the virus that eventually infects the infant and the virus in mother's breast milk, it's the same. But it doesn't mean it couldn't be the result of contact with blood."

Thursday, October 10, 2013

HIV Vaccines Elicit Immune Response in Infants

A new analysis of two HIV vaccine trials that involved pediatric patients shows that the investigational vaccines stimulated a critical immune response in infants born to HIV-infected mothers

The finding at the AIDS Vaccine 2013 meeting in Barcelona, Spain, examined samples from two previously completed pediatric HIV vaccine trials - called PACTG 230 and PACTG 326 - to determine whether they elicited a key immune response that has only recently been associated with reduced HIV infection.
Searching for evidence of an anti-V1V2 IgG antibody response - the newly identified mechanism for protection against HIV - the researchers found that both of the old pediatric vaccine candidates triggered this key immune defense. While babies born to HIV-infected mothers had maternally acquired anti-V1V2 IgG antibodies at birth, infants who were vaccinated had better and longer-lasting antibody responses than their counterparts who received a placebo vaccine.

"Effective infant HIV vaccination may be affected by the presence of maternal HIV-specific antibodies and the immaturity of the infant immune system," said the study's lead author, Genevieve Fouda, M.D., PhD, of Duke. "Our findings suggest that vaccination of infants born to HIV-infected mothers can elicit a robust anti-HIV envelope IgG immune response."

Fouda said the results of the study highlight the importance of including pediatric populations in HIV vaccine studies. "Mother-to-child transmission continues to be an important public health issue in resource limited areas," Fouda said. "Every year, approximately 300,000 infants are infected with HIV. Antiretroviral drugs have reduced the rate of mother to child transmission rate in the United States below 2 percent, but overall in low and middle income countries less than 60 percent of known HIV infected women receive drugs to prevent transmission to their infants. Immune-based interventions such as a vaccine are needed to eliminate pediatric HIV."

Friday, October 4, 2013

Anabolic steroids help people with HIV put on weight and muscle mass

People with HIV who are treated with anabolic steroids to prevent AIDS wasting may realize modest gains in weight and muscle mass.


The review covered 13 studies of adults age 24 to 42 with HIV, 294 of whom received anabolic steroids for at least six weeks and 238 of whom received placebo. The average weight increase in those taking anabolic steroids was nearly three pounds.

“The magnitude of weight gain observed may be considered clinically relevant,” said lead author Karen Johns, a medical assessment officer from the agency Health Canada. “One hopes there would be greater weight gain with the long-term use of anabolic steroids; however, this has not been proven to date in clinical trials.”

AIDS wasting, which leads to significant weight loss in people with HIV, causes severe loss of weight and muscle and can lead to muscle weakness, organ failure and shortened lifespan. Researchers have long sought to reverse this common, destructive effect of HIV with mixed success.

The wasting stems from loss of the body’s ability to grow muscle and from low levels of testosterone.

Anabolic steroids are synthetic substances similar to the male sex hormone testosterone that promote growth of skeletal muscle and the development of male sexual characteristics.

Although most recently in the news for their misuse by professional athletes, anabolic steroids have legitimate medical application for men with low testosterone and people with certain types of anemia. Two anabolic steroids available in the United States, nandrolone decanoate and stanozolol, have been used to help increase weight and muscle mass in small studies of people with wasting.

Conversely, anabolic steroid use has been associated with increased rates of HIV in those who share needles or use nonsterile needles when they inject steroids.
In the review studies, anabolic steroids were administered to patients either orally or by injection. The main side effects were mild and included abnormal liver function tests; acne; mild increase in body hair; breast tenderness; increased libido, aggressiveness and irritability; and mood swings — all common side effect of anabolic steroid use.

“The risks and side effects of taking anabolic steroids long-term are certainly of concern,” Johns said. “We were unable to assess these risks in our review due to the short duration of treatment in the studies.”

Wayne Dodge, M.D., the HIV/AIDS program director at the Group Health Cooperative in Seattle, suggests that clinicians should obtain blood testosterone levels, “if an HIV-infected individual has had significant weight loss, significant fatigue or muscle wasting, and particularly if associated with a significant decrease in libido and erections. If [testosterone] is in the low or low-normal range then a trial of [steroids] could be tried. The individual and the clinician should decide what result would constitute a successful trial: weight gain of 15 pounds, a 30 percent improvement in sense of well-being [or] a successful erection once a week.”

The reviews authors conclude that further studies are needed to determine if increase in weight leads to improved physical functioning and quality of life, and ultimately increased survival, as well as the potential for serious side effects, especially with prolonged use.