New UK draft guidelines on the management of HIV infection in pregnant women recommend that efavirenz-based treatment should no longer be avoided in pregnant women or women who want to have a baby.
Pregnant women were previously recommended to avoid efavirenz treatment, as were women hoping to become pregnant, due to the theoretical risk of birth defects if the foetus was exposed to the drug in the first trimester of pregnancy.
But after rigorous review of the published evidence, the British HIV Association guidelines panel concluded: “there are insufficient data to support the former position [of avoiding the drug] and [we] furthermore recommend that efavirenz can be both continued and commenced during pregnancy.”
Women who conceive while taking an efavirenz-containing regimen should continue on it, and women taking any effective HAART regimen should continue on it even if it does not contain AZT (zidovudine), the panel recommends.
World Health Organization guidelines on antiretroviral treatment for the prevention of mother-to-child transmission in resource-constrained settings first recommended the use of efavirenz during pregnancy in 2009, but United States guidelines updated in 2010 recommend avoiding the drug during the first trimester of pregnancy.
The draft guidelines are available for comment until Friday February 24 at the BHIVA website.
Key recommendations from the guidelines
Women who need HAART for their own health
Women requiring HAART for their own health should commence treatment as soon as possible as per the adult treatment guidelines.
In terms of the NRTI backbone, there is most evidence and experience in pregnancy with zidovudine plus lamivudine. Tenofovir plus emtricitabine or abacavir plus lamivudine are acceptable alternatives.
In the absence of specific contraindications it is recommended that the third agent in HAART should be nevirapine if the CD4 count is less than 250 or efavirenz or a boosted PI.
No routine dose alterations are recommended for ARVs during pregnancy if used at adult licensed doses but consider third trimester TDM, particularly if combining tenofovir and atazanavir.
For women who do not need HAART for their own health
In the absence of specific contraindications it is recommended that HAART should be boosted-PI-based. The combination of zidovudine, lamivudine and abacavir can be used if the baseline viral load is <100,000 HIV RNA copies/ml plasma.
Zidovudine monotherapy can be used in women planning a caesarean section who have a baseline VL of <10,000 and a CD4 of >350. Women who do not require treatment for themselves should commence temporary HAART at week 14 if the baseline VL is >30K (Consider starting earlier if VL> 100,000). All women should have commenced HAART by 24 weeks.
A woman who presents after 28 weeks should commence HAART without delay. If the viral load is unknown or >100K a 3 or 4 drug regimen that includes raltegravir is suggested.
An untreated woman presenting in labour at term should be given a stat dose of nevirapine and commence fixed-dose zidovudine with lamivudine and raltegravir.
Women presenting in labour/ROM/requiring delivery without a documented HIV result must be recommended to have a HIV diagnostic point of care test (POCT). A reactive POCT result must be acted upon immediately with initiation of the interventions to PMTCT without waiting for formal serological confirmation.
ART can be continued in all women who commenced cART for MTCT with a CD4 count of between 350 and 500 cells during pregnancy.
ART should be discontinued in all women who commenced cART for MTCT with a CD4 count of > 500 cells unless there is discordance with her partner (see above) or co-morbidity.
Mode of delivery
Vaginal delivery is recommended for women on HAART with an HIV viral load <50 HIV RNA copies/ml at gestational week 36.
Delivery by pre-labour caesarean section (PLCS) is recommended for women taking zidovudine monotherapy irrespective of plasma viral load at the time of delivery and for women with viral load >400 regardless of ART.
Vaginal delivery is recommended for women on HAART with a HIV viral load <50 HIV RNA copies/ml plasma at gestational week 36.
Delivery by PLCS is recommended for women taking zidovudine monotherapy irrespective of plasma viral load at the time of delivery (Grading: 1A) and for women with viral load >400 regardless of ART.
Infant prophylaxis
Zidovudine monotherapy is recommended if maternal viral load is <50 HIV RNA copies/ml at 36 weeks gestation/delivery (or mother delivered by PLCS whilst on ZDV monotherapy), irrespective of the mother’s viral resistance pattern or drug history.
Infants <72 hours old, born to untreated HIV-positive mothers, should initiate three drug therapy immediately.
Three drug infant therapy is recommended for all circumstances where maternal viral load at 36 weeks gestation/delivery is not <50 HIV RNA copies/ml.
Three drug infant therapy is recommended for all circumstances where maternal viral load at 36 weeks gestation/delivery is not <50 HIV RNA copies/ml.
Neonatal PEP should be continued for 4 weeks.
Infant feeding
All mothers known to be HIV infected, regardless of antiretroviral therapy, and infant PEP, should be advised to exclusively formula feed from birth In the very rare instances where a mother who is on effective HAART with a repeatedly undetectable viral load chooses to breast feed, this should not constitute grounds for automatic referral to child protection teams. Maternal HAART should be carefully monitored and continued until one week after all breastfeeding has ceased. Breastfeeding, except during the weaning period, should be exclusive and all breastfeeding, including the weaning period, should have been completed by the end of 6 months
Prolonged infant prophylaxis during the breastfeeding period, as opposed to maternal HAART, is not recommended.
Intensive support and monitoring of the mother and infant are recommended during any breastfeeding period, including monthly measurement of maternal HIV plasma viral load, and monthly testing of the infant for HIV by PCR for HIV cDNA or RNA (viral load).
HIV DNA PCR (or HIV RNA testing) should be performed on the following occasions.
During the first 48 hours and prior to hospital discharge
2 weeks post infant prophylaxis (6 weeks of age)
2 months post infant prophylaxis (12 weeks of age)
On other occasions if additional risk (e.g. breast-feeding)
HIV antibody testing for seroreversion should be done at age 18 months.