The AIDS Clinical Trials Group (ACTG) is evaluating alendronate, a widely used oral osteoporosis drug, as a potential latency-reversing therapy in people with HIV after an earlier ACTG study unexpectedly found reductions in total HIV DNA among participants receiving the bisphosphonate. The 30-patient STAIR-HIV study will prospectively test whether once-weekly alendronate can reduce the persistent viral reservoir in people whose HIV is suppressed by antiretroviral therapy.
The hypothesis emerged from ACTG study A5163, which originally evaluated weekly oral alendronate for bone mineral density rather than HIV persistence. A subsequent analysis of stored samples found reduced total HIV DNA among alendronate recipients, prompting investigators to design STAIR-HIV as a prospective, placebo-controlled test of the finding.
The trial enrolls participants receiving antiretroviral therapy (ART). Alendronate inhibits farnesyl pyrophosphate synthase, an enzyme in the mevalonate pathway, disrupting protein prenylation involved in cellular signaling. Investigators are testing whether effects on this pathway can induce HIV expression from latently infected cells and ultimately reduce the persistent viral reservoir, although the mechanism underlying the HIV DNA reduction observed in A5163 remains under investigation.
No therapy has been approved specifically to reduce the latent HIV reservoir. Previous latency-reversing approaches have included HDAC inhibitors such as vorinostat and romidepsin, which demonstrated that HIV transcription could be induced during suppressive ART but did not produce substantial reservoir reductions. Alendronate targets a different cellular pathway and enters prospective testing after the signal observed retrospectively in A5163.