ArticleReproductive sciences (Thousand Oaks, Calif.)2026
TLD-Based Antiretroviral Therapy Compromises Ovarian Function and Reserve: Evidence from Experimental and Clinical Studies.
Article in Reproductive sciences (Thousand Oaks, Calif.), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
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 mg/kg), and dolutegravir alone (2.5 mg/kg) groups, administered orally for 28 days. Estrous cycle, histology, oxidative stress, reproductive hormones, and ova count were assessed. Both TLD-based cART and dolutegravir significantly prolonged diestrus (p = 0.0083 and p = 0.0007, respectively) and reduced metestrus (p = 0.0057 and p = 0.0083, respectively). Treated groups showed significantly reduced ova counts (p = 0.0002 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 (p = 0.0421) and decreased glutathione (p = 0.0046) and catalase activities (p = 0.0411), indicating oxidative stress. Serum follicle-stimulating and luteinizing hormones were significantly reduced in both treated groups (FSH: p < 0.0001 and p = 0.0002; LH: p < 0.0001 and p = 0.0108, respectively). In the clinical investigation, serum anti-Müllerian hormone (AMH) levels were evaluated in HIV-positive women (n = 20) receiving TLD-based cART. Ten participants (50%) had AMH in low/very low categories ( < 1.0 ng/mL), while 11 (55%) had AMH below the normal reference range ( < 1.5 ng/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.
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