Francesc Català‐Moll, Carlos Blázquez-Bondia, Judit Farré-Badia, Ferran Torres, Christian Manzardo, Eva Bonfill, Adrià Curran, P. Domingo, D Podzamczer, Lluís Force, Vicenç Falcó, Mariona Parera, María Casadellà, José M. Miró, Marc Noguera-Julian, Roger Paredes, ADVANZ-4 MISTRAL investigators, Alessandra Borgognone, Nel Marín, Oriol Careta, Valentina Ramírez Triviño, Anna Cruceta, Núria Climent, F. Ramírez Lozano, M. Plana, Juan Ambrosioni, Cristina Rovira, Carmen Hurtado, María J. Maleno, Alexy Inciarte, Anna Castelli, Emma Fernández, Carmen Ligero, Sandra Serrano, Maria Angeles Marcos, E. Rubio, J. Llach Vila, Elisa de Lazzari, JM Gatell, Daniela Marlano-Barletta, Paula Suanzes, Esteve Ribera, Ariadna Torrella, Bibiana Planas, Mar Gutierrez, Gràcia Mateo, J. Ena Muñoz, Ana García, Kanura Lamarca, Lucía Millan, Judit Fernández, Isabel Mur, Noemí Corbacho, M. Ema Molas, María Saumoy, Laura Acerete, Nerea Rozas, Elena Ferrer, Benito Garcia, María Silvana DiYacovo, Josefa López Torres, Ana Silva, Juan Manuel Tiraboschi, Arkaitz Imaz, Cristina Rodríguez Padilla, Pilar Barrufet, Xavier Boquet, Glòria Sempere
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/mm3) 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. Advanced HIV-1 infection is associated with gut dysbiosis, and it’s not known whether this is reversed with antiviral therapy. The ADVANZ-4 MISTRAL trial shows that dolutegravir restores gut microbiota in late-stage HIV1 patients better than darunavir, and that recovery is linked to improved immune reconstitution.