{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T02:16:45Z","timestamp":1788574605469,"version":"build-2803163510"},"reference-count":33,"publisher":"American Society for Microbiology","issue":"2","license":[{"start":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T00:00:00Z","timestamp":1771286400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T00:00:00Z","timestamp":1771286400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["AI164561"],"award-info":[{"award-number":["AI164561"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["AI164567"],"award-info":[{"award-number":["AI164567"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["AI126619"],"award-info":[{"award-number":["AI126619"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Fundacao para a Ciencia e Tecnologia","award":["PTDC\/MAT-APL\/31602\/2017"],"award-info":[{"award-number":["PTDC\/MAT-APL\/31602\/2017"]}]},{"DOI":"10.13039\/100008902","name":"Los Alamos National Laboratory","doi-asserted-by":"publisher","award":["20230853PRD2"],"award-info":[{"award-number":["20230853PRD2"]}],"id":[{"id":"10.13039\/100008902","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["J Virol"],"published-print":{"date-parts":[[2026,2,17]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>HIV-1 plasma viral load decays in a biphasic manner during antiretroviral therapy (ART). It was hypothesized that this is due to infection of different cell types, namely CD4+ T cells and macrophages. We studied this possibility directly by modeling the decay of HIV-1 in humanized mice. We utilized previously published data from humanized T-cell only mice (TOM) and myeloid-only mice (MOM) infected with HIV-1 and treated with a potent ART regimen. Viral load decay dynamics were modeled using either a single or a biexponential decay fitted using nonlinear mixed effects techniques. Fits were compared using the corrected Bayesian information criterion (BICc). In TOM, the biphasic model was significantly better than a single-phase decay model (\u0394BICc \u2248 16) despite additional parameters. In MOM, the biphasic decay was statistically better, but there was substantial uncertainty because the virus goes below detection very fast. The first-phase half-life was consistent between groups (1.2 days in MOM and 1.3 days in TOM) and similar to the half-life estimated in human infection. The second-phase decay in these mice was minimal likely due to low initial viral loads. Additional analyses with mice containing both CD4+ T cells and macrophages or X4-tropic virus-infected MOM mice confirmed the biphasic pattern, demonstrating the robustness of this result. The biphasic decline in HIV-1 occurs, even with only CD4+ T cells, refuting the hypothesis that distinct cell populations (CD4+ T cells and macrophages) drive each decay phase. These findings support an alternative model in which the observed dynamics arise from intrinsic properties of the viral infection lifecycle rather than from cellular compartmentalization.<\/jats:p>\n                    <jats:sec>\n                      <jats:title>IMPORTANCE<\/jats:title>\n                      <jats:p>It is well known that when antiretroviral therapy is started in people infected with HIV, the decay of virus in the periphery is biphasic early on (followed by other slower phases). One possibility for this pattern of decay is infection of two different types of cells (suggested previously to be CD4+ T cells and macrophages), with different turnovers giving rise to the biphasic decline. We addressed this issue directly in a humanized mouse model of HIV, taking advantage of mice reconstituted with just T cells and treated with antiretroviral drugs. We found that the observed decay is biphasic, which eliminates the hypothesis that the biphasic decline is due to the co-existence of the two types of cells. It is possible that integration dynamics, as we previously proposed, are responsible for the observed biphasic decline.<\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/jvi.01321-25","type":"journal-article","created":{"date-parts":[[2025,12,30]],"date-time":"2025-12-30T15:00:41Z","timestamp":1767106841000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":1,"title":["The decay of HIV under anti-retroviral therapy is biphasic even in humanized mice with just T cells"],"prefix":"10.1128","volume":"100","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2976-0949","authenticated-orcid":true,"given":"Jasmine A. F.","family":"Kreig","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01e41cf67","id-type":"ROR","asserted-by":"publisher"}],"name":"Theoretical Biology and Biophysics, Theoretical Division, Los Alamos National Laboratory","place":["Los Alamos, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela","family":"Wahl","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/008s83205","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Microbiology, University of Alabama at Birmingham","place":["Birmingham, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabete","family":"Fernandes","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01c27hj86","id-type":"ROR","asserted-by":"publisher"}],"name":"Faculdade de Medicina, Universidade de Lisboa","place":["Lisbon, Portugal"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4715-6796","authenticated-orcid":true,"given":"Jenna B.","family":"Honeycutt","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases, Center for AIDS Research, The University of North Carolina at Chapel Hill","place":["Chapel Hill, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3726-0482","authenticated-orcid":true,"given":"J. 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