Q&A with Max Essex: Infants and HIV

Max Essex photo Kent Dayton

For over 20 years, the Harvard AIDS Initiative (HAI) has been conducting research on how best to care for mothers with HIV and their children. Martha Henry, Editor of Spotlight, sat down with Dr. Max Essex, Chair of HAI, to review the progress made and the challenges remaining.

HAI began working in Botswana in 1996. At that time, if a pregnant woman was infected with HIV, what was the outlook for her and her child?

In Africa in the late 1990s, the chances that an HIV-positive woman would infect her infant in utero or through birth or breastfeeding was about 30 to 40%. At least one out of three babies born to HIV-positive mothers would get infected.

In Botswana, a third or more of pregnant women were infected with HIV. You can extrapolate to say that one in nine kids born in Botswana in that period was infected with HIV. Most of those kids would die within five to ten years. By most, I mean 90 to 95%. And most of the infected mothers would die within eight to ten years.

Starting around 2002, more and more adults in Botswana got treated with antiretroviral (ARV) drugs that would keep them alive and in reasonably good shape. Remember, the existence of programs for ARVs—what was then called the triple-drug cocktail—didn’t happen anywhere in the world until 1994 to 1996. The mortality rate for mothers with HIV dropped rapidly in relation to how rapidly the Botswana government could implement ARV programs.

Progress for infants took longer. It wasn’t until 2006 to 2009 that we recognized the best ways to prevent infant infections, even while mothers were breastfeeding.

What part has HAI played in saving infants from HIV infection?

We’ve done quite a lot. Even before Botswana, we were involved in Thailand. With Marc Lallemant, we published several key papers in The New England Journal of Medicine and elsewhere about the use of AZT and nevirapine to prevent transmission from mothers to infants.

In the 1990s, multiple drugs were shown to be more effective in the treatment of adult AIDS patients. We showed that giving multiple drugs to prevent mother-to-infant transmission in utero and through breastfeeding was better than the use of single drugs. That now seems pretty obvious, but it sure wasn’t then. That was a major accomplishment in preventing infant infections.

We showed that mothers could transmit HIV to their infants through breastfeeding. We then did a study to determine if giving AZT to the mother could prevent the mother from transmitting HIV to the infant and showed that it could prevent transmission quite successfully.

But the question remained about whether it was safer for HIV-infected mothers to breastfeed or formula feed their uninfected infants. In resource-limited settings in Africa, there’s often a lack of clean water and an increased risk of disease. Breastfeeding increases the risk of transmitting HIV, but also boosts a child’s immune system and helps protect against infectious disease. In the Mashi study, we compared infant feeding methods and showed that breastfeeding was at least equal overall in preventing deaths as compared to formula feeding. The Mashi study helped to establish the importance of protecting infants who are born to HIV-positive mothers, even if they’re not infected with HIV.

In the Mma Bana study led by Roger Shapiro, we compared different drug regimens to prevent mother-to-child transmission of HIV though pregnancy, delivery, and breastfeeding. Our team in Botswana showed an overall infant HIV infection rate of less than 1%, the lowest rate ever for a study in Africa or among breastfeeding infants.

Melissa Zahralban-Steele, Dr. Max Essex, and Dr. Vladimir Novitsky in the Essex Lab, photo by Kent Dayton
Melissa Zahralban-Steele, Dr. Max Essex, and Dr. Vladimir Novitsky in the Essex Lab, photo by Kent Dayton

At this point, can we declare success for preventing mother-to-child transmission of HIV?

I think we can declare tremendous success from the standpoint of research discovery on how to prevent infant infections with HIV. Yes, unequivocally. Obviously, we can only declare partial though substantial success in realizing the implementation of those discoveries at the policy level in sub-Saharan Africa. There are still situations where governments or health care systems don’t apply what we’ve learned to save enough infant lives.

Why are we just now recognizing that HIV-Exposed Uninfected (HEU) infants face major health challenges?

Because only recently did we have a situation where we saved enough infants from HIV infection and death to then closely examine the health of kids who were born exposed but without the virus.

If we’ve learned how to successfully prevent mother-to-child transmission of HIV, why are we putting time and resources into infant cure research?

Two reasons. First, infant cure research represents one of the best opportunities to understand cure research at all. We’re more likely to find infants with recent infections than adults. And with infants, there’s a better defined and controlled situation. You can apply research knowledge and hypotheses more efficiently to test how best to limit the infection or, hypothetically at least, eventually even eliminate the infection.

Second, remember that infants will have to be on drugs their whole lives, so possibly 60 to 70 years. Adults, if they get infected, will be on drugs only half to two-thirds as long. Looking at the expense in terms of medical care and drugs and everything else, saving infants, besides being the right and compassionate thing to do, is more logical as an investment for cost-effectiveness than anything else.

Today in Botswana, if a pregnant woman is infected with HIV, what’s the outlook for her and her child?

Very good. We’ve seen a huge positive change. Now the mother can expect to live a fairly normal life. In most cases, the infant will be born uninfected and saved from death from AIDS. Ten to fifteen years ago nobody dreamed this would be possible.

Does that answer extend to the rest of southern Africa?

It should and it’s starting to. Botswana is ahead of most other countries in Africa, but fortunately, because of policies from the World Health Organization and more progressive governments, now including South Africa, other countries are starting to catch up.