December 11, 2009
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.