Transcript: HIV and Women

May 11, 2009

At the 16th Conference on Retroviruses and Opportunistic Infections (CROI) in Montreal, David Evans talks with Valerie Stone, MD, a researcher and physician at Harvard Medical School and Massachusetts General Hospital about disease progression in women, challenges with contraceptives and screening for cervical cancer. To view the video click here.

David Evans: Hi, this is David Evans, I’m associate editor of AIDSmeds.com and POZ Magazine. And I’m here with Dr. Valerie Stone. And Dr. Stone is an associate professor of medicine at Harvard University School of Medicine and treats HIV patients at Massachusetts General. And, welcome.

Valerie Stone: Hi, David. I’m glad to be here.  

DE: Thanks! And we’re going to talk a little bit today about HIV in women and some of the kinds of information that came out at the conference here in Montreal. And there was a study that was an analysis that the FDA did that they reported here. And what did that tell us?

VS: This was an analysis by Dr. Kim Struebel at the FDA, which I thought provided very important data.  What she did is look at all of the randomized control trials of heart regimens to date, looking at each of the study arms in each of those studies, I think it was a total of 48 studies, and found that when they looked at the efficacy, that is the effectiveness of the arms, in virtually all cases there was no difference by gender, the arms were just as efficacious in the women as they were for the men. And when they looked at effect size of a subset of the studies, those in fact showed similar effect sizes in the women as compared to the men. I think this is incredibly reassuring data, showing that the treatments we are using for HIV today are just as effective in women as they are in men. And importantly we hadn’t had this data before.
 
DE: Sure.

VS: And I think we sometimes wondered.  But this is the largest study of its type to be done and I think we can now feel more comfortable treating women and knowing that these regimens are effective in them as well.  One thing I’d like to add though is that they didn’t look at adverse events, they didn’t look at side effects, and I think they plan to do that in the future, but I think we still have unanswered questions and we often perceived that some of the side effects that we are observing may be more severe or may be more common in women as compared to men. So we’ll look forward to hearing more about that going forward.

DE: Mm. Okay. I know that is so important because in so many of the studies that the companies report to the FDA for approval their percentage of women is often 30 percent or less, so that is really vital that they do that sort of analysis.   What other kinds of data were presented that struck you as being meaningful or important?

VS: I think the most important data I saw besides this one study we just talked about was data having to do with the levels of antiretrovirals during pregnancy.  There were three separate studies that I noticed that were looking at this, and all of them looked carefully at the levels of protease inhibitors during the third trimester. One looked at atazanavir (Reyataz), one looked at lopinavir/ritonavir, that is Kaletra, and one looked at nelfinavir (Viracept). And all three of those studies found that the levels were lower than ideal, lower than our target AUCs for non-pregnant people, during the third trimester.

DE: So their blood levels just didn’t get up to where we want them to be?

VS: Right, essentially they didn’t stay where we wanted them to be. They showed that they were high enough during the second trimester, but there were dramatic drops in the blood levels at the same dose during the third trimester.  There’s lots of reasons why this might be. Women of course have a larger volume of blood during the latter part of pregnancy, and this may be the reason, but it doesn’t change the fact that it probably is important to check levels at 30 weeks, which is the recommendation, and increase the dose that the woman are given during pregnancy to keep the levels at a therapeutic range.  We don’t know for sure that these lower levels mean the woman is less likely to have a non-detectable viral load and more likely to be transmitting HIV, but we don’t want to take any chances. Future studies need to look at that issue a bit more closely in order to understand whether we truly need as high levels during the latter part of pregnancy, but for now we should do everything we can to keep women in that therapeutic range when they are in the latter part of pregnancy.  

DE: Mm, mm. You know, a number of our readers were intrigued last summer when the Swiss made the declaration about how transmissible HIV is when the partner has an undetectable viral load. And some of the things that we saw at this conference had to do with what kind of HIV levels were in people’s genital secretions, male and female, and I’m wondering, there was an interesting study about contraceptive use and genital levels in women, what did that have to say?

DS: Well there were some very nice studies done by several different groups on genital shedding, and most of them were not surprising findings, but I think one of the most important findings was that Depo Provera (hormonal birth control) increases the likelihood that a woman will be shedding HIV in her genital secretions. And this is probably not harmful to the woman herself, but it would make her more likely to transmit to her partner if that partner is uninfected. So it’s very important that if women are on Depo Provera or any hormonal contraceptive that they use condoms even if their viral load is non-detectable.  I think, as you’re implying, many of us think that transmitting is quite unlikely when someone has an undetectable viral load, but we have to remember that the amount of virus in the genital secretions is not the same as in the blood, and sometimes people can have completely non-detectable virus in the blood but still have virus coming out in their genital secretions, so they have to be careful and use barrier protection.  

DE: You know, when it comes to hormonal contraceptives, there have been concerns over the years that they might actually hasten a woman’s disease progression. What did we learn about that?   

VS: There have been a lot of studies about that question, and some of them have been conflicting. And some of them have suggested that women would progress more rapidly if they were taking contraceptives.  There is an excellent international analysis that was presented here, and it in fact showed that there was no association with hormonal contraceptives, either oral contraceptives or Depo Provera, or any of them, with progression. And that in fact when a woman takes these oral contraceptives it is not likely that they will not progress more rapidly than other women. So, I think that is very reassuring data that tells us it’s fine for women to take OCPs who are HIV-infected. One issue that we have to keep in mind is what we just talked about though, is that they must use barrier contraception as well as those oral contraceptives then.  

DE: Sure. You know, as people living with HIV, both men and women, are aging, which is a good thing, you know, that people are living, but there are also growing concerns with things like cardiovascular disease and cancers, and I think you had mentioned to me earlier that there was a study looking at rates of cervical cancer screening in HIV positive women that wasn’t so great?

VS: Yeah, the CDC presented a very important analysis looking at cancer screening for cervical cancer in all HIV-infected women in the United States. They looked at, I believe, a recent year, I think the year 2006.   What they found was that unfortunately 23% of the HIV-infected women had not received a Pap smear in that entire year. This is particularly concerning because, as you know, HIV-infected women have a much higher risk of cervical cancer than do other women. And what they found to be the most important predictor of not getting a Pap smear was older age.  And there is really no excuse for this because the risk for cervical cancer for HIV-infected women does not decline with advancing age, and in fact it’s probably more important that those women get screened. So HIV-infected women should be making sure they get those pap smears every year. Similarly we have to remember that breast cancer screening should start at age 40, and now that women with HIV are getting into that age range, living longer, we have to make sure that they are getting mammograms as well.  I found that with my own patients it seems to be harder for them to get mammograms.  Or harder to get them to get mammograms. I often find that I am rescheduling them and encouraging them to go, and they often don’t realize how much at risk they are for breast cancer.  And recent analyses have in fact shown that there are higher rates of breast cancer of women living with HIV than other women, and so we have to take this seriously and get screened and make sure that if there is breast cancer, that it is diagnosed early.

DE: Sure, sure. And I guess just as a final note, one thing that has been getting clearer and clearer with each conference is the importance of what we call modifiable risk factors.  So unfortunately, and I’m a former smoker so I know how hard it is to quit, a lot of people living with HIV still smoke. And that is still a risk factor for many types of cancer, including cervical cancer, right?  

VS: Um hm. That’s completely true, and of course we have to think about the fact that smoking is one of the major risk factors for coronary artery disease, and so much of what we heard at this conference is that there are many things about having HIV that contribute to an increased risk of cardiovascular disease. There are things about HIV that are pro-inflammatory, there are things about the treatment that are pro-inflammatory, but meanwhile people who have the traditional risk factors for cardiovascular disease are the most at risk.  So, smoking is one of the important ones, people living with HIV--women, men, everyone--should do their best to quit smoking, and if they can’t quit, to at least cut down.

Similarly, we should encourage losing weight, getting exercise, that’s another very important modifiable risk factor, and of course many patients who used to struggle with low weight are now struggling with elevated weight and obesity.

DE: Well thank you so much for taking the time.

VS: My pleasure, thank you.

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