DELILAH trial in 60 people with HIV will test whether switching to an islatravir combination pill changes their biological age

DELILAH trial in 60 people with HIV will test whether switching to an islatravir combination pill changes their biological age

The University of Texas Health Science Center at Houston (UTHealth Houston) has registered a trial in which 60 adults whose HIV is suppressed by treatment will either switch to a doravirine/islatravir pill or continue their current treatment. After 24 weeks, their biological age will be compared using an epigenetic clock, an algorithm that estimates age from chemical marks on DNA. The ClinicalTrials.gov record for NCT07871552 was posted on October 13, with the trial scheduled to start on October 30.

The protocol focuses on LINE-1, a mobile segment of the genome called a retrotransposon. LINE-1 copies itself through an RNA intermediate and inserts the copy at a new location. This process requires reverse transcriptase, an enzyme that makes DNA from RNA. LINE-1 encodes its own reverse transcriptase, and HIV uses the same type of enzyme. As cells age, LINE-1 becomes less effectively suppressed, and its DNA copies in the cytoplasm trigger an interferon response and inflammation, much as a viral infection does. Nucleoside analogues are a class of HIV drugs that substitute for a building block in a growing DNA strand and terminate it. Experiments in 2011 showed that four of these drugs, including lamivudine, inhibit LINE-1 reverse transcriptase and reduce LINE-1 copying in cells; in 2019, John Sedivy’s group showed that lamivudine reduces the interferon response and inflammation in old mice.

A February preprint (a manuscript that has not yet been peer reviewed) describes an experiment involving 99 retired sled dogs. The dogs received lamivudine or placebo for about 30 months. In females, lamivudine temporarily slowed the epigenetic clock, but the effect disappeared after treatment stopped.

The closest preceding human study to DELILAH is a March preprint whose authors include Kristine Erlandson, the DELILAH contact at the University of Colorado. Using blood samples from two earlier trials, the authors calculated epigenetic clock measures in healthy people aged 18 to 50 without HIV after 12 weeks of treatment with two combinations of nucleoside analogues. Among 36 people taking emtricitabine with tenofovir alafenamide, the pace of aging measured by DunedinPACE decreased by 0,061 years per year, while age estimated by a clock calibrated to mobile genomic elements decreased by 2,78 years, a result at the threshold of statistical significance. Among 43 people taking emtricitabine with tenofovir disoproxil, no significant changes were found. The authors suggest that the determining factor is the “concentration of tenofovir diphosphate inside immune cells.” This is the drug’s active form in the blood cells whose DNA is used to calculate the clock measures. This concentration is approximately seven times higher with alafenamide than with disoproxil.

Islatravir is also a nucleoside analogue that inhibits HIV reverse transcriptase. The pill combines it with doravirine, another HIV drug (0,25 and 100 mg, respectively). The pill is taken once daily. After a single 30 mg dose of islatravir, the concentration of its active form in blood cells falls by half over 8,1 days. On April 21, 2026, the FDA approved the pill for adults with suppressed HIV. Coadministration with lamivudine or emtricitabine is contraindicated because these drugs can substantially reduce the concentration of islatravir’s active form.

DELILAH has three groups. The first will switch to the pill from a regimen containing lamivudine or emtricitabine together with tenofovir. The second will switch to the pill from regimens without nucleoside analogues, and the third will continue their current treatment. Epigenetic clock measures will be calculated from blood DNA at baseline and at week 24. Comparisons between the groups will test whether changes in biological age depend on the previous regimen. The protocol assesses LINE-1 activity through its downstream effects: its stated aim is to measure biological age “as downstream indicators of LINE-1 retrotransposon activity.”