The Body Covers: The 14th Conference on Retroviruses and Opportunistic Infections
CROI 2007 Wrap-Up: An Interview With Howard Grossman, M.D.
March 26, 2007
There was a lot of good information [presented at CROI] about two new classes of drugs. [The] integrase inhibitors prevent the virus from integrating its genetic material into the host genetic material. We saw a couple of these [integrase inhibitors], one from Merck [Click here and here to view studies of Merck's integrase inhibitor] and one from Gilead [click here and here to view studies of Gilead's integrase inhibitor]. Then we had, also, new groups of entry inhibitors -- the CCR5 inhibitors that block entry into the cell. Some of that data looks very good, too. [Click here and here to view studies on the CCR5 inhibitor maraviroc.]
People were saying that this is the biggest change in HIV treatment since the 1996 International AIDS Conference in Vancouver, when the effects of highly active antiretroviral therapy first became clear.
They keep saying that. I think the big [question] is whether or not this will represent a chance to shift the paradigm. Up till now, we always talk about having a backbone of nucleosides [nucleoside reverse transcriptase inhibitors], having two nucleosides in any formula. Well, we know that there are lots of problems with the thymidine analogs -- AZT [zidovudine, Retrovir] and d4T [stavudine, Zerit] -- and we've moved away from them, in many ways. That limits what's left to choose from. The question is whether we can move away from that idea of a nucleoside backbone. I think it will be a slow process, even when the new drugs come on line.
Certainly, having other classes of drugs gives us the option of doing a nucleoside-sparing regimen that really might work and be tolerable, and be easy to do. We've seen nucleoside-sparing regimens before with non-nukes [non-nucleoside reverse transcriptase inhibitors] like efavirenz [EFV, Sustiva, Stocrin] and [ritonavir (RTV, Norvir) boosted protease inhibitors. I think, in many cases, the tolerance has been limited or the efficacy hasn't been as good as we want it to be -- that kind of thing. So, this may give the first chance to really shift that way of thinking.
It will take a long time because in most of the world nucleosides are about all they've got as a backbone. Even in this country, people are comfortable with the nucleoside backbones, so I think it will be some years before we see really what I would call a paradigm shift. That's really what people are talking about, more than anything.
There was a lot of good information about all of that and several of those drugs are available on expanded access. Plus, we have darunavir [TMC114, Prezista] . That is available. So there are a whole bunch of new drugs that [have] suddenly become available, some of which treat [drug]-resistant virus, some of which are [members of] a new class of drugs. I think that, with the integrase inhibitors and the CCR5 entry inhibitors, we still don't know long-term toxicity. We still don't know if there are long-term effects that we haven't seen yet. We still don't know a lot about drug-drug interactions with some of them. So there is a lot of information that needs to be developed before they end up in widespread use.
So you're not entirely enthusiastic about these developments.
Oh, I'm very enthusiastic. I think this is an exciting time. I think a lot of drugs we've been waiting for, for a bunch of years, are coming. The idea of having six classes of drugs is really pretty exciting. We had three just a couple of years ago.
Other information I thought was really important: More for the developing world, but still relevant to the U.S., has to do with breastfeeding. [Read the abstracts of studies by Onyango et al, Coovadia et al, Atashili et al and Sinkala et al.] For years data's been coming in about the fact that babies ... born to HIV-infected mothers should either be breastfed only for the first six months, or formula only. What's happened in much of the third world is that they've developed these nutrition programs and they've tried to get formula out to mothers, in general. So their heads are into giving formula.
Well, in most of these places -- and I think it's true here [in the United States] as well -- if women use formula, they also tend to breastfeed, at least some of the time. It turns out that that combination of formula plus breastfeeding is far more likely to transmit HIV to the baby. So, talk about paradigm shifts: This would be a major paradigm shift for many developing countries, to say, "No, if you're HIV positive, you should breastfeed only."
I've heard from people that they have had a lot of trouble with the nutrition people in their own governments who are so stuck in this idea of getting infant formula out, not to mention the lobbying by some of the manufacturers for infant formula. It probably has something to do with the effects of foreign proteins in the formula on the gut in the infant who is less than six months old. [Formula] probably makes some kind of irritation or reaction that makes it more permissive for the transmission of HIV. For women who breastfeed exclusively during those first six months, the [HIV] transmission rates are extremely low, actually.
How low are we talking about?
Like 1 or 2%, about the same as what you get with antiretroviral therapy. I think that is very, very important. It has big implications. Certainly here [in the United States], a lot of women use formula, but also breastfeed. For HIV-positive women, I think they need to make a choice [between exclusive breastfeeding and exclusive formula], right from the start.
Do you think physicians in the United States should now allow their [HIV-positive] patients to breastfeed?
It's not a matter of allowing.
I'm asking because whether or not HIV-positive women can breastfeed has become a legal question. There's was a case in Los Angeles, involving an HIV-positive woman who insisted on breastfeeding her children.
Right, but if she's going to breastfeed, then she should only breastfeed. It's clear that [breastfeeding is] the way to go, and that it has a low risk of transmission during the first six months of life. So, yes, she should be allowed to breastfeed, but only breastfeed.
But that's very hard for women in the United States.
Right. It has severe implications for HIV-positive women here. They have to make a choice right off the bat.
Were there any other studies that really interested you?
There were a number of studies that showed rising incidences of STIs (sexually transmitted infections), among men who have sex with men. What we have seen here in the U.S. and in Western Europe for several years now, is also now occurring all over the world -- South America, there was some stuff from Southern Europe, Eastern Europe. We see a large rise in STIs, and with them, I would imagine, is going HIV infections.
We're seeing the drivers of the epidemic:
I think that we need to face that problem head-on. Unprotected sex feels better. It just does. It's time we realized that and stopped trying to beat around the bush and trying to say, "Oh, it's just as good." It's not. It's not just as good to use a condom, but we have to. It's a matter of teaching people about maturity and self-respect, and doing the things you have to do to protect yourself, by facing the reality of the situation. That's, I think, very important.
I think it's scary because we see money being pulled away from MSM [men who have sex with men] projects all over the world, whether it's in Southeast Asia or in Europe [or] in other places. Money that was going into doing prevention programs with MSM is being taken away, and people are being told, "Your patient population isn't really important to us anymore," by entities in this country like the CDC [U.S. Centers for Disease Control and Prevention] and the NIH [U.S. National Institutes of Health]. That's scary, and that means that, once again, the gay community is going to have to pick up the slack for themselves.
Do you think there's mobilization to do that now?
No, I don't think so. I think many organizations in the GLBT [gay, lesbian, bisexual and transgender] community have, in fact, moved away from HIV because it was more under control and they've been able to now finally deal with some other political issues. But I think in many ways they are going to have to come back to GLBT health overall, and become big players again.
Are you concerned about the transmission of NRTI- or NNRTI-resistant mutations?
Are you talking about transmission of [drug]-resistant virus?
I'm talking about sexually transmitted infections. The number of young men who are having unprotected anal intercourse -- there are several studies on this -- is very high. There were some studies that showed men who knew they were positive, having unprotected anal intercourse with men of unknown or negative status. It may be that these guys just feel like, "Well, I already got it so what do I care?" It may be that it's become harder to disclose again, because it's easier to look healthy with HIV now. You have to choose to disclose [now], whereas, when people were getting a lot of lipodystrophy and before that, when people were getting very sick, disclosure was forced on them.
I think we need to create safe spaces for people again to disclose that they are HIV positive. As physicians and healthcare workers, nurse practitioners and PAs [physician assistants], we need to bring these topics up. We need to talk about sex.
I just got back from working in western Nepal, far western Nepal, in a pretty remote area, for the last seven weeks. It was almost impossible to teach them [clinicians about taking a patient's] sexual history. I felt like a sex maniac, because I would just talk about it, because it's just so involved with so much of people's lives. There, for example, the problem is among migrant workers, and many of the women that have been infected by men who went to work in India and came home with HIV.
They are widows now. Once you become a widow in Nepal, you sort of stop being a woman. They [the medical professionals] wouldn't take gynecologic histories. They weren't taking obstetrical histories. When I asked why, they would say, "Well, she's a widow."
I'm like, "Yeah? So?" But [they believe] you [can] stop being a woman. I think that's true in many cultures.
So whether it's there [in places such as Nepal] or here, we need to talk about sex. People are having [sex], and if you don't ask, you don't find out [their STI status].
But this is a revolution you're asking for! [Laughing.]
I've been asking for this revolution for 30 years. That stuff is frightening. I think the level of what's happening in MSM communities around the world ... Certainly, when you look at developing countries, the drive is still to get married [even if you are gay], whether you're talking about India, Nepal, China.
In India, for example, in some studies, upwards of 60 to 70% of men who have sex with men are married. So we're talking about vectors for transmission into larger society, and it's something that affects women. Until people feel comfortable identifying as gay and living a gay life, they are going to continue to get married [to women] and have children, because this is what society expects of them.
Masculinity is much more role based, so having children and being married makes you a man. Even if you're screwing men, you're OK. But if you're gay-identified, then you're like a woman, which, in those societies, is a bad thing. It's the thing that was brought up with the down low stuff here in the U.S. Although that, of course, was a lot of hysteria, because there are a lot of, for example, African-American men who are well integrated into some kind of gay community.
There certainly are plenty of people here across the board who also still fall victim to the expectations of heterosexual society; they get married, and they serve as a means of transmission. They are not reachable through the gay community. They are not reachable through the channels that we use for a lot of our education. That's the challenge -- to reach them.
But you can find these people across ethnicities, don't you think?
It's across ethnicities.
In any case, do you believe that the down low is a black phenomenon?
Oh, please! You've got farmers in the Midwest [on the down low]. There's a great book on rural gay men that came out a couple of years ago that has all the stories of people in these farm towns, who meet for sex. They end up getting married and they have kids. So it's a worldwide problem that needs to be addressed. [For one of many books on rural gay men, click here.]
[In terms of other research at CROI of interest,] there are a lot of new resistance mutations that people are finding out about as they look further and further out in the virus -- genetic material that is becoming important. Transmitted resistance is certainly a big problem. There was one poster that showed that transmitted resistance is really a nationwide problem in the U.S. [Click here to read coverage of the study.] If you look at the Northeast, South, West and Midwest, the numbers [of infections with resistant virus] are about the same. You're talking up to about a quarter of new infections have some transmitted resistance. That's a challenge, and it means we really need to focus on resistance testing -- which is not available in most of the world.
What can we do to change this?
We need less expensive ways for doing it. The not-for-profits that are getting T-cell [testing] machines out there and things like that need to think about ways of doing resistance [testing]. There were some posters looking at transport using filter paper. The blood is placed on filter paper and placed in an envelope and apparently stable for some time, and can be shipped from Africa to Europe, for example, which is what they did in the study. Then you can get resistance testing, or you can get viral loads.
So developing new transport methods, heat stable things -- those are all ways that [you] can do it. But you know, you're talking about places that don't even necessarily have a liver function test or a CBC [complete blood count] machine. A lot of the HIV organizations that are working in the developing world, they decided to take a narrow focus on HIV. So they don't put these machines there. But then you think: You have people on nevirapine [NVP, Viramune], for example. How do you prescribe nevirapine without liver function tests, safely?
So I think there needs to be less silos, a more broad approach to this. At least take care of the problems -- the full spectrum of problems -- that people with HIV have. I think, then, HIV serves as an example for teaching for all the other [i.e., HIV-uninfected] populations. Also, the equipment that you provide can be used by the hospitals ... at their own expense, then, to treat the rest of the population. [That] opens the doors to proper medical treatment. I think we need to really start thinking in that direction. Right now, we have got TB [tuberculosis] in one silo and HIV in another, malaria in another. There needs to be more integration of effort.
To hear other HIV clinicians review research presented at CROI 2007, click here.
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