Case report of short-term HIV remission from adding oral nicotinamide to intensified ART

22 July 2020. Related: Conference reports, Cure-related research, World AIDS 23 Virtual 2020.

Simon Collins, HIV i-Base

An HIV cure study from Brazil presented early news from the AIDS2020 virtual conference.

This included an HIV positive man who has stayed off HIV treatment for more than a year without viral rebound after using oral drugs that added nicotinamide to intensified antiretroviral treatment (ART). The same response was not seen in four other people using this intervention.  [1]

Overall, the study included 30 participants randomised to one of five different interventions, or to a control group that only used ART. Results were presented by Ricardo Diaz from University of Sao Paulo.

The case involved a 35 year old man who was diagnosed HIV positive in 2012 with a CD4 count of 372 cells/mm³ and viral load of 20,000 copies/mL. He started ART with efavirenz/AZT/3TC and maintained undetectable viral load, switching NRTIs to TDF/FTC after two years.

In 2015 after joining this study (when CD4 count was 720), nicotinamide was added and ART was intensified by adding dolutegravir and also maraviroc (which might also induce HIV transcription and cell activation). Nicotinamide is an HDAC inhibitor that has multiple mechanism of action that might to induce HIV transcription, cell activation and latency reversal. [2]

ART was given at standard doses and nicotinamide at 500 mg twice-daily, all for 48 weeks. Routine ART was then continued for another three years before an analytic treatment interruption (ATI) in March 2019. Of note, total HIV DNA was not detectable in PBMCs just before the treatment interruption.

His viral load has remained undetectable for 64 weeks. However, HIV antibody titres declined during the intervention and on regular ART afterwards and were not detected during the ATI.

The results were presented as extremely preliminary, requiring further follow-up to determine how long they might continue and also that the single case could not show that any of the interventions were directly responsible for the outcomes.

Other interventions in the study include a dendritic cell vaccine using autologous HIV and auranofin (to decrease the ratio of long-lived central memory/transitional memory CD4+ T-cells). One arm includes all four interventions (ie also including ART intensification and nicotinamide). [3]

The presentation is due to be live on Wednesday 8 July at 14.24 (PDT) as a prime channel live session.

comment

This report is still tentative, with many of the expected investigations (testing lymph samples etc) being delayed due to restricted research during COVID-19.

As with most things that seem to good to be true, this might prove to be the case here. Even if this individual remains in remission, this might be more due to an individual Visconti-like response this strategy producing a cure. This is especially as a similar response was not seen in the other four participants in this arm and that treatment intensification and the use of HDAC inhibitors have not been particularly effective interventions in other studies.

The full study was presented the following day and a more detailed analysis from Richard Jefferys is included in the next article. [4]

It is a shame that IAS continues to release important scientific news by press release rather than giving researchers an appropriate time to first present their results in full. As a result, the headline news in both mainstream and community media have already reported the conclusions, before the detailed results have been presented.

References

1. Diaz R et al. The first long-term remission of chronic HIV-1 infection without myeloablation? AIDS2020. OAXLB0105
   https://cattendee.abstractsonline.com/meeting/9289/presentation/3496
2. Samer S et al. Nicotinamide activates latent HIV-1 ex vivoin ART suppressed individuals, revealing higher potency than the association of two methyltransferase inhibitors, chaetocin and BIX01294. The Brazilian Journal of Infectious Diseases 24(2);150-159. (March – April 2020).
   https://doi.org/10.1016/j.bjid.2020.01.005
3. ClinicalTrials.gov. Multi interventional study exploring HIV-1 residual replication: a step towards HIV-1 eradication and sterilizing cure. NCT02961829.
   https://www.clinicaltrials.gov/ct2/show/NCT02961829
4. Jefferys R. New HIV remission case report at AIDS 2020: full report. HTB (22 July 2020).
   https://i-base.info/htb/38408

The report was first posted on 7 July 2020.