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Sci."],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Combination antiretroviral therapy (cART) has improved human immunodeficiency virus (HIV) management, but long-term use is associated with reproductive dysfunction. This study investigated TLD (Tenofovir, Lamivudine and Dolutegravir)-based cART effects on ovarian function using animal models and exploratory clinical investigations in women living with HIV. In the animal study, female Wistar rats were randomized into control, TLD-based cART (22\u00a0mg\/kg), and dolutegravir alone (2.5\u00a0mg\/kg) groups, administered orally for 28\u00a0days. Estrous cycle, histology, oxidative stress, reproductive hormones, and ova count were assessed. Both TLD-based cART and dolutegravir significantly prolonged diestrus (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.0083 and\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.0007, respectively) and reduced metestrus (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.0057 and\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.0083, respectively). Treated groups showed significantly reduced ova counts (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.0002 and 0.0003, respectively). Histology revealed structural alterations of the ovary, including atretic follicles, distorted stroma, and sparse theca cells. Additionally, treated groups showed increased malondialdehyde (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.0421) and decreased glutathione (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.0046) and catalase activities (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.0411), indicating oxidative stress. Serum follicle-stimulating and luteinizing hormones were significantly reduced in both treated groups (FSH:\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.0001 and\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.0002; LH:\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.0001 and\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.0108, respectively). In the clinical investigation, serum anti-M\u00fcllerian hormone (AMH) levels were evaluated in HIV-positive women (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200920) receiving TLD-based cART. Ten participants (50%) had AMH in low\/very low categories (\u2009&lt;\u20091.0\u00a0ng\/mL), while 11 (55%) had AMH below the normal reference range (\u2009&lt;\u20091.5\u00a0ng\/mL). Menstrual interval and dysmenorrhea showed no significant changes. These preliminary findings suggest Dolutegravir and TLD-based cART may negatively affect female reproductive function by altering ovarian structure, hormonal balance, and ovarian reserve, potentially predisposing women living with HIV to fertility complications.\n                  <\/jats:p>","DOI":"10.1007\/s43032-026-02229-x","type":"journal-article","created":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T16:13:13Z","timestamp":1791475993000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["TLD-Based Antiretroviral Therapy Compromises Ovarian Function and Reserve: Evidence from Experimental and Clinical Studies"],"prefix":"10.1007","author":[{"given":"Martha","family":"Ugwu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Airat A.","family":"Bakare","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tawakalitu","family":"Nafiu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olufunke O.","family":"Dosumu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8690-7778","authenticated-orcid":false,"given":"Edidiong N.","family":"Akang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,10,8]]},"reference":[{"key":"2229_CR1","unstructured":"World Health Organization. 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