{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T04:12:51Z","timestamp":1788581571509,"version":"build-2803163510"},"reference-count":67,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Therapeutic Advances in Infection"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Two-drug antiretroviral regimens are increasingly explored to simplify HIV-1 treatment while maintaining durable viral suppression. Doravirine combined with Islatravir (DOR\/ISL) represents a novel non-integrase strand transfer inhibitor (non-INSTI) regimen. However, comprehensive synthesized evidence remains limited.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To systematically evaluate the efficacy and safety of fixed-dose Doravirine (100 mg) plus Islatravir (0.25 or 0.75 mg) for HIV-1 treatment in adults.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design<\/jats:title>\n                    <jats:p>Systematic Review and Meta-Analysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Data Sources and Methods<\/jats:title>\n                    <jats:p>\n                      Comprehensive searches of PubMed, Embase, Scopus, Cochrane CENTRAL, ICTRP, and\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/ClinicalTrials.gov\">ClinicalTrials.gov<\/jats:ext-link>\n                      were performed to identify RCTs evaluating Doravirine\/Islatravir for HIV-1 treatment. The primary outcome was viral suppression (HIV-1 RNA &lt;50 copies\/mL) at 48 weeks. Secondary outcomes included immunological and safety endpoints.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Seven RCTs (N = 3,589) were included. In primary analyses restricted to the approved 0.25 mg dose (four RCTs, N = 1,639), DOR\/0.25 mg ISL achieved non-inferior viral suppression compared to standard ART at 48 weeks (RR = 1.01, 95% CI: 0.97-1.04, p = 0.63), with consistent efficacy across virologically suppressed and treatment-na\u00efve cohorts. DOR\/0.25 mg ISL showed no significant differences versus controls in CD4+ cell count (MD = -6.35 cells\/\u00b5L, p = 0.51) or total lymphocyte count changes (MD = -0.02 x 10\n                      <jats:sup>9<\/jats:sup>\n                      \/L, p = 0.54). Statistically significant declines in CD4+ and lymphocyte counts were strictly restricted to the discontinued 0.75 mg dose. Overall adverse events and treatment discontinuations due to adverse events were comparable between groups.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>DOR\/ISL provides non-inferior virologic efficacy compared with standard antiretroviral therapy with a favorable safety profile. The 0.25 mg Islatravir dose maintains antiviral efficacy while avoiding the immunologic declines observed with 0.75 mg dose, supporting its suitability as a simplified two-drug regimen.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Registration<\/jats:title>\n                    <jats:p>\n                      This review protocol was prospectively registered with PROSPERO (\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/www.crd.york.ac.uk\/PROSPERO\/view\/CRD420261321479\">CRD420261321479<\/jats:ext-link>\n                      ).\n                    <\/jats:p>\n                  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