Background: In the United Kingdom, 90% of HIV^+ve women are of reproductive age, and increasing numbers are having children. Maternal serum genetic screening is routinely offered; comprising a triple assay of serum α-fetoprotein (αFP), human chorionic gonadotrophin (hCG), and unconjugated estriol (uE3). Previous studies have shown variation in hCG and αFP levels with HIV-status and treatment regimen. Raised levels of hCG are associated with an increased risk of Down's syndrome and the screen-positive rate may be higher in HIV^+ve than in HIV^–ve women. We have sought to confirm and extend these findings.

Methods:  Triple assay results of all HIV^+ve pregnant women attending antenatal clinics at participating centres (2003 to 2006) were reviewed and matched with HIV^–ve women. Continuous variables were compared for using paired or unpaired t-tests as appropriate. Data from the National Study of HIV in Pregnancy and Childhood (NSHPC), a U.K.-based prospective study of the health of children born to HIV-infected mothers, were used to determine the incidence of Down's syndrome in live births and terminations.

Results:  Study criteria were met by 94 HIV⁺ women, 48 of whom were antiretroviral untreated (ART^–); 24 were protease inhibitor (PI) un-exposed (ART⁺PI^–); 22 were PI exposed (ART⁺PI⁺); 77 were successfully matched. hCG multiples of the median (MOM) were significantly higher in the HIV⁺ group compared with the HIV^– group:  1.33 vs 1.09 (p = 0.028). HIV⁺ women receiving ART were found to have significantly higher levels of αFP:  1.33 vs 1.07 (p = 0.0196). ART⁺PI⁺ was associated with significantly reduced αFP MOM than ART⁺PI^– (p = 0.01). A non-significant trend for ART⁺PI⁺ to have lower hCG MOM than other treatment regimens (p = 0.12) or no treatment (p = 0.09). There was a non-significant (p = 0.723) increase in post-screening calculated Down's risk in the HIV⁺ group compared with the HIV^– group (1 of 657 compared to 1 of 782). The observed incidence of children with Down's syndrome in the 5763 women in the NSHPC database was not elevated.

Conclusions:  hCG is raised in HIV^+ve women, increasing the predicted screen-adjusted risk of Down's syndrome. However, observed incidence of Down's syndrome was not increased. hCG concentrations are normalized by PI⁺ regimens. Non PI-based therapy, but not HIV per se, tended to be associated with increased αFP levels. Thus HIV infection and some therapeutic regimens are associated with changes in serum genetic screen analyte measures and an increase in predicted, but not observed, risk.