How has the treatment of pregnant women changed with the times, and with our increased understanding of how the virus works? How have the official U.S. HIV treatment guidelines reflected those changes? And, most important, how do those changes translate into the lives and options of pregnant women living with HIV? To get some answers, we sat down with renowned HIV care provider and researcher Monica Gandhi, M.D., M.P.H.. Dr. Gandhi directs the AIDS Consult Service at San Francisco General Hospital and is an HIV and primary care provider in the Women's HIV Program at the University of California, San Francisco. She's also a research investigator with the Women's Interagency HIV Study, a large, multisite prospective cohort.
We drilled down into the newest edition of the official U.S. HIV treatment guidelines for pregnant women living with HIV and discussed some of the most notable changes -- with a healthy helping of wisdom from Dr. Gandhi's extensive experience treating HIV-positive women -- through the lens of some important questions a pregnant woman might likely ask about her treatment.
Whether you're considering getting pregnant or you're already there, it is vital to find a provider you trust, who supports what you're doing. To deepen the conversation about your treatment options, consider sharing the article below with your providers.
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I'm not on HIV meds yet. Should I start taking them before I start trying to get pregnant?
Short answer: Yes, if you're able to delay conceiving until you feel comfortable with your HIV treatment regimen.
Back in the day (and by "the day," we mean prior to March 27, 2012), there was no mandate for everyone living with HIV to be on antiretroviral therapy. The official guidelines for treating HIV in the U.S. indicated CD4 count cut-offs below which treatment was recommended. Oftentimes providers would suggest that women who were trying to get pregnant not start therapy until the second trimester of their pregnancy because of the chance they'd feel sick during the first.
What has changed in the last year, in both the general treatment guidelines and the guidelines specifically dealing with pregnancy, is that it's now recommended that every HIV-positive person in the United States be on HIV therapy, no matter what. There have been a number of big studies recently that spurred this change -- not the least of which is HPTN 052, which revealed that effective treatment is also good for HIV prevention, to the tune of an up-to-96 percent decrease in the likelihood of transmitting HIV.
So ideally, a woman who is trying to get pregnant and knows she's HIV positive should likely be on HIV meds already; in fact, she should start taking meds as soon as she's diagnosed.
However, just because an official recommendation recently changed does nothing to eliminate the myriad social factors and structural barriers that lead to so few people in this country being on therapy and having their virus under control. Of the 1.1 million people living with HIV in the U.S., only 25 percent have undetectable viral loads, according to the U.S. Centers for Disease Control and Prevention (CDC).We still have far to go in making the optimal conditions described within the guidelines into a reality for all people living with HIV.
The unfortunate state of HIV care in the U.S. won't change overnight, but Gandhi believes it will also never be the same following this recent recommendation that all people with HIV start treatment. One of the best things to do when preparing to conceive, for your own health and the health of your baby, is to make sure (as soon as possible) that you're on a stable regimen that works for you, even before you get pregnant. With the current wealth of treatment options available in 2012, there's bound to be a comfortable regimen out there for you.
As Dr. Gandhi says to many of her patients: "If you're having a side effect, it is not your fault; it is my fault. We have so many options, I should be able to find a regimen where you can feel relatively side-effect free." Once you're settled into a stable regimen, just go ahead and get pregnant; then relax, try not to worry too much, and prepare to watch your family grow!
If I'm already pregnant, when should I start taking meds?
Short answer: As soon as you're comfortable, but no later than the start of your second trimester.
If you're already pregnant, talk to your provider about whether you want to start meds right away or wait until 12 weeks into your pregnancy, when you may be feeling a bit better (in terms of first-trimester nausea and discomfort) and more ready to adhere. It is also after the 12-week mark that mother-to-child HIV transmission becomes more of a risk, making HIV medications more important for the mother-to-be.
Pregnancy is a particularly fraught situation, because it's a time when treatment matters not just for the health of the mother, but for the fetus as well, in terms of protecting it from acquiring HIV. But if you're concerned you won't be able to take your HIV meds properly, here's some good news: Amazingly, many studies have shown that pregnancy is often a time where women who don't otherwise want to be on antiretroviral therapy really pull it together. They may not be able to take medications before or after their pregnancy because of any number of adherence barriers, yet they manage to take their meds faithfully during pregnancy, to protect their babies.
We'll never go back to a time in which CD4 count cut-offs are used to guide therapy decisions; from here on out, providers will be guided to recommend HIV meds for anyone who's found to be HIV positive. That includes women at any stage of pregnancy. "What people do from there is up to them; and how we as providers help support them around that is up to us," Dr. Gandhi says.
Does my viral load need to be undetectable before I start trying to get pregnant?
Short answer: No.
The risk of vertical, or mother-to-child, transmission in the first trimester is actually quite low, which is why, prior to the latest iteration of the guidelines, many pregnant women were counseled by providers to start HIV meds in the second trimester. There are certainly overall health benefits to being on antiretroviral therapy. Some women find that their fertility increases when their virus is suppressed and their immune system is on the mend. That's one incentive, for people of childbearing age: Getting on HIV meds is going to help you be, essentially, more fertile. Besides, the body generates a stress response when it's fighting a condition, especially on its own. That's not the ideal environment for a baby to be conceived and begin to grow, so HIV meds can be helpful in this regard. But there's no mandate that a woman should have an undetectable viral load before she gets pregnant. Of course, if a woman's partner is a man and he's HIV negative, and they are going to try to conceive through unprotected sex, her undetectable viral load renders him less likely to become HIV positive.
Beyond that, the bottom line is that preparing for pregnancy is a time for a woman to ensure that her body is as healthy as possible. In the spirit of taking prenatal vitamins, getting more rest, eating a balanced diet and, ideally, not drinking, drugging or smoking while trying to conceive, being on HIV meds can be another way to prepare your body to be a healthier body, to help integrate that pregnancy.
Which HIV meds are safe for me to take while I'm pregnant?
Short answer: Virtually all of them are believed to be OK, but since very few have been studied extensively in pregnant women, making official recommendations is a bit tricky.
Although we just got done touting the importance of the guidelines when it comes to the "when to start" question, it's a slightly different story for the "what to take" question. As Dr. Gandhi puts it: It's wonderful that we have these thorough, well thought-out, frequently updated guidelines, but providers with a lot of experience often use different medications than the ones that are recommended in the guidelines. This is because the guidelines are very cautious when it comes to giving a thumbs-up to the use of specific HIV medications during pregnancy, out of concern for the health of the soon-to-arrive child; but providers with a lot of experience with other medications usually feel safe using them.
The guidelines rely heavily on long-term, cumulative data -- HIV drugs that have been extensively studied in pregnant women and found to be not only effective, but safe for both mother and child. As a result, meds that are recommended in the guidelines tend to be older, since they're the ones we've had the most time to study. This is good, because we know pretty conclusively that they're safe. But it also means that the drugs that have been studied specifically in pregnancy are not necessarily the ones that would ever be used nowadays to treat any adult, since more effective HIV drugs have been approved in the meantime.
For instance, the guidelines state that a pregnant woman's regimen should include a pair of NRTIs that have been around for well over a decade: the drug commonly known as AZT (generic name: zidovudine; brand name: Retrovir) and Epivir (3TC, lamivudine) -- which are available together in one pill as Combivir -- are still considered "preferred agents" for use in the first trimester and throughout pregnancy. That's a fair thing for guidelines to say, since we have the most data among pregnant women using that particular combination.
But AZT in particular is considered a bit of an old-fashioned choice among people who treat many women living with HIV. It's still a twice-a-day regimen. It causes anemia. It's more likely than many other HIV meds to cause nausea, which can be difficult for women whose pregnancy already has them nauseous.
While they may be mere "alternative agents" in the pregnancy guidelines, Ziagen (abacavir)-based and Viread (tenofovir)-based regimens are commonly used in centers where there's been a lot of experience treating pregnant women. Among these seasoned clinicians, according to Dr. Gandhi, providers have pretty much phased out prescribing AZT with Epivir (or the combo pill Combivir), and are instead using either Epzicom (abacavir/3TC, Kivexa) or Truvada (tenofovir/FTC) as the backbone for the regimen. These experienced health care professionals know that there aren't as many studies with these drugs in pregnancy, but that they have been proven safe in general, as well as powerful and effective at reducing the mother's viral load (which is really the primary aim for protection of the fetus from HIV).
NRTIs are only part of the story, however. An effective HIV treatment regimen needs to be anchored by drugs from additional classes, such as NNRTIs and protease inhibitors. Again, the guidelines aren't the best reflection of how top clinicians choose to prescribe these anchor drugs today.
For instance, the NNRTI Viramune (nevirapine) is still considered a preferred agent. But in the U.S., we don't use Viramune much because of its liver toxicity issues and its risk of triggering an allergic reaction (usually a bothersome rash), and because it's not supposed to be prescribed to women who have a CD4 count greater than 250 -- that's because those side effects are enhanced at higher CD4 counts.
Meanwhile, two newer NNRTIs, Edurant (rilpivirine) and Intelence (etravirine), are listed in the guidelines under "insufficient data to recommend." The phrase has an ominous ring to it, but it simply means that although there's not enough evidence that the drug is great for a pregnant woman to take, there's also not enough evidence that it's bad. If there were ever data that made experts scared for the health of a pregnant woman or her child-to-be, then the drug would be earmarked in the guidelines for greater concern. In the case of drugs such as Edurant and Intelence, providers out there still may prescribe them for pregnant women, because they have been shown to be generally safe and very effective. It's just that these drugs have yet to be extensively studied in pregnant women, so the guidelines are reluctant to openly recommend them.
There is one NNRTI that does have a complicated relationship with women who are pregnant or considering becoming pregnant: Sustiva (efavirenz, Stocrin), which is contained within the popular single-pill regimen Atripla (efavirenz/tenofovir/FTC). We'll discuss Sustiva in more detail in the next section.
As for protease inhibitors: Prior to the most recent pregnancy guidelines update, there was just one preferred agent from that drug class, Kaletra (lopinavir/ritonavir). But Kaletra can be difficult for pregnant women because it includes a high dose of Norvir (ritonavir), which is associated with nausea and other gastrointestinal side effects. It also needs to have its dose increased in the third trimester, which can make it even harder to take a drug that already was sometimes hard to take.
Just as with the other classes, though, there are many other protease inhibitor options that providers may choose to prescribe. Of these, two are used most commonly: Reyataz (atazanavir) and Prezista (darunavir).
Reyataz was recently bumped up in the guidelines from an alternative agent to a preferred agent -- though not without some controversy, because some studies suggest the dose of Reyataz may need to be increased during the third trimester.
Prezista also got a promotion, from a protease inhibitor on which there was insufficient data to an alternative agent. Experienced providers feel pretty good about their anecdotal experience with it, because it's relatively easy to take.
Of course, there are other classes of "anchor" drugs beyond just NNRTIs and protease inhibitors. In more recent years, a few entry inhibitors and integrase inhibitors have been approved for use in the U.S. One integrase inhibitor, Isentress (raltegravir), is listed under "insufficient data" in the guidelines, but similar to other "insufficient data" drugs, it may be prescribed by experienced providers. This is because Isentress, and all integrase inhibitors, can reduce HIV viral load very rapidly. This can make it a very attractive drug in certain situations -- for instance, on those occasions when a woman comes into care in her third trimester with a high viral load and hasn't yet received any prenatal HIV care. The biggest goal in these instances is to get her viral load down as quickly as possible, to reduce the risk of transmission to the fetus. In those circumstances, providers who know what they're doing have prescribed Isentress as part of a regimen of HIV medications.
Is Sustiva dangerous to take when I'm pregnant?
Short answer: Not necessarily, but it should be taken with caution.
The NNRTI Sustiva (a component of the combo pill Atripla) is currently one of the most frequently prescribed HIV medications in the U.S. However, Sustiva's official prescribing information states that women should not become pregnant while taking it or for 12 weeks after stopping it. This is based mostly on studies of monkeys, as well as some case reports in humans, that suggest Sustiva use during the first trimester (while the baby's organs are developing) can interfere with the baby's development, potentially leading to central nervous system defects.
But even that earlier research has been called into question: A recent study showed that risk of fetal neural tube defects, when Sustiva was taken during the first trimester, was not unusually high compared to the general population. The guidelines still recommend avoiding Sustiva if you are a woman of childbearing age who is trying to get pregnant. That isn't likely to change anytime soon. But Dr. Gandhi notes that whatever risk Sustiva may pose to babies' growing central nervous systems, it's low.
But if women who may become pregnant are encouraged to avoid Sustiva, then why shouldn't women who are pregnant stop taking it? As we noted above, the only known possible risk with Sustiva impacts the first trimester. Usually, by the time women find out they're pregnant and seek care, they're at least four to six weeks into their pregnancies, and fetal organ development is complete by six weeks. By that time, there's not much further concern about risk of birth defects. So, if a pregnant woman comes into for her first prenatal doctor's visit and she's on Sustiva already -- and if her HIV treatment is working well (i.e., her viral load is undetectable) -- there is no longer a recommendation that she switch off Sustiva. That's a really significant change to the guidelines that seems to have gone largely under the radar.
Also, just to be clear: If you accidentally got pregnant, or you didn't share with your provider that you were trying to conceive, and you'd been taking Sustiva (or the combo pill Atripla, which contains Sustiva), you have no need to panic, and neither does your provider. Don't rush to switch -- even if it's the first trimester -- because the most important thing is to keep that virus suppressed and reduce the risk of passing HIV to your unborn child.
Finally, for those women who become pregnant via a man who is HIV positive and is taking Sustiva: If you're concerned that the Sustiva will affect his sperm in any way that could be harmful to a resulting fetus, the answer is no, absolutely not. The concern with Sustiva has to do only with the fetus' exposure to the drug in your uterus.
Are there any side effects of certain regimens that might be particularly severe in a pregnant woman? If so, how are they managed?
Nausea. Protease inhibitors, in general, tend to be particularly difficult for women. The Norvir dose that's required with Kaletra, mentioned above, can be quite nauseating for people. Then again, any medication that you used to tolerate well, in the context of a nauseating stage like pregnancy, may be extra nausea-producing.
In Dr. Gandhi's practice, providers are definitely very proactive about nausea management. A lot of women seem very concerned about taking anti-nausea medications during pregnancy. But there are antiemetics that are absolutely safe during pregnancy that pregnant women have been using for many years. There's no reason to suffer even more than you already may be during pregnancy.
Acid reflux. Many women have pretty severe regurgitation or heartburn during pregnancy, and Reyataz is a drug that should not be used in combination with acid-reducing proton pump inhibitors given at too high of a dose, or too frequently. That can be difficult for women suffering from heartburn, who many want to take a lot of antacids. Talk to your provider about the proper way to take antacids when experiencing acid reflux while taking Reyataz.
Itching. One of the benign side effects with Norvir-boosted Reyataz in people who aren't pregnant is a mild rise in indirect bilirubin (a waste product from the breakdown of red blood cells, which is processed by the liver). This bilirubinemia can lead to itching; that can be exacerbated in pregnancy, when you may be extra-itchy anyway due to fatty changes to the liver in pregnancy. The combination of the itching from Reyataz and the itching from pregnancy can be very problematic. Plus, stretching skin on a pregnant belly and elsewhere are already itchy as well.
Some moms have said that oatmeal baths as a home remedy are very helpful with the itching. It's also safe to give antihistamines like Benadryl during pregnancy. If it gets bad enough, or if the bilirubinemia is a problem, there's no compelling reason not to talk to your provider about switching off Reyataz. There's no reason to go around itching all the time. There are so many reasons for itchiness during pregnancy, so why add one?
How should I handle a switch in HIV med regimens during my pregnancy?
Short answer: Carefully, and with communication between you and your provider.
As we discussed in the case of Sustiva during pregnancy, switching off a regimen you're accustomed to and comfortable with, and you've figured out a way to be adherent to, is not the best strategy in the setting of pregnancy. But if that regimen is no longer comfortable for you, it is absolutely time to switch. If you do make that decision, it's ideal to switch directly from an old regimen to a new one without an interruption in treatment. However, make sure you get detailed counseling from your provider about food requirements and other details of the new regimen before you start taking it. The main concern with any switch in meds is the potential increase in viral load -- because the person didn't understand the new regimen, didn't know when to take it, that they were supposed to take it with food or on an empty stomach, and ended up not taking it correctly.
It's already not a good thing to have viral load spikes; but in the case of pregnancy, it can lead to a transmission event. So counseling and communication are key to ensure a smooth transition between regimens during pregnancy. Once a woman has given birth, there's no problem at all in switching back to whatever regimen she wants to be on.
Should I give birth vaginally or via Cesarean (C-section)?
Short answer: Unless there's a viral load of 1,000 or greater, or some other medical indication, the default birth method in the U.S. is vaginal birth.
This is not necessarily something that a woman needs to feel anguished over deciding. Barring any other HIV-unrelated condition that would lead to C-section being recommended, the HIV-related circumstance in which C-section is indicated would be if the mother's viral load is not only detectable, but at a level of 1,000 copies/mL or greater. That's when there would be worry about increased risk of HIV transmission during a traumatic natural birth.
While there is a long history of C-sections among HIV-positive women, and this was once considered the safest alternative for keeping a baby HIV negative, there has been a trend moving away from C-sections in pregnant women living with HIV. The thinking that a woman living with HIV needs to have a C-section in order to have a healthy baby is actually quite old-fashioned. It dates back to when we didn't have effective HIV meds, and we didn't know how to get a person's viral load to undetectable levels. And that's no longer true.
In fact, there's a general trend in the U.S. toward discouraging elective C-sections, instead reserving them for cases where they're deemed medically necessary (though research suggests that the umbrella of what's considered a "medical indication" for a C-section may be wider than it should be, in general). Vaginal birth is better for the human body than trying to recover from major abdominal surgery while caring for an infant.
Will I need intravenous (IV) HIV treatment during labor and while I'm delivering my baby?
Short answer: No, if your viral load is less than 400.
This is another aspect of the pregnancy guidelines that has recently changed. The results of PACTG 076, a landmark 1994 New England Journal of Medicine study, dictated that the best way to reduce vertical HIV transmission was oral AZT to the mother during pregnancy, IV AZT to the mother while she was giving birth, and then oral AZT to the baby. Now we have such highly effective regimens that, as with C-sections, IV AZT can be reserved for specific scenarios, namely if a woman's viral load is 400 copies/mL or greater. That same person who had a viral load greater than 1,000 copies/mL who needed a C-section will also need IV AZT during labor. Someone who comes in and the first time she's even found out she's HIV positive is when she's giving birth, and her providers don't even know what her vial load is, should also definitely be given IV AZT.
But if you've been on an effective HIV med regimen for your entire pregnancy, and you've had an undetectable viral load almost the whole time, and especially at 36 weeks into your pregnancy: That's when you'd be encouraging to have a vaginal delivery, and you would not immediately be given IV AZT. It's expensive; it's difficult to administer; it discourages labor and birth outside of hospital settings.
Is it possible for me to give birth in a birthing center, or even at home, with HIV-trained professionals in attendance?
Short answer: Likely? No. Possible? Yes!
Let's be very clear: There is no discussion in the official U.S. HIV treatment guidelines about giving birth anywhere but in a hospital. The overwhelming majority of women in the U.S., whether they are living with or without HIV, give birth in hospitals, according to CDC. But with qualified midwives and other professionals involved, no complications detected, and a plan in place to transfer mom and/or baby to a hospital if medically necessary, a planned out-of-hospital birth -- in a birth center, or at home with qualified home birth midwives -- can be a safe alternative to birth in a hospital setting for low-risk women. And if an HIV-positive woman's viral load is undetectable, her labor is proceeding normally and there are no other complications present, she should not be considered high risk. There's no reason to pathologize the experience of giving birth while living with HIV; and there's no more reason for a pregnant woman living with controlled HIV to view her birth as a medical event than there is for an HIV-negative low-risk woman to do so. In these ideal circumstances, with contingencies in place to transfer to a setting for a C-section if needed, Dr. Gandhi sees no reason for a woman who wanted to explore out-of-hospital birth not to do so. In her opinion, the fact that the latest iteration of the guidelines no longer recommends IV AZT for women whose viral loads are less than 400 may open the door to wider consideration of HIV-positive women giving birth -- and HIV-knowledgeable professionals supporting these births -- in less medicalized settings.
What treatment will I be giving my baby, and when? How will I know if the meds are harming my baby?
Short answer: Liquid AZT, every 12 hours, for six weeks. Babies whose moms' viral loads were detectable during birth may get another drug in their regimen. Nearly two decades of monitoring babies born to HIV-positive moms has shown these to be safe regimens for newborns.
One aspect of the pregnancy guidelines that remains unchanged: Every baby born to an HIV-positive mom should get six weeks of oral AZT. Babies born to women whose viral loads were detectable when they delivered would likely get combination therapy, usually containing Viramune, as opposed to AZT by itself. Giving an infant six weeks of medications may be challenging for a new mother who's already exhausted. But this is another case in which studies have shown that people are really willing to keep up with that regular dosing, again, for the health of their babies. And in the past, dosing for babies was far more frequent; nowadays, dosing at 12-hour intervals, or twice a day, can make the process smoother. (Read four women's accounts of giving their babies AZT, and waiting for the infants' HIV test results.)
The major concern with AZT is anemia. It's not uncommon in newborns taking AZT, but it tends to disappear after they've stopped the drug. A baby's pediatrician would be monitoring the baby's hemoglobin levels throughout her or his six weeks on AZT.
For those who are concerned about the effects of HIV meds on a baby, a note to ease your minds: The Antiretroviral Pregnancy Registry, a program run by U.S. health authorities, has been monitoring babies born to women living with HIV since 1994. So far, they have found no evidence of long-term side effects in children of moms who took HIV meds during pregnancy. Women are encouraged to talk to their providers about enrolling them in the registry.
Is it safe for women living with HIV to breastfeed their babies?
Short answer: No; in areas of the world where replacement feeding is safe and available, the risks of breastfeeding with HIV outweigh the benefits.
The World Health Organization's most recent guidelines for infant feeding in the setting of HIV do not discourage mothers living with HIV from breastfeeding in the majority of the world. That's because in the parts of the world where women living with HIV are most likely to reside, the risks of not breastfeeding your baby -- in terms of other communicable diseases that could be acquired through the water used to mix infant formula, or because the baby failed to receive immunities through Mom's breast milk -- are more significant than the risk of HIV transmission. In these settings, breastfeeding may be encouraged whether or not HIV meds are available to the mother and/or the baby. Individual countries are supposed to set their own recommendations for infant feeding, taking into account the WHO's guidelines as well as the conditions in their own nation as far as availability of replacement feeding or HIV meds. Again, we're talking about areas of the globe where options are severely limited; in highly resourced countries such as the U.S., where water systems are clean and infant formula plentiful, breastfeeding is not recommended by the WHO, on the basis that any risk is unacceptable when there are other available options.
It may be difficult to be an expectant mom living with HIV -- often one who may already have had the experience of breastfeeding a previous child -- witnessing the American Academy of Pediatrics and many other institutions, and individuals, pushing breastfeeding as the best thing for bonding and for infant nutrition, while she and other moms living with HIV get a completely different message. In some areas there's even stigma associated with not breastfeeding. But it is still completely possible to nourish and bond with a baby who's not being breastfed.
Olivia Ford is the community manager for TheBody.com and TheBodyPRO.com.