Dolutegravir restores gut microbiota in late-stage HIV-1 unlike darunavir: an open-label, randomized clinical trial
Late presentation of HIV-1 infection is linked to gut dysbiosis, impaired immune reconstitution, excess inflammation, immune activation, and increased morbidity and mortality. It is unclear if antiretroviral therapy initiation can reverse HIV-associated gut dysbiosis at all, or if specific antiretroviral regimens are more effective in restoring the gut microbiota than others. This has important implications for the long-term health of individuals with HIV. In this multicenter, open-label, randomized clinical trial (NCT02337322), 88 antiretroviral-naïve individuals with advanced HIV-1 infection (median CD4+ T cells of 34 cells/mm<sup>3</sup>) were randomized (1:1) to initiate lamivudine/abacavir plus either dolutegravir or ritonavir-boosted darunavir, and were followed for 2 years. Both groups had similar HIV-1 suppression rates and recovery of CD4+ T cells. However, treatment with dolutegravir led to increased gut microbial richness and diversity and enrichment of specific microbial taxa and metabolic pathways. These changes were associated with reduced inflammation and lower immune activation, outcomes that did not occur with darunavir/ritonavir. After two years, participants on dolutegravir-based therapy had gut microbiota profiles more closely resembling those of people without HIV, compared to individuals taking darunavir/ritonavir. In summary, dolutegravir-based therapy restores the gut microbiota more effectively than darunavir/ritonavir in patients who present late with HIV.
Authors
- Mariona Parera (ORCID: https://orcid.org/0000-0002-0756-8307)
- Josefa López Torres
- E. Rubio
- Anna Castelli
- Cristina Rodríguez Padilla (ORCID: https://orcid.org/0000-0002-9209-3341)
- F. Ramírez Lozano
- Núria Climent (ORCID: https://orcid.org/0000-0002-0791-656X)
- Nel Marín
- Francesc Català‐Moll (ORCID: https://orcid.org/0000-0002-2354-8648)
- María J. Maleno (ORCID: https://orcid.org/0000-0002-8549-0779)
- Valentina Ramírez Triviño
- J. Llach Vila
- Carlos Blázquez-Bondia
- Carmen Ligero
- Francesc Torres (ORCID: https://orcid.org/0000-0002-9360-0034)
- María Casadellà (ORCID: https://orcid.org/0000-0002-4115-2305)
- Glòria Sempere
- Alessandra Borgognone (ORCID: https://orcid.org/0000-0001-5487-3016)
- María Silvana DiYacovo
- Emma Fernández
- D Podzamczer
- P. Domingo
- Sandra Serrano
- JM Gatell
- M. Plana
- Gràcia Mateo
- J. Ena Muñoz
- José M. Miró
- Judit Farré-Badia
- Kanura Lamarca
- Lluís Force
- ADVANZ-4 MISTRAL investigators
- Eva Bonfill
- Marc Noguera-Julian
- Adrià Curran
- Arkaitz Imaz
- Maria Angeles Marcos
- María Saumoy
- Christian Manzardo
- Anna Cruceta
- Juan Manuel Tiraboschi
- Noemí Corbacho
- Elena Ferrer
- Carmen Ligero
- Elisa de Lazzari
- Roger Paredes
- Judit Fernández
- Benito Garcia
- Isabel Mur
- Oriol Careta
- M. Ema Molas
- Ana García
- Nerea Rozas
- Ana Silva
- Lucía Millan
- Paula Suanzes
- Juan Ambrosioni
- Daniela Marlano-Barletta
- Xavier Boquet
- Laura Acerete
Institutions
- Universitat Autònoma de Barcelona (ES)
- Real Academia Española (ES)
- Hospital de Sant Pau (ES)
- Bellvitge University Hospital (ES)
- IrsiCaixa (ES)
- Centro de Investigación Biomédica en Red (ES)
- Hospital Clínic de Barcelona (ES)
- Vall d'Hebron Hospital Universitari (ES)
- Hospital de Mataró (ES)
- Hospital Universitari Germans Trias i Pujol (ES)
- Case Western Reserve University (US)
- Universitat de Barcelona (ES)
- Universitat Politècnica de Catalunya (ES)
Publication Details
- Journal
- Nature Communications
- Published
- 2026-03-04
- DOI
- https://doi.org/10.1038/s41467-026-69846-7
- Primary Topic
- Gut microbiota and health
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- ViiV Healthcare
- European Commission