{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T02:03:56Z","timestamp":1773713036686,"version":"3.50.1"},"reference-count":27,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2023,9,26]],"date-time":"2023-09-26T00:00:00Z","timestamp":1695686400000},"content-version":"vor","delay-in-days":25,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Medical Virology"],"published-print":{"date-parts":[[2023,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>As the introduction of antiretroviral therapy (ART) during primary HIV\u20101 infection (PHI) could restrict the establishment of HIV reservoirs, we aimed to assess the effect of three different ART regimens on HIV\u2010DNA load in people living with HIV (PLWH), who started ART in PHI. Randomized, open\u2010label, multicentric study, including subjects in PHI (defined as an incomplete HIV\u20101 Western blot and detectable plasma HIV\u2010RNA) in the Italian Network of Acute HIV Infection cohort. Participants were randomly assigned (10:10:8) to a fixed\u2010dose combination of tenofovir alafenamide fumarate (TAF) 10\u2009mg plus emtricitabine (FTC) 200\u2009mg, darunavir 800\u2009mg, and cobicistat 150\u2009mg once daily (group A), or TAF 25\u2009mg plus FTC 200\u2009mg, dolutegravir 50\u2009mg once daily (group B), or an intensified four\u2010drug regimen (TAF 10\u2009mg plus FTC 200\u2009mg, dolutegravir 50\u2009mg, darunavir 800\u2009mg, and cobicistat 150\u2009mg once daily) (group C). The primary endpoint was the decrease of HIV\u2010DNA copies\/10<jats:sup>6<\/jats:sup> peripheral blood mononuclear cells (PBMCs) at weeks (W) 12 and 48. Secondary endpoints were increased in CD4+ cells and in CD4+\/CD8+ ratio and percentage of PLWH reaching undetectable HIV\u2010RNA. HIV\u2010DNA was quantified by Droplet Digital PCR (Biorad QX100) and normalized to RPP30 reference gene. This study was registered in <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/ClinicalTrials.gov\">ClinicalTrials.gov<\/jats:ext-link> (number NCT04225325). Among 78 participants enrolled, 30 were randomized to group 1, 28 to group 2, and 20 to group 3. At baseline, median CD4+ count was 658\/\u00b5L (476\u2013790), HIV\u2010RNA 5.37 (4.38, 6.12) log<jats:sub>10<\/jats:sub>\u2009copies\/mL, without statistical difference in their change among groups at weeks 12 and 48 (<jats:italic>p<\/jats:italic>\u2009=\u20090.432 and 0.234, respectively). The trial was prematurely discontinued for slow accrual and for COVID\u201019 pandemic\u2010associated restrictions. In the per\u2010protocol analysis, PLWH (<jats:italic>n<\/jats:italic>\u2009=\u200972) with undetectable viral load was 54.3% at W12 and 86.4% at W48. Interestingly, the CD4\/CD8 ratio progressively increased over time, up to normalization in almost half of the cohort by week 48, despite a deflection in group 3; no difference was observed by the Fiebig stage (I\u2013III vs. IV\u2013VI). HIV\u2010DNA decreased from 4.46 (4.08,\u20094.81) log<jats:sub>10<\/jats:sub>\u2009copies\/10<jats:sup>6<\/jats:sup> PBMCs to 4.22 (3.79,\u20094.49) at week 12, and 3.87 (3.46,\u20094.34) at week 48, without difference among groups. At multivariable analysis, HIV\u2010DNA delta at W48 was associated only with the increase of CD4+ count by 100\u2009cells\/mm<jats:sup>3<\/jats:sup> but not with the Fiebig stage, the CD4+\/CD8+ ratio, and treatment arm, despite a higher decrease in group 3. Six adverse events were recorded during our study, which did not cause any withdrawal from the study. We observed a decrease in HIV\u2010DNA from baseline to W48 in PLWH treated during PHI, associated with an increase in CD4+ count, unrelated to the treatment arm.<\/jats:p>","DOI":"10.1002\/jmv.29114","type":"journal-article","created":{"date-parts":[[2023,9,27]],"date-time":"2023-09-27T06:45:55Z","timestamp":1695797155000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["HIV\u2010DNA decrease during treatment in primary HIV\u20101 infection with three different drug regimens: Italian Network of Acute HIV Infection (INACTION) clinical trial"],"prefix":"10.1002","volume":"95","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3601-7686","authenticated-orcid":false,"given":"Elena","family":"Bruzzesi","sequence":"first","affiliation":[{"name":"Vita\u2010Salute San Raffaele University Milan Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2657-8025","authenticated-orcid":false,"given":"Arianna","family":"Gabrieli","sequence":"additional","affiliation":[{"name":"Dipartimento di Scienze Biomediche e Cliniche (DIBIC) Milan Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8771-5428","authenticated-orcid":false,"given":"Davide","family":"Bernasconi","sequence":"additional","affiliation":[{"name":"Bicocca Bioinformatics Biostatistics and Bioimaging Centre \u2010 B4 School of Medicine and Surgery University of Milano\u2010Bicocca Monza Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8860-8632","authenticated-orcid":false,"given":"Giulia","family":"Marchetti","sequence":"additional","affiliation":[{"name":"Clinic of Infectious Diseases, Department of Health Sciences, ASST Santi Paolo e Carlo University of Milan Milan Italy"},{"name":"School of Medicine and Surgery University of Milan Milan Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2534-8815","authenticated-orcid":false,"given":"Andrea","family":"Calcagno","sequence":"additional","affiliation":[{"name":"Unit of Infectious Diseases, Department of Medical Sciences University of Turin Turin Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6702-6668","authenticated-orcid":false,"given":"Diego","family":"Ripamonti","sequence":"additional","affiliation":[{"name":"Infectious Disease Unit ASST Papa Giovanni XXIII Bergamo Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2121-4684","authenticated-orcid":false,"given":"Andrea","family":"Antinori","sequence":"additional","affiliation":[{"name":"National Institute for Infectious Diseases Lazzaro Spallanzani IRCCS Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7608-6045","authenticated-orcid":false,"given":"Nicola","family":"Squillace","sequence":"additional","affiliation":[{"name":"Infectious Disease Unit Fondazione IRCCS San Gerardo dei Tintori Monza Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3793-2755","authenticated-orcid":false,"given":"Antonella","family":"Cingolani","sequence":"additional","affiliation":[{"name":"Istituto Clinica di Malattie Infettive Universit\u00e0 Cattolica del Sacro Cuore Rome Italy"},{"name":"UOC Malattie Infettive Fondazione Policlinico Universitario A. 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