Choosing a regimen

Asymptomatic women who do not require antiretroviral treatment for their own health, according to current BHIVA treatment guidelines, may be treated with short-term antiretroviral therapy (START). This should start in the second trimester and aim to achieve an undetectable viral load prior to delivery. The BHIVA/CHIVA guidelines recommend that this regimen should contain AZT (zidovudine, Retrovir) and 3TC (lamivudine, Epivir) unless there are any contraindications. It is also recommended that this regimen should contain a boosted PI. PIs have a greater barrier to resistance development than NNRTIs and can be stopped concurrently with the NRTI backbone. In addition, PI pill burden and tolerance are improving with newer formulations and there is a low incidence of severe short-term side-effects.

If NNRTIs are used, these must be discontinued carefully in a planned manner to cover the NNRTI ‘tail’ and avoid the development of maternal drug resistance.

The optimal time to commence START is unclear but the aim should be to start by 28 weeks.  Commencing prior to foetal viability (24 weeks) may be prudent.

An earlier start between 20 and 24 weeks may be advisable for a woman with a high baseline viral load who is aiming to achieve an undetectable viral load by 36 weeks in order to try to have a vaginal delivery. If the viral load is <50 copies/ml at 36 weeks, it is considered safe for a woman to do so. Intravenous AZT is not considered necessary in this situation and oral dosing of HAART should continue throughout delivery.

An alternative approach, in women who do not require treatment for themselves, and who repeatedly have a viral load of <10 000 copies/ml, is to use AZT monotherapy, combined with a pre-labour caesarean at 38 weeks. In this case, the guidelines recommend an AZT infusion starting four hours prior to the operation. The risk of vertical transmission is low, and this reduces antiretroviral exposure of the foetus in pregnancy. The risk of pre-term delivery is significantly lower with this approach than with the use of HAART.

In addition, maternal toxicity is reduced and the risk of the development of resistance in the mother, when used at this level of viral load, appears minimal. The optimal time to start AZT monotherapy is unclear but ideally this should be started by 28 weeks, and starting prior to foetal viability (24 weeks) may be prudent.

Women who need to start treatment for their own health should do so early, although it can usually be deferred until after the first three months of pregnancy. It is recommended that these women should be treated with antiretroviral regimens as outlined in the BHIVA treatment guidelines.

The decision about which drugs to use should be made by considering safety and efficacy data available in pregnancy, tolerability and whether treatment is likely to be continued after delivery. Combination therapy is the standard of care.

Most information is available on AZT and 3TC as the NRTI backbone, which is therefore usually recommended in combination with either a PI or an NNRTI drug (see below for more detail). If an undetectable viral load is achieved by 36 weeks, a vaginal delivery may be possible as in scenario 1. If the viral load is >50 copies/ml at 36 weeks, see scenario 4.

If a mother is already on HAART when she becomes pregnant, has an undetectable viral load, and is tolerating the combination well, she should discuss the pros and cons of continuing this regimen with her healthcare team. As a general principle, however, in this situation she should be encouraged to continue this regimen, even if it contains efavirenz.

There have been concerns that HIV treatment during pregnancy may involve a risk of birth abnormalities (teratogenecity). Animal studies on efavirenz had shown a risk of birth defects if taken during pregnancy, particularly in the first three months. However, a study covering a 17-year period and reported in 2009 showed that no individual anti-HIV drug (incuding efavirenz and ddI) was associated with an increased risk of birth abnormalities.³ 

Obstetric management should be as per scenario 2, with the option of a vaginal delivery, or a pre-labour caesarean at 39 weeks depending on the women's wishes or her obstetric history.

If the mother conceives on a failing regimen, this should be changed appropriately to ensure the lowest possible viral load at the time of delivery. Resistance testing can help to identify the best options. If the viral load is <50 copies/ml at 36 weeks than she can proceed as above; if not, see scenario 4.

A genotype test should be performed and treatment changed to the best option. A pre-labour caesarean should be planned for 38 weeks, with four hours of intravenous AZT if the genotype does not show resistance to this drug.

Combination post-exposure prophylaxis (PEP) should be prescribed for the baby, based on the genotype identified.

Doctors may also prescribe a single dose of nevirapine (Viramune) for the mother, to 'load up' the baby.

With improved turn-around times for viral load testing, a woman who is only diagnosed with HIV at 32 weeks of pregnancy may still be able to have her HIV managed with a view to a possible vaginal delivery if she starts treatment and achieves an undetectable viral load (<50 copies/ml) by the time she is 36 weeks pregnant, as in scenario 2.

If her viral load is >50 copies/ml at 36 weeks, the woman will need to have a pre-labour caesarean at 38 weeks with intravenous AZT, and the baby should receive combination PEP.

A vaginal swab should be taken for check for possible infection. If the woman is less than 34 weeks' pregnant, she should be given two doses of intramuscular steroids, 24 hours apart, to help the baby's lungs mature. If the mother has not yet been on treatment, she should have her CD4 count and viral load tested, and HAART should be started.

Nevirapine should be included in the regimen as it crosses the placenta rapidly. This can be in the form of single-dose nevirapine, started at the same time as PI-based treatment if the CD4 cell count is high or unknown, or an ongoing nevirapine-containing regimen if the CD4 cell count is low. If ongoing nevirapine is started without knowing the woman's CD4 cell count, the baseline CD4 result shoud be checked and the nevirapine substituted if the CD4 cell count is high.

If the mother is already on treatment, but her viral load is >50 copies/ml, her regimen should be reviewed and her treatment optimised, with single-dose nevirapine added for the reasons given above. For the mother on HAART with a viral load of >50 copies/ml, HAART should be continued, but single-dose nevirapine considered, especially if she is not already on an NNRTI and is less than 32 weeks' pregnant.

Once two doses of steroids have been administered, doctors will decide whether or not to perform an emergency caesarean section at <34 weeks. The timing of this procedure will involve balancing the risk of mother-to-child transmission with the risks of severe prematurity (less than 30 weeks' gestation). This should involve multidisciplinary discussion with the obstetricians, neonatologists and HIV physicians. The decision to deliver will balance HIV transmission risk with foetal age and size and neonatal facilities. After 30 weeks, this balance may be tipped towards doing an emergency caesarean once two doses of steroids have been administered, and at 34 weeks or more an emergency caesarean should be performed as soon as possible. There have been no randomised controlled trials to inform these decisions.

In the scenario of threatened pre-term labour, or early rupture of the membranes, in a patient either not yet on HAART or with a known viral load of >50 copies/ml, as well as taking the measures above, it may be worth commencing intravenous AZT. This can be reviewed later, taking into consideration which drugs have been started, the woman's viral load, and the likely timescale of delivery.

The antiretroviral management in this situation is the same as for scenario 6. HAART should be started, including single-dose nevirapine and intravenous AZT, and a caesarean done after two to four hours. If the mother is on HAART with a fully suppressed viral load, a decision should be made as to whether induction of labour, as opposed to an emergency caesarean section, is possible.

Post-exposure prophylaxis (PEP) should be given to the baby as soon as possible, where:

• It has only become clear that the women has HIV after her baby has been born.
• Treatment was introduced after labour had started.
• The woman did not agree to treatment or other interventions.

There are observational data indicating that AZT can reduce transmission in this situation if given within 48 hours of delivery.

It would seem logical, and consistent with other PEP regimen recommendations for high-risk exposure, to offer triple-combination therapy for four weeks, although there are no data on this.

If the mother’s HIV status is unknown, a rapid test should be performed where possible and a reactive result must be acted on immediately.

If the result is reactive or she is known to be HIV-positive, baseline blood samples should be taken and nevirapine-containing HAART started (either as single-dose nevirapine with a PI-containing regimen, or as an ongoing nevirapine regimen; see scenario 6). Intravenous AZT should also be started.

If the mother is not about to deliver, an emergency caesarean section should be performed at least two hours after the nevirapine has been administered.