Protease inhibitors and preterm delivery: another piece in the puzzle.

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/l or less [odds ratio 1.99 (1.02, 3.85)] and with CD4(+) cell count more than 350 cells/l [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.