HIV and pregnancy

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Women diagnosed with HIV/AIDS may transmit the infection to their child during pregnancy. The infection may spread during pregnancy, childbirth, or breastfeeding. However, the risk of mother-to-child transmission of HIV may be reduced by the use of HIV medications known as antiretroviral therapy (ART). These medications may be used by women before, during, and after pregnancy. After delivery, children are also given the medication to reduce the risk of infection. Because HIV may be spread through breast milk, mothers with the infection should avoid breastfeeding their children.[1]

Infection with HIV/AIDS is not a contraindication to pregnancy. Women with the disease may choose to become pregnant if they desire, however, they are encouraged to talk with their doctors beforehand. Some women are unaware they have the disease until they become pregnant. In this case, they should begin antiretroviral therapy as soon as possible.[1] With the appropriate treatment, the risk of mother-to-child infection can be reduced to below 1%.[2] Without treatment, the risk of transmission is 15-45%.[3]

There are approximately 1.4 million HIV positive women who become pregnant and contribute to more than 300,000 neonatal and fetal deaths each year.[4] With the use of ART, transmission of HIV from the mother to child has decreased according to reports by the World Health Organization (WHO). In 2009, there were an estimated 400,000 children born with HIV and by 2013, there were 240,000.[5] Countries in Southern Africa are worst affected by the HIV/AIDS pandemic. In 2010, 30% of all pregnancies in the region were affected by HIV. In 2011, HIV was responsible for 50% of the deaths for children below the age of 5.[6] In the United States, fewer than 200 babies are born with HIV every year.[1]

As of 2015, Cuba has become the first country in the world to eradicate mother-to-child transmission of HIV. In 2010, the WHO partnered with the Pan American Health Organization (PAHO) to implement an initiative that would provide early prenatal care and HIV testing for all pregnant women in the country. For women who tested positive, ART was provided for both the mother and child, cesarean sections were performed, and alternatives to breastfeeding were provided. In implementing these measures, the country was successfully able to eradicate HIV transmission during pregnancy.[7]

Pregnancy planning[edit]

In couples where the male and female are both HIV positive, conception may occur normally without concern for disease transmission. However, in couples where only one partner is HIV positive, there is risk of transmitting the infection to the uninfected partner. These couples, known as serodiscordant couples, are advised not to engage in unprotected intercourse. Instead, assisted reproductive methods are recommended.[8] In all serodiscordant couples, the infected partner is advised to begin ART so that levels of the infection are undetectable prior to attempting conception.[9]

In couples where the woman is HIV negative and the man is HIV positive, sperm is collected from the male partner using a technique called sperm washing. This process is then followed by intrauterine insemination (IUI) or in vitro fertilization (IVF). Couples may also use donor sperm from a non-infected male if desired.[10]

In couples where the woman is HIV positive and the man is HIV negative, artificial insemination is recommended.[10]

In areas where assisted reproductive techniques such as IUI or IVF are not available, techniques to reduce the transmission of HIV during conception can be attempted to reduce, but not eliminate, the risks.[11] Most importantly, the HPTN 052 trial showed that when HIV infected partners were on ART there was 96% less transmission of HIV and none from partners with undetectable viral loads.[12]

Many serodiscordant couples use pre-exposure prophylaxis (PrEP) to limit transmission of the infection to the uninfected partner. Daily use of PrEP has been shown to decrease transmission of the infection by an average of 63-75%. However, use of PrEP during pregnancy has not yet been studied and its long-term effects are unknown and should not be the only safety feature in the prevention process.[13]

Although assisted reproductive techniques are available for serodiscordant couples, there are still limitations to achieving a successful pregnancy. Women with HIV have been shown to have decreased fertility which can affect available reproductive options.[14] Women with HIV are also more likely to be infected with other sexually transmitted diseases, placing them at higher risk for infertility. Males with HIV appear to have decreased semen volume and sperm motility which decreases their fertility.[8] Antiretroviral drugs may also affect both male and female fertility and some drugs can be toxic to newly developed embryos.[15] Additionally, there have been cases where an HIV-negative partner was infected with the disease despite using processed artificial insemination.[16]

HIV testing in pregnancy[edit]

The Centers for Disease Control and Prevention (CDC) recommends HIV testing for all pregnant women as a part of routine prenatal care. The test is usually performed in the first trimester of pregnancy with other routine laboratory tests. HIV testing is recommended because HIV-infected women who do not receive testing are more likely to transmit the infection to their children.[17]

HIV testing may be offered to pregnant women on an opt-in or an opt-out basis. In the opt-in model, women are counseled on HIV testing and elect to receive the test by signing a consent form. In the opt-out model, the HIV test is automatically performed with other routine prenatal tests. If a woman does not want to be tested for HIV, she must specifically refuse the test and sign a form declining testing. The CDC recommends opt-out testing for all pregnant women because it improves disease detection and treatment and helps reduce transmission to children.[17]

If a woman chooses to decline testing, she will not receive the test. However, she will continue to receive HIV counseling throughout the pregnancy so that she may be as informed as possible about the disease and its impact. She will be offered HIV testing at all stages of her pregnancy in case she changes her mind.[18]

HIV testing begins with a screening test. The most common screening test is the rapid HIV antibody test which tests for HIV antibodies in blood, urine, or oral fluid. HIV antibodies are only produced if an individual is infected with the disease. Therefore, presence of the antibodies is indicative of an HIV infection. Sometimes, however, a person may be infected with HIV but the body has not produced enough antibodies to be detected by the test. If a woman has risk factors for HIV infection but tests negative on the initial screening test, she should be retested in 3 months to confirm that she does not have HIV.[19] Another screening test that is more specific is the HIV antigen/antibody test. This is a newer blood test that can detect HIV infection quicker than the antibody test because it detects both virus particles and antibodies in the blood.[20]

Any woman who has a positive HIV screening test must receive follow-up testing to confirm the diagnosis. The follow-up test can differentiate HIV-1 from HIV-2 and is a more specific antibody test. It may also detect the virus directly in the bloodstream.[19]

Prevention of mother-to-child transmission[edit]

HIV/AIDS may be vertically transmitted from a mother to her child. This means the infection may be spread during pregnancy, labor, delivery, or breastfeeding. 70% of transmissions are believed to occur during delivery when the baby comes into direct contact with the mother's infected blood or genital secretions/fluid in the birth canal. 30% of infections occur in utero during the pregnancy with 66% occurring within the last 14 days of a pregnancy.[21] The mechanism for in utero infection is not well understood, but the current belief is that infected maternal secretions may cross the placenta during the pregnancy.[22]

The risk of HIV transmission from a mother to child is most directly related to the plasma viral load of the mother. Untreated mothers with a viral load >100,000 copies/ml have a transmission risk of over 50%.[23] For women with a viral load < 1000 copies/ml, the risk of transmission is less than 1%.[24] In general, the lower the viral load the lower the risk of transmission. For this reason, ART is recommended throughout the pregnancy so that viral load levels remain as low as possible and the risk of transmission is reduced.

Women with an established diagnosis of HIV often begin ART before becoming pregnant to treat the infection. It is recommended that all pregnant women begin ART regardless of CD4 counts or viral load to reduce the risk of transmission. The earlier ART is initiated, the more likely the viral load is to be suppressed by the time of delivery.[25] Some women are concerned about using ART early in the pregnancy as babies are most susceptible to drug toxicities during the first trimester. However, delay in ART initiation may prove less effective in reducing infection transmission.[26]

Antiretroviral therapy is used at the following times in pregnancy to reduce the risk of mother-to-child transmission of HIV:[1]

  • During pregnancy: pregnant women infected with HIV receive an oral regimen of at least three different anti-HIV medications.
  • During labor and delivery: pregnant women infected with HIV and already on triple ART are recommended to continue to their oral regimen. If their viral load is >1,000 copies or there is question about whether medications have been taken consistently, then intravenous zidovudine (AZT) is added at the time of delivery.[27] Pregnant women who have not been on ART prior to delivery should also be given intravenous zidovudine (AZT).

Indications to start medications[edit]

According to current recommendations by the WHO, US CDC and U.S. Department of Health and Human Services (DHHS), all individuals with HIV should begin ART. The recommendation is stronger under the following conditions:[28]

  • CD4 count below 350 cells/mm3
  • High viral load (>100,000 copies/ml)
  • Progression of HIV to AIDS
  • Development of HIV-related infections and illnesses
  • Pregnancy

Women are encouraged to begin treatment as soon as they are diagnosed with HIV. If they are diagnosed prior to pregnancy, they should continue with ART during the pregnancy. If the diagnosis of HIV is made during the pregnancy, ART should be initiated immediately.[28]

Medications during pregnancy[edit]

The goal of antiretroviral use during pregnancy is to reduce the risk of transmission of HIV from mother to child. It is important to choose medications that are safe for the mother and the fetus and which are effective at decreasing the total viral load. Some studies have shown an increase in stillbirths, preterm delivery, and delayed fetal growth in women using high doses of antiretroviral drugs during pregnancy. However, the overall benefits of ART are believed to outweigh the risks and all women are encouraged to use ART for the duration of their pregnancy.[29]

Due to physiological changes in the body during pregnancy, it may be necessary to alter the dosing of medications so that they remain effective. Generally, the dose or the frequency of dosing are increased to account for these changes.

The recommended ART regimen for HIV-positive pregnant women consists of drugs from 4 different classes of medications listed below. In the United States, the favored regimen is a three-drug regimen where the first two drugs are NRTIs and the third is either a protease inhibitor, an integrase inhibitor, or an NNRTI.[30]

  • Nucleoside reverse transcriptase inhibitors (NRTIs) are considered the "backbone" of ART and 2 medications are generally used in combination. Due to its known safety profile and extensive use in pregnant patients, zidovudine-lamivudine (ZDV/3TC) is the preferred choice as the NRTI backbone. Zidovudine may worsen anemia, so patients with anemia are advised to use an alternative agent. For women who are coinfected with Hepatitis B, tenofovir with either emtricitabine or lamivudine is the preferred NRTI backbone.[30] NRTI use may cause lactic acidosis in some women, so it is important to monitor patients for this complication. Deaths from lactic acidosis and liver failure have been associated with the use of two NRTIs, stavudine and didanosine (Zerit and Videx, respectively); therefore, combinations involving these drugs should be avoided in pregnancy.[1]
  • Protease inhibitors (PIs) have been studied extensively in pregnancy and are therefore the preferred third drug in the regimen. Atazanavir-ritonavir and darunavir-ritonavir are two of the most common PIs used during pregnancy. There is conflicting data regarding their association with preterm births, so women who are at a high risk for premature delivery are advised not to use PIs.[30] Some PIs have been associated with hyperglycemia but is unclear whether they add to the risk of developing gestational diabetes.[1] Some PIs have been noted to cause hyperbilirubinemia and nausea, so these side effects should be monitored for closely.
  • Integrase inhibitors (IIs) are generally the third drug in the regimen when a PI cannot be used. They rapidly reduce the viral load and for this reason, they are often used in women who are diagnosed with HIV late in the pregnancy. Raltegravir is the most common II used.
  • Non-nucleoside reverse transcriptase inhibitors (NNRTIs), the most popular being efavirenz and nevirapine, may be used during pregnancy. However, there are significant toxicities associated with their use, making them a less desirable option.
    • Efavirenz (brand name Sustiva, and a component of the combination drug Atripla) is classified as a category D drug by the US Food and Drug Administration indicating there are risks associated with its use during pregnancy. In a study analyzing the use of the drug in pregnant women, 2.3% of births were associated with birth defects.[31] However, a systematic review of the safety of efavirenz use in humans during the first trimester found no increase in birth defects among women using the drug.[32] Given the uncertain potential for risk the U.S. DHHS recommends against using efavirenz in the first trimester of pregnancy or in women who may become pregnant. They instead recommend a protease inhibitor based regimen with lopinavir or atazanavir.[33] However, to simplify regimens and provide a uniform recommendation for HIV-infected individuals during pregnancy, the WHO continues to recommend efavirenz as a first line agent for HIV positive women.[34] Women using efavirenz prior to their pregnancy may continue with the drug as it is more dangerous to stop or change medications during pregnancy because this can result in improper control of the viral load.[32]
    • Nevirapine (trade name Viramune) increases the risk of very serious liver damage in women with CD4 counts greater than 250 cells/mm3 . It is generally avoided in pregnant women. Women taking nevirapine safely prior to pregnancy may continue with the medication because nevirapine-related liver damage has not been seen in women previously using the medication.[1]

Labor & Delivery[edit]

Women should continue their ART regimen through childbirth. In addition to the three-drug regimen outlined above, intravenous (IV) zidovudine should be administered if the maternal viral load is >1,000 copies/mL or if it is unknown.[35] This will help reduce the risk of HIV transmission during labor and delivery.

The viral load helps determine which mode of delivery is safest for the mother and the baby. In cases where the viral load is low (<1000 copies/mL), the risk of transmission is low and a vaginal delivery may be performed. A cesarean section, on the other hand, is generally performed at 38 weeks gestation under the following circumstances:[36]

  • Viral load is high (>1000 copies/mL) or unknown at the time of delivery
  • Mother did not receive ART during the pregnancy
  • Mother is concerned about exposing her child to infected blood and genital secretions during the delivery

If, before her scheduled cesarean section, a woman's water breaks and she goes into labor, a cesarean section may not significantly reduce the risk of infection transmission. Under this circumstance, if there is no other medical reason to proceed with a cesarean section, a vaginal delivery may be performed and may be the safest for the mother and the baby.[1]

Women who present to the hospital in labor with an unknown HIV status should undergo immediate HIV testing. If the initial screening test is positive, the mother should immediately be started on IV zidovudine and the baby should receive prophylactic ART after birth. A confirmatory HIV test should also be performed in the meantime. If the test results are positive, treatment should continue with the antiretrovirals. If the results are negative, the medications may be stopped.[36]

Breastfeeding[edit]

Women may transmit HIV to their child via breastmilk. For this reason, breastfeeding is discouraged amongst HIV-positive women. In a study conducted in South Africa, 14.1% of children born to HIV-infected mothers were infected within 6 weeks of breastfeeding and 19.5% were infected by 6 months of age.[37] A study in Malawi found that the risk of HIV transmission through breastfeeding was 7% in children who breastfed for one year and 10% in children who breastfed for two years. The risk of HIV infection appears to be highest in the early months of breastfeeding and HIV-infected mothers should avoid breastfeeding entirely if possible.[38]

In developed countries where clean water and infant formula are both accessible and available, HIV-positive women should not breastfeed. They should use formula to reduce the risk of transmitting HIV to the child. Even if the mother is on ART, she should avoid breastfeeding as HIV can still be transmitted through the breastmilk. Some women elect to use donor milk (breast milk donated from non-HIV infected mothers) instead of formula so that their child may receive the health benefits of breast milk, the most notable being increased immunity.[39]

In underdeveloped countries where clean water and formula are not available, breastfeeding is encouraged to provide the child with adequate food and nutrients. The benefit of nourishment outweighs the risk of HIV transmission, malnutrition, and other infections and so breastfeeding is acceptable.[34]

Other considerations during pregnancy[edit]

Pregnant women with HIV may still receive the trivalent inactivated influenza vaccine and the tetanus, diphtheria, and pertussis (Tdap) vaccination during pregnancy.[40]

Many patients who are HIV positive also have other health conditions known as comorbidities. Hepatitis B, hepatitis C, tuberculosis and injection drug use are some of the most common comorbidities associated with HIV. Women who screen positive for HIV should also be tested for these conditions so that they may be adequately treated or controlled during the pregnancy. The comorbidities may have serious adverse effects on the mother and child during pregnancy, so it is extremely important to identify them early during the pregnancy.[41]

Postnatal care[edit]

Babies born to HIV-positive women should receive a 6-week course of zidovudine (AZT). The medication should be started within the first 6 to 12 hours of life. The baby should be tested for HIV at 14 to 21 days of life, at 1 to 2 months of age, and once more at 4 to 6 months of age. Usual antibody based testing is unreliable in infants due to the transmission of maternal antibodies. A qualitative HIV DNA PCR assay is recommended as it will detect pro-viral HIV DNA since HIV RNA may be suppressed by ART.[42] In order to ensure the baby is HIV-negative, there must be two negative test results. Since zidovudine has been known to cause or worsen anemia, the baby's blood count should be routinely checked during AZT therapy.[43]

To reduce the risk of developing Pneumocystis jirovecii pneumonia (PCP), all infants born to HIV-positive mothers should receive trimethoprim/sulfamethoxazole at age 4–6 weeks.

Although the risk is very low, HIV can also be transmitted to a baby through food that was previously chewed (pre-chewed) by a mother or caretaker infected with HIV. To be safe, babies should not be fed pre-chewed food.[1]

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World Health Organization. (2013). SEXUALLY TRANSMITTED INFECTIONS (STIs). Retrieved from http://apps.who.int/iris/bitstream/10665/82207/1/WHO_RHR_13.02_eng.pdf

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