ACTG launches alendronate trial to test HIV reservoir clearance
ACTG, the world's largest HIV-focused clinical trials network, has opened enrolment on STAIR-HIV, a randomised double-blind placebo-controlled study assessing whether alendronate, a bisphosphonate routinely prescribed for osteoporosis, can reduce the latent HIV reservoir in people living with the virus whose viral load is controlled by antiretroviral therapy.
The trial, formally designated A5428, will enrol 30 participants aged 18 to 65 who have been on ART for between one and ten years and are virally suppressed. Twenty participants will receive 70 mg of oral alendronate weekly; ten will receive a matched placebo. Treatment runs for 24 weeks, with an eight-week follow-up period to assess whether any reservoir effects persist after the intervention concludes. At least a quarter of enrolled participants are expected to be women, reflecting a deliberate effort to improve demographic representation in HIV cure research.
Scientific rationale
The hypothesis behind STAIR-HIV is grounded in earlier ACTG work. Study A5163, which examined alendronate's effect on bone mineral density in people with HIV, yielded an exploratory finding that the drug also reduced total HIV DNA levels in stored samples. Because A5163 was not designed to measure reservoir effects, that observation could not be treated as definitive. STAIR-HIV was created specifically to test the question under controlled conditions.
A subset of participants will undergo sigmoidoscopies before and approximately 22 weeks into the study to assess the impact of alendronate on HIV reservoir levels in gut tissue, where a significant proportion of latent virus is known to reside. The inclusion of mucosal sampling marks the study as more procedurally intensive than standard clinical trials, which is why it sits within ACTG's Small Clinical Trials Advancing HIV Remission and Cure pathway, a dedicated infrastructure channel for experimental, single-site or limited-site cure studies.
"STAIR-HIV seeks to translate years of systematic work into what could become an important component of future cure strategies for people living with HIV," said Joseph J. Eron, ACTG Chair and professor at the University of North Carolina. He was careful to note that the trial does not promise a standalone cure, framing the goal as understanding whether modulating metabolic and immunological pathways in the reservoir can advance the field toward durable remission.
Market and competitive context
The latency-reversing agent field has attracted sustained research interest over the past decade, with candidates including histone deacetylase inhibitors such as vorinostat and romidepsin, toll-like receptor agonists, and protein kinase C activators having been evaluated in earlier ACTG and academic studies. Results to date have been mixed: many candidates successfully perturb the reservoir in vitro but have failed to produce meaningful reductions in vivo. Alendronate's mechanism is distinct from these approaches, acting partly through modulation of osteoclast activity and downstream immune signalling pathways, which may affect the myeloid and lymphoid cells that harbour latent HIV.
The NIH's NIAID and NIMH are co-funding STAIR-HIV alongside the broader ACTG infrastructure grants, meaning the study does not depend on commercial sponsorship. That independence matters: if alendronate, an off-patent generic, shows reservoir activity, the finding would be immediately relevant to combination cure strategies without the pricing or access complications that typically accompany novel investigational compounds. The next key milestones will be interim mucosal biopsy data and, ultimately, the primary reservoir readout expected after the 24-week treatment period concludes.