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.

Tuesday Morning Sessions at AIDS 2016 Conference Durban - Plenary Session "Where are we now?" and "Hep C treatment in HIV infected patients".

A number of barriers to treatment and reduction in transmission were discussed. Of notable repetition was the barrier of cost. This was raised by the speakers as well as protestors at the sessions. A protestor raised the issue of pharmaceutical companies overcharging for medication such as Hep C treatment at $96K in the US. The speaker responded that this was expensive, but indeed cheaper than the cost of Hep C to the health system overall, and was therefore still cost effective. The protestor responded that people were selectively being treated in the US and were not getting equal access to treatment and therefore a cure. Whilst it may seem cost effective, governments need to be willing and in a position to fund these treatments. In Africa, there are many countries in which patients simply cannot afford any of the treatment options.

In Australia, we are quite fortunate in that that our health system has embraced treatment for Hep C and HIV treatment despite costs and can offer treatment to all residents. Currently Australia is involved in studies for PrEP to help provide a case for funding. We are certainly grateful to Pharmaceutical Companies who have developed effective treatments and cures but there is a need to advocate for lower prices so that we can more easily move towards our goal of zero transmission!

 

Tagged in: AIDS2016

My notes from the Thursday Morning Plenary

 

Professor Deborah Persaud – Paediatrics Johns Hopkins University School of Medicine. Known for the “Mississippi Baby”. Time magazine top 100 most influential people in 2013.

 

Children with HIV - 2.6 mil

New HIV in 2014 - 220 000

Deaths due to AIDS in 2014 -150 000

Decreasing number of mother to child transmission around the world due to treatment.

 

Early treatment of babies in the perinatal treatment allows a 99% survival at 6 years. Without treatment 50% die by age 2.

 

Effects of HIV in Children: Lipoatrophy, substance abuse, bone disorder, mental health issues, learning disabilities, abnormal lipids, STIGMA

 

Barrier to HIV -1 Cure

 

  • Viral Reservoirs. Sites that protected the virus from antiretrovirals. Within 2 weeks of cessation of treatment, the virus returns.

  • Exists in resting memory CD4 T Cells. Memory response after naïve cells are activated by initial HIV infection. Cells are present all over the body. High concentration in lymphoid tissue. They have a half-life of 3.6yrs. An Adult would need to take ARV for 78 yrs to get rid of 1000000 million memory CD4 Cells.

  • Treating a child for 10 years doesn’t change the rebound time of 2 weeks.

 

Goals of HIV -1 Cure

 

  • Eradicate latent reservoir (as in the Berlin patient)

    • Bone marrow transplants for those who need BMT for other conditions

  • Control viral rebound off ART (Sustained Virologic remission)

    • Early treatment to limit reservoir. Other immunosuppressive treatment.

 

Infant Immune System

 

  • Lower immune cell activiation. Slower memory cells. Less memory cells.

  • Unlike adults early treated children end up having a much lower number of infected cells/reservoir.

  • This shows that the reservoir doesn’t evolve over time.

 

 

 

Very Early ART at less than 48hrs of age (Mississippi Baby)

 

Baby was started on AZT 3TC and Neviripine. Started within 48hrs but not immediately after birth due to lack of resources at location of birth. Drug was ceased at 18 months. At this time there was no plasma viremia, no HIV antibodies, no latent reservoir. No protective genetic alleles. No evidence of immune response. The child however ended up having a vira rebound at 27 months.  Small latent reservoir can lay dormant for 1-2 yrs when child is treated very early.  No adverse effects of rebound and child was effectively treated after to viral suppression.

 

 Findings – early treated with ARV is feasible safe, and ideal.

 

AZT, 3TC, Nevirapine is the only current recommended treatment for immediate treatment. Kaletra can be used from 2 months.

 

Long acting injectables to neutralize antibodies early on to reduce reservoir in early infancy are currently being developed to last for 6 months.

 

Tagged in: AIDS2016

A brief blog reviewing the Bernard Fields Lecture. Monday 22nd Feb.

T Cells Control of HIV: Implications for Vaccines and Cure.

Speaker: Dr Bruce D Walker (Harvard, MA, USA)

In summary CD8 T cell immunity is still undergoing vital research in assessing how it impacts on overall immunity specifically relating to HIV. Can it help us in a cure or vaccine development? 

Known that CD8 T Cells can kill infected cells before progeny virions are produced. Yang 1997 showed that In vitro CD8 cells can kill HIV infected cells.

In order to assess T Cell response in initial pre peak viremia infection they are studying HIV infected babies in Durban, South Africa. FRESH program was implemented. It was noted within these patients that the rate of increase in viral load was similar across all new infection babies, but the actual peak viral load number and time to reach that in an individual varied. http://ragoninstitute.org/international/fresh/

 From current findings they have found that CD8 cells increase their activity within the human body just after initial exposure to HIV, a substance known as PD-1 is expressed and the more of this that is expressed over time there appears to be some correlation with the immune system getting turned down in regards to response. This was apparently similar to what has been noticed with cancer modulating cells and immune response impact.

They have been able to show that HIV some how activates CD8 activity –they hypothesize that perhaps active CD8 T cells are HIV specific. It was noted that an increased level of CD8 cell activated initial stages of infection was linked with a lower viral load set point.

Two other markers noted to be of relevant were, BCL-2 and perforin. As BCL-2 was activated CD8 cells underwent increased apoptosis, and similarly as there was a loss in perforin there was a progressive decline in CD8 functionality.

Overall early treatment does impact the overall quality of the immune response. To further hypothesis but if CD8 cell functions were maintained by commencing treatment in the pre-viremia stages of infection exposure could this help in the development of a cure and it’s effectiveness.

At the conclusion of the talk, despite being moderately confused with the biochem aspects, I got the impression that for now in order to help the development of future effectiveness of a potential cure we need to maintain baseline immunity of newly diagnosed HIV positive patients as much as possible, and prevent the exhaustion or destruction of CD8 cells after peak viremia.

I’m not sure if I would use this particular pitch to promote early commencement of ARVs in patients or for increased testing programs to detect earlier, but it’s food for thought as to why there is a possible other reason to suppress viral loads as early as possible.

 

I attended the talk by Prof Sharon Lewin this afternoon titled ‘HIV cure research: current strategies and challenges’

Sharon started off by saying that sustained remission off ART is achievable. Some examples of this are the Visconti cohort and the Mississippi baby.

Early ART has a greater impact in limiting persistence of the HIV reservoir than later treatment (as found by Ananworanich and Chomont , Curr Opin HIV AIDS 2015). However, post treatment control is a rarity following ART in acute HIV infection and biomarkers to predict cure/remission are required (e.g. in the Swiss HIV cohort study, HIV DNA predicted time to rebound).

Sharon touched on latency reversing agents now in clinical trials e.g. HDAC inhibitors , TLR agonists, activators of NF-kB and others such as disulfiram.

Sharon said that activation of latent HIV was possible in vivo with HDAC inhibitors, disulfiram and TLR7 agoinsts but there is a need for more potent, less toxic and more specific agents.

Combination of agents (e.g. HDAC inhibitors and smac mimetics) as well as modulating immunity via vaccination or immune checkpoint inhibition are also in the pipeline and gene therapy is also an avenue to be explored.

After this talk I felt very inspired about the work Sharon and other researchers searching for a HIV cure are doing!

 

 

 

 

 

 

 

Tagged in: HIVAIDS2015

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

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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