Asuptegravir Lowers HIV-1 RNA up to 2.36 Logs in Early Monotherapy

Asuptegravir (Jiangsu Aidea Pharmaceutical), an investigational integrase strand transfer inhibitor, reduced HIV-1 RNA by 1.49 to 2.36 log10 copies/mL after 10 days of monotherapy in treatment-naive people with HIV, with a clear dose-response relationship.¹ Hong Qin, MD, PhD, chief medical officer of Aidea, presented phase 1 and phase 1/2 data at IDWeek 2026, held October 21-24 in Washington, DC.^1,2 A third poster reported final 48-week results from the RECOVER study of fostemsavir in immunologic nonresponders.³

Asuptegravir is metabolized by UGT1A1 and is being evaluated alongside emtricitabine and tenofovir alafenamide (FTC/TAF).² Immunologic nonresponders, defined as people with CD4+ T-cell counts persistently below 350 cells/mm³ despite at least 2 years of viral suppression, face higher risks of AIDS progression, non-AIDS events, and death.³

Asuptegravir Antiviral Activity and Pharmacokinetics in Phase 1 and 1/2 Trials

In the phase 1/2 study, treatment-naive adults with HIV-1 were assigned to 3 dose cohorts (5, 40, or 80 mg; n = 12 each) and randomized 5:1 to asuptegravir or placebo for 10 days.¹ All participants then received open-label asuptegravir plus FTC/TAF for 18 days, including those who had received placebo. HIV-1 RNA declines at day 11 were significant for every dose vs placebo (P < .001), with a dose-response trend (P < .001).¹

After combination therapy, mean HIV-1 RNA declines at day 29 reached 2.81 to 2.83 log10 copies/mL, with no significant difference by dose (P = .929).¹ Virologic suppression below 50 copies/mL at day 29 occurred in 9 of 10, 9 of 10, and 8 of 10 participants in the 5-, 40-, and 80-mg groups, respectively.¹

Viral load declined by 0.15 to 0.25 log10 copies/mL per day through day 11 and 0.10 to 0.11 per day through day 29.¹ Steady state was reached after 3 to 4 days of once-daily dosing, and adverse events were similar to placebo, with no discontinuations.¹

In the phase 1 healthy volunteer study, single doses of 5 to 120 mg produced a median time to peak concentration of 3.00 to 3.84 hours and a mean half-life of 10.49 to 13.12 hours.² Food increased peak concentration by 73.6% and 24-hour exposure by 65.5%, while FTC/TAF did not significantly affect asuptegravir pharmacokinetics.²

Treatment-related adverse events occurred in 11.1% of participants across the phase 1 studies, with no deaths or grade 3 or higher serious adverse events.² The investigators also built a physiologically based pharmacokinetic model to project antiviral activity in people with HIV.²

RECOVER 48-Week Results for Fostemsavir in Immunologic Nonresponders With HIV

RECOVER (NCT05220358) was a prospective, open-label study adding fostemsavir (Rukobia; ViiV Healthcare) 600 mg twice daily to the existing regimens of 25 virally suppressed immunologic nonresponders.³ Each participant served as their own control, contributing CD4+ T-cell data from the 2 years before fostemsavir. Eligible participants had CD4+ counts always below 350 cells/mm³ despite at least 2 years of suppressive therapy.³

At week 48, mean and median CD4+ T-cell counts increased by 38 cells/mm³ (P = .015) and 28.7 cells/mm³ (P = .016), respectively, compared with pre-fostemsavir values.³ The rate of CD4+ T-cell gain rose from 1.25 to 3.93 cells per month (difference, 2.68; P = .047). Change in CD4/CD8 ratio was not significant (+0.012; P = .495).³

Male sex, non-Hispanic ethnicity, and baseline CD4+ T-cell counts below 200 cells/mm³ were associated with larger gains.³ The investigators cited in vitro data suggesting temsavir may limit immune activation driven by gp120 and protect uninfected CD4+ T cells.³ Incomplete immune reconstitution has been linked to persistent immune activation, reduced CD4+ T-cell production, and greater T-cell exhaustion.³

The investigators noted the small sample size and lack of a randomized control group as limitations, and a biomarker substudy is planned.³ Qin disclosed a board role and ownership interest in Aidea, which developed asuptegravir.¹

References

1. Qin H, Zhang F, et al. Viral kinetics, pharmacokinetics, and exposure-response analysis of monotherapy of multiple ascending dose asuptegravir, a new-generation integrase strand transfer inhibitor, followed by combination with emtricitabine and tenofovir alafenamide in treatment-naive people living with HIV-1: a two-period, randomized, placebo-controlled phase 1/2 study. Presented at: IDWeek 2026; October 21-24, 2026; Washington, DC. Poster P-231.

2. Qin H, Zhang F, et al. Pharmacokinetics, predicted antiviral activity, and safety of single-ascending-dose asuptegravir, a new-generation integrase strand transfer inhibitor, in healthy adults: a two-period, randomized, placebo-controlled phase 1 study. Presented at: IDWeek 2026; October 21-24, 2026; Washington, DC. Poster P-230.

3. Rolle CP, Castano J, Nguyen V, Hinestrosa F, DeJesus E. Immune recovery following the addition of fostemsavir in virally suppressed immunologic non-responders living with HIV: final 48-week results from the RECOVER study. Presented at: IDWeek 2026; October 21-24, 2026; Washington, DC. Poster P-220.