Switching to Integrase Inhibitors and Cardiovascular Disease Risk in Treatment-Experienced People With HIV: A Sequential Target Trial Emulation in the Swiss HIV Cohort Study
Tristan T Lee, Matthias Cavassini, Annalisa Marinosci, David Haerry, Marcel Stöckle, Patrick Schmid, Luigia Elzi, Christoph A Fux, Philip E Tarr, Lukas Baumann, Huldrych F Günthard, Gilles Wandeler, Niklaus D Labhardt, Bernard Surial, Frédérique Chammartin, , I A Abela, K Aebi-Popp, A Anagnostopoulos, E Bernasconi, D L Braun, H C Bucher, A Calmy, M Cavassini, A Ciuffi, G Dollenmaier, M Egger, L Elzi, J S Fehr, J Fellay, S Frigerio Malossa, C A Fux, H F Günthard, A Hachfeld, D H U Haerry, B Hasse, H H Hirsch, M Hoffmann, I Hösli, M Huber, D Jackson-Perry, C R Kahlert, D Kaufmann, O Keiser, T Klimkait, R D Kouyos, H Kovari, K Kusejko, N D Labhardt, K Leuzinger, B Martinez de Tejada, C Marzolini, K J Metzner, N Müller, J Nemeth, D Nicca, J Notter, P Paioni, G Pantaleo, M Perreau, A Rauch, L P Salazar-Vizcaya, P Schmid, O Segeral, R F Speck, M Stöckle, B Surial, P E Tarr, A Trkola, G Wandeler, M Weisser, S YerlyAbstract
Background
Integrase strand transfer inhibitors (INSTIs) are highly effective components of antiretroviral therapy for HIV. Recent studies suggest increased cardiovascular disease (CVD) risk after INSTI initiation, but findings remain inconsistent. The Swiss HIV Cohort Study is nationally representative, collects high-quality data, and provides an ideal setting for independent evaluation using causal methods, avoiding participant overlap in multicountry HIV-cohort consortiums.
Methods
We emulated sequential target trials from November 2011 to September 2025 to estimate the effect of switching from non-INSTI to INSTI-based treatment on 6-year CVD risk among treatment-experienced people with HIV. Eligible participants were ≥18 years old, INSTI-naive, virally suppressed, and without CVD history. For each trial, participants were assigned to remain on non-INSTI or switch to INSTI. Intention-to-treat (ITT) and per-protocol (PP) effects were estimated using pooled logistic regression with baseline adjustment (ITT) and inverse probability weighting (PP).
Results
Among 8815 individuals contributing 539 017 person-trials, 5750 switched to INSTI, and 507 CVD events occurred. In ITT analyses, the adjusted risk ratio for switching versus remaining on non-INSTI was 1.34 (95% confidence interval 1.03–1.69) after 1 year, and 1.03 (0.88–1.16) after 6 years. Absolute risk differences were small, ranging from 0.20 percentage points (0.02–0.37) after 1 year to 0.13 (-0.49 to 0.58) after 6 years. Per-protocol estimates were similar.
Conclusions
Switching to INSTI-based treatment did not substantially increase long-term CVD risk in treatment-experienced individuals with well-controlled HIV. The early increase in absolute risk was small and was not expected to be clinically meaningful. This further contextualizes results from multicountry analyses.