Outcomes in infants exposed to lopinavir/ritonavir in utero
Polly Clayden, HIV i-Base
A systematic review of outcomes of infants born to women receiving lopinavir/ritonavir (LPV/r) in pregnancy – performed by investigators from the originator company – suggests that in utero exposure may not increase the risk of preterm birth.
M Martinez presented data from an assessment of the vertical transmission rate and risk of adverse infant outcomes among women treated with LPV/r based regimens in pregnancy at the 4th HIV & Women Workshop, 2014.
The investigators searched PubMed/EMBASE databases and HIV conferences for studies published to the end of January 2013 or March 2013 respectively. They looked for randomised trials or prospective/retrospective cohort studies of outcomes of infants exposed to LPV/r in utero as a primary or secondary endpoint.
The investigators also searched the AbbVie Global Safety Database for the infant outcome of prematurity to the end of December 2011.
They included 27 publications (n=12) and abstract presentations (n=15) describing 17 studies in the review. These studies reported on 4331 women receiving LPV/r in pregnancy, of these 2263 received LPV/r 800/200 mg/day, 101 received >800/200 mg/day, and for 1967 the dose was undocumented. Table 1 shows the results.
|Outcome||Studies reporting outcome (n)||Rate reported (%)|
|Vertical transmission||10||0 – 2.8|
|Preterm birth||13||8.7 – 25.0|
|Very preterm birth||6||0.4 – 5.0|
|Low birth weight||6||0.4 – 5.0|
|Very low birth weight||4||0.3 – 3.0|
|Still birth||5||1.0 – 4.8|
|Infant mortality||4||0 – 5.8|
Post-marketing safety data from the company database showed a preterm rate of 0.66/10,000 patient treatment years for LPV/r.
One study showed similar preterm, low birth weight and vertical transmission rates for women receiving 800/200 mg and >800/200 mg LPV/r.
Three studies reporting birth defects showed a prevalence of 2% to 8.5%, which compared to the Antiretroviral Pregnancy Registry (APR) rate of 2.4%.
In one study the incidence of mortality among preterm infants was similar with LPV/r based treatment to that for women treated with triple NRTIs.
The authors concluded: “Preterm birth rates in the included studies reflected the rate for the geographical area in which the study was conducted; these data and post-marketing safety data suggest that in utero exposure to LPV/r may not increase risk of preterm birth. Infants born to women who received LPV/r 800/200 mg/day and those born to women who received >800/200 mg/day had similar rates of preterm birth, low birth weight, and MTCT.”
Although analyses (particularly conclusions) performed by the originator company need to be approached with a little caution, these can be useful and results from this one supports the current APR data for LPV/r.
Martinez M et al. Systematic review of clinical outcomes of infants born to women receiving lopinavir/ritonavir-based antiretroviral therapy (ART) during pregnancy. 4th International Workshop on HIV & Women, Washington DC. 13-14 January 2014. Oral Abstract_21.