{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T09:49:10Z","timestamp":1785750550206,"version":"3.56.0"},"reference-count":41,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2021,7,19]],"date-time":"2021-07-19T00:00:00Z","timestamp":1626652800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Bristol-Myers Squibb","award":["\/\/"],"award-info":[{"award-number":["\/\/"]}]},{"name":"Prin projects","award":["20179JHAMZ"],"award-info":[{"award-number":["20179JHAMZ"]}]},{"name":"Prin projects","award":["2017TYTWZ3_002"],"award-info":[{"award-number":["2017TYTWZ3_002"]}]},{"name":"Italian Foundation for Antiviral Studies and Research (AVIRALIA FOUNDATION)","award":["\/\/"],"award-info":[{"award-number":["\/\/"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Background: If analytical antiretroviral-treatment (ART) interruption (ATI) might significantly impact quantitative or qualitative peripheral-total HIV-DNA is still debated. Methods: Six chronically HIV-1 infected patients enrolled in APACHE-study were analysed for peripheral-total HIV-DNA and residual viremia, major-resistance-mutations (MRMs) and C2-V3-C3 evolution at pre-ATI (T1), during ATI (T2) and at achievement of virological success after ART-resumption (post-ATI, T3). These data were obtained at three comparable time-points in five chronically HIV-1 infected patients on suppressive ART for \u22651 year, enrolled in MODAt-study. Results: At T1, APACHE and MODAt individuals had similar peripheral-total HIV-DNA and residual viremia (p = 0.792 and 0.662, respectively), and no significant changes for these parameters were observed between T1 and T3 in both groups. At T1, 4\/6 APACHE and 2\/5 MODAt carried HIV-DNA MRMs. MRMs disappeared at T3 in 3\/4 APACHE. All disappearing MRMs were characterized by T1 intra-patient prevalence &lt;80%, and mainly occurred in APOBEC3-related sites. All MRMs persisted over-time in the 2 MODAt. C2-V3-C3 genetic-distance significantly changed from T1 to T3 in APACHE individuals (+0.36[0.11\u20130.41], p = 0.04), while no significant changes were found in MODAt. Accordingly, maximum likelihood trees (bootstrap &gt; 70%) and genealogical sorting indices (GSI &gt; 0.50 with p-value &lt; 0.05) showed that T1 C2-V3-C3 DNA sequences were distinct from T2 and T3 viruses in 4\/6 APACHE. Virus populations at all three time-points were highly interspersed in MODAt. Conclusions: This pilot study indicates that short ATI does not alter peripheral-total HIV-DNA burden and residual viremia, but in some cases could cause a genetic diversification of peripheral viral reservoir in term of both MRMs rearrangement and viral evolution.<\/jats:p>","DOI":"10.3390\/v13071403","type":"journal-article","created":{"date-parts":[[2021,7,19]],"date-time":"2021-07-19T10:07:37Z","timestamp":1626689257000},"page":"1403","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Impact of Analytical Treatment Interruption on Burden and Diversification of HIV Peripheral Reservoir: A Pilot Study"],"prefix":"10.3390","volume":"13","author":[{"given":"Rossana","family":"Scutari","sequence":"first","affiliation":[{"name":"Department of Experimental Medicine, University of Rome Tor Vergata, 00133 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5207-8147","authenticated-orcid":false,"given":"Valentino","family":"Costabile","sequence":"additional","affiliation":[{"name":"Department of Oncology and Hemato-Oncology, University of Milan, 20122 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Galli","sequence":"additional","affiliation":[{"name":"Infectious Diseases, San Raffaele Scientific Institute, 20132 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7717-2343","authenticated-orcid":false,"given":"Maria Concetta","family":"Bellocchi","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, University of Rome Tor Vergata, 00133 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"Carioti","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, University of Rome Tor Vergata, 00133 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Barbaliscia","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, University of Rome Tor Vergata, 00133 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Poli","sequence":"additional","affiliation":[{"name":"Infectious Diseases, San Raffaele Scientific Institute, 20132 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Galli","sequence":"additional","affiliation":[{"name":"Infectious Diseases, San Raffaele Scientific Institute, 20132 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlo Federico","family":"Perno","sequence":"additional","affiliation":[{"name":"Unit of Diagnostic Microbiology and Immunology, Department of Laboratories, Bambino Ges\u00f9 Children\u2019s Hospital, IRCCS, 00165 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6228-1114","authenticated-orcid":false,"given":"Maria Mercedes","family":"Santoro","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, University of Rome Tor Vergata, 00133 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonella","family":"Castagna","sequence":"additional","affiliation":[{"name":"Infectious Diseases, San Raffaele Scientific Institute, 20132 Milan, Italy"},{"name":"Faculty of Medicine and Surgery, Vita-Salute San Raffaele University, 20132 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Ceccherini-Silberstein","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, University of Rome Tor Vergata, 00133 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Alteri","sequence":"additional","affiliation":[{"name":"Department of Oncology and Hemato-Oncology, University of Milan, 20122 Milan, Italy"},{"name":"Multimodal Medicine Research Area, Bambino Ges\u00f9 Children\u2019s Hospital, IRCCS, 00165 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincenzo","family":"Spagnuolo","sequence":"additional","affiliation":[{"name":"Infectious Diseases, San Raffaele Scientific Institute, 20132 Milan, Italy"},{"name":"Faculty of Medicine and Surgery, Vita-Salute San Raffaele University, 20132 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,7,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1038\/387188a0","article-title":"Decay characteristics of HIV-1-infected compartments during combination 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