12 Questions About HIV Treatment and Care in Pregnancy
November 29, 2012
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.
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.