Women on lopinavir/ritonavir-based regimens at conception at higher risk of preterm delivery in UK study

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Polly Clayden, HIV i-Base

HIV positive pregnant women receiving lopinavir/ritonavir (LPV/r)-based regimens were at higher risk of preterm delivery compared with those on NNRTI-based ones in UK and Ireland.

This was according to findings from the UK and Ireland National Study of HIV in Pregnancy and Childhood (NSHPC) presented at CROI 2017 – but this association was only among women who were receiving ART at conception.

Pregnant women on other ritonavir boosted PI-based regimens were also at higher risk compared to women on NNRTI-based regimens but the association was only apparent in women with CD4 counts of 350 cells/mm3 or more.

Some studies suggest that HIV positive women on boosted PI-based ART in pregnancy might be at higher risk of preterm delivery (<37 weeks of gestation) but evidence is not consistent. There is also conflicting evidence as to the contribution of timing of ART start, immune status and interaction with other antiretrovirals on preterm delivery risk.

NSHPC is a large national study that collects population-based surveillance data on all HIV positive pregnant women and children in care in the UK and Ireland. The study previously reported an increased preterm delivery risk with in women receiving 3-drug or more ART vs mono/dual therapy delivering from 1990 to 2005: 14 vs 10%, respectively.

In order to better characterise this finding, NSHPC investigators conducted a study to assess whether antenatal boosted PI-based regimens – particularly LPV/r ones – increase the risk of preterm delivery compared with NNRTI-based regimens in women delivering from 2007 to 2015. And to look at whether of ART at conception and first antenatal CD4 count affect these associations.

The evaluation included singleton live births to diagnosed women. The most recent pregnancy was included if women had repeated pregnancies during the study period. Women received NNRTI + 2NRTI or PI + 2NRTI; those who changed a drug or regimen during pregnancy were excluded. Women with a history of IDU were also excluded.

The investigators used logistic regression analyses adjusted for: calendar year, maternal age, region of origin, parity, ART at conception, and CD4 count (stratified by below and above 350 cells/mL).

There were 1889 (31.1%) pregnant women on NNRTI + 2NRTI, 2368 (39%) on LPV/r + 2NRTI, and 1816 (29.9%) on another boosted PI + 2NRTI, included in the analysis. There were 169 (9%), 284 (12%) and 176 (9.7%) preterm deliveries respectively across the three groups; 1577 (83.5%), 565 (23.9%) and 948 (52.2%) women conceived on ART, respectively.

The investigators found that women on LPV/r-based regimens were at higher risk of preterm delivery irrespective of CD4 count compared to women receiving NNRTI-based ones: aOR 2.01 (95%CI 1.03 to 3.91) and aOR 1.64 (95% CI 1.08 to 2.47), for <350 and >350 cells/mm3 respectively.

Women receiving another boosted PI at conception only had an elevated risk of preterm delivery with <350 cells/mm3: aOR 2.05 (95% CI 1.07 to 3.89).

Increased preterm delivery risk was also associated with: first antenatal CD4 <350 cells/mm3, aOR 1.28 (95% CI 1.04 to 1.58); older age (>36 vs <28 years), aOR 1.41 (95%CI: 1.05 to 1.89), and ART at conception, aOR 1.27 (95%CI: 1.01 to 1.61).


Favarato G et al. Do HIV+ women on protea se inhibitors deliver preterm? Findings from a UK study. Poster abstract 778. (abstract and poster)

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