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Protease inhibitors and preterm delivery: another piece in the puzzle

Favarato, Graziellaa; Townsend, Claire, L.a; Bailey, Heathera; Peters, Helena; Tookey, Pat, A.a; Taylor, Graham, P.b; Thorne, Clairea

doi: 10.1097/QAD.0000000000001694
Epidemiology and Social

Background: Questions remain regarding preterm delivery (PTD) risk in HIV-infected women on antiretroviral therapy (ART), including the role of ritonavir (RTV)-boosted protease inhibitors, timing of ART initiation and immune status.

Methods: We examined data from the UK/Ireland National Study of HIV in Pregnancy and Childhood on women with HIV delivering a singleton live infant in 2007–2015, including those pregnancies receiving RTV-boosted protease inhibitor-based (n = 4184) or nonnucleoside reverse transcriptase inhibitors-based regimens (n = 1889). We conducted logistic regression analysis adjusted for risk factors associated with PTD and stratified by ART at conception and CD4+ cell count to minimize bias by indication for treatment and to assess whether PTD risk differs by ART class and specific drug combinations.

Results: Among women conceiving on ART, lopinavir/RTV was associated with increased PTD risk in those with CD4+ cell count 350 cells/μl or less [odds ratio 1.99 (1.02, 3.85)] and with CD4+ cell count more than 350 cells/μl [odds ratio 1.61 (1.07, 2.43)] vs. women on nonnucleoside reverse transcriptase inhibitors-based (mainly efavirenz and nevirapine) regimens in the same CD4+ subgroup. Associations between other protease inhibitor-based regimens (mainly atazanavir and darunavir) and PTD risk were complex. Overall, PTD risk was higher in women who conceived on ART, had low CD4+ cell count and were older. No trend of association of PTD with tenofovir or any specific drug combinations was observed.

Conclusion: Our data support a link between the initiation of RTV-boosted/lopinavir-based ART preconception and PTD in subsequent pregnancies, with implications for treatment guidelines. Continued monitoring of PTD risk is needed as increasing numbers of pregnancies are conceived on new drugs.

aPopulation, Policy and Practice Programme, UCL Great Ormond Street Institute of Child Health, University College London

bSection of Virology, Faculty of Medicine, Imperial College London, London, UK.

Correspondence to Dr Graziella Favarato, PhD, Population, Policy and Practice Programme, UCL Great Ormond Street Institute of Child Health, University College London, 30 Guilford Street, London WC1N 1EH, UK. Tel: +44 (0)20 790 42341; e-mail:

Received 7 August, 2017

Revised 21 September, 2017

Accepted 29 September, 2017

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