NAIROBI — Each week, about 6,000 women aged between 15 and 24 are infected with HIV. Women and girls are the most vulnerable to the infection, and scientists are still trying to investigate why.
In Kenya, researchers are trying to better understand this transmission route into the female body. Scientists at KAVI Institute of Clinical Research, at the University of Nairobi, are examining how the virus interacts with the mucus lining in the female reproductive tract, with an ultimate aim to find a technique that stops HIV at one of its entry points. This is the first research of its kind in sub-Saharan Africa.
“This is the first time a lab in sub-Saharan Africa will be able to visualize this kind of virus and human cell system interactions.”— Dr. Marianne Mureithi, team leader, KAVI
“For a very long period of time, we've been studying HIV in the blood system, where the infection has already occurred,” said Dr. Marianne Mureithi, team leader at KAVI. “What we have really concentrated on now is the more elite part of the immune system and how it interacts with HIV.”
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Information gathered from this research will be used for the development of a vaccine, antibodies or microbicide to prevent HIV transmission in women and girls, researchers said.
“If we understand the events that occur during infection, we may be able to come up with a solution on how to formulate a barrier that will prevent the infection from happening,” Mureithi said. “To do that, we really need to understand the mucosal environment.”
Questions around the mucus
Dr. Thomas Hope, professor of cell and developmental biology and obstetrics and gynecology at the Feinberg School of Medicine at Northwestern University in the United States, has been examining these questions since the early 1990s. The new studies are an extension of the ongoing research in which he has used the mucus in the reproductive tracts of primates.
In 2016, this research began in Nairobi where researchers are using actual human female reproductive tracts. To do this, they receive donated tissues from hysterectomies from Kenyatta National Hospital, located next-door to the laboratory. They also receive donations of vaginal cervical mucus from women in Nairobi. This includes samples of both HIV-positive and HIV-negative individuals.
The researchers then introduce the HIV virus and watch as it infects the tissue.
The ability to watch the virus as it moves through the tissue is possible because of a microscope that costs about $225,000 — one of only two on the African continent. KAVI researchers have nicknamed the microscope “mpenzi,” “my love” in Swahili. The other microscope, at the University of Cape Town, is examining HIV transmission in male genital foreskins.
“This is the first time a lab in sub-Saharan Africa will be able to visualize this kind of virus and human cell system interactions,” Mureithi said.
As the HIV virus moves through the female reproductive tract, it has to pass through the cells that line the vagina to reach underlying immune cells. The virus spreads in the tissue and ultimately reaches the immune system, Hope said. The point at which the HIV virus is in the blood system is when a person is considered infected.
Essentially, researchers want to better understand the biological barriers — the mucosal environment — that women have to prevent HIV infection, Mureithi said. Researchers are looking at which cells interact with HIV at this point of entry in the vagina, uterus, fallopian tubes, with a particular focus on the ectocervix and endocervix, because those are the tissues the researchers get from the hysterectomy procedures.
“If we can find infected individuals that have shown evidence of trapping the virus in the mucus, and we can show that is because of antibodies, then we can try to understand what those antibodies are and try to get a vaccine,” Hope said.
Researchers are also examining questions around how the mucosal layer is influenced by factors such as a person’s age, other infections, menstrual cycles, and diet, Mureithi said.
There are also efforts to better understand the microbiome — or community of organisms — that exist in the reproductive tract, she added. Researchers are examining how the role these organisms play influences the susceptibility of acquiring HIV.
Local tissue and glowing HIV samples
Nairobi has a unique advantage over the work conducted at the Northwestern University campus because it’s much easier to obtain intact tissue samples from hysterectomies.
In Chicago, when Hope asked for tissues from a local hospital, surgeons were less willing to collect the sample before surgery, whereas in Nairobi they were willing to do that, he said.
One of the reasons this is important, is that during surgery health workers sterilize as much as they can of the vaginal tract, which destroys the microbiome, he said.
There have also previously been some challenges around a surgical technique where tissue was ground up inside a person’s body during surgery and sucked out through a tube, Hope said. But that practice has since stopped.
There are also multiple groups competing to get access to tissue in the U.S. Parts of samples are also stored in pathology departments for record-keeping, he said. This can cause delays, while it’s ideal the research starts on the tissue as soon as possible after the surgery, Hope said.
“The sooner we can do that sampling, the more confident we can be that the tissue is what it was like when it was in the person. Those sorts of things can make a big difference in the quality of the sample,” Hope said.
Because of this, the work at Northwestern University has focused on animals — which doesn’t give a comprehensive view of the transmission that occurs in humans, Mureithi said.
In Nairobi, researchers have collected about 100 hysterectomy samples from women.
“Our proximity to the largest hospital in East and Central Africa is a really a good plus for getting samples,” Mureithi said. “Within 10 minutes of the surgery, we get the samples.”
But unfortunately, researchers can’t simply use HIV viruses sourced locally. They must send the viruses that are collected in Kenya to Northwestern University, where the infectious component is modified to glow so that it can be seen in the microscope. The glowing viruses are then sent back to Kenya. KAVI does not have the lab capacity to alter the virus in this way.
Having a strain of the virus from sub-Saharan Africa is important because the antibody response is different depending on the strain, Hope said.
“We are looking at how antibodies in the mucus are interacting with viruses. It's important that we follow viruses that sort of match what is there locally,” he said, adding that answering all of these questions won’t be quick but could have a significant payoff.
“I think that is going to take us a couple years, but if we can figure out how that works, then I think it’s going to give ourselves and others a chance to maybe come up with an intervention that could really slow down the virus,” Hope said.