Important note: Information in this article was accurate in May 2009. The state of the art may have changed since the publication date.
Efavirenz conceptions in Soweto
HIV Treat Bull - 2009 Sep/Oct;10(9/10): 13
Polly Clayden, HIV i-Base
A poster from the Perinatal Research Unit in Soweto, South Africa, showed findings on the rate of miscarriages and still births from a retrospective review of women receiving efavirenz (EFV) in pregnancy.[1]
Although EFV is FDA category D, increasingly women are conceiving while already receiving this antiretroviral.
In this review, the investigators looked at records of 886 women receiving HAART between August 2004 and March 2008. Among this group, 117 pregnancies were recorded and 83 women (70.9%) had conceptions that were EFV-exposed for a mean duration of 97.05 days (range 12-343 days). Of these, 3/83 (2.6%) miscarried, 1/83 (1.2%) was a stillbirth, and 28/83 (33.7%) were electively terminated.
The remainder of HAART exposed conceptions, 34/117 (29.1%), were EFV-unexposed; of these 5/34 (14.7%) miscarried, 1/34 (2.9%) were stillbirths, and 2/34 (5.9%) were electively terminated.
The investigators found that compared to live births, elective termination of pregnancy (TOP) rates were significantly higher among EFV-exposed than non-EFV exposed, p=0.00418.
They also note that South African public sector surveillance reports a miscarriage rate of 6.3% (2001), a stillbirth rate of 2.4% (2006-07), and an elective termination of pregnancy rate of 13.6% (2001).
They suggest that this high rate of TOP in women receiving EFV-containing HAART may reflect provider teratogenicity counselling. Additionally, they suggest that it reflects provider choice to initiate EFV-containing regimens for women not expressing the desire to have children. They note that they did not find an increase in miscarriage or stillbirths in women receiving EFV compared with the general population.
Comment:
The investigators explained that this evaluation was performed in response to findings from Brazil showing a higher rate of miscarriage among EFV-exposed pregnancies.[2]
In our Comment's concerning the Brazilian data[3] we wrote:
“These data should be treated with extreme caution. The miscarriage rate reported from this notes review is extremely low (1.38%). It is generally thought that approximately 30% of conceptions are miscarried. The potential for biased reporting is very high and this is more likely to be seen with efavirenz than other antiretroviral drugs. Although the congenital anomaly rate is reported to be more than twice the background for Rio de Janeiro (2.2% v 0.8%) the later figure is only about one third of the normally cited of congenital malformations and 2.2% is a more realistic figure.”
This South African review did not find a higher rate of miscarriage or stillbirth among women receiving EFV at conception.
However, the high rate of termination of pregnancy among women taking efavirenz is striking and the investigators suggest that this may reflect provider teratogenicity counselling. FDA category D states that there is evidence that the drug is associated with teratogenicity in humans. This is a relative contraindication and this FDA classification also states that the benefits may outweigh the potential risk (category X states that the drug should not be prescribed in pregnancy because of the risk). Despite this categorisation, the Antreroviral Pregnancy Registry, which now has sufficient numbers of first trimester efavirenz exposures to detect at least a two-fold increase in risk of overall birth defects, report no such increase to date, 14/477, 2.9% (95% CI, 1.6-4.9%).[4]
The data from DART above show that even in a clinical trial with pregnancy counselling 4.8% of women conceived per annum. In this cohort from Soweto 13% of the women on HAART conceived with the majority (71%) taking an efavirenz-based regimen.
So, as the investigators suggest, consideration needs to be given both to provider antiretroviral choice and to provider counseling with women of child-bearing age who may or do become pregnant.
References:
Joao E et al. “Increased incidence of spontaneous abortion during first trimester exposure to efavirenz.” IAS Conf HIV Pathog Treat 2007 Jul 22-25;4th: Poster abstract TUPEB113.
Clayden P. “Increased incidence of miscarriage with efavirenz use”, HIV Treat Bull 2007 Aug/Sep; 8(8/9):19
Antiretroviral Pregnancy Registry Steering Committee. Antiretroviral Pregnancy Registry International Interim Report for 1 January 1989 through 31 January 2009.
2009-09-10
IB2009-09-13
©2009. I-BASE HIV Treatment Bulletin. Permission to reproduce courtesy of HIV i-Base, Third Floor East, Thrale House, 44-46 Southwark Street, London SE1 1UN - T: +44 (0) 20 7407 8488 F: +44 (0) 20 7407 8489
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