Jillian Lau
Clinician researcher in Melbourne 🇦🇺🐨
All about HIV cure
NHMRC EL1 Fellow
- More on the reservoir. The AGING cohort in Argentina (defined as 50 or older!!!) looked at total DNA and pro-inflammatory cytokine profiles longitudinally over 1 year. No changes but a short follow up time. I’d be interested in following this cohort over time w longer follow up analyses #IAS2025
- This #IAS2025 poster looked at the #HIV reservoir in the Rakai cohort Uganda, measured w QVOA. As we know, QVOA < total HIV DNA. Interestingly QVOA doubled over 5 years for women in the cohort pre- and post-menopause. More evidence that female sex hormones impact reservoir. IPDA data coming
- Always an excellent and engaging speaker Katie Bar, #IAS2025 Track A rapporteur summarises 3 days packed with science in 14 minutes. What an amazing job! Check out the recording for a really nice overview of the basic sciences presented here in Kigali
- #HIVcure in the poster hall at #IAS2035 on Thursday! Social & behavioural research done as part of FRESH cohort #ATI study in Africa. So important to include this work w the biomedical analysis. Family & partners of study participants underwent in-depth interviews - concerns raised abt risks
- Qualitative interviews and quantitative surveys on mental health, decision making certainty, self esteem and resilience were performed at multiple timepoints on the FRESH cohort participants. The investigators stress the importance of conducting mental health assessments throughout these trials
- Reposted by Jillian Lau[Not loaded yet]
- AGT-103-T: autologous gene modified CD4 T cells via lentiviral vectors #HIVcure clinical trial with #ATI - increased and sustained T cell expansion and on second ATI smaller viral rebound and quicker resuppression.
- Modified IPDA (because of the lentiviral vector) demonstrated sustained reduction in intact provirus even if plasma viral load increased and necessitated restart ART
- More from @westmeadinst.bsky.social at #IAS2025 at the cutting edge Basic Science session Josefina Marin presents on IMAP (immunoinformatic analysis pipeline) which selects peptides found within >85% Los Alamos database) - known as IMAP peptides.
- Rebound virus from participants of the PULSE study #ATI was sequences and IMAP peptides are found in 90-100% Their peptide pool able to trigger immune responses in transient virus controllers, response varies between donors
- So there have been a few #HIVcure clinical trials recently w dual long acting bNAbs 3bnc117+101074 -RIO: acute treated all male cohort mainly subtype B, Europe -FRESH: acute Rx, + VES, all female, SSA -Caskey study: chronic Rx + N803, USA -PAUSE: SSA majority female no bNAb sensitivity screening
- All and primary endpoints of viral rebound at 20-24 weeks. When long acting bNAbs will still be circulating. The studies that have presented #ATI data have shown distinct patterns of rebound - quick - delayed - vascilating with some control
- CAR-T cells are hot right now in #HIVcure science. These cells can engineered to recognise HIV antigens to be used as a “shock & kill” agent. Fabulous summary of where we are at with CAR-T at #IAS2025 Currently studied in a few phase I safety clinical trials.
- Challenges in CAR-T cell therapy for #HIvcure and opportunities to address these issues
- Several strategies explored to improve CAR-T cell activity in HIV
- A really nice summary of where CAR-T cell therapy in #HIVcure is at. Briefly - promising but a while to go to address issues including lack of HIV antigens in PLWH on ART I’ll be coming back to relisten to this talk!
- #IAS2025 ICHESA study looking at NK cell function in elite controller compared to non-controllers Elite controllers have distinct NK cell profiles and understanding mechanisms of immunological control in elite controllers can teach us a lot for #HIVcure
- Another #HIVcure #ATI study from Southern Africa: PAUSE study a 3bnc117 & 101074 LS-J versions. bNAb screening NOT conducted pre-enrolment Primary endpoint again is viral rebound at 24w when therapeutic bNAb levels are still circulating - like RIO & Marina Caskey’s bNAb study presented yesterday
- N=32 majority female 16 reviewed by safety monitoring committee and 2/3 had experienced viral rebound by week 12. Possibly indicating subtype C virus not sensitive to the bNAbs? Study stopped enrolment as per pre-specified criteria. Further virology immunology and reservoir data to follow
- In the immunological control for #HIVcure session at #IAS2025, my friend @jespergunst.bsky.social presents beautifully about what we know & what we don’t know about predictors of post treatment control & post intervention control with a shout out to the HIV reservoirs consortium.
- Poster for the FRESH cohort ATI study mentioned at the #IAS2025 #HIVcure preconference. Single arm toll like receptor agonist + 2 bNAbs w ATI in acute treated women w HIV This poster looked at VES pharmacodynamics and immune activation.
- Study from Aus 🇦🇺🐨🦘 in the poster hall #IAS2025 Our friends at @westmeadinst.bsky.social looked at cells from blood & pleural effusion fluid from people w HIV w active pleural TB. TB coinfection impairs HIV specific CD8 T cells causing more genetically intact provirus in pleural effusion cells.
- Implications for #HIVcure? TB/HIV is an incredibly common coinfection and we need to understand sites and mechanisms of persistence if we are to address barriers to a cure
- Whoops what did I do to my photo??? Here is the poster
- #HIVcure in the poster hall at #IAS2025 on Wednesday This poster from Duke Transplant Centre highlights the HOPE Act in USA: 500 transplants in PLWH receiving organ transplants from HIV+ donors. This is a rich opportunity to biobank discarded lymphoid tissue from the operation for research
- #HIVcure in the poster hall on Tuesday at #IAS2025 This Thai cohort started on ART very very early in #HIV infection - Fiebig stage I-V. 5 years after brief ATI clinical and psychosocial outcomes were compared b/w those who underwent #ATI vs those who declined to do so
- No differences found between cohorts for CD4 & CD8 trajectories, viral blips, adverse events, or “mood outcomes”. No reservoir work done or HIV specific immune responses. I would like to see time to viral resuppression data somewhere but assuming everyone resuppressed on ART restart
- Of note, one death from depression-related suicide >3 years post #ATI.
- Gus Valen in the innovative virology section - from DIPS to TIPS. His team engineered a therapeutic from a natural process that causes viral load vascilations in plasma. Tested in monkey model - single dose TIPS led to lower viral set point. Track A #IAS2025
- Marina Caskey at the #bNAb session at #IAS2025: 2bNAbs - 3bnc117-LS and 10-1074-LS and N-803 (immunotherapy)
- No bNAb screening pre-enrolment bNAbs administered IV, n-803 given IM. No major safety concerns but not unexpected injection site reactions with n-803. Viral rebound data compared to RIO (dual bNAb study presented at CROI)
- 3 participants remained off ART at wk 72 timeline. One chose to go back on ART virus despite control off ART.
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View full threadtotally worth mentioning in Marina’s talk - 2 of the study participants were taking ART during #ATI! Without the investigators being aware of it. Picked up on ARV levels done frequently during the protocol. Definitely something that needs to be discussed in consent & future -#HIVcure trials
- Joseph Eron - LEN plus 3bnc117 and 101074 (bought by Gilead and now “TAB and ZAB”). I think this was a TREATMENT study. 6 monthly dosing of LEN TAB and ZAB. 3 virological failures (but Joseph using the wording of viral rebound as if the participants underwent treatment interruption).
- No changes in HIV specific CD4 and CD8 T cells over time. Even in the participants who had viremia. My take - this study shows TAB ZAB & LEN look good for treatment (6 monthly infusion/injection) but demonstrates that to trigger immune responses & functional cure, more antigen needed (ie viremia)
- Zoe Stylianidou shows how her group’s hybrid CAR-T cells were able to secrete bNAbs in cell line models and also induce NK cell degranulation
- In vitro humanised mouse model had lower plasma viral loads after administration of their hybrid CAR-T cells with detection of bNAb in plasma. Exciting and impressive work done in Zoe’s PhD!
- Fabulous talk by Katie Bar about her team’s efforts to find complementary bNAbs that can be used together much like the work horses in the field - 3bnc117 and 101074. They’ve found some candidates and hopefully they have broader application and efficacy, particularly in non-subtype B HIV
- Track A session on strategies targeting the #HIV reservoir at #IAS2025! Marina Tuyishme presenting on the impact of latency reversal agents (LRAs) in blood and lymph nodes in people with and without HIV. Detailed analysis of the reservoir including transcriptomic data
- Rory Shepherd from our lab not looking at all stressed while presenting about the impacts of psychological stress on the latent HIV reservoir. Always an engaging and entertaining speaker ⭐️
- Rory shows us evidence of latency reversal and HIV transcription in a clinical trial of participants samples before during & after induced psychological stress, with no changes to the size of the reservoir measured by total HIV DNA
- #HIVcure front and centre at #IAS2025. The plenary session of Day 2 of the conference starts with an overview of immunological strategies towards an HIV cure, including an update on the San Fransisco and Esperanza exceptional elite controllers
- Studying elite controllers(EC): EC has HIV integrated into non-genic or transcriptionally silent parts of the genome more so than non-EC with clones seen across blood and lymph nodes
- Xu Yu (the opening plenary speaker) highlights how much we can learn from studying elite controllers, people on long term ART (over 20 years), and comparing sex difference between females and males
