Food fungus worsens African AIDS epidemic

I keep coming across factors that, while not directly related to the nature of the human immunodeficiency virus (HIV), are nonetheless driving the African AIDS epidemic.

Take the recent news about a study from the School of Public Health, which found that a type of fungus coating much of the stored corn, rice and nuts in many African and Asian countries may be weakening immune systems and encouraging HIV infection.

Kept in sacks piled in warehouses, food stores in countries near the equator are often contaminated by Aspergillus flavus and A. parasiticus, fungi that produce a toxic substance called aflatoxin.

About 4.5 billion people worldwide are exposed to aflatoxin at unsafe levels, and chronic exposure has been linked to liver damage and related cancers.

Work by Pauline Jolly, Ph.D., professor in the Department of Epidemiology within the UAB School of Public Health, argues that aflatoxin exposure may be taking an even greater toll in areas where millions are infected with HIV. The research team divided 314 HIV-positive people from Kamasi, Ghana, into four groups based on their level of aflatoxin exposure.  The team found that those in the highest exposure group were 2.6 times more likely to have a high HIV viral load than those in the lowest exposure group. Higher viral load translates into higher rates of HIV transmission. For information, please see our news release and related coverage by the New York Times.

Along the lines of non-viral factors worsening the AIDS epidemic was another study published this past August, also from the School of Public Health. Janet Turan, Ph.D., associate professor in the Department of Health Care Organization and Policy, and her team found that the fear of being labeled HIV-positive was strong enough to keep mothers from Kenya from having their babies in health-care facilities. Communities there have come to see clinics and skilled care as mostly for HIV-positive women, and HIV often is linked to promiscuity in the eyes of a woman's family.

In Nyanza, Kenya, a region where one in five pregnant women is HIV-positive, skilled care during pregnancy and birth increases the likelihood that those infected will receive antiretroviral drugs that prevent the passing of HIV from mother to child.

It just seems like Africa can’t get a break.

More troubling yet, the search for solutions to the epidemic's many contributors is not accelerating in the age of research budget cuts. The grants that paid for Jolly's research into the aflatoxin and HIV have ended, leaving her unable to pay for a full data analysis of the consequences of combination exposure on sets of immune cells. She does not know where her next round of funding will come from.

“A fungal contribution to HIV transmission will only be proved once and for all by larger randomized studies for which there now is no funding," Jolly said. "The scientific and world-health communities need to decide soon whether or not this question is worth answering.”

Image post 3: dangerous clumps of fungus

While most posts from The Mix feature a science story, we have also begun sharing images coming out of UAB research. Below is a brief description of what we are looking at and how related work may help to diagnose and treat fungal infections.

Here is a scanning electron microscope image of the fungus called Aspergillus. It's in the process of germinating, or emerging from round spores (at the center) to begin growing. The fungus has sprouted long, branching filaments called hyphae.

Most people breathe in Aspergillus spores daily without incident, but those with lung diseases or weakened immune systems can contract Aspergillosis, symptoms of which range from allergic reactions to severe lung infections. The fungus is a major player in some forms of allergic asthma, as clumps of hard-to-remove hyphae build up in the lungs.

According to the CDC, fungal infections pose an increasing threat to public health because of the growing number of people with weakened immune systems, including AIDS, cancer and transplant patients. In addition, treatment-resistant fungal infections have emerged as a growing problem in hospitals. Global warming may be contributing to an increase in infections, as fungi thrive in warm, moist conditions. Please see the CDC fungal page for more.

Current treatments are largely incapable of reducing morbidity and mortality in Aspergillosis, said John Kearney, Ph.D., professor in the Department of Microbiology within the UAB School of Medicine. He and his team are developing a new kind of vaccine that could provide protection against invasive Aspergillosis. Bacteria elicit a stronger human immune response than fungi but contain some of the same proteins (e.g. chitin). Based on these common building blocks, it may be possible to develop a vaccine where bacterial protein vaccine ingredients are used to activate immune cells that also target a fungus and remove it from the body.

This image was made by Dr. Jeffrey Sides from the Kearney laboratory at UAB using an instrument made available by the UAB School of Engineering.

HIV "cure" might fill a gap

It's strange when the discovery of a "cure" points to another, some say even greater, achievement. For instance, the news this week was that researchers used aggressive drug treatment to "cure" a Mississippi baby born with the AIDS virus. We had a quick talk about the story with Michael Saag, M.D. co-director of the UAB Center for AIDS Research.

The baby's mother, living in a poor, rural community, had been infected and passed the virus to her fetus, but had received no prenatal care before she went into labor. So the baby was born before anyone knew it was infected. As in many stories of discovery, what happened next included some accidents.

The hospital was out of the usual treatment, so the baby was referred to doctors that decided to use a high-dose, three-drug combination for older children instead of the usual low-dose treatment recommended for babies. They also administered the drugs quickly after birth.

After 18 months on the treatment, the baby and its family dropped out of the system, and the child went on an unplanned "treatment holiday." When the family reappeared, doctors realized that the child had been off the medications for a year but had no signs of infection.

As amazing as this case is, what jumps out at me is its rarity. In nearly all cases, HIV-infected mothers in the United States are tested and treated months before giving birth; nearly all of their babies are born with undetectable viral levels (functionally cured). In that light, this week's cure, should it be confirmed, would apply to the very few HIV positive babies in the U.S. that are not treated before birth. Somewhat lost in the excitement over a cure for the few exceptions is the massive achievement by the U.S. system of virtually eliminating mother-to-child HIV transmission.

"This case goes to show that once drugs are invented, as complex as that is, the field then faces the even more daunting task off getting them to everyone who needs them, and using them in the best way for each group of patients," said Saag. "That said, the new technique may fill a vital gap if it reduces viral load to almost zero in babies born to mothers that have slipped through HIV surveillance systems."

This week's discovery could have the most meaning outside of the United States, said Saag. The poorest African countries, for instance, have high infection rates, and only about 60 percent of pregnant women get treatment that can keep them from passing the virus to their babies.

Moving forward, Saag said, it is important for the field to understand why the baby was cured. Early on in exposure to the HIV, the infection either takes or it does not. If it takes, the virus goes into a latent state where it hides and quietly multiplies indefinitely, weakening the immune system while it grows strong. Once a pool of latent virus is present, it is harder to kill enough virus with antiviral drugs to get a cure. In the Mississippi case, Saag said it looks like strong, quick treatment after the initial infection may have prevented the establishment of a latent pool of infected cells.

As explained in this article in USA Today, it will take some time before the global impact of this week's cure is understood. In the best case scenario, babies not treated during pregnancy may receive more aggressive treatment at birth to spare them the burden of taking so many medications for a lifetime.

HIV infection follows poverty south

HIV research and AIDS treatment in the United States are the focus of a recently published feature article in the journal Science. The article was timed to set the stage for the first U.S.-hosted International AIDS Conference in 22 years, which started yesterday in Washington, D.C. The meeting’s organizers had shunned the U.S. for decades due to a ban on the immigration of HIV-infected people imposed by Congress in 1987 – a ban that President Obama ended in 2010.

The AIDS epidemic has shifted over 31 years from a disease of white, economically secure gay men on the coasts to one of poor African Americans – gay and straight – in the South, home to 43 percent of the country’s HIV-infected people, according to the article.

Michael S. Saag, M.D., is director of the UAB Center for AIDS Research. Before flying to the AIDS conference, Saag sat down with us for the very first podcast from The Mix, the new UAB research blog. Saag helped to found the 1917 Clinic at UAB – a comprehensive HIV clinic serving Birmingham, Ala., and one of 10 efforts nationally highlighted in the Science feature.

Show notes from the interview

1:38 HIV infection risk has now been proven to depend less on the stereotypical notions of the past – multiple partners, lack of condom use, prison time, etc. 

1:51 Poverty is the single, overwhelming driver of HIV infection risk in African Americans, explaining why the epidemic is hitting so hard in the South.  

2:18 Many more people who are poor contract HIV due to lack of access to healthcare and the close ties between poverty and drug addiction. With more infected people living in poor communities, the risk of passing it to fellow community members is higher. Those living in poverty are also more likely to be focused on day-to-day survival, which drives risky behavior.

3:32 AIDS symptoms may be ignored or hidden more in the African American community due to cultural differences with respect to tolerance of homosexuality, says Saag. Being gay is taboo in both African American and white communities, but is especially so among African Americans, and even more so among African American churchgoers. This means that gay men often hide their orientation, living publically in heterosexual relationships while secretly having gay sex, which further spreads the disease.

5:09 HIV funding from the CDC shifted in 2012, with $40 million of its $338 million budget meant to have greater impact in harder-hit locales, according to the Science article. Medications are now available that have turned HIV into a chronic disease, enabling people to live for decades. The problem is that many poor people do not know they are infected, have little access to care or ability to maintain treatment regimens.  

5:58 Infected patients who don’t know they are infected represent 25 to 40 percent of those infected in the United States, says Saag. Public education campaigns in hard hit communities are needed to get more people tested, as are special programs that link newly diagnosed patients to treatment programs. 

7:15 UAB’s 1917 Clinic has conducted more than 300 clinical trials since its founding in 1988, and have made every major AIDS drug, and later the most powerful drug cocktails, available to poor communities. 

7:36 Testing, diagnosing and getting more patients into permanent care will be the focus of the HIV medical establishment over the next 10 years, rather than drug development, although that will continue. Excellent drugs are available. The challenge is to get people to know they need them and to keep taking them. 

8:41 The International AIDS Conference has returned to U.S. soil for first time in 22 years, which is important because the U.S. has been a major contributor to AIDS research and should participate fully in global discussions on how to improve care.

10:12 AIDS research themes that will gain the most attention at the conference should include how testing can drive people into care, how effective treatment can prevent transmission, pathways to a future cure and policy discussions about how countries afford and make accessible mass treatment, says Saag.

11:37 Treatment as prevention is a hot topic with the recent FDA approval of Truvada, shown to lower the risk of infection when given to people at high risk but not yet infected. The advent of preventive treatment creates many policy questions that will be discussed, including the potential for the use of vaccines.  

12:22 Resources for getting more information about AIDS and HIV include the CDC HIV/AIDS home page, and for researchers, the National AIDS Treatment Advocacy Project, which offers excellent coverage of meetings and abstracts, Saag says.

13:37 Support for the 1917 Clinic can take the form of volunteering and community outreach, or donations to the 1917 Clinic Development Fund, which helps program development (testing, linkage-to-care initiatives), and the 1917 Clinic Patient Assistance Fund, which helps people gain access to treatment during gaps in coverage. 

14:35 End

About the Podcaster

Greg Williams @gregscience @themixuab is research editor within Media Relations at the University of Alabama at Birmingham.