Types of regimen

There are more than 20 drugs currently licensed for specific treatment of HIV infection in the UK. AZT (zidovudine, Retrovir) is the only one specifically indicated for use in pregnancy.¹

AZT was the first antiretroviral drug to be used in pregnant women with HIV and remains the best studied. Its effectiveness has been demonstrated in a number of large randomised, controlled studies and supported by epidemiological surveys.

The placebo-controlled ACTG 076 trial proved that AZT use could reduce mother-to-child transmission of HIV among pregnant women with CD4 cell counts above 200 cells/mm³ who had not previously taken AZT.² The AZT arm had three components:

• AZT was given to pregnant women by mouth starting between weeks 14 and 34 at a dose of 100mg five times a day.
• During labour, women were treated with intravenous AZT.
• After birth, AZT syrup was given to the infants for the first six weeks of life.

Only 8% of the women randomised to AZT transmitted HIV to their babies compared to 26% among those on placebo.

A subsequent observational study of 939 infants born to HIV-positive mothers in New York confirmed the need for all three components of AZT treatment. When AZT was started in the prenatal period, the transmission rate was 6% but there was a 10% transmission rate among babies born to women who began AZT only during delivery. Similarly, the course of AZT given to the newborn was found to be necessary for maximal reductions in transmission.³

Some studies since ACTG 076 have shown that shorter courses of AZT can also reduce the rate of mother-to-child transmission, with one suggesting that starting at week 28 of pregnancy can be as effective as starting at week 14.⁴ This can be useful in situations where women are diagnosed later in pregnancy.

Viral load is an important predictor of transmission and AZT reduces transmission at all viral load levels, by between 67% (when administered with the three components listed above) to 50% with shorter courses started at 36 weeks of pregnancy and with no treatment of the baby, to 30% where the baby is not treated and is breastfed.¹ It may also work as post-exposure prophylaxis in the newborn.⁵

In the age of highly active antiretroviral therapy, some people have questioned whether AZT monotherapy is the best treatment option for mother and baby. Both UK and US guidelines recommend that a woman's health status should determine treatment. If the woman has a high viral load (>10,000 copies/ml), even with the risk reduced by two-thirds with the use of AZT, it remains a significant risk and the BHIVA/CHIVA guidelines recommend treatment with HAART.¹ Only if a pregnant woman has a high CD4 count and low viral load, and does not require treatment for her own disease, should AZT monotherapy be considered.

Two studies looking at the addition of 3TC (lamivudine, Epivir) to AZT reported that this was an extremely effective way of preventing mother-to-child transmission and reduced the rate of MTCT to between 2 and 3%.^{6 7}

However, the risks of resistance are now thought to outweigh these benefits and BHIVA/CHIVA do not recommend this regimen.¹

Results from two large studies in Africa have shown that one or two doses of the NNRTI nevirapine (Viramune) during and after labour can reduce the rate of mother-to-child transmission significantly.^{8 9}

However, use of two-dose nevirapine in this way is now restricted to places where other interventions are not practical because of the risk of the woman developing resistance to this drug and possibly to the NNRTI class as a whole - which can could limit her future treatment options significantly.  

Single-dose nevirapine can be used as an emergency in labour in some situations (see scenarios four, six, seven and nine in Choosing a regimen), provided care is taken to avoid resistance.

Between 20 and 60% of women who receive single-dose nevirapine become resistant to the NNRTI class because it is eliminated very slowly from the body compared to other antiretroviral drugs. The presence of sub-optimal drug levels for up to a week after taking a single dose creates an environment where resistance emerges easily. (Now, however, many people resistant to this class may benefit from treatment with etravirine [Intelence], the latest, powerful NNRTI with a high barrier to resistance.¹⁰)

However, resistance to nevirapine can be significantly reduced by the use of a single dose of tenofivir (Viread) and FTC (emtricitabine, Emtriva), taken in addition to the single-dose nevirapine during labour.¹¹ And more recent studies have shown that short courses of more than one anti-HIV drug after delivery can almost eliminate the risk of nevirapine resistance.^{12 13} This is called 'covering the tail' as nevirapine leaves the body. 

Studies have shown that combination therapy does reduce mother-to-child transmission of HIV, and that protease inhibitor-containing combinations are more effective than other regimens.

The North American Women and Infants Transmission Study showed a reduction in transmission from 7.8% in mothers and babies given AZT monotherapy, to 1.1% in those given triple therapy including a PI.¹⁴ In the Pediatric AIDS Clinical Trials Group (PACTG) 367, the transmission rate fell from 4.2% in 1998 to 0.5% in 2002.¹⁵

However, although transmission rates have fallen since the introduction of combination therapy, recent UK studies have not shown any difference between women treated with AZT alone or triple-drug therapy, if they had a pre-labour caesarean.¹

The choice of drugs in pregnancy will, in part, depend on the potential side-effects of the drugs for the woman herself. Some toxicity is related to changes in the way a woman's body processes drugs when she is pregnant. In some cases, the way a drug is dosed may have to be changed because of pregnancy-related changes in absorption and metabolism.

More information can be found in NAM's HIV Treatments Directory, and detailed information on particular side-effects of individual anti-HIV drugs and drug classes are listed in the BHIVA/CHIVA guidelines.