{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T03:21:23Z","timestamp":1788405683057,"version":"build-2803163510"},"reference-count":9,"publisher":"American Society for Microbiology","issue":"4","license":[{"start":{"date-parts":[[2024,4,2]],"date-time":"2024-04-02T00:00:00Z","timestamp":1712016000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2024,4,2]],"date-time":"2024-04-02T00:00:00Z","timestamp":1712016000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100000866","name":"International AIDS Vaccine Initiative","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100000866","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Microbiol Spectr"],"published-print":{"date-parts":[[2024,4,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:sec>\n            <jats:title\/>\n            <jats:p>\n              Phenotypic changes and functional impairment of natural killer (NK) cells occur early in HIV-1 infection. Antiretroviral therapy (ART) effectively restores CD4+ T cell counts and suppresses HIV-1 to undetectable levels. The role and efficacy of immediate ART initiation in mitigating NK cell aberrations remain to be elucidated comprehensively. This study hypothesized that HIV-1 infection negatively influences NK cell evolution and that early ART initiation restores these perturbations. Blood samples were collected longitudinally from five acutely HIV-1 infected men who have sex with men in Nairobi, Kenya. Participants were immediately initiated on ART after HIV-1 diagnosis. Blood samples were drawn pre-infection and at sequential bi-weekly post-infection time points. Peripheral blood mononuclear cells were stained with panel NK cells surface markers to assess HIV-induced phenotypic changes by flow cytometry. Some cells were also stimulated overnight with K562 cell line, IL-2, and IL-15 and stained for flow cytometry functionality. HIV-1 infection was associated with significant reductions in the production of IFN-\u03b3 (\n              <jats:italic>P<\/jats:italic>\n              = 0.0264), expression of CD69 (\n              <jats:italic>P<\/jats:italic>\n              = 0.0110), and expression of NK cell inhibitory receptor Siglec7 (\n              <jats:italic>P<\/jats:italic>\n              = 0.0418). We observed an increased NK cell degranulation (\n              <jats:italic>P<\/jats:italic>\n              = 0.0100) and an upregulated expression of cell exhaustion marker PD-1 (\n              <jats:italic>P<\/jats:italic>\n              = 0.0513) at post-infection time points. These changes mainly were restored upon immediate initiation of ART, except for Siglec7 expression, whose reduced expression persisted despite ART. Some HIV-associated changes in NK cells may persist despite the immediate initiation of ART in acute HIV-1 infections. Our findings suggest that understanding NK cell dynamics and their restoration after ART can offer insights into optimizing HIV-1 treatment and potentially slowing disease progression.\n            <\/jats:p>\n            <jats:sec>\n              <jats:title>IMPORTANCE<\/jats:title>\n              <jats:p>Natural killer (NK) cells play a crucial role in controlling of HIV-1 replication and progression to disease. Perturbations of their functionality may therefore result in deleterious disease outcomes. Previous studies have demonstrated reduced NK cell functionality in chronic HIV-1 infection that positively correlated to HIV-1 viral load. This may suggest that control of HIV-1 viremia in acute HIV-1 infection may aid in enhancing NK cell response boosting the inate immunity hence effective control of viral spread and establishment of viral reservoir. Antiretroviral therapy (ART) effectively supresses HIV-1 viremia to undectable levels and restores CD4+ T cell counts. Our study highlights the significant role of early ART initiation in mitigating NK cell disruptions caused by acute HIV-1 infection. Our results suggest that early initiation of ART could have benefits beyond suppressing viral load and restoring CD4+ T cell counts. In addition, it could boost the innate immunity necessary to control disease progression.<\/jats:p>\n            <\/jats:sec>\n          <\/jats:sec>","DOI":"10.1128\/spectrum.03570-23","type":"journal-article","created":{"date-parts":[[2024,2,16]],"date-time":"2024-02-16T20:26:20Z","timestamp":1708115180000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":5,"title":["Early antiretroviral therapy and its impact on natural killer cell dynamics in HIV-1 infected men who have sex with men: a cross-sectional pilot study evaluating the impact of early ART initiation on NK cell perturbation in HIV infection"],"prefix":"10.1128","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3665-9304","authenticated-orcid":false,"given":"Matrona","family":"Akiso","sequence":"first","affiliation":[{"name":"KAVI Institute of Clinical Research, University of Nairobi, Nairobi, Kenya"},{"name":"Department of Medical Microbiology and Immunology, University of Nairobi, Nairobi, Kenya"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Muema","sequence":"additional","affiliation":[{"name":"KAVI Institute of Clinical Research, University of Nairobi, Nairobi, Kenya"},{"name":"HIV Pathogenesis Programme, University of KwaZulu-Natal, KwaZulu-Natal, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Langat","sequence":"additional","affiliation":[{"name":"KAVI Institute of Clinical Research, University of Nairobi, Nairobi, Kenya"},{"name":"Division of Surgical Outcomes and Precision Medicine Research, Department of Surgery, University of Minnesota Twin Cities, Twin Cities, Minnesota, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kewreshini K.","family":"Naidoo","sequence":"additional","affiliation":[{"name":"HIV Pathogenesis Programme, University of KwaZulu-Natal, KwaZulu-Natal, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geoffrey","family":"Oino","sequence":"additional","affiliation":[{"name":"KAVI Institute of Clinical Research, University of Nairobi, Nairobi, Kenya"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gaudensia","family":"Mutua","sequence":"additional","affiliation":[{"name":"International AIDS Vaccine Initiative, New York, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina","family":"Thobakgale","sequence":"additional","affiliation":[{"name":"Faculty of Health Sciences, School of Pathology, University of Witwatersrand, Witwatersrand, South Africa"},{"name":"Centre for HIV and STIs, National Institute for Communicable Diseases, Johannesburg, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Ochiel","sequence":"additional","affiliation":[{"name":"International AIDS Vaccine Initiative, New York, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kundai","family":"Chinyenze","sequence":"additional","affiliation":[{"name":"International AIDS Vaccine Initiative, New York, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Omu","family":"Anzala","sequence":"additional","affiliation":[{"name":"KAVI Institute of Clinical Research, University of Nairobi, Nairobi, Kenya"},{"name":"Department of Medical Microbiology and Immunology, University of Nairobi, Nairobi, Kenya"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9119-3167","authenticated-orcid":false,"given":"Marianne W.","family":"Mureithi","sequence":"additional","affiliation":[{"name":"KAVI Institute of Clinical Research, University of Nairobi, Nairobi, Kenya"},{"name":"Department of Medical Microbiology and Immunology, University of Nairobi, Nairobi, Kenya"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_6_2_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0167640"},{"key":"e_1_3_6_3_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2009-06-226332"},{"key":"e_1_3_6_4_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2336091100"},{"key":"e_1_3_6_5_2","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.02875"},{"key":"e_1_3_6_6_2","doi-asserted-by":"publisher","DOI":"10.4102\/ajlm.v10i1.1056"},{"key":"e_1_3_6_7_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2249.2003.02329.x"},{"key":"e_1_3_6_8_2","doi-asserted-by":"publisher","DOI":"10.1089\/vim.2011.0096"},{"key":"e_1_3_6_9_2","doi-asserted-by":"publisher","DOI":"10.1111\/sji.12455"},{"key":"e_1_3_6_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2019.02.010"}],"container-title":["Microbiology 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