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As CROI 2007 drew to a close, we asked Michael Mugavero, M.D., University of Alabama-Birmingham to discuss what he felt was the most interesting research presented at the conference. David Wohl, M.D., from the University of North Carolina-Chapel Hill joined our conversation.

Dr. Mugavero, what presentation at CROI was most interesting for you at this conference?

Michael Mugavero: [I will start with] Matthias Egger's plenary session, [which] looked at cohort data and ... comparisons in different regions of the world -- in both industrialized and in developing countries. It was very interesting in that it showed some striking similarities. I think one of his most striking slides was, [when] he had a map of the world and introduced, kind of country by country, the initial CD4+ [cell] count of persons with HIV starting therapy. Across the globe, except for a few, rare exceptions, patients are starting with CD4+ [cell] counts below 200. So, everyone is really starting therapy late. ... The implication of that [is not good]. There were [even] some countries in sub-Saharan Africa that [had patients starting on treatment at] even lower [counts] -- but across the board, [people are starting treatment with] really advanced disease.

Michael Mugavero, M.D.

David Wohl, M.D.

Some of the interesting things he showed were, so far as outcomes go and mortality, [that] while there was higher mortality [observed in] ... four African cohorts that had very good follow-up data (compared to the ART-CC [ART Cohort Collaboration], which is 16 cohorts in Europe and North America), once you counted for CD4+ [cell] count differences, those differences became closer. Actually some of the North American and European cohort mortality [rates], as far as number of deaths and patient years, were the same as was seen in the African countries.

Also, an interesting slide looked at the timing of death. So in Africa -- I think it's been well described -- you see a lot of early deaths after starting HAART -- and there [is the] question -- is it immune reconstitution syndrome or tuberculosis, [or] other opportunistic infections. But then after that initial period of high mortality, the slopes of kind of death over time compared to industrialized countries seem to be fairly similar. So that, really [there were] striking differences, but, I think more so [there were striking] similarities, [when] looking at industrialized and developing countries [in terms of HIV treatment].

Why was that unexpected?

I just think if you polled most persons, they would have not expected that. I think it's similar to [a presentation at] the International AIDS Conference, and there was a recent publication looking at adherence in Africa compared to industrialized countries. I think there are a lot of persons, before the rapid rollout and scale up of ART [antiretroviral therapy], expressing some reservations about adherence -- whether it's due to different factors in less developed countries, [such] as access to care. [Also], people's ability to get medications and take them might not be as good. But their data looked really good. In Africa, adherence is as good or better than it's been in North America and Europe. So I would suspect a lot of people, before seeing Matthias's data, would expect the same thing -- that the outcomes would be very dissimilar in these different regions, because of largely, I think, structural and infrastructural barriers.

But it seems like, with good infrastructure -- I think the important thing is that the four settings that he kind of compared to the North American [settings] had really good systems, infrastructure and follow-up and delivery of health care and delivery of medications. With that level of programming, you can achieve outcomes very comparable to what we're seeing in industrialized countries.

What were the specific places that he mentioned?

Gosh, I can't remember off the top of my head. Do you remember the four sites, David?

David Wohl: There are different sites, depending on the analyses, but there was a site in Côte d'Ivoire. There was a site in Malawi, which is a UNC [University of North Carolina] site. ... There were two other places -- one, I think, in Uganda.

Michael Mugavero: There was one in South Africa.

David Wohl: One might have been in South Africa. Yes, it was. So I think that it's a pretty diverse group of places in Africa. They've done a lot of data before, comparing AIDS. I also think that it was really remarkable that the number of antiretroviral regimens [used] ...

Michael Mugavero: ... the regimen difference ...

David Wohl: ... and the choices. They are able to achieve in these places comparable success rates with ART as we are, with much fewer therapeutic options. So the menu of options here ... we have over 59 different combinations, possible combinations that people would start on. They had much fewer, much less than a tenth of that.

Michael Mugavero: [They had six possible regimens].

David Wohl: Six.

Michael Mugavero: No, I think the numbers were striking.

David Wohl: Three to six in most of the places.

Michael Mugavero: [Matthias] showed, in North America, Canada, Europe, the number of different initial regimens over this time period, which was fairly contemporary. I think he focused on 2003 to 2005, so he really tried to focus on a pretty contemporary period. Then, [he] would show [his data] for the African nations, and it was three to six.

David Wohl: Three to six, yes.

Michael Mugavero: [That] was the number of different regimens for initial therapy.

David Wohl: So I think that is really impressive. Again, I agree completely with you, Michael, that if you asked most people, they would say, "No, people in Africa just don't get as much success [taking HIV treatment] as we do here."

We just learned, of course, also, in the New England Journal of Medicine, there was an article from Haiti, where they rolled out therapy, and it's turning out to have success rates that are historically, at least, comparable [to success rates in the U.S.].

Wasn't the adherence in fact found to be better in Haiti?

David Wohl: Well, you know, it depends. I think they have a good program where they have people who accompany people to clinic, and they go to their houses: home-based care. So adherence can be very good there, and that may explain part of it. But we're finding in Africa that people are super-adherent.

Michael Mugavero: They do really, really well, yes. It was really nice, the paper in JAMA [Journal of the American Medical Association], and then they had a poster presentation at the International AIDS Conference, just showing adherence being as good, or better, than it's been over here.

David Wohl: As long as they can afford it, as long as it's provided.

Michael Mugavero: As long as medications are provided for free.

David Wohl: For free. If they're not provided for free, adherence drops off completely. Because who could afford it?

So this talk, it was really good news for the developing world, but not such good news for the industrialized world?

Michael Mugavero: Oh, I think it was still good for the industrialized world. I still think the outcomes were quite good, and what we all are experiencing. I think there are still problems highlighted. I think one of the things Matthias highlighted was the ... loss [due to] to [lack of] follow-up. He focused on that specifically in the developing world, but from personal experience and interests, we have similar problems here, with patients being lost to follow-up, falling out of care, coming back into care. I think that's an important thing domestically, [in addition to] understanding some of the barriers and problems that people are facing; that are keeping them from consistently remaining engaged in care.

Is that particularly a problem in the South? You work in Alabama.

Michael Mugavero: I know it is for us, and in the South. There's not a lot published about adherence to care or attention to care nationally. But when you see -- commonly, you'll experience patients missing visits. Across studies, patients who miss visits tend to be worse [off], with various outcomes, whether it's receiving medications, achieving viral suppression, clinical endpoints, clinical outcomes. There's a small, but pretty strong -- as you'd expect -- evidence base saying patients who stay in care, in continuous care, do well. From our own personal experience, we do [see that]. We have a lot of patients with missed visits, [who are] kind of falling out of care. To think about some of the potential barriers -- the high comorbid [conditions of] substance use, mental illness. Are they playing roles? Competing needs -- transportation, housing, childcare -- there's a lot of reasons to suspect why [patients are missing medical visits]. Not to mention the stigma and lack of trust. A lot of other factors might be playing a role for a person to stay in care. Then [there are] system level things, too. I mean, what can we do to make the system and the clinic a place that's easier to come to, and easier to make visits, and to stay in care?

David Wohl: If you turn around, there's a poster [by Lucy Wilson et al called "Rural Versus Urban HIV/AIDS Clinical Outcomes: A Multi-state Perspective." It's looking at clinical outcomes, based upon rural and urban environments. So it's not exactly the South, because if you look, there are not a lot of places in the South that are represented, especially rural South -- which is a shame for this analysis.

Michael Mugavero: I was interested, too [in that study]. Because in looking at the numbers, I think this is an important question, and one that we could, with you [in North Carolina] ... really answer: of 8,600 patients [in the Wilson study], 170 are rural. Where, if we looked at your clinic and at our clinic in North Carolina, in Birmingham [Alabama] -- and even CDC [U.S. Centers for Disease Control and Prevention] data -- [we would see that] the majority of rural persons with HIV live in the South. It's really another understudied area, I think.

David Wohl: People haven't looked at it. This is a first attempt -- like, a stab at it. I think it's really important. But with this poster, which has been conducted under the auspices of a bunch of different people -- but the lead author [Wilson] is from [Johns] Hopkins [University in Baltimore, M.D.] -- I think it's interesting ... that there was no difference in the kind of outcomes you would care about in people who are living in an urban environment versus a rural environment. That's reassuring. But there were less visits, office visits, by people in rural areas. I think that's exactly what Michael is talking about: There are obstacles in the South that don't exist necessarily in other places. There are not a whole lot of transportation systems, public transportation. People live far away from their clinics. You just can't drop a token, and go see your doc[tor]. I think, in this particular instance, [the] big take-home message for me [from the Wilson study] was how African Americans were more likely not to receive HIV therapy -- whether in an urban environment, or a rural environment.

So, rurality didn't turn out to [be] as big a deal as being black. I think this is something we're seeing fairly consistently over the last few years, and that's more concerning to me. It would be nice, though, to have this rounded out with a real representative population from the Southern HIV experience that's much more rural.

OK. Thank you both.

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.