HIV and pregnancy

HIV in pregnancy is the presence of HIV in a woman while she is pregnant. HIV in pregnancy is of concern because women with HIV/AIDS may transmit the infection to their child during pregnancy, childbirth and while breastfeeding. However, the risk of mother-to-child transmission of HIV may be reduced by treatment of the HIV infection with antiretroviral therapy (ART). This lifelong therapy may be initiated in women before, during, and after pregnancy. After delivery, children are also given the medication temporarily as a prophylactic measure to reduce the risk of infection. Because HIV may also be spread through breast milk, mothers in the United States who are infected are encouraged to avoid breastfeeding.[1] However, in developing countries such as South Africa, where the risk of death of the infant associated with avoiding exclusive breastfeeding is higher than the risk of contracting HIV, exclusive breastfeeding in a mother who is virally suppressed is encouraged.[2]

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%.[3] Without treatment, the risk of transmission is 15–45%.[4]

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.[5] 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.[6] Countries in Sub-Saharan 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 of children below the age of five.[7] 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 Cuba. 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.[8]

Pregnancy planning

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, assistive reproductive methods are recommended.[9] In all serodiscordant couples, the infected partner is advised to begin ART so that their viral load is undetectable prior to attempting conception.[10]

In couples where the woman is HIV negative and the man is HIV positive, sperm is collected from the male partner and HIV is removed from the specimen 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.[11]

In couples where the woman is HIV positive and the man is HIV negative, artificial insemination is recommended.[11]

In areas where assistive reproductive techniques, such as IUI or IVF, are not available, techniques used during intercourse can be attempted to reduce, but not eliminate, the risk of HIV transmission.[12] Most importantly, the HPTN 052 trial showed that when HIV infected partners were on ART and their viral load was undetectable no transmission occurred; in partners with a detectable viral load on ART there was 96% less transmission.[13]

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 on the foetus are unknown.[14]

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 the available reproductive options.[15] 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.[9] ART may also affect both male and female fertility and some drugs can be toxic to embryos.[16] Additionally, there have been cases where an HIV-negative partner was infected with the disease despite artificial insemination with washed sperm.[17]

HIV testing in pregnancy
Further information: Diagnosis of HIV/AIDS

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.[18]

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.[18]

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.[19]

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.[20] 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.[21]

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.[20]

Prevention of mother-to-child transmission

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.[22] 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.[23]

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%.[24] For women with a viral load <1000 copies/ml, the risk of transmission is less than 1%.[25] 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 will be suppressed by the time of delivery.[26] 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.[27]

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 (such as tenofovir, emtricitabine and efavirenz).
  • During labor and delivery: pregnant women infected with HIV and already on triple ART are recommended to continue with their oral regimen. If their viral load is >1,000 copies/ml or there is question about whether medications have been taken consistently, then intravenous zidovudine (AZT) is added at the time of delivery.[12] Pregnant women who have not been on ART prior to delivery or who have been on ART for less than four weeks should also be given intravenous AZT or a single dose of nifedipine (NVD), tenofovir (TDF) and emtricitabine (FTC) and a three-hourly dose of AZT.[28]

Indications to start medications

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:[29]

  • 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.[29]

Medications during pregnancy

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.[30]

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.[12]

  • 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 (TDF) with either emtricitabine (FTC) or lamivudine is the preferred NRTI backbone.[12] 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 (d4t and ddl, 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 (ATV/r) and darunavir-ritonavir (DRV/r) 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.[12] 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 their pregnancy. Raltegravir (RAL) is the most common used.
  • Non-nucleoside reverse transcriptase inhibitors (NNRTIs), the most popular being efavirenz (EFV) and nevirapine (NVP), may be used during pregnancy. However, there are significant toxicities associated with their use, making them a less desirable option.
    • Efavirenz (brand name Sustiva, shortened as EFV, 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 EFV 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 EFV in the first trimester of pregnancy or in women who may become pregnant. They instead recommend a protease inhibitor based regimen with lopinavir (LPV) or ATV.[12] 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.[33] Women using EFV 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, and shortened NVP) 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 NVP safely prior to pregnancy may continue with the medication because NVP-related liver damage has not been seen in women previously using the medication.[1]

Nutritional supplements

Vitamin A plays a role in the immune system and is a low-cost intervention that has been suggested to help with preventing mother-to-child transmission of HIV. A Cochrane review[34] summarised the evidence of five trials conducted in Malawi, South Africa, Tanzania and Zimbabwe between 1995 and 2005, where none of the participants received antiretroviral therapy. They found that giving vitamin A supplementation to pregnant women or to women after they delivered a baby probably has little or no effect on mother-to-child transmission of HIV. The intervention has been largely superseded by antiretroviral therapy.

Labor and delivery

Women should continue their ART regimen through childbirth.

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:[35]

  • 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 given a single dose of nifedipine (NVD), tenofovir (TDF) and emtricitabine (FTC) and a three-hourly dose of zidovudine (AZT) and the baby should receive prophylactic ART after birth. This will help reduce the risk of HIV transmission during labor and delivery. A confirmatory HIV test should also be performed in the meantime. If the test results are positive, treatment should continue. If the results are negative, the medications may be stopped.[28][35]

Breastfeeding

Women may transmit HIV to their child via breastmilk. For this reason, breastfeeding is discouraged in the United States amongst HIV-positive women.[1] However, in developing countries such as South Africa, where the risk of death of the infant associated with avoiding exclusive breastfeeding is higher than the risk of contracting HIV, exclusive breastfeeding in a mother who is virally suppressed is encouraged.[2]

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.[36]

In underdeveloped countries, where clean water and formula are not as readily available, breastfeeding is encouraged to provide the child with adequate food and nutrients. The benefit of nourishment outweighs the risk of HIV transmission so breastfeeding is acceptable.[33] The South African Department of Health guidelines state that HIV-infected mothers should exclusively breastfeed, that is the infant's diet should consist of breastmilk only and should not be supplemented with water, other liquids or foods, for 6 months after birth. After 6 months, the mother should introduce complementary foods while continuing to breastfeed for up to 24 months.[28][2]:7

In a study conducted in South Africa, 1.1% of children born to HIV-infected mothers who were uninfected at 6 weeks of age, were infected within 1 month of breastfeeding and 4.0% 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 who are not virally suppressed should avoid breastfeeding entirely if possible.[38] In contrast, a systematic review commissioned by the WHO found that there is a very low risk (1.1%) of postnatal HIV transmission in infants breastfed by mothers on lifelong ART that was initiated in early to mid pregnancy. The overall risk of transmission was 3.3%, including exposures in utero and during childbirth.[39] Another systematic review found that prolonged breastfeeding for infants born to mothers on lifelong ART is beneficial in terms of HIV‐free survival at least up to 24 months of age – increasing HIV-free survival rates from 89% to 96%.[40]

If the mother has a high HIV viral load (>1000 copies/L), replacement feeding, such as formula, is only initiated as per the UNAIDS guidelines, termed the AFASS criteria, "where replacement feeding is acceptable, feasible, affordable, sustainable, and safe."[41][28]:95-6 A mother may only be given infant formula, as explained by the WHO, if the following conditions are met:[2]

  • "Safe water and sanitation are assured at the household level and in the community; and
  • the mother or other caregiver can reliably provide sufficient infant formula milk to support the normal growth and development of the infant; and
  • the mother or caregiver can prepare it cleanly and frequently enough so that it is safe and carries a low risk of diarrhoea and malnutrition; and
  • the mother or caregiver can exclusively give infant formula milk in the first six months; and
  • the family is supportive of this practice; and
  • the mother or caregiver can access health care that offers comprehensive child health services."

Discrimination during pregnancy

Despite advances made in preventing transmission, HIV-positive women still face discrimination regarding their reproductive choices.[42][43] In Asia, it was found that half the women living with HIV were advised not to have children and as many as 42% report being denied health services because of their HIV status.[44]

Compulsory sterilisation in an attempt to limit mother-to-child transmission has been practiced in Africa, Asia, and Latin American.[45][46][47] Women are forced to undergo sterilisation without their knowledge or informed consent, and misinformation and incentives are often used in order to coerce them into accepting the procedure. The forced sterilisation of HIV-positive women is internationally recognised as a violation of human rights.[48]

Legal advocacy against this practice has occurred in some countries. In Namibia, litigation was brought against the government by three HIV-positive women who claimed they were coerced during labour into signing consent forms that gave permission for the hospital to perform a sterilisation.[49] The LM & Others v Government of Namibia case is the first of its kind in sub-Saharan African to deal with coerced sterilisation of HIV-positive woman. The court ruled that these women were sterilised without their consent but failed to find that this was due to their HIV status.[50] A 2010 case in Chile have also aimed to seek government accountability for violation of sexual and reproductive rights of women living with HIV.[51]

Considerations during pregnancy

Pregnant women with HIV may still receive the trivalent inactivated influenza vaccine and the tetanus, diphtheria, and pertussis (Tdap) vaccination during pregnancy.[52]

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.[53]

Postnatal care

Babies born to HIV-positive women should receive a 6-week or 12-week course of zidovudine (AZT). The medication should ideally be started within the first 6 to 12 hours of life, but can be started up to 72 hours after birth.[28] A 6-week course should be initiated if the mother has been on ART for more than four weeks before birth, and a 12-week course should be initiated if the mother is newly diagnosed or has been on ART for less than four weeks before birth.[28] The baby should be tested for HIV at birth, 4 weeks after cessation of AZT (10 weeks or 16 weeks, depending on length of AZT course, after birth), 6 weeks after cessation of breastfeeding and at 18 months.[28] Usual antibody based testing is unreliable in infants until the age of 18 months 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.[54] 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.[55]

To reduce the risk of developing Pneumocystis jirovecii pneumonia (PJP), all infants born to HIV-positive mothers should receive trimethoprim/sulfamethoxazole (cotrimoxazole) from 4–6 weeks after birth, and stop prophylaxis when they are no longer at risk of contracting HIV from their mother.[28]

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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