ASHM Report Back

Clinical posts from members and guests of the Australasian Society for HIV, Viral Hepatitis and Sexual Health Medicine (ASHM) from various international medical and scientific conferences on HIV, AIDS, viral hepatitis, and sexual health.

Christina Chang

Christina Chang

Christina is an infectious diseases physician at The Alfred Hospital and an NHMRC postdoctoral research fellow at The Doherty Institute. She currently works on understanding the establishment of the HIV reservoir and strategies for its eradication. Christina conducted her PhD on cryptococcal meningitis, HIV and IRIS based in South Africa.

I missed the START session as I was presenting and noticed there's no ASHM blog on what is a tremendously important study, hence thought I'd quickly rectify this. You will all recall the landmark SMART study published in NEJM in 2006 where they enrolled 5472 HIV-infected patients,  with a CD4 of >350 into an RCT with a a drug conservation arm (start when CD4 <250, stop when >350) and a viral suppression arm where they started ART immediately and didn't stop. The drug conservation arm was associated with increased risk of opportunistic infections, increased death from any cause and increased major cardiovascular, renal and hepatic diseases. We learnt then that drug holidays were unwise, and we needed to start ART earlier.   

Since then, we have had some strong observational data and implied data through basic science research suggesting starting at an even more robust CD4 was wise. Earlier ART not only reduces OI and complications but also improves CD4 recovery and reduces the HIV viral reservoir etc. The US for instance has been recommending for early ART in all patients for a number of years. We have been somewhat slow in adopting this.   

The START study now gives unequivocal data that all patients should start ART regardless of their CD4 count. In brief, they enrolled 4685 HIV-infected patients with CD4s >500 in 35 high-income and resource-limited settings. This study was stopped by the data and safety monitoring board in May 2015 as interim analysis showed their primary outcome had been met. The median VL was 12749, and median CD4 was 651. The composite primary end point (any serious AIDS-related event, serious non-AIDS-related event, or death from any cause) occurred in 42 patients in the immediate-initiation group (1.8%) as compared with 96 patients in the deferred-initiation group (4.1%); hazard ratio of 0.43. Frequency of TB, Kaposi, lymphoma, and cancer were lower in the immediate arm. The risks of a grade 4 event were similar in the two groups, as were the risks of unscheduled hospital admissions. You will find the full paper in this week's NEJM.

The TEMPRANO study, also published in the same NEJM issue, enrolled HIV-infected patients with a CD4<800 in Cote d'Ivoire. They examined the role of immediate vs deferred ART and isoniazid prophylaxis in comparison to WHO guidelines. They found that immediate ART and 6 months of IPT led to reduced rates of severe illness overall and also among those with CD4 >500. 

WHO will be publishing new guidelines recommending ART for ALL. We will need to reflect on how we can do this better (and quicker) in Australia. What is the lag time from acquisition to testing; from testing to diagnosis; from diagnosis to treatment?? San Francisco General Hospital is able to start ART within 24hours in patients with newly diagnosed HIV. The Thai group led by Dr Aranowich are able to start ART at acute HIV infection. The TEMPRANO group was able to do this is Cote d'Ivoire. How will we respond in Australia?????

 

 

 

 

Tagged in: IAS2015

Most of you may have already heard/ read/ watched Saez-Cirion's presentation on Monday 20th July where he presented data on a new post-treatment controller. To recap: 

Born at 37(+5d)/40 and mum on mono ddC since 13/40 with uncontrolled viremia 4.63M RNA copies, CD4 T-cells 81 and CD4/8 ratio 0.16. Baby was given ZDV prophylaxis immediate, RNA was undetectable at d3 and DNA ind at d3, d14 then positive at W4. ZDV was unfortunaelt interrupted at W6 and HIV-RNA reached a peak of 2.1x106 copies/ml at 3 months of age when cART (zidovudine, lamivudine, didanosine, ritonavir) was initiated. HIV-RNA was undetectable one month later and remained below assay-detection limits while on cART, except at 15 and 21 months of age. Between 5.8 and 6.8 years of age cART was discontinued by the family but HIV-RNA was undetectable when the child returned to clinical care at 6.8 years of age and cART was not resumed. HIV-RNA has remained < 50 copies/ml for more than 12 years except for 2 blips. This was not due to HLA type and raised the possibility if a defective provirus or an immune mediated phenomenon. 

Locally in Melb, we've seen a few unique post treatment controllers and elite controllers recently and are currently interested in exploring their immunological, virological and HLA features. You may have seen a few in your practice too and we'd be interested to hear from you. 

 

There was also some debate about the role of structured treatment interruption in this meeting. See also "ultrastop" data (Katlama). Should we risk-stratify? Do we know how to risk-stratify? Is it safe? How closely should we monitor? Is it necessary?

Tagged in: IAS2015

Those interested in the concept of post-treatment controllers and treatment remission, please head to Saez-Cirion's (of Visconti fame) presentation tomorrow (Monday 20 Juyl) at the 11am - persistently seeking virus. I will write a detailed post after the session as this abstract is currently under embargo.

Tagged in: IAS2015

Greetings from Vancouver IAS 2015! Reporting back after Day 1 of the 2-day IAS Cure symposium. 

Our key speakers today included:

  • Dan Kuritzkes who gave a nice overview of the progress and challenges in HIV cure research
  • John Mascola on neutralising antibodies including bispecific (combination) antibodies and the "ideal" antibody - cheaper, longer half life, subcutaneous delivery, more potent, greater breadth. There are two good sessions on neutralising antibodies MOBS03 on 20 July 11am and WESY06 on 22 July for those interested in this topic. Both should be terrific sessions.
  • Marcus Altfeld spoke about immune recognition following latency reversal, and drew on his expertise on NK cells. They have a new nef inhibitor.
  • Matthew Sharp - reminded us to keep the community engaged and also highlighted a great resource CUREiculum http://www.avac.org/cureiculum. Take a look.

We had two "roundtables" today: one on paediatric HIV cure research and the other on combination therapy. There was robust discussion about the need to advance cure research in paediatric children in parallel with adults, but at the same time being sensitive to the issues of risk and acceptability. Some of the most interesting work in HIV cure research is being done in hyper-acute/ very-very early commencement of ART in paediatrics with the aim to reduce the establishment of the latent HIV viral reservoir, +/- in combination with neutralising antibodies +/- structured treatment interruption. Did you know there is an infant monkey model? Well, there is!

Some new ideas presented today included Ingenol a Protein kinase C inhibitor (Planelles), and CD4 mimetics (Finzi), AGS004 a fully autologous DC-based immunotherapy electrophorated with autologous HIV RNA and genetic differences in the reservoir (Karn). 

 

David Evans from Project Inform reminded us on the need to manage the excitement about progress in cure research.

The oral abstracts are under embargo so I cannot detail those here. For those interested in HIV cure research, please follow the road mapHIV Pathogenesis (Molecular Biology - Virology - Reservoirs) found on the IAS website. 

Till next time.

 

Tagged in: IAS2015

Please join us for a memorial event celebrating the life of one of Australia’s leading HIV advocates, Levinia Crook… https://t.co/N7dof5xaGa

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