December 11, 2009
Table of Contents
Bonnie Goldman: Hello and welcome to HIV Management Today -- a new, clinical management series from TheBodyPRO.com. This podcast is entitled: "Clinical Management of the HIV-Infected Woman" and it's the second podcast in the series. I'm Bonnie Goldman, editorial director of TheBodyPRO.com.
Joining us are two of the top HIV clinician/researchers in the United States. Dr. Valerie Stone is an associate professor of medicine at Harvard Medical School and an HIV/AIDS clinician at Massachusetts General Hospital, where she was Director of the Women's HIV/AIDS Program from 2002 to 2008. Dr. Kimberly Smith is associate professor of medicine in the Department of Infectious Diseases at Rush University Medical Center and an active investigator and chair of several studies in the AIDS Clinical Trials Group. In our short discussion they will summarize the top issues in managing the care of the HIV-infected woman.
Welcome Dr. Smith and Dr. Stone. Let's start at the very beginning. Dr. Smith, I wonder if you can describe how you evaluate an HIV-infected woman's care differently from the care of a man.
Kimberly Smith: How I approach women is not hugely different than how I approach men. First, I try to get a feel for their emotional state in dealing with this disease. Most of the time, I see patients within days, or a couple of weeks, of them having gotten the diagnosis. I try to assess how they cope with the situation. I try to understand what their history is with regard to where they may have acquired HIV, and to what degree they have an idea about that. So, my first step is always to get a feel for where they are.
Once I can assess if the patients are really ready to start thinking about their HIV care, then I try to educate them about HIV. I tell them, in lay terms, what happens as a result of the virus and what we will be trying to accomplish in the first visit, which is to get an idea about whether they have any symptoms at all. Have they lost any weight? Are they having chronic diarrhea?
One of the differences with HIV-infected women is that some of the symptoms that they may have can be things like vaginal discharge, itching or a yeast infection. I try to get at those types of questions.
To sum up my approach toward women at their initial visit: I try to assess first their social situation, their coping skills, whether they are symptomatic and if they have any issues that are going on at present; then I try to educate them about what we're doing today and where we're going forward. But that's not hugely different than how I approach men, except that the symptoms that may be present in women can be different than in men.
Bonnie Goldman: What kind of symptoms would be more common?
Kimberly Smith: As I mentioned, I'm mostly looking for whether they have any gynecological issues. Are they having any kind of discharge? Do they have vaginal pain, or itching? Are they having pain with sexual intercourse? Are they currently sexually active?
I try to get those kinds of questions answered pretty early on. Those are the things that are dramatically different from men, as far as the history that you take straight off the bat.
Valerie Stone: I completely agree with Dr. Smith. I would just emphasize some of the things she's said. I've found over the years that many women come to their initial appointment with set things that they want answered, that they want to get educated about. If those things aren't taken care of, the women often can feel frustrated and disappointed. Sometimes this stems from prior negative experiences with the health care system. This is true particularly for minority women, women of color.
I try to be really clear at the beginning of the appointment about what they want to accomplish in that visit. As Dr. Smith said, I also try to make clear to them the things that I think are important for us to try to accomplish in that first visit. We try to get through as much of both of those sets of goals as possible. If necessary, the full evaluation may get stretched to a second appointment so that we make sure that everything that's necessary gets done -- that not only do I get an understanding of who they are and where their disease is, but that they, also, get to take care of symptoms or concrete needs and services that they may want to take care of in those first visits.
Kimberly Smith: One of the other things that I think can be different when we're looking at men versus women is that men tend to lose weight sooner. A lot of the men that I see, even before they have progressed to more advanced disease, are losing weight. Whereas women -- particularly African-American women -- tend to not have lost weight. They may have somewhat of a change in their appetite, but they are typically still, weight-wise, doing about the same as they were. So, I don't look for weight loss as being a symptom of HIV in women as much as men.
Bonnie Goldman: Is there an understanding of the mechanisms responsible for that?
Kimberly Smith: Probably the same reasons why it's easier for men to lose weight when they are trying to. [Laughs.]
Bonnie Goldman: Dr.Stone, can you discuss antiretroviral regimen selection in women?
Is regimen selection different with an HIV-infected woman?
Valerie Stone: Adherence is very important for all patients living with HIV today. But often, women may have more life challenges, and more things that they are trying to juggle, than men do. So I think often women are looking for the simplest regimen possible. It's important to keep that in mind when selecting regimens for women.
On the other hand, it's also important to realize that the once-a-day regimen Atripla (a combination of efavirenz [EFV, Sustiva, Stocrin], tenofovir [TDF, Viread] and emtricitabine [FTC, Emtriva]) is a regimen that we have to be very careful about prescribing to women of reproductive potential, because efavirenz is teratogenic. If that's a regimen we are considering, we have to be very clear about whether the woman is sexually active. If she is, she needs to have a hormonal contraceptive in place, as well as be using barrier contraception.
If that regimen is not a good choice for the woman, because she's sexually active and doesn't have ideal contraception, or because she does not want to take any risks, which might be a good choice, then we should consider other simple regimens that are known to be potent.
I think one particular regimen to keep in mind is boosted atazanavir [ATV, Reyataz] and Truvada [tenofovir/emtricitabine, TDF/FTC], because it's only three pills a day, and just once a day. But there are many other simple regimens that I think can be considered.
What I often do, rather than jump to a specific regimen with patients, is try to understand their life situation -- again, whether they are sexually active, if they are of reproductive potential.
In addition, I try to understand what side effects would concern them, and which ones wouldn't bother them so much; also, what level of complexity they are willing to deal with.
If they have taken a lot of medications on and off during their life because of other chronic illnesses, it may be that taking three pills twice a day, for example, wouldn't be a challenge for them. So I try to understand the patient's own views on that, and then we try to select a regimen together.
Kimberly Smith: I agree with Dr. Stone. I think that the point that she made about efavirenz is a touchy one, and can be controversial. When I have spoken to clinicians around the country, people have come down on both sides.
One side tends to avoid the use of efavirenz in women of childbearing age, because they are concerned that the woman may -- even though you inform her -- forget about the concern about not getting pregnant while on efavirenz. They don't want to make the patient vulnerable and, in turn, to some degree, make themselves vulnerable, since we do live, unfortunately, in a pretty litigious society.
People are worried that if you prescribe a medication to a woman of childbearing age and she becomes pregnant, then you're vulnerable. Because some folks would argue you should have never offered it to her to begin with.
Some people come down with that fairly hard-line position. I believe that it's not fair to not offer what is ultimately the simplest regimen, just on the basis of a woman being of childbearing age. So, I explain the issue to women from the beginning, and put that in the context of other regimens like the ones that Dr. Stone has described. But I don't take it off the table.
Not only do I document it in the record, but in some cases, I will ask the woman to even sign a consent form. The important thing, I think, when starting a woman on a regimen that includes efavirenz is not only having that conversation with her on the initial visit, or even on the visit where you start her on medications, it's having that conversation with her on a regular basis. Because sometimes, in those early visits, they get so much information that it can be overwhelming. It's important to have them have "take-home" points, and then reiterate some of those points later on, particularly if you choose a regimen that includes efavirenz for a childbearing-aged woman.
The other point that I will make is that now new agents have come along -- agents like raltegravir [RAL, Isentress] -- we have more choices for women of childbearing age. It used to be that either you went down the non-nuke [non-nucleoside reverse transcriptase inhibitor (NNRTI)] route -- which, as Dr. Stone pointed out, in the United States mostly means efavirenz -- or you chose a boosted protease inhibitor.
I think now, with the new data that we have on raltegravir in treatment-naive patients, that raltegravir might be a choice that would make sense for a lot of women. You can still offer them a fairly simple regimen, with the downside being that it's twice a day, but the tolerability of raltegravir may balance out the downside of having to take it twice a day.
Bonnie Goldman: Has raltegravir tested well with pregnant women?
Kimberly Smith: It's not excluded. It's not a pregnancy category D drug, so it's not known to be teratogenic in women. It's not a drug that you would avoid on that basis. It's not a drug that I would choose for a pregnant woman, because it's not recommended.
But if we're talking about a woman of childbearing age, there's no reason why I would avoid that drug in her with the concern that she might become pregnant.
Bonnie Goldman: Are there any gender-specific pharmacologic considerations when selecting an antiretroviral regimen?
Valerie Stone: We have never had as much information as we would like about the interaction between hormonal birth control pills, or other hormonal contraception, and antiretrovirals. But there are good data, from the past year, showing that Depo-Provera [medroxyprogesterone injection], specifically, doesn't have any important interactions with most antiretrovirals, because it's a progestin.
But efavirenz and most of the protease inhibitors have interactions with oral contraceptive pills [OCPs] that make us concerned about their effectiveness, when taking both types of medications together. I tend to encourage patients to try to think of birth control options other than OCPs, if they are using efavirenz. I think Depo-Provera is an excellent choice. Also, an IUD [intrauterine device] is an excellent choice for women on efavirenz.
I don't think we have as much information as we would like with hormone replacement therapy and antiretrovirals.
Kimberly Smith: I agree with Dr. Stone's comments about contraception. There aren't as many studies as we would like. I would encourage clinicians to always look up drug interactions for every individual drug that they might want to prescribe. That's true for contraceptive agents, as well.
Depending on whether you have a birth control pill that is mostly estrogen, or has some progestin in it, [the interactions can be different]; there are different combinations of pills, and so you need to look up the specific drug that you are going to prescribe and see whether there is an interaction with any of the HIV medicines that a patient is on, or that you're interested in prescribing. I don't think that we can make a judgment across the board because, again, we have limited studies.
When it comes to understanding some of the toxicity differences, we know that, for example, with nevirapine [NVP, Viramune] there is more rash, and there is potentially more liver toxicity in women. What we also know is that women, in general, have had a slightly different pattern of side effects from the protease inhibitors.]
For example, most of the studies have suggested that women tend to have a little bit more nausea from protease inhibitors, whereas men tend to have a little bit more diarrhea. That was true in one of the most recent studies, the GRACE [Gender, Race and Clinical Experience] study that looked at boosted darunavir [Prezista]. That's been shown previously in studies looking at even drugs as early as nelfinavir [NFV, Viracept]. I think that was also true in Kaletra [lopinavir/ritonavir, LPV/r] studies comparing men to women.
You have to warn patients ahead of time, based upon knowing that. I, for example, have a patient who I put on a boosted protease inhibitor which typically has very limited GI [gastrointestinal] side effects. I warned her that there was a potential for side effects while on the boosted atazanavir regimen, but told her that the frequency was pretty low.
Her experience was completely different than that. She had terrible nausea, and has been essentially unable to tolerate that regimen, and any other protease inhibitor regimen. Mostly, maybe it's gender; maybe it's that she's a small-statured woman. Regardless, we have to anticipate those challenges from the beginning, and warn patients about them.
If we don't warn patients about particular side effects, and make them think that it's going to be easy to take these medications, then it interferes with their ability to trust us going forward. So I try to warn people ahead of time about the worst-case scenario of what they may experience. I think the GI side effects are probably the ones that really stand out the most for women.
Bonnie Goldman: Is there a role for therapeutic drug monitoring in women, particularly women who are of small stature to avert these adverse affects?
Valerie Stone: It's very uncommon for clinicians to use therapeutic drug monitoring. I think it's an excellent question, though, since we have set doses that are essentially exactly the same for the drugs that we're using today.
In the old days, we were using more ddI [didanosine, Videx] and d4T [stavudine, Zerit], which did have different dosing levels based on weight. But we have no weight-based dosing right now. It does make sense that for some smaller women, it may turn out that they experience more toxicity, and have drug levels that are too high, on our standard dosing amount.
It's not clear how best we should approach that. But my approach has been that, if a woman of small size tells me that she's having substantial side effects, I will consider the possibility that it's due to high drug levels. In some cases, I have decreased the dosing frequency, or the dosing amount, based on that.
In particular, I've felt comfortable doing that with Sustiva-based regimens, based on the FOTO [Five Consecutive Days on Treatment with Efavirenz, Tenofovir, and Emtricitabine Followed by Two Days Off Treatment Versus Continuous Treatment] study that Dr. Cal Cohen was PI [principal investigator] of.
It showed that if patients take Atripla for five days out of the week, and are off treatment for the weekend, they do just as well [as those who took standard seven days per week therapy]. I have had two small-sized women who were having lots of side effects for whom I've used that approach.
But I think it makes sense to consider that for other regimens as well, although, since most of them come only in one pill size, it's hard to do.
Kimberly Smith: This might be the one place where Dr. Stone and I disagree. Back to the initial question about therapeutic drug monitoring, I haven't used it. There aren't any good studies that have shown us that it is that helpful for populations, in general, not specifically looking at the question of whether it may be more predictive of toxicity in women.
When I have a woman -- or anyone, really -- with side effects to the medications, I am very cautious about adjusting doses. I'm much more likely to give them an alternative agent.
With all due respect to Dr. Cohen, the FOTO study is somewhat frustrating to me, the reason being that it's a very small study. In an observed analysis, the folks who took the five days on and two days off did as well as the individuals who took it every day. Again, it's an observed analysis, because it's such a small study. I think it's too small of a study to be able to draw conclusions.
Certainly, we know that a drug like efavirenz and drugs like tenofovir and emtricitabine have long half-lives, and they probably will hang around for an extra day or two after a missed dose. So, yes, you can probably get away with it. But how long can you get away with it? Can everybody get away with it? It's still to be determined.
This is why I always have been very critical of studies like that -- studies that may lead to some confusion among patients. Because when we spend so much time trying to convince patients that "you've got to take your drug every day," and then we come out with a study, and it gets splashed across the lay media as, "Well, it may be OK to take your medicines five days a week, rather than seven," I think that gives patients the wrong message and potentially could lead to poor consequences.
I just don't think that we know enough to be able to dose reduce medication for HIV. Again, my strategy tends to be to prescribe an alternative medication if they don't think they can fight through it. We had to have some controversies.
Valerie Stone: Absolutely. I think it's great for people to see that experts will differ, and that there are different approaches.
I completely agree with Dr. Smith that it was a study with a small number of patients. Which is why, whenever I make changes like that, I do monitor patients very closely. Certainly, if it looks like they are doing poorly, I would make a change then. Again, I have only done it with very small patients who don't weigh very much.
But I completely understand what Dr. Smith's point of view. Her approach is much more data driven than mine.
Bonnie Goldman: Let's turn to adherence. Do you find that adherence is different for women? Are there any adherence tools that work or that you use, specifically for women? Dr. Smith?
Kimberly Smith: Is adherence different for men and women? I would have to say that we can't answer that question very well. I think there's a limited amount of data out there that suggests that there may be more discontinuation of medications in some women than in men, maybe somewhat poor adherence.] But I think part of the challenge with some of those data is that we may be looking at not just gender differences, but differences that have to do more with what's going on in their lives.
For example, I think a lot of times when we look at cohort comparisons of men versus women, often what we're looking at is a comparison of women in WIHS [Women's Interagency HIV Study] to men in MACS [Multicenter AIDS Cohort Study].
Men in MACS are very, very different than women in the WIHS cohort. Until they opened it up and added more men of color, men in MACS were overwhelmingly Caucasian, were mostly employed and tended to be middle class or on the higher earning end of things. They had a different type of lifestyle than the average woman in WIHS.
One of the studies in WIHS looked at the average household income for women in that study. The median household income for women in that study was $4,500 a year. Around 80% of the women in the study were unemployed. You're talking about completely different lifestyle issues. So the difference that we see in adherence, when we compare some of these big cohorts like that, may not be gender difference as much as socioeconomic difference.
I'm hesitant to say that there's a good study that tells us that adherence is not as good for women, or better for women. I think it really depends on who your population is. So that's the answer to the first question regarding whether adherence differs in HIV-infected women compared to HIV-infected men.
With regard to my strategies around adherence in women, sometimes women just tend to need a lot of encouragement and a lot of support. I have some patients that may need to just be called and reminded and encouraged. But that's true for a lot of my male patients as well.
Bringing this back to my personal experience: I can count on one hand the number of patients that don't have suppressed viral load in my clinic here at Rush [University Medical Center]. Unfortunately, most of those are women. What are the issues that keep those few women from being undetectable? Depression. Different priorities in their life. They prioritize the lives of, often, their children or their partners over their own situation, and so taking care of everybody else is important. Getting around to taking their medicine becomes secondary.
I do think that it's those kinds of issues that are probably prevalent more with women, who tend to be the caretakers, than they are with men, who tend to only have themselves to care for.
Bonnie Goldman: Dr. Stone?
Valerie Stone: I want to avoid repeating everything that Kim said all over again, because I think that it was right on the mark. I would just say it a little differently.
As Kim already said, it has a lot to do with who the individual is, but a lot of the women living with HIV have many of the known challenges to adherence.
Specifically, they are more likely to be depressed, more likely to have a current or past history of substance abuse or alcohol dependence, more likely to have a chaotic lifestyle, more likely to have low health literacy and more likely to have not disclosed their HIV to key people in their life. Each of those things makes them more likely to be nonadherent, or to be intermittently adherent.
I think we have to be both cognizant of that and actually really acknowledge that. Clinical programs need to build adherence programs, interventions and at least approaches around the fact that many HIV-infected women will be challenged because of these things.
I agree that in terms of adherence interventions, we don't do, and I don't do, anything that's rocket science. Basically, I think that most women just want more encouragement, more contact and more than one provider who is the person that they relate to around their medicine.
We have primary nurses in our practice here. We make sure that our women patients meet their primary nurse at their first visit. The nurse often gives them a follow-up call after we start them on medicine to make sure that they understand how they are supposed to take the medicine.
I tend to have more frequent follow-up visits within the first two months after starting women patients on antiretrovirals to make sure they understand, and that they are encouraged and that they have their questions answered, particularly around side effects. I think that this often goes a long way in terms of optimizing their adherence over time. It's just getting off to the right start over those first couple of months.
Bonnie Goldman: Let's switch to pregnancy. Dr. Stone, what are the current treatment recommendations regarding pregnant HIV-infected women?
Valerie Stone: I think that it's very important that providers be completely encouraging and open to the idea of their women patients with HIV having children.
I've been treating patients with this disease for so long and, I remember a time when there was actually a debate in the literature 15 years ago about whether that was something that was ethically correct.
I think that we really see this as an important part of life for women, and men, as well, and that women with HIV should know that they can be very effectively treated during pregnancy.
There are guidelines from the U.S. Public Health Service regarding what regimens are recommended during pregnancy. They haven't changed very much over time. The regimen that's most clearly recommended is boosted lopinavir with Combivir -- that is AZT [zidovudine, Retrovir] and 3TC [lamivudine, Epivir]. That's probably the most common regimen used in the United States.
Most of the other protease inhibitors don't have as clear-cut data documenting safety, and none of the other two NRTI [nucleoside reverse transcriptase inhibitor] backbones have clear-cut safety data that goes across enough patients to truly recommend other regimens.
There is becoming a tendency, I think, for some providers to use boosted darunavir. I think over time we're going to have substantial experience with that regimen, but it's not one that's clearly recommended at this time.
I should add that it's also recommended that we could use nevirapine as the anchor drug, along with Combivir, if the woman has a CD4 count of 250 or below. It actually is uncommon in the United States for us to be taking care of women who present in that CD4 count range, but it is, in fact, part of the recommendation.
Kimberly Smith: Obviously, the situation varies, depending on the woman's history. If you have a situation in which a woman is diagnosed with HIV while already pregnant, then you need to make a decision about when to start therapy. The guidelines, in general, tend to say that you would start based upon the needs of the mother.
If the mother has more advanced disease, has a low CD4 cell count, you probably want to start her on treatment immediately. But if she's stable and her T-cell count is OK, then you may want to wait until after she's completed the first trimester, in order to try to minimize some of the potential drug effects in the first trimester.
With regard to the medications, Dr. Stone has summarized those well. One of the challenges that exist with the medications is that anyone who has ever been pregnant knows that one of the major side effects of pregnancy is nausea. Unfortunately, that's the most common side effect associated with zidovudine, and it also can be a side effect of lopinavir/ritonavir [RTV, Norvir]. So, when we start using these in practice, there can be some challenges related to that.
Under those circumstances, alternatives can be used. There's an increasing amount of data now with regard to the protease inhibitors about using atazanavir in pregnant women. Certainly, there has always been the concern about bilirubin associated with atazanavir and the infant's exposure to bilirubin. But there don't seem to be any excess toxicities associated with the use of atazanavir in pregnancy. So, some clinicians are using that as an alternative if lopinavir/ritonavir is not very well tolerated.
In the nucleoside category, again, with zidovudine being associated with quite a bit of nausea, the alternative that some people move towards is abacavir [ABC, Ziagen], which is pretty well tolerated, in general, with regard to the GI side effects.]
You can obviously check HLA [human leukocyte antigen] to minimize the likelihood of there being a hypersensitivity reaction. It can be a reasonable alternative.
Most clinicians do tend to avoid tenofovir in pregnant women, mostly because of concerns about there potentially being some toxicity with bone development.
The OB/GYN [obstetrics and gynecology] folks, and pediatricians in particular, tend to be pretty nervous about the use of ritonavir in pregnant women. So, those are some of the alternatives.
Bonnie Goldman: Are you seeing a growth in the number of women having children in your practice? Dr. Stone?
Valerie Stone: I'm not. I think it really depends on where you're practicing, and the population of women who come to you. Our practice still has a lot of women who acquired HIV through injection drug use and tend to be older and already have children. Or, at least, they tend to have already had their children at the time they get diagnosed. We also tend to have a lot of immigrants who also have already had their children and are presenting to us when they are in their 30s.
So, no, we're pretty stable. There are three of us who co-manage the women who get pregnant each year. We're managing maybe 12 to 15 pregnant women over the course of each year. It's been pretty stable across the last five years or so.
Bonnie Goldman: Are there any data regarding infertility in HIV-infected women? Has that been a common issue? Dr. Smith?
Kimberly Smith: That's a good question. I don't know of there being data around infertility in women who are healthy with HIV (i.e., women who are appropriately on antiretroviral therapy, with a suppressed virus and that sort of thing).
Now, someone who is more ill from HIV -- one who has tended to lose weight -- often won't have regular periods. They tend to have some more hormonal shifts, as a result of malnutrition from weight loss and that sort of thing.
It would be presumed that the fertility for those women would be challenged. But I can't think of any studies that have looked at women who are on therapy and suppressed to see whether they are any less likely to get pregnant. My experience is that if they are not careful, they can become pregnant.
Dr. Stone, do you know of any fertility studies in women?
Valerie Stone: No. I haven't seen any at all. We are using infertility approaches here for women who are in discordant partnerships -- for example, using assisted reproduction, and so forth. But we haven't had any problems with any of our women getting pregnant who wanted to, and I haven't seen any studies in that regard.
Kimberly Smith: Dr. Stone talked a little bit in the beginning about the issue of counseling HIV-infected women in our clinic about reproductive options. I do think that that is an important point that is sometimes lost. Not enough clinicians are making women who are HIV infected, but have a suppressed virus and are doing well, aware of their options for having a baby if they want one.
It might be worth running through some different scenarios. One scenario is the situation Dr. Stone described, where you have a discordant couple (i.e., an HIV-infected woman and an HIV-negative man). Under that circumstance, how do you counsel about having a baby?
The most appropriate thing to recommend would be, as Dr. Stone suggested, artificial insemination. You'd talk to your fertility specialist about alternatives to the old-fashioned way of getting pregnant so you don't have to put the male partner in any kind of jeopardy.
But in another scenario you may have an HIV-infected woman who is with an HIV-infected man. The thing that I always try to hammer home to couples like this is that, even though they both are infected, that doesn't mean that it is OK for them to have unprotected sex.
The recommendation that I would make to an HIV-positive woman with an HIV-negative man about how they would go about getting pregnant is the same recommendation I would make to a couple where both are infected.
Because, again, presuming that both of them have suppressed virus, even though the likelihood of a superinfection is probably pretty low, it's not zero. In those circumstances, again, artificial insemination would be the most appropriate way to go.
The last scenario is a situation where you have an HIV-negative woman and an HIV-infected partner who want to have children. There have been a number of studies outside of the United States that have shown that you can use sperm washing techniques where you separate the semen from the sperm and basically wash the sperm, test it for HIV with a PCR [polymerase chain reaction], and then use artificial insemination. Those strategies have been successful.
There are lots of options for HIV-infected women, and for couples in which there is a negative woman and a positive man, to be able to still have reproductive choices.
Bonnie Goldman: Let's quickly turn to complications. With HIV now being called a risk factor for bone disease, how do you manage bone disease in an HIV-infected woman?
Valerie Stone: I have not had a different approach than I would have with HIV-uninfected women. I begin getting bone density studies, either at age 50 or at the time of menopause, whether it's later or earlier. Certainly, I have a lot of women living with HIV who have had hysterectomies. If they have had surgically induced menopause, then I start checking their bone density within a year or two after that time. I would put the women on treatment for bone density loss, if I found it.
I also do recommend very aggressively to all of my women patients that they take calcium and vitamin D. I check for vitamin D deficiency in all of my patients, and I replete any vitamin D deficiencies that we find. I don't know what it's like in the other parts in the North, but in Boston about 80% to 90% of people of color have vitamin D deficiency when we test for it.
I think that's an important part of keeping their calcium absorption in an appropriate range, and avoiding early bone loss. Other than that, I'm not doing anything special.
Kimberly Smith: I agree with Dr. Stone. I'm following the recommendations for uninfected individuals, unless a person has something that makes me concerned that they may have a problem.
For example, if someone has a fracture under a circumstance in which it would be unusual, then that would make me be more aggressive about doing a DXA [dual-energy X-ray absorptiometry] scan or a bone marrow density study in that person.
But I am not routinely looking at all of my HIV-infected patients with those types of studies, if they don't fit into that age group automatically.
But I agree with Dr. Stone about the issues of calcium and vitamin D. I'm beginning to encourage my patients to just start to replace. Unlike Dr. Stone, I'm not checking everybody; mostly because I'm pretty much assuming that the majority of our patients are deficient. The number that you're quoting, Dr. Stone, of around 80%, is not only just in the North. Our friend, Dr. Joe Gathe, who is in Houston, has looked at his patients and found similar rates. And that's in an environment where they are getting a lot more sun.
Valerie Stone: Where, at least, there is a lot more sun. They may not be getting it.
Kimberly Smith: Well, that's true. You can't presume, though, just because they are in a warmer climate, that they necessarily don't have this challenge. But I think what is only beginning to be understood is that vitamin D deficiency is very common in the population, in general.
It's not quite clear that we're seeing it that much more commonly in our HIV-infected patients; or now that we're looking, we're seeing it, and that it's just something we're not looking for so much in the general population.
Valerie Stone: That's true. It is important to realize, though, that there are several studies that show that if you don't replete with high doses, you will not achieve repletion into the normal range.
Kimberly Smith: Right.
Valerie Stone: If you just start giving everybody supplementation at the normal amounts that are recommended of 1,000 to 2,000 IUs [international units] per day, they won't get repleted if they started out deficient. That's part of the reason why we check.
Bonnie Goldman: What's the recommendation currently?
Valerie Stone: If someone is vitamin D deficient, if they are between 20 and 32, then you would give them either 50,000 IUs per week, for four to eight weeks. If they have a level under 20, then you would give them 50,000 IUs per week, for 12 weeks. After that, you resume. In the days in between, you'd give them standard supplementation: between 1,000 and 2,000 IUs of vitamin D.
Bonnie Goldman: Moving right along, let's turn to: What are the non-infectious comorbidities that are more common in HIV-infected women? Dr. Smith?
Kimberly Smith: You could debate whether it's non-infectious, certainly, one of the ones that stands out the most is cervical cancer. That obviously modifies our management for women, although I will say that men are starting to catch up in the sense that now we're doing rectal Pap smears that are parallel to the cervical Pap smears that we have been doing for women forever.
Valerie Stone: I would add that we know that obesity is most common in African-American women in the United States. Probably, obesity is most common in that subset of people living with HIV.]
I think that I have seen data on that. I have not seen data that shows clearly that diabetes or high blood pressure are most common with either women with HIV or women of color with HIV. But it follows that it may be the case, particularly diabetes.
Kimberly Smith: I agree with you about the obesity issue. But if we think about hepatitis C, we're not seeing that more commonly in women than in men. Same thing would be true for hepatitis B; not more common -- if anything, it's less common in women than in men.
Some of the typical comorbidities that we're managing the most are cardiovascular disease related, but they are not more common in women.
It's not like HIV disease transforms women into something different than what they are when they are not HIV infected. The differences that exist between men and women who aren't HIV infected are obviously not changed. I can't think of anything that HIV adds to the mix, other than the AIDS-associated cancers. There's really not a big gender difference.
Valerie Stone: I do think that mental health challenges are common in HIV-infected people, but that depression is clearly more common in HIV-infected women than men. And it's quite prevalent.
I also think that a history of substance abuse, particularly serious substance abuse, tends to be more common in women living with HIV than men.] Of course, that depends on the population you look at. But when you look at a very mixed population like we follow here at Massachusetts General Hospital, it's clear that there are more challenges with substance abuse in the women, compared to the men.
There is a lot of underreporting of the alcohol abuse and other substance abuse among gay men.] But for the ones that underreport it, it often is in the range where they are functional. So I do think the challenges in that regard are greater for women than for men with HIV.
Bonnie Goldman: What are the primary care guidelines regarding monitoring for cervical cancer? Dr. Smith?
Kimberly Smith: I know there's this debate now about whether they should be spread out for HIV-negative women (i.e., not done every year, but done every couple of years). For HIV-infected women, there hasn't been a change. Basically, HIV-infected women should be screened at least every year and, arguably, every six months if they've ever had an abnormal Pap smear. There's not really been much change from that standpoint. The controversy with HIV-negative women is that there's some suggestion that we're probably overdoing it by doing Pap smears every year; and that they probably can be spread out to every two years for women who have never had an abnormal Pap, and maybe even further than that; and that you don't need to start doing them until women are at least 21 years of age.
It's controversial, and it should be. Because, depending on the populations that you're talking about, if you don't start looking for some of the women who may be at more high risk until they are 21, you may be finding more women with more advanced disease that you could have caught earlier if you were starting earlier. But it really depends on the population that you're talking about.
Bonnie Goldman: In closing, do you think that with the growth in the numbers of female researchers that more questions will be answered about gender differences in HIV? Dr. Stone?
Valerie Stone: I think that there's a wide range of different questions out there, and I think that there's a tremendous amount of interest in disparities in the care of women with HIV among women researchers. I've been really impressed with new data and important new questions in that regard, that we've seen with the growth of women researchers and researchers of color.
I think, when it comes to clinical trials, Dr. Smith is better equipped to answer this than me; but I think that we've been seeing a growth in the number of women researchers over the past 10 to 15 years. I think that there's been incredible progress in the approach to getting women in clinical trials, and also in cohort studies that have enrolled women, followed them closely, and answered a lot of important clinical questions - as in, for example, both HERS [Heart and Estrogen/progestin Replacement Study] that the CDC [U.S. Centers for Disease Control and Prevention] funded and, over the past 10 years or so, WIHS, which the NIH [U.S. National Institutes of Health] has funded.
So, I think the answer is yes, but I think we've been seeing that for a few years now.
Bonnie Goldman: Dr. Smith?
Kimberly Smith: I think that what has happened in the last few years is that women researchers have been pushing for there to be more industry-based studies that enroll higher numbers of women, and that there's an effort to really study drugs as they come out in large numbers of women. I do think that the FDA [U.S. Food and Drug Administration] has somewhat responded to that demand, and so we are starting to see some of the larger studies making sure that they enroll a substantial proportion of women.
Some studies -- for example, the GRACE study -- are being designed specifically to look at newer drugs in women. I think that move is an important one. If we don't have enough women in the trials from the beginning, then we won't identify drug toxicities that may be more prevalent in women until very late into the process, years after they have been approved. So I do think that those demands coming from female HIV investigators have started to bear some fruit.
Obviously, WIHS has contributed a tremendous amount to our understanding about HIV disease in women. What we're getting from that is invaluable. It's one thing to be able to answer some questions in cohort studies, sort of understanding the natural history of HIV disease in women, which is a lot of what WIHS is able to do.
What other groups, like the ACTG, have done, and are continuing to do, are answer more clinical trial type questions. One of the big ACTG studies that is enrolling at present, is the PROMISE [HAART Standard Version of the Promoting Maternal and Infant Survival Everywhere] study, and it is looking at whether women who have a high CD4 cell count and are basically only starting therapy because they are pregnant -- and might not otherwise, based on the guidelines, need therapy -- are better off.
Once they deliver, should they stay on antiretroviral therapy, or should they go off treatment until their T-cell count drops down to a point where they would need therapy based on the guidelines? Questions like that are everyday types of questions that are really important for us to answer for women for their long-term health. They are controversial questions. But I think it's important to be doing those studies.
The experience of female HIV investigators, as well as that of some male HIV investigators that have taken an interest in women, has led to a number of unanswered questions. I think that we're beginning to start to see studies that are really designed to answer those questions. I'm encouraged that there's a lot more important information coming forward in the future.
Bonnie Goldman: Thank you so much, Dr. Smith and Dr. Stone, for an enlightening discussion. There's so much to cover, and so little time, this was a good beginning, thanks again!
This transcript has been lightly edited for clarity.
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