Managing HIV during pregnancy

Dr Suneeta Kochhar, Dr Stephen French and Miss Prabha Sinha explain how to minimise transmission risks.

HIV infection is associated with significant maternal and fetal morbidity and mortality, which may be improved by highly active antiretroviral therapy (HAART).

In the UK, it is estimated that 80,000 adults are infected with HIV, of which one-third are unaware of their diagnosis.The incidence of heterosexually acquired HIV infection has increased, and so the prevalence of pregnant women who are HIV positive has also increased.

Photograph:ANTONIA REEVE / SCIENCE PHOTO LIBRARY

Delivery by caesarean section reduces mother-to-child HIV infection

Mother-to-child transfer
Mother-to-child transmission of HIV can be prevented using universal antenatal screening of HIV status, HAART, an operative delivery, and by the mother formula feeding.1

The major obstetric factors that may increase perinatal transmission include vaginal delivery in the absence of HAART, duration of membrane rupture, chorioamnionitis and preterm delivery.2

There is no evidence for a plasma viral load threshold below which transmission does not seem to occur, but high maternal plasma viral load is linked to a higher rate of mother-to-child transmission.3

Antenatal care
Observational studies have shown that HIV infection is linked to increased spontaneous abortion, stillbirth, intra-uterine growth restriction and low birth weight.1

The initial assessment should involve considering the degree of immunodeficiency and recommendations for beginning or continuing with antiretroviral therapy.

All pregnant women who are HIV positive should be offered antiretroviral therapy.4 Women who do not require treatment for their own health require antiretrovirals to prevent mother-to-child transmission.2

There should be a discussion with the mother about reducing the risk of perinatal HIV transmission, to increase her understanding of the use of the medication and to increase compliance.

The fetus is the most susceptible to teratogenic effects during the first 10 weeks of gestation; therefore some women may choose to delay initiation of antiretroviral therapy.

If the clinical or immune status of a woman in the first trimester would be compromised by stopping treatment, the benefits of early treatment outweigh the potential risk to the fetus.

There should be a discussion and counselling of long-term pregnancy planning for the care of the child in the event of maternal illness and adherence to a treatment regimen.5

Fetal and drug monitoring
Women should be monitored for drug toxicities and have a detailed fetal anomaly scan.6

This is particularly important after first trimester exposure to HAART and folate antagonist therapy (used to prevent Pneuomocystis carinii pneumonia, PCP). Invasive testing should only be considered after full counselling and with caution, because the risk of transmission is unknown.

Monitoring should include measuring CD4 cell count and HIV RNA levels every trimester to determine the need for or alteration in medication.

Those on protease inhibitors should be monitored for development of hyperglycaemia (pregnancy may itself be a risk factor for hyperglycaemia). Symptoms or signs of pre-eclampsia or cholestasis may indicate drug toxicity.

It is not recommended that nevirapine be initiated as part of combination therapy in pregnant women with CD4 counts >250/mm3 unless the benefit outweighs the risk of hepatic dysfunction.3 Nevirapine has been shown to cause hepatotoxicity, so LFTs are necessary if this is used.

Efavirenz and the combination of didanosine and stavudine should be avoided during pregnancy.

Zidovudine prophylaxis reduces transmission regardless of maternal RNA levels.

Zidovudine monotherapy reduces perinatal transmission, but combination therapy may be optimal for a woman's health. Monotherapy may allow emergence of a resistant virus, which may compromise therapeutic options for maternal health.

Antiretrovirals are usually commenced between 28 and 32 weeks of gestation and should be continued intrapartum. Therapy may be initiated earlier if there are risk factors for preterm labour.2

Drug interaction
Intrapartum management should include a review of maternal medications and potential adverse drug reactions.

For example, midazolam should be avoided in women receiving protease inhibitors as metabolism may be delayed.

Mode of delivery
The risk of perinatal transmission of HIV is minimised by preventing infant exposure to maternal blood and secretions.4

Elective caesarean section may prevent a maternal-fetal microtransfusion that occurs with uterine contractions during vaginal delivery.

Elective caesarean section and use of zidovudine in combination reduces transmission by 85 per cent.1

According to the RCOG guideline, women with a detectable plasma viral load and/or who are not taking HAART should be offered elective caesarean section to reduce the likelihood of vertical transmission.

Intravenous therapy should commence four hours before surgery and be continued until the umbilical cord has been clamped. A maternal sample for plasma viral load should be taken at delivery.

The recommendation is that the cord should be clamped and the baby bathed immediately.2

Where the mother is taking HAART and the viral load is low, the risk of operative delivery may outweigh any potential benefits.

The benefit is lost when the procedure is performed after the onset of labour or rupture of membranes.

It has been suggested that an elective procedure at 38 weeks of gestation avoids the potential risk for labour and membrane rupture while minimising the risk of respiratory complications in the neonate.5

If a woman chooses to undergo a vaginal delivery after being appropriately counselled, artificial rupture of membranes and invasive procedures such as fetal scalp electrodes should be avoided.

Episiotomy may increase the exposure of the infant to HIV during delivery and increase the risk of transmission.2 The duration of membrane rupture is linked to risk of transmission, so labour should be augmented as necessary.

Antiretrovirals should be continued during labour or pre-operatively to maximise efficacy and to minimise the risk of drug resistance. However, stavudine has been shown to have an ant-agonistic effect with zidovudine so only one of these drugs should be used at any one time.

An emergency caesarean section may be necessary to avoid a prolonged labour and rupture of membranes.6

Postpartum therapy
Women should be advised to avoid breastfeeding even if taking antiretroviral therapy. The efficacy of maternal antiretroviral therapy for preventing postnatal transmission through breast milk and the toxicity of chronic antiretroviral exposure to the infant is unknown.

Continuation of therapy during the postpartum period depends on whether the therapy was only commenced to reduce mother-to-child transmission.

Generally all medications may be stopped, but because of the long half-life of the non-nucleoside reverse transcriptase inhibitors some clinicians may continue these to minimise drug resistance.5

Care of the neonate
After birth, an FBC and differential should be taken from the neonate as a baseline evaluation prior to administrating zidovudine.

Following the zidovudine prophylaxis regimen, all infants born to HIV-infected women should be given PCP prophylaxis at six weeks of age, regardless of CD4 count or infection status.

After 12 months, prophylaxis is continued only in infected children depending upon the CD4 count.

Conclusion
Healthcare workers must provide adequate information, education and counselling that is supportive and non-judgmental to allow mothers to make informed decisions.

A better understanding of the timing and pathogenesis of perinatal HIV transmission may be useful in elucidating further interventions.

Mother-to-child transmission continues to represent a major public health issue in resource-poor countries.

  • Dr Kochhar is GP VTS SHO at Conquest Hospital, Hastings, Dr French is GP VTS SHO at Royal Sussex County Hospital, Brighton, and Miss Sinha is consultant in obstetrics and gynaecology at Conquest Hospital, Hastings, East Sussex

References

1. Gray G E, McIntyre. HIV and pregnancy. BMJ. 2007; 334: 950-3.

2. RCOG Guideline No. 39 (2004) Management of HIV in pregnancy.

3. Semprinin A E, Fiore S. HIV and pregnancy: is the outlook for mother and baby transformed? Curr Opin Obstet Gynaecol. 2004; 16: 471-5.

4. Peckham C, Gibb D. Mother-to-child transmission of the human immunodeficiency virus. N Engl J Med. 1995; 333:298.

5. Foster C J, Lyall E G. HIV in pregnancy: evolution of clinical practice in the UK. Int J STD AIDS 2006; 17: 660-6.

6. Watts DH. Management of human immunodeficiency virus infection in pregnancy. N Engl J Med. 2002; 346: 1,879.

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