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We know viruses [live] in breast milk, and there were a number of posters and presentations [at CROI 2007] that actually talked about what is in breast milk. [Read the abstracts of studies by Kourtis et al, Mirochnick et al, Semrau et al and Walter et al.] [They] correlated high viral loads in breast milk to transmission. We knew that already. Also, they showed that sicker women are more likely to transmit HIV. We knew that already, too.

The issue still outstanding was: if these women continued to breastfeed, what would be the risk of mortality [for the babies]? Actually, if the women stopped breastfeeding in the countries where they have an inadequate water source and are unable to completely guarantee safe formula, then the risk of mortality was significantly higher [for the babies] in stopping breastfeeding. The babies died of diarrheal diseases; they got more bacterial infections. [For some of the CROI research on this, read the abstracts of studies by Kafulafula et al and Creek et al here and here.] The death rates were substantially higher in the group of infants who stopped breastfeeding.

It's astonishing that we're 25 years into the HIV epidemic, and we're just finding this out now. Why did it take so long for someone to study the ramifications of discontinuing breastfeeding?

I think they have really started doing the careful studies, where they could actually do the [necessary] lab support. These are projects that we would think would be easy in the U.S., but [the researchers] needed to make sure that they could actually diagnose HIV in the mothers and in the babies, [and] that they could guarantee follow up.

Most of these breastfeeding studies are part of broader prevention studies that actually use antiretrovirals. [Therefore, in] all these studies, the mothers had antiretroviral therapy -- either short course for prevention or long course because they needed it for their own health. In spite of that, we were still seeing excess HIV transmissions from breastfeeding. The researchers needed to say, "If we just stopped the breastfeeding now that we have these networks in place to support it and study it, what would really happen?" [So they have now done the studies and discovered] that it's convincing that breastfeeding should not be stopped because the mortality rates are so much higher in those babies [that aren't breastfed].

Who does this new information really apply to? Is it only applicable in rural areas of the developing world? I mean, if you're a mother in an urban area of the developing world, such as Johannesburg, South Africa, what would be the new recommendations?

There are another couple of things, too, that I think were very important. Number one is that exclusive breastfeeding actually was found to be critical. If you mix-feed -- some breastfeeding, some formula feeding, water, foods -- those babies have an increased risk of transmission. We're starting to get much clearer information now.

Why is that?

That probably has to do with a couple of factors that form proteins in a baby's gut. Sometimes they're irritating, and if you interrupt mucosal barriers in the gut, you have a higher risk of HIV transmission through the gut. That's maybe one of the risks if you do [mix-feeding] -- i.e., formula, foods and breastfeeding -- that the rate of HIV transmission is higher. Therefore, it's either exclusive breastfeeding or exclusive formula feeding that you can actually have success with. For the formula feeding option you must have reliable water sources.

Maybe in a more [affluent nation where] the formula supply can be guaranteed, you can give a different recommendation, like we do in our country [the U.S.] and in Europe. But for folks who don't have that -- and I think the majority of women in Africa do not have access ...

Is this about Asia, also?

And Asia.

So it's the developing world?

I would say developing world. Everywhere breastfeeding actually is essential in children growing up, because of the risk of diarrheal diseases and death from diarrheal diseases. These researchers just carried it out one step further and said that even with HIV the babies do better to breastfeed exclusively.

[The researchers] had some more recommendations -- safety issues for transmission -- and women whose CD4+ cells were greater than 350 had a much lower risk of transmission. They could be counseled to continue their breastfeeding up into two years [of age], which is more what they would [normally] do. Again, the outcomes there are better because of the nutrition issues.

As long as their CD4+ counts stayed above a certain level?

Yes. Over 350 seemed to be a really good cut-off to continue. Now there are some studies that are ongoing that will provide us more important data. [For research on this subject, read the abstracts of studies by Awino et al, Palombi et al and Jamisse et al.] If we treat the mothers during their breastfeeding, will that reduce transmission? Do you get benefits both ways? They've showed that antiretrovirals, [specifically] 3TC [lamivudine, Epivir] and nevirapine [NVP, Viramune], do get into breast milk. Not reliably, but they do in a number of cases. This may be another way that they can treat women and treat babies. I think that was exciting information.

The other one that's an add-on is the issue of nevirapine resistance with a single dose of nevirapine. There were a lot of concerns about it, since that is the standard for prevention programs not only in developing countries in Africa, but in Eastern Europe, where they still have difficulty with resources. So, you use nevirapine single-dose -- What about resistance in the mothers? Very high rates [of resistance] shortly after delivery.

The studies now have gone out far enough to show that these resistances decay over time, and one very, very nice study showed actually that it did not impact the failure when that woman needed to be started on her own ART. [Read the abstract of studies by Palmer et al and Micek et al.] In that particular study, actually, it was 3TC resistance that predicted failure.

These [studies] are reassuring. It sort of says, single dose nevirapine is important in that first transmission phase, and it does not appear to be hugely detrimental. Other studies this time show that shorter courses of AZT/3TC [zidovudine/lamivudine, Combivir] could also benefit reducing the amount of nevirapine resistance, as well. So, more strategies.

I thought that resistance mutations are archived, and that they can re-emerge. What do you mean by decay?

Well, I think that's another really interesting [development] --I'm not sure how this is going to fit in, because I think this is the first time we've had some papers that described the issue of minor variants. You know the minor resistant variants, and their impact on later treatment. I still think we need further data with that to say how big an impact they do have. Clearly, if you look at traditional measures of measuring resistance, it goes away. If you have from 12 to 24 months out from the time of the single dose of nevirapine, reinstituting a therapy with nevirapine or efavirenz [EFV, Sustiva, Stocrin] seems to be successful in most of the cases. That's very important and good news for developing countries.

That was the biggest thing you took away from it?

For me, it's two things: one, nevirapine does look good, at least in that subset of women who have CD4+ cells less than 200. One other study suggested that it may be safe in the 200 to 350 CD4+ count range. It's not a huge study -- about 500 women -- but it suggested they didn't have this severe liver disease that they saw in other studies. That needs to be reconfirmed because it will give us even more leeway to use nevirapine in that patient population, for the hepatotoxicity. That makes me feel better about being able to use a nevirapine- or efavirenz-based regimen later on. [Two,] the breastfeeding [studies] clarified many, many issues for a lot of us who do work in some of the resource-limited settings. [Now,] we can provide some science to the recommendations.

Do the studies that you've mentioned have any real significance for developed world? For the United States or Europe?

We do use some single-dose nevirapine for prevention [in developed nations], but it's generally in emergency situations when we have women coming in who haven't been on prophylaxis. This is sort of a way to do that. So, we do have some women who are getting single-dose nevirapine. There is, I think, some information for us here.

The breastfeeding issue reaffirms what we tell mothers here in the U.S. You have an alternate source [for feeding your baby], even in a cultural setting. We'd like to give you tools so that you can say to your mother, your grandmother, "You can't breastfeed." [Our goal is to] ... give you some tools on how to say that.

I think it's very, very clear that is something that we now, scientifically, can back up. There's some relevance. There are a lot more studies about what drugs are being used in pregnancy and their safety. Our armamentarium [of antiretroviral agents] in the United States is expanding because we can safely use a lot more of the protease inhibitors now during pregnancy [Click here to read a CROI abstract looking at atazanavir use in pregnancy. To hear the author's summary, click here. For the full powerpoint of his study, click here]. We needed that because of the growing problem of HIV drug resistance.

To read or listen to more interviews with HIV clinicians about what they felt was the most important research presented at CROI 2007, click here.