Side effects common but mostly mild in women taking higher dose protease inhibitors in pregnancy

No difference in toxicities was observed between women receiving either high dose atazanavir/ritonavir (ATV/r) or lopinavir/ritonavir (LPV/r) during pregnancy in a retrospective analysis at a single centre in Chicago.

Pharmacokinetic changes during pregnancy reduce antiretroviral drug exposure. US guidelines recommend the use of high dose protease inhibitors (PI) ATV/r and LPV/r, during later stages of pregnancy – dose adjustment is not routinely recommended in the UK.

The study was conducted to determine rates of adverse events (AEs) requiring PI discontinuation, dose reduction, or treatment of symptoms. The retrospective cohort included HIV positive pregnant women receiving high dose ATV/r or LPV/r-based ART between September 2007 and January 2013. The primary endpoint was a comparison between the groups of a composite of the AE rate, symptomatic treatment initiation related to AEs, dose reduction or discontinuation of the PI.

Overall, 65 women were included in the analysis, of these 52 received LPV/r and 13 ATV/r at doses of 600/150 mg and 400 /100 respectively.

Women were similar in both treatment groups with a median age of 29 years old, most were black (65%), and had been HIV positive for about 8 years. Time to PI dose increase was shorter for women receiving ATV/r – a median of 137 days compared to 189 in the LPV/r group, p=<0.05. The investigator noted that this was because the product labeling recommends dose adjustment during the second trimester of pregnancy.

Most women in the ATV/r group (84.6%) took tenofovir and FTC concurrently while most of those in the LPV/r group (55.8%) received 3TC/AZT.

During the study period 77% of women in the ATV/r group achieved an undetectable viral load (<48 copies/mL) compared to 84% in the LPV/r group, p=0.32. There were 11 composite endpoints in the ATV/r group and 44 (84.6%) in the LPV/r group, both 84.6%, p=0.99. A greater proportion of women receiving ATV/r had a laboratory abnormality, 52.6% vs 31.7%, p=0.08. This was mostly because of hyperbilirubinaemia.

The groups had similar rates of clinical interventions: symptomatic agent 31.6% vs 42.6%; dose reduction 0% vs 4.6% and antiretroviral discontinuation 7.8% vs 0.77% in the ATV/r and LPV/r groups respectively. Grades of AEs were also similar, respectively 78.9% vs 70.3% Grade 1 and 21.0% vs 29.7% Grade 2 to 4.

Antiretroviral discontinuations occurred in one woman who had constipation with ATV/r and one who had anaemia with LPV/r. The three dose reductions in the LPV/r group were related to transaminitis.

Comment

It would be interesting to see a comparison between side effects occurring with high and low doses of PIs in pregnancy. US guidelines recommend increasing the dose of PIs in pregnancy routinely whereas BHIVA guidelines do not – both countries report very low transmission rates.