tenofovir disoproxil orotate (Virreal)

An intravaginal ring for HIV pre-exposure prophylaxis: assessment of safety and pharmacokinetics in a randomized, placebo-controlled clinical trial.

Vincent Kathleen L KL, Moss John A JA, Marzinke Mark A MA, Pyles Richard B RB et al.

In Eastern and Southern Africa, 63% of new HIV infections occurred in women and girls, with adolescent girls and young women representing a particularly vulnerable subpopulation. Effective vaginal products for HIV prevention are desirable because they are underrepresented in the currently approved portfolio and have attributes motivating product use. In this trial, we evaluated an innovative intravaginal ring (pod-IVR) as a platform for HIV pre-exposure prophylaxis (PrEP). To measure the safety and multicompartment pharmacokinetics (PKs) of a pod-IVR delivering tenofovir disoproxil fumarate (TDF) combined with emtricitabine (FTC) in healthy women over 28 days. The Phase 1 clinical trial consisted of a randomized order, controlled, double-blinded, crossover design. Ten women received either an active TDF-FTC pod-IVR or a placebo pod-IVR for 28 days, determined by 1:1 randomization, followed by product crossover for another 28 days. Safety was assessed in terms of adverse events related to product use, colposcopic examination, cervicovaginal epithelium thickness measurement by optical coherence tomography, and culture-independent assessment of the vaginal microbiome. Drug and/or drug metabolite concentrations were measured in cervicovaginal fluid (CVF), vaginal tissue, rectal tissue, rectal fluid, and plasma. There was no evidence of a statistically significant difference in related adverse-event counts between study products. There also was no evidence suggesting the study product altered the vaginal microbiome systematically or reproducibly. Systemic plasma exposure to tenofovir (TFV) and FTC was low, consistent with topical delivery. High median CVF concentrations of TFV (38.9 ng mg-1; 135×103 fmol mg-1) and FTC (239 ng mg-1; 966×103 fmol mg-1) were measured. Median vaginal tissue concentrations of the anabolites responsible for inhibition of HIV reverse transcriptase exceeded our target concentrations: TFV diphosphate 0.651×103 fmol mg-1 and FTC triphosphate 0.180×103 fmol mg-1. Drug concentrations in rectal tissue samples generally were below the analytical lower limits of quantification, but were quantifiable in rectal fluids, 130 (TFV) and 300 (FTC) times lower than in CVF. The TDF-FTC pod-IVRs were safe and well-tolerated over the 28 days of consecutive use. The PK data met the target benchmarks associated with protection from vaginal HIV infection. https://clinicaltrials.gov/study/NCT03255915, identifier NCT03255915.

Efficacy and Tolerability of Tenofovir/Lamivudine/Dolutegravir among Antiretroviral Therapy Naive Human Immunodeficiency Virus Infected Patients of a Tertiary Care Center in Eastern India.

Sengupta Debroop D, Ghosh Sandip S, Pain Shantasil S, Chatterjee Nandini N

Understanding community questions about HIV pre-exposure prophylaxis (PrEP): A thematic analysis of reddit threads to inform development of an AI chatbot for PrEP education.

Vincent-Paulraj Alexandar A, Wood William W, Marzolini Catia C, Chiong Justin J et al.

Despite growing availability of HIV pre-exposure prophylaxis (PrEP), many potential users turn to online forums for advice and information collection. These forums provide a window into real-world questions, concerns and misinformation. They serve as a tool for users to query for sensitive information without revealing their identities. These platforms could therefore be a potential source of understanding of the unmet needs of users. This study systematically analyses the social media posts referring to the four drugs mentioned in the study to identify common questions and thematic concerns among the community and uses this insight to inform the design of an AI-driven, privacy-preserving chatbot for PrEP education based on evidence. Between May 2011 to October 2025, we found 1168 relevant Reddit posts mentioning one of the four names for PrEP therapies, by either brand or generic name: Truvada (Tenofovir disoproxil fumarate + emtricitabine (TDF/FTC)), Descovy (Tenofovir alafenamide + emtricitabine (TAF/FTC)), Apretude (long-acting cabotegravir), Yeztugo (lenacapavir) using a systematic search. We used Natural Language processing (NLP) techniques to understand user needs. Seven distinct discussion themes were identified within PrEP social media discourse, with side effects emerging as the most frequently discussed primary topic among 1076 posts. Across all medications, weight changes were the most frequently mentioned side effect. Truvada was the most frequently discussed PrEP medication. 96.7% of the dataset comprised questions, showing that Reddit serves as a primary information-seeking platform. Early period discussions were emphasized basic access and effectiveness questions, with more recent discussions (2022-2025) displaying increased attention to injectable and long-term safety considerations. Reddit users demonstrate persistent uncertainty about PrEP side effects, drug interactions and medication switching. Drug interactions represented the most frequently identified information gap (26.5% of posts). These empirically derived information needs will inform the design of a privacy-preserving PrEP chatbot trained on authoritative UK sources (hiv-druginteractions.org, BHIVA guidelines, NHS resources).

Preservation of MHC-Ia protective allele suppression of SIVmac239 in aged rhesus macaques.

Marenco Alejandra A, Varco-Merth Benjamin B, Nkoy Candice C, Govindan Aparna A et al.

Major histocompatibility complex class Ia (MHC-Ia)-restricted CD8⁺ T cell responses play a central role in the host defense against HIV-1, with certain MHC-Ia alleles known to be associated with cytotoxic T lymphocyte responses having an increased potential for viral control. However, the impact of immune aging on the effectiveness of such protective alleles remains unclear. In this study, we assessed SIVmac239 replication in aged (17-23 yr old) rhesus macaques (RMs) exhibiting low frequencies of naïve T cells and expanded effector memory T cells, that were further stratified by the presence (MHC⁺) or absence (MHC-) of 3 known "protective MHC-Ia alleles" (Mamu-A*01, Mamu-B*08, or Mamu-B*17). All RMs were infected with SIVmac239 and viral dynamics monitored longitudinally. MHC⁺ RMs demonstrated significantly lower plasma viral loads (PVLs) through 70 d postinfection compared with MHC- RMs. At 70 d postinfection, half of the RMs from each group initiated suppressive triple antiretroviral therapy comprising dolutegravir, emtricitabine, and tenofovir disoproxil fumarate (TDF) for 15 wk, followed by suboptimal TDF monotherapy for an additional 21 wk. While antiretroviral therapy substantially reduced PVL in both groups, viral decline was accelerated in MHC⁺ RMs relative to MHC- RMs. Moreover, upon switching to TDF monotherapy, PVL rebounded by almost 3 logs in MHC- RMs, while MHC⁺ RMs maintained viral suppression. Collectively, these findings indicate that protective MHC-Ia alleles can mediate viral control in aged hosts, even under suboptimal treatment conditions, and highlight the potential role of optimized CD8+ T cell responses in strategies targeting viral persistence in aging populations.