Antiretroviral Therapy in Pregnancy: How Safe It Is?

Risks of HIV infection during pregnancy

HIV infection is a serious medical condition that can lead to AIDS and death from a number of different opportunistic infections. For HIV-infected pregnant women there are special concerns in addition to managing the disease and preventing disease progression and deterioration of the immune status of the mother. These additional worries mainly concern the health of the unborn child.

One important thing to consider is the risk of transmission of the infection to the baby. While placental transmission of the virus i.e. infection of the unborn child in the womb is considered impossible or at least extremely unlikely, the child can become infected during birth (perinatal infection) or later through breast feeding.

The likelihood of perinatal infection can be decreased by reducing the virus load i.e. the amount of virus in the blood of the mother. This can only be done by using an effective antiretroviral treatment that has to be individualized based on the treatment history of the mother. However, when using antiretroviral therapy during pregnancy, one question comes up immediately: How safe is it?

Highly active antiretroviral therapy (HAART)

The current state of art of the treatment of HIV infections that is recommended for all patients is to try to achieve virus loads in the blood that are below the detection limit. This is usually achieved with a combination of several (typically three or four) antiretroviral medications that target different sensitive spots in the life cycle of the virus at once to prevent it from mutating and developing resistance to one of the drugs. Drug combinations used in HAART can consist of drugs that inhibit the replication of the genetic material of the virus (reverse transcriptase inhibitors), viral assembly (protease inhibitors), drugs that prevent the entry of the virus into the human cells (entry inhibitors), and/or drugs that prevent the integration of the virus DNA (its genes) into the human DNA (integrase inhibitors). Each of these medications has its own set of side effects, and risk associated with pregnancy.

Pregnancy registry

The FDA has a registry that pregnant women who took/take antiretroviral drugs can enroll in to evaluate the safety of the drugs. This is the only way the effects of antiretroviral drugs on human pregnancies can be determined and will answer the question of how safe antiretroviral drug are during pregnancy.

Zidovudine and pregnancy

Zidovudine is a very common reverse transcriptase inhibitor and is frequently used as antiretroviral therapy during pregnancy either alone or in combination with other antiretroviral drugs as a component of HAART.

Zidovudine crosses the placenta and is present in the chord blood in similar concentrations as in the blood of the mother. It can also be found in breast milk.

It has been shown in clinical trials that the use of zidovudine can decrease the rate of transmission of the virus from the mother to the child, and no study, so far, was able to show a increased risk of birth defects with the use of zidovudine during pregnancy. 

All nucleoside reverse transcriptase inhibitors can cause a side effect that can lead to the build up of lactic acid in the blood. This can be a concern for the mother and the baby during the pregnancy and should therefore be monitored by the treating physician.

Nonnucleoside Reverse Transcriptase Inhibitors

Efavirnenz and Delavirdine are newer drugs that, similar to Zidovudine, inhibit the reverse transcriptase of the HIV, but by a different mechanism. They are two of the few known teratogens among antiretroviral drugs. A teratogen is a substance that can cause birth defects. These two drugs should therefore be avoided in pregnant women and in HIV-infected women of the child bearing age who do not use effective birth control.

Another Nonnucleoside Reverse Transcriptase Inhibitor (Nevirapine) is considered safe for the baby, but can cause liver damage in the mother, especially when the mother has never taken any antiretroviral therapy before, or if her CD4 cell counts are greater than 250 cells/mm3.

Antiretroviral drugs in general: Protease inhibitors

Although there is not much known at this time about the potential of birth defects when using this class of antiretroviral drugs in general, one member, Nelfinavir, has recently raised the issue of safety in pregnancy. The production of Nelfinavir production requires a chemical called ethyl methane sulfonate (EMS), and in 2007, high levels of EMS were detected in Nelfinavir that was produced in Europe. EMS can cause cancer in humans and has caused cancer and birth defects in animals. The FDA has since established a limit for EMS allowed in Nelfinavir, but due to the risk of EMS causing birth defects even at low levels in humans, Nelfinavir should not be used during pregnancy or in women who might become pregnant.

In general all protease inhibitors have the side effect of raising blood sugar levels, worsening the effects of diabetes mellitus, and they can cause a condition in diabetics with very high blood sugar that is known as ketoacidosis. Ketoacidosis in pregnancy can be dangerous for the mother and the child, so that diabetic patients who are using protease inhibitors and are pregnant need to be especially watchful about their blood sugar. Pregnancy itself can also worsen the symptoms of diabetes mellitus and increase the blood sugar, but it is unknown whether the use of protease inhibitors in pregnancy combines to increase this risk even further.

Read More: Health Problems During Pregnancy

Entry inhibitors

No proven or suspected cases of birth defects have been found so far with this category of antiretroviral drug. However, this is rather a lack of information currently available rather than conclusive evidence about how safe drugs of this class are during pregnancy.

Integrase inhibitors

There is not enough information about this new class of antiretroviral drugs to conclusively answer the question of how safe they are during pregnancy.