Overcoming barriers, driving progress: Clinical science at IAS 2025

Introduction The 13th IAS Conference on HIV Science, held in Kigali, Rwanda (13-17 July 2025), highlighted key advances in clinical research. Presentations focused on sustaining HIV treatment and prevention amid financial constraints, innovations in long-acting oral antiretrovirals, and the management of comorbidities and co-infections, particularly tuberculosis (TB) and mpox. Discussion Significant progress was reported on long-acting oral antiretrovirals, including a weekly treatment regimen and a promising monthly option for pre-exposure prophylaxis. These strategies could expand the current antiretroviral therapy (ART) portfolio to better meet individual needs. Additionally, the use of currently available long-acting regimens in non-suppressed individuals warrants further exploration, supported by growing evidence of their potential in this clinical context. Intermittent ART, previously studied as a means to reduce toxicity, is now gaining attention as a potential cost-saving strategy. However, more research is needed to define its role across diverse settings. While data from high-income countries is encouraging, results have been less favourable in resource-limited settings and among key populations such as adolescents. Two-drug and injectable regimens, increasingly used and supported by international guidelines in high-income settings, are now being explored in resource-limited contexts and incorporated into clinical guidelines-narrowing the gap between recommendations for high- and low-income regions. As the ART portfolio evolves towards regimens without tenofovir, hepatitis B reactivation emerged as a key topic at the conference. Management of TB, a long-standing clinical challenge, was also addressed in Kigali with trial data supporting early empiric TB treatment and the safety of same-day ART initiation in selected clinical scenarios. The UNITY trial on tecovirimat for mpox treatment showed no significant clinical benefit, underscoring the need to revise current management guidelines. Research on comorbidities examined ART-associated weight gain, showing that switching ART once obesity is established has a limited impact on weight outcomes. Studies in paediatric populations highlighted predictors of treatment failure and the benefits of dolutegravir-based regimens. Conclusions In the face of growing economic pressures, innovation in HIV treatment and prevention remains essential. The conference emphasized the importance of sustainable public health strategies and individualized care approaches to ensure continued progress in the global HIV response.