Treatment with highly active antiviral therapy has made it possible to reduce the rate of transmission between the mother and the fetus.
The provision of highly active antiviral therapy (HAART) to HIV-infected pregnant women can reduce the transmission rate to 0.1 per cent if treatment is successful at achieving an undetectable viral load at delivery.1 This, coupled with the widespread uptake of universal antenatal screening for HIV in pregnancy, has led to a very low risk of mother-to-child transmission in Australia.
Perinatal transmission of HIV can occur during pregnancy, during delivery or during breastfeeding. There is a higher risk of transmission at each stage when the viral load is high, for example, early infection or very advanced. HAART can reduce transmission in several ways, by reducing maternal viral load in blood and bodily secretions and by transplacental absorption of HAART to the fetus. This supplies pre-exposure prophylaxis to the fetus for the transit through the birth canal. Post-exposure prophylaxis with zidovidine (AZT) is then given to the newborn and breastfeeding is discouraged.
Women and HIV
The goals of antiviral therapy for both men and women are the same. Studies show similar response to HAART for men and women.2 Recommendations for commencing treatment are moving towards earlier treatment with advantages in preserving immune function, preventing comorbidities such as cardiovascular disease and reducing some HIV-associated cancers.
After diagnosis, reassurance should be given to women about their reproductive options. Throughout a woman’s care, discussions should be had about her intentions to have children. Provision of safe and effective contraception is important to minimise unplanned pregnancy. Women not on HAART may use any form of appropriate contraception and are encouraged to use condoms to prevent transmission.
Women on HAART may have their contraceptive options limited due to interactions between antivirals and hormonal contraception. Hormonal contraceptives, including the combined oral contraceptive pill, the progesterone-only pill, the combined hormonal ring and the progesterone implant, are ineffective with efavirenz, nevirapine and boosted protease inhibitors owing to liver enzyme induction. Depo medroxyprogesterone acetate given as an injection every 12 weeks is metabolised completely during each passage through the liver so cannot be induced further. Intrauterine contraceptive devices, both the progesterone releasing and copper bearing, are also suitable.
Prevention of HIV transmission to a negative partner is important while trying to conceive. Recommendations include commencing HAART to minimise transmission. In the HTPN 052 trial in HIV-discordant couples, the HIV-infected partners were randomised to initiate or delay HAART. In this study, almost all of the participants were in heterosexual relationships, all participants received risk-reduction counselling and the absolute number of transmission events was low: one among ART initiators and 27 among ART delayers.3 Other measures, such as screening and treating other STIs, timed sex and artificial insemination, may be considered.
Choice of HAART is guided by resistance testing, as it is possible to acquire virus that is resistant to some antivirals.4 Resistant virus can also occur due to poor adherence if there is a prior treatment history. Genotypic resistance testing is a part of standard of care at initial diagnosis. The result is most valuable soon after acquisition as ‘resistant virus’ is less robust and will be archived with time, while wild virus with no resistance will dominate. If an antiviral combination is commenced that the archived virus is resistant to, this virus will be able to multiply again and become the dominant virus. Resistance testing is also valuable to guide treatment change when virological failure occurs. If a woman needs to start therapy for her health or the health of the fetus, then waiting for the results of resistance testing is not warranted. Treatment changes can be made when results are available.
Both European and US guidelines recommend combinations that should include one or more nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) with good placental passage (zidovudine, lamivudine, emtricitabine, tenofovir or abacavir). Avoid combining these with efavirenz in the first trimester as it may have teratogenic risks, although this is disputed.
The NRTIs are combined with a boosted protease inhibitor mostly lopinavir/ritonavir. However, some women can experience unacceptable side effects of nausea and diarrhoea with lopinavir/ritonavir and alternatives are atazanavir/ritonavir or darunavir/ritonavir.5 Choice should be guided by resistance testing, any history of treatment failure and stage in pregnancy. There is some concern about the risk of preterm delivery with protease inhibitors, but results of studies on the association of HAART and preterm delivery are conflicting, with some studies implicating boosted protease inhibitors while others don’t.6
As well as the usual antenatal screen tests, it is important to assess risk of other sexually transmitted infections then test and treat appropriately. After starting HAART, the viral load should be tested at two to four weeks, at least once each trimester, at 36 weeks and at delivery.7 The aim is to have an undetectable load at delivery. Liver and renal function should be checked for drug-induced toxicities.
When to start
Women who are pregnant and need HAART for their health should start immediately. This would include women with a CD4 count less than 350, co-infection with hepatitis B or C and any opportunistic infection. Those with a good CD4 count and low viral load can delay commencing treatment until 12 weeks. Those who are already on HAART and become pregnant should stay on treatment even if it contains efavirenz8 (provided it is working).
Late presenters, after 12 weeks, should start HAART as soon as possible. Consideration should be given to include raltegravir as part of HAART to achieve a rapid fall in viral load, especially if they present after 28 weeks.9 If they first present in labour the recommendations are for zidovudine infusion during labour and the infant given combination antiretroviral therapy rather than zidovudine monotherapy.10
Mode of delivery
Women can have a vaginal delivery if the HIV viral load is undetectable and they do not need zidovudine infusion. They should continue successful HAART throughout delivery. Planned caesarean section combined with intravenous zidovudine is indicated for those with a viral load above 1 000 copies/ml close to delivery.11
A decision can be made whether the woman would like to continue HAART post-delivery on an individual basis. Breastfeeding is not recommended, but if the woman insists and she has had virolgical suppression with HAART prior to delivery, then continuing HAART until rapid weaning carries only a low risk of transmission.12
Infants born to women with virological suppression close to delivery receive zidovudine monotherapy. The UK guidelines recommend four weeks and the US guidelines recommend six weeks.
Infant testing is usually done with HIV DNA in the first 48 hours, two weeks post antiretroviral prophylaxis, two months post antiretroviral prophylaxis and an HIV antibody test at 18 months. Maternal HIV antibodies pass the placenta so this test needs to be delayed until 18 months.13
Cooperation between HIV treating doctors and the maternity team to ensure timely diagnosis, appropriate choice of antivirals, regular monitoring for virological success, appropriate delivery and antiviral prophylaxis for the newborn can dramatically decrease the transmission of HIV from mother to child in pregnancy.
- de Ruiter A, Taylor G, Clayden P et al. Bhiva Guidelines for the management of HIV infection in pregnant women 2012. p.20.
- Panel on Antiretroviral Guidelines for Adults and Adolescents.Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. Department of Health and Human Services 2012.p.133.
- Cohen MS, Chen YQ, McCauley M et al. Prevention of HIV-1 infection with early antiretroviral therapy. N Engl J Med. Aug 112011;365(6):493-505.
- de Ruiter A, Taylor G, Clayden P et al. Bhiva Guidelines for the management of HIV infection in pregnant women 2012. p.27.
- Panel on Treatment of HIV-Infected Pregnant Women and Prevention of Perinatal Transmission. Recommendations for Use of Antiretroviral Drugs in Pregnant HIV-1- Infected Women for Maternal Health and Interventions to Reduce Perinatal HIV Transmission in the United States.2012. Table 5 p.52.
- Sibiude J, Warszawski J, Tubiana R et al. Premature Delivery in HIV-Infected Women Starting Protease Inhibitor Therapy During Pregnancy: Role of the Ritonavir Boost? Clinical Infectious Diseases 2012;54(9):1348–60.
- de Ruiter A, Taylor G, Clayden P et al. Bhiva Guidelines for themanagement of HIV infection in pregnant women 2012. p.27.
- de Ruiter A, Taylor G, Clayden P, et al. Bhiva Guidelines for themanagement of HIV infection in pregnant women 2012. p.42.
- de Ruiter A, Taylor G, Clayden P et al. Bhiva Guidelines for themanagement of HIV infection in pregnant women 2012.p.42.
- Panel on Treatment of HIV-Infected Pregnant Women and Prevention