CROI 2025: LAPTOP, EC rebounds after 32 years, two more HSCT cures

12 April 2025. Related: Conference reports, Antiretrovirals, Treatment strategies, CROI 32 San Francisco 2025.

Simon Collins, HIV i-Base

The following shorted reports link to important posters and presentations that should now be available online.

Further studies will be added to these reports this week.

• LAPTOP study: INSTI- vs PI-based ART in very advanced HIV
• Long-term elite controller becomes detectable after 32 years
• Two new cure cases following stem cell transplants

LAPTOP study: INSTI- vs PI-based ART in very advanced HIV

Results from a large randomised open-label European study reported bictegravir/FTC/TAF (B/F/TAF) to be non-inferior to darunavir/cobicistat/F/TAF (D/C/F/TAF) in 442 participants starting ART during advanced HIV infection. This was an independent investigator study as part of the NEAT network.

This was based on a composite primary endpoint of viral load >50 c/mL at week 48, viral reductions < 1 log by week 12 and clinical events. The failure rate was relatively high at 23% vs 33% in the modified ITT analysis [adj HR 0.70 (95%CI: 0.48 to 1.00), p=0.052] in favour of B/F/TAF.

Viral failure and insufficient viral response were both significantly less common with B/F/TAF: 13% vs 23% (p=0.013) and 12% vs 23% (p=0.014), respectively. Side effects were also less common although this was driven by low-level grade 1 and 2.

This was notable for being a very advanced cohort. The median CD4 count was only 41 (IQR: 17 to 79) and 85% had baseline CD4 less than 100 cells/mm3. Median viral load was 400,000 with 44% (n=197) >500,000 copies/mL. Participants were 80% men, 62% white and 18% Black.

Please see online poster for further details, although resistance data and responses to second-line were not yet available.

Ref: Integrase Inhibitor- Versus Protease Inhibitor-Based Therapy for People With Advanced HIV Disease. CROI 2025. Poster abstract 658.
https://www.croiconference.org/abstract/3751-2025/ (abstract and poster)

Long-term elite controller becomes detectable after 32 years

Details of an elite controller in Spain (heterozygous for CCR5 delta-32) who was diagnosed in 1985 and with a recorded HIV history from 1990.

Subsequent longitudinal viral load results (n=16 from 19 to 37 years after diagnosis) were persistently undetectable except for four low level blip results <150 copies/mL.

Viral load significantly rebounded in December 2016 and he started ART in October 2021 with a CD4 count <500 cells/mm³.

The poster reports viral changes ver time, including dynamic changes in the reservoir with HIV DNA showing that 95% of these cells contained defective virus.

Ref: Loss of Virologic Control 32 Years After HIV-1 Diagnosis in an Exceptional Elite Controller. CROI 2025. Poster 494.
https://www.croiconference.org/abstract/2382-2025/ (abstract and poster)

Two new cure cases following stem cell transplants

Two posters presented details about two cases of HIV cure following haematopoietic stem cell transplantation (HSCT).

The first case was notable for viral load becoming detectable and rebounding after HSCT which subsequently became undetectable.

This was a 67-year-old man with acute myeloid leukemia (AML) who received successful reduced-intensity HSCT from a 10/10 CCR5∆32/∆32 matched unrelated donor.

After 12 months wild-type CCR5 DNA was undetectable in PBMC and HIV antibodies levels similar to HIV negative controls. However, after stopping ART, viral load rebounded to 780 copies/mL at week 8 but there was no cell-associated RNA or DNA in PBMCs (< 0.14 copies/million) which remained 100% donor.

ART was restarted for the next two years, and after a second interruption viral load has remained undetectable for 7 months.

The second case, the Oslo patient, is a 58-year-old male who had been diagnosed and on ART for 14 years who underwent HSCT for myelodysplastic syndrome.

This case was notable because the donor was his HLA-identical brother who was homozygous for CCR5 delta-32 compared to the heterozygous recipient who carried CCR5 delta 32/wild-type. He developed severe acute graft versus host disease (GvHD) and had complete donor chimerism in peripheral blood by day 90.

Post HSCT viral load HIV RNA remained undetectable and ART was stopped after two years. No replication competent virus was detected in 65 million CD4 cells.