Increased risk of ART-related hepatotoxicity in HIV positive pregnant women

Polly Clayden, HIV i-Base

Evidence from the UK and Ireland that pregnancy increases the risk of liver enzyme elevation (LEE) among pregnant women on antiretroviral treatment (ART) was shown at the 2014 HIV Drug Therapy Glasgow Congress.

Susie Huntington – who presented data, on behalf of colleagues from the UK Collaborative HIV Cohort (UK CHIC) study and the UK and Ireland National Study of HIV in Pregnancy and Childhood (NSHPC) -noted that previous studies comparing the rate of LEE in pregnant and non-pregnant women on ART have produced conflicting results.

The analysis included combined data from UK CHIC – an observational cohort study of HIV positive women at 19 collaborating centres – and NSHPC – an observational surveillance study of HIV positive women accessing antenatal care in the UK and Ireland.

Pregnant and non-pregnant women aged 16 – 49 years, starting ART 2000 – 2012, with at least one alanine aminotransferase (ALT) measurement on ART were included. Ten women with severe baseline LEE were excluded.

ALT data was assessed according to the Division of AIDS toxicity guidelines to identify factors associated with LEE (grade 1 – 4). LEE was defined as > 1.25 times the upper limit of normal (ULN) women with baseline ALT<ULN (n=3511) and ALT > 1.25 times the baseline ALT women with baseline ALT>ULN (n=304).

The investigators used Cox proportional hazards to assess the associations between fixed covariates -ethnicity, exposure group, HBV/HCV co-infection, prior ART use, and age, year, pregnancy status, viral load and CD4 count at ART start -and time-dependent covariates -pregnancy status, age, year, CD4 count, viral load, duration on ART, antiretroviral drugs in regimen – and the risk of LEE.

Among 3815 women, the rate of LEE was 14.5/100 person years (95% CI 11.4 – 17.5) in pregnancy and 6.0/100 person years (95% CI 5.6 – 6.4) outside pregnancy. ART was started in pregnancy in 541 and 735 conceived on ART, the respective LEE rates were for these women were: 36.3/100 person years (95% CI 27.3 – 45.2) and 5.8/100 person years (95% CI 3.5 – 8.0).

LEE occurred at a median of 30 weeks (IQR 25 – 33) gestation and 8 weeks (IQR 4 – 12) after ART was started in women who began treatment in pregnancy. For those who conceived on ART LEE occurred at median 16 weeks (IQR 9 – 28) gestation.

The risk of LEE was increased during pregnancy, adjusted hazard ratio (aHR) 1.66 (95%CI: 1.3 – 2.1), p<0.001.

Other factors associated with LEE were: lower CD4 count (<250 vs 251-350 cells/mm3) aHR 1.25 (1.02-1.54), p=0.05; HBV/HCV co-infection, aHR 1.85 (1.5 – 2.3), p<0.001; HIV acquired through injecting drug use, aHR 1.55 (1.1 -2.2), p=0.02 vs heterosexually; and calendar year, aHR 1.05 (1.0 -1.1), p<0.001 per one year increase.

Two antiretrovirals were associated with increased risk of LEE: efavirenz aHR 1.26 (1.1 -1.5), p=0.005; and nevirapine aHR 1.54 (1.3 -1.9), p <0.001.

AZT was associated with decreased risk of LEE, aHR 0.73 (0.6 -0.9), p<0.001; as was increasing time on an NNRTI-based regimen, aHR 0.9 (0.9 – 1.0), p<0.001 per additional year.

Pregnancy status, CD4 count or previous ART use, when starting ART, ethnicity or age, were not associated with increased risk of LEE.


Huntington S et al. Does pregnancy increase the risk of ART-induced hepatotoxicity among HIV-positive women? HIV Drug Therapy Glasgow Congress, 2-6 November 2014. Oral abstract O133. Journal of the International AIDS Society 2014, 17(Suppl 3):19486

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