A promising anti-HIV drug poses a dilemma

If you live in a wealthy country, you have choices about your medical care.

Let's say you're a young woman who is HIV-positive and find out there's a new treatment that's much better for your long-term health. But there's a potential problem: If you get pregnant, the drug could cause a serious birth defect in your baby.

In the U.S., Europe and other wealthy areas, a doctor will explain the benefits and the risks. If you choose the new drug, the doctor will prescribe birth control. If you want to get pregnant, the doctor will guide you through a period of taking the old drug, then get you back on the better drug when it no longer could endanger the fetus.

Now, say you live in a poor country. There aren't enough doctors and nurses to explain the risks and benefits of the new drug to every patient. Your country may not have the resources to keep supplies of two different drugs on the shelves. And there is no consistent access to effective birth control.

So what will those poor countries do in this kind of situation? Some will offer the new, better drug only to men and to women beyond child-bearing years. Some won't offer the new drug at all. Many younger women will get the second-best treatment for AIDS simply because they're of child-bearing age.

That's the dilemma for many countries that don't have the resources to offer patients the same choices that people in rich countries have. The problem was explored in a new study released this month in the Annals of Internal Medicine. Unexpected finding The new study was a response to a surprising result from a clinical trial comparing two AIDS treatments. Between November 2016 and May 2018, 426 HIV-positive pregnant women in Botswana were given a new drug designed to treat their symptoms and help prevent HIV transmission to the baby and to the women's sex partners. First reports from the clinical trial published in June 2018 in the Lancet showed that the new drug was, indeed, more effective than the old drug with fewer side effects.

But as time went by and more babies were born, the researchers became alarmed about the drug's impact. Among the group of women who took the new drug during the period that they conceived the child, four of them gave birth to infants with severe brain defects. In a flash, a promising international AIDS treatment strategy that was on the verge of being rolled out in sub-Saharan African countries was thrust into a world of uncertainty.

The new study estimated what could happen if millions of poor HIV-positive African women of child-bearing age were given the new, more effective drug. How many babies might be harmed? On the other hand, if the more effective drug were withheld, how many adult women would suffer health consequences? It has become a complicated equation, calling attention to a larger problem: How do very poor countries balance the health of women with the health of the babies they might bear?

At first, a clinical trial found no apparent danger from the new drug, according to a Lancet study looking at births to HIV-infected women in Botswana from 2014 through September 2017. The 6,322 women in the study were receiving two different AIDS treatment drugs. The first reported results of the study showed no difference in birth defects among babies born to women who were taking a new HIV-treatment drug called dolutegravir compared to those taking an older treatment drug called efavirenz. That was good news. The price of the new drug, thanks to negotiations by international organizations, had just been dropped to an affordable level. In September 2017, the Bill and Melinda Gates and the Clinton foundations had worked with dolutegravir's manufacturer to provide the drug to developing countries for less than $75 a year per patient — a fraction of its cost in wealthy nations. Several sub-Saharan nations started making plans to provide it for their HIV-positive populations, says Dr. Caitlin Dugdale, lead author of the new study and infectious disease specialist and researcher at Massachusetts General Hospital. (Editor's note: The Gates Foundation is a funder of NPR and this blog.)

Dolutegravir has been the first-line treatment for HIV in the U.S. and Europe since 2014. Like efavirenz, the pill is taken just once a day. But the newer drug is even more effective, has fewer side effects like lethargy and is less likely to stop working if people occasionally forget to take their pills, Dugdale says.

With the newly negotiated price reduction "we could provide incredible care for AIDS patients in resource-poor countries," says Dr. Rochelle Walensky, infectious disease specialist and senior author of the study. "There was this massive effort to make [dolutegravir] available around the world." Stopping distribution ... but not everywhere

But just then, in May 2018, the bad news about possible birth defects hit, bringing the rollout efforts in many poor countries to a halt.

The four babies whose mothers took dolutegravir were born with part or most of their brain missing – and they died as a result. It was a small risk — about 0.9% — but the risk was far greater than the 0.1% risk of such a brain defect among the women taking the older drug.

The numbers are small, and more research is needed to determine whether the fatal brain defects were the result of dolutegravir or some other factor like inadequate folic acid.

"This is a signal, not a finding," says Dr. Anne Drapkin Lyerly, an OB-GYN and professor of bioethics at the University of North Carolina at Chapel Hill. "We don't really know if [dolutegravir] is a risk."

Until more is known, the hope in the global health community around this new, improved AIDS treatment fell. "There was this screeching halt to efforts to supply dolutegravir," says Walensky. "There was fear."

And the fear was specific to using the new drug in poor countries. Dolutegravir is still widely used in wealthy countries with enough doctors and good access to birth control.

Healthgap, an international agency that advocates for access to life-sustaining HIV drugs, put out a report in November 2018 noting that some 70 low- and middle-income countries are reevaluating their plans to roll out the new drug. Trying to predict the future

As poor countries began to put the brakes on plans to roll out dolutegravir, researchers got busy. Walensky, Dugdale and others developed a mathematical model projecting health outcomes for 3.1 million South African HIV-positive women of child-bearing age and their children over the next five years. They believed it was crucial to give policymakers in poor countries the best possible estimation of the health consequences to both adults and babies if women were given — or if they were denied — access to the new drug. They compared outcomes assuming different possible policies. What would happen if all HIV-infected women took the newer, more effective drug, dolutegravir? And what would happen to their children if the drug does in fact cause the defects? How did that compare to a scenario where all those women took the currently available drug, efavirenz?

What they found were difficult trade-offs. The newer drug would save thousands of women's lives and halt the spread of HIV to tens of thousands people—but at the cost of fatal brain defects in a few thousand infants.

But, of course, not all women of child-bearing age want to become pregnant. And it would be indefensible if poor countries developed policies that would give all women the older, less effective drug because they might get pregnant, says Daniel Wikler, professor of ethics and population health at Harvard's T.H. Chan School of Public Health. "That would mean that some women are going to die because they're at risk for pregnancy," he says, even if they have no plans to become pregnant. A call for equality

Women are making it clear that they want control over their options for treatment, says Dugdale. At the July 2018 meeting of the International AIDS Conference, she met 39 women with HIV from AfroCAB (African Community Advisory Board), a network of community HIV treatment advocates. "These women were passionate about this topic," she says. "And they were well-informed." They know that it's likely that older men, not women of child-bearing age, are the people making decisions about which drug treatment will be available in their countries, Dugdale said.

They wrote a statement at the AIDS conference that said, in part: "We believe in our ability to make decisions about our reproductive health, including when to have children and what medications are best for us." And they asked for improved access to birth control.

In other words, they want the same right to choose their treatment and their destiny as women in wealthy countries.

Susan Brink is a freelance writer who covers health and medicine. She is the author of The Fourth Trimester, and co-author of A Change of Heart. Copyright 2019 NPR. To see more, visit https://www.npr.org.