BACKGROUND: Questions remain regarding preterm delivery (PTD) risk in HIV-infected women on antiretroviral therapy (ART), including the role of ritonavir-boosted protease inhibitors (PI/r), 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 PI/r-based (n=4184) or non-nucleoside reverse transcriptase inhibitors (NNRTI)-based regimens (n = 1889).We conducted logistic regression analysis adjusted for risk factors associated with PTD and stratified by ART at conception and CD4 count to minimise 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/ritonavir was associated with increased PTD risk in those with CD4 ≤350 (aOR 1.99[1.02, 3.85]) and with CD4>350 (aOR 1.61[1.07, 2.43]) versus women on NNRTI-based (mainly efavirenz and nevirapine) regimens in the same CD4 sub-group. Associations between other PI-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 countand were older. No trend of association of PTD with tenofovir or any specific drug combinations were observed. CONCLUSIONS: Our data support a link between the initiation of ritonavir-boosted/lopinavir-based ART pre-conception 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.