Management of HIV in pregnancy

HIV infection in young children most commonly arises as a result of mother-to-child transmission (MTCT), also called vertical transmission. It is thought that only 1.5-2% of MTCT occurs transplacentally during pregnancy.¹ The vast majority occurs due to maternofetal transmission of blood during parturition or postnatal breastfeeding.

Screening

All pregnant women are recommended screening for HIV infection, syphilis, hepatitis B and rubella in every pregnancy at their booking antenatal visit. If a woman declines an HIV test, this should be documented in the maternity notes, her reasons should be sensitively explored and screening offered again at around 28 weeks.

A negative maternal HIV test at booking does not preclude neonatal infection - maternal infection and seroconversion can occur at any time during pregnancy and lactation. This is well-documented in countries with a high prevalence of HIV and has been seen in the UK.²

How common is HIV in pregnancy?(Epidemiology)^{3 4}

• The prevalence of UK-born women living with HIV has increased from approximately 17,000 in 2006 to 30,000 in 2019.

• Approximately 1200 of these women fall pregnant each year.

• Antenatal testing for HIV in 2019 has a low rate of new diagnoses (0.014%) as most HIV-positive pregnant women have been diagnosed prior to pregnancy.

• Without intervention, between 15-45% of babies born to HIV-infected mothers in the most severely affected countries are also infected.⁵ With appropriate interventions transmission rates can be reduced to less than 1%. In the UK in 2012-14 the MTCT rate was 0.3%

Risk of MTCT

This is increased with:

• Higher levels of maternal viraemia.

• HIV core antigens.

• Lower maternal CD4 count.

• Primary HIV infection occurring during pregnancy.

• Chorioamnionitis.

• Co-existing other sexually transmitted disease.

• Possibly malaria.⁶

• Invasive intrapartum procedures - eg, fetal scalp electrodes, forceps, ventouse.

• Rupture of membranes (especially if delivery is more than four hours after the membranes ruptured).

• Vaginal delivery.

• Preterm birth.

• Female babies more likely to be infected early (transplacental/perinatal routes).⁷

• Advanced maternal age.

• The firstborn of twins (born to an HIV-infected mother).

Factors that decrease risk of transmission are:

• Higher levels of neutralising HIV antibody.

• Combined antiretroviral therapy.

• Less invasive monitoring and intrapartum procedures.

• Pre-labour caesarean section.

• Formula feeding.

Treatment and management of HIV in pregnancy⁸

Mother-to-child transmission (MTCT) of HIV infection can be greatly reduced through early diagnosis of maternal HIV infection.

• Pregnant women should be offered screening for HIV early in pregnancy because appropriate antenatal interventions can reduce MTCT of HIV infection.

• Interventions to reduce MTCT of HIV during the antenatal period include antiretroviral therapy (ART), pre-labour caesarean section delivery and avoidance of breastfeeding after delivery.⁹

• These interventions can reduce the risk of mother-to-child HIV transmission from 25-30% to less than 1%.

• All pregnant women who are HIV-positive should be screened and appropriately treated for genital infections during pregnancy. This should be done as early as possible in pregnancy and repeated at about 28 weeks.

• Presentation with symptoms or signs of pre-eclampsia, cholestasis or other signs of liver dysfunction during pregnancy may indicate drug toxicity and early liaison with HIV physicians is essential.

Drug therapy^{8 9}

• Women who conceive on effective combined antiretroviral treatment (cART) should continue treatment throughout pregnancy and lifelong.

• Recommended regimes in pregnancy usually consist of triple therapy. There is less evidence for safety and efficacy of newer anti-retrovirals and evolving combinations such as dual therapy.

• Choice of therapy should be individualised to the patient in accordance with their wishes and standard treatment guidelines.

• Zidovudine remains the only antiretroviral agent licensed for use in pregnancy. Non-pregnant adults are rarely prescribed this drug as part of cART due to toxicity concerns. There is no data to support routinely switching to zidovudine or adding it in to a combination of anti-retrovirals that is already suppressing viral load.

• HIV positive women who are not already taking cART should start during pregnancy and continue lifelong.

• Timing of commencement of therapy is dependent on viral load, but is usually in the second trimester.

• Recommended cART is tenofovir DF or abacavir with emtricitabine or lamivudine as a nucleoside backbone. 3rd agent in cART should be efavirenz or atazanavir/r.

• Women who present after 28 weeks of gestation should commence cART without delay.

• There are specific drug recommendations for untreated HIV positive women who present in labour at term.

• There is growing evidence that many antiretroviral drugs are not teratogenic. In 2018 it was reported that the following drugs when used in the first trimester show congenital malformation rates within the expected range: darunavir, efavirenz, indinavir, raltegravir, rilpivirine. There is not yet enough data on newer agents to comment on their teratogenicity.

In sub-Saharan Africa, access to services is improving. Between 2010 and 2019 ART coverage during pregnancy increased from 33% to 69%. In the same time period vertical transmission reduced from 27% to 17%.^{10 11}

Other interventions⁸

A decision about mode of delivery should be made at 36 weeks of gestation after a review of HIV viral load. The proportion of HIV-diagnosed women who took some form of ART prior to delivery rose to 98% in 2010. This was reflected in an increase in vaginal deliveries and a drop in pre-labour caesarian sections.

• For women with a viral load less than 50 HIV RNA viral copies/ml, vaginal delivery should be supported. Women who opt for a planned vaginal delivery should have their membranes left intact for as long as possible. Use of fetal scalp electrodes and fetal blood sampling should be avoided.

• If the viral load is 50-399 HIV RNA viral copies/ml pre-labour caesarean section should be considered and if viral load is >400 it is recommended.

• Women with HIV and hepatitis C virus co-infection can have a vaginal delivery providing they are taking effective ART and the HIV viral load is suppressed

• Delivery by pre-labour caesarean section for obstetric indications is usually performed at 39 weeks in women whose plasma viral load is less than 50.

Studies suggest that for women with a viral load above 50 the risk of placental transmission is half that for pre-labour section compared to vaginal delivery. Below that level, there is no difference.

Breastfeeding^{8 12}

Breastfeeding should be avoided, as it increases MTCT by approximately 15%. In the UK and other high-income countries, women living with HIV are advised to formula feed. However, in developing countries, where caesarean section is unavailable and there is no alternative to breastfeeding, the World Health Organization (WHO) recommendations are that HIV-infected pregnant women should be offered ART during the period of risk of mother-to-child transmission and continuing lifelong either for all women or for women meeting eligibility criteria for their own health. Infants should receive either zidovudine monotherapy or combination post-exposure-prophylaxis (PEP) dependent on risk levels for up to four weeks from birth.

Prognosis

MTCT of HIV is largely preventable where universal antenatal HIV screening is undertaken, exclusive artificial formula feeding is feasible and where there is the provision for ART and delivery by caesarean section when necessary.

• In the absence of intervention, MTCT transmission occurs in 15 -45% of cases of women living with HIV who give birth.

• cART, caesarean section and avoidance of breastfeeding can further reduce the risk of transmission to less than 1%. The WHO is aiming for virtual elimination of vertical transmission.

• In the UK, MTCT rates declined from 2.2% in 1998 to 0.3% in 2012-14.³ Current data suggest that pregnancy has no effect on accelerating the development of AIDS, HIV-related diseases or severe immunosuppression for up to one year after delivery or abortion.¹³

• HIV infection may adversely affect pregnancy, especially in terms of the overall risk of spontaneous abortion and maternal postpartum endometritis.

• ART is given to prevent MTCT and to prevent maternal disease progression. The optimal regimen is determined on a case-by-case basis according to prevailing guidelines.