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.

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The Implications of HIVSTI on Sex Workers

Udesha Chandrasena - Policy Officer at Scarlet Alliance, Australian Sex Workers Association

This was an very interesting session focusing on the accessibility of "self-test" HIV test kits that are currently available online and that have been made available to people in rural areas of Australia. With the changes and increase in availability of technologies that will allow for fast results, with some accuracy, to determine someone's HIV status, Udesha presented that this has potential to impact positively and negatively on sex workers.

The ability to have people attend tests at non-clinical locations can have great potential benefit in allowing for confidential testing in a private setting but can also have potential for significant issues.

Sex workers in Australia have been shown across Australia to have lower rates of HIV than the general population and also when compared to rates of sex workers overseas. This has been made possible through strong peer group programs in Australia and can only be measured in this population as a success, something that should be recognised. However this is not new data and across Australia every state and territory has it's own legislation regarding sex workers and a persons HIV status. This has potential to impact this population at risk with emerging new technologies that laws may not be keeping up with.

The advent of technologies with the ability to test a person on site or that need to be sent elsewhere for results may lead to an increase in the number of people tested but could also open workers up to potentially dangerous practices in their workplace. This could lead to bullying within brothels to be tested, to have workers be coerced by other workers, clients or brothel owners or managers to test in their presence. This has potential to impact on the workers safety, ability to work or force people to change practices or even be stopped from working. With differences between testing kits, techniques and potential technical issues with these technologies, this could lead to issues with false negative outcomes which would be managed differently in a clinical setting or with more "traditional" testing techniques.

Udesha argues that the current high rates of voluntary testing among the sex worker population be acknowledged and that changes to legislation across the country be made to ensure safety for workers.

In conclusion, there is potential for an increase in the numbers and scope of testing, however this can also negatively impact on sex workers. Changes in legislation across Australia is necessary to accompany this new technology.

Posted by on in Testing and Treatment

So having digested all the scrumptious brain teasing morsels at yesterday’s info picnic what was on the menu for Day 2 at #EACS2017?

 

To begin the day Dr Roy Gulick, Professor of Medicine and Chief of the Division of Infectious Diseases at Weill Medical College of Cornell University (also see Mark Ryan’s post) presented the Future of HIV Therapy.  He began by summarising approved ART first line regimens in 2017 and the world-wide opinion to start at all CD4 counts whenever the patient is ready.  He discussed the developments of ART properties in terms of

1)           Antiretroviral activity - mentioning the future of two new classes of drugs HIV Maturation Inhibitors and HIV Capsid Inhibitors,

2)           Safety and tolerability- giving TDF -> TAF switch as an example of similar viralogical efficacy but improvements in renal and bone markers. 

3)           Convenience- recapping the history of ART with many daily pills to the current single tablet regimes and then the possibilities in the future of new co-formulations with longer half-lives lending themselves of less frequent dosing, and long acting methods in the form of injectables and subdermal implants.

4)           Access and Cost – Highlighting the numbers of people living with HIV globally and improvements in those accessing treatment as the cost of ARV’s decreases.

5)           Life expectancy as those with HIV live longer and healthier lives and in closing stated “possibly longer than the general population … apparently getting healthier is good for you”

 

 

Laura Benjamin (Wellcome Trust Liverpool Glasgow Centre for Global Health Research) presented her research on a cohort of HIV patients suffering stroke in Malawi. She found an increased risk associated with lower CD4 count but not with viral load. The strokes were mainly ischaemic rather than haemorrhagic. There is increasing evidence of stroke as a co-morbidity and it is thought to be due to HIV- related vasculopathy causing inflammation and endothelial dysfunction. It is important to consider treatment failure with opportunistic infection if stroke occurs in someone on ART. 

 

Neurocognitive impairment remains an important problem in HIV patients despite ART. Carmela Pinnetti (Italian Ministry of Health) presented a study exploring the  association between neuronal injury markers and NCI. She confirmed that plasma and CSF markers were important indicators of impending NCI. Valentina De Zan (Department of Microbiology, Verona University) then pointed out that despite ART, the HIV  virus may persist in CSF and can escape causing neurological symptoms. She studied 46 neuro-symptomatic. She found CSF viral detection at a higher rate than plasma as well as undiscovered viral resistance. Optimisation of ART led to 65% recovery although a few relapsed at a later date.

 

Aoife Cotter (Consultant in Infectious Diseases at the Mater Misericordiae and St Vincent’s University Hospitals)presented the POPPY study. This looked at an aging group of HIV patients, over and under 50yrs against controls over 50yrs. The older patients had lower BMD after correcting  for other variables. A higher CD4 count and current  ART were associated with lower BMD. Tara McGinty (Clinical Research Fellow, UCD School of Medicine, Dublin) confirmed HIV as an independent predictor of reduced BMD but stressed the need to assess trabecular bone score as well, (this is also reduced in HIV.) The lumbar spine is more effected and predictably smoking, and prior fracture were the most important predictors of more severe osteoporosis 

 

Pablo Ryan (Hospital Universitario infant Leonor, Madrid) pointed out that osteonecrosis is more common in people living with HIV (PLWH.) They require THR. He compared complication rates in HIV vs controls in 348,000 patients who underwent THR in Spain including 1018 HIV+ve. ON rates were higher in HIV but there were no differences in surgical complication rates.

 

 

The Future of HIV Therapy

Dr Roy Gulick (Professor of Medicine and Chief of the Division of Infectious Diseases at Weill Medical College of Cornell University) from New York provided a great summary of current treatment guidelines and new developments underway with ART.

In summary:

ART is now recommended to commence at any CD4 count when a patient is also ready to start. If resources are a priority then treatment should be offered first to those with a CD4 <350.

There are currently 29 approved HIV medications and up to 10 starting regimes.

5 broad mechanistic classes (NRTI, NNRTI, PI, INSTI,EI)

Recommended standard strategy is 2NRTI +(NNRTI,PI,or INSTI)

 

If there is multiclass failure to the 29 drugs two new entry inhibitor class drugs are showing promise.

1 Fostemsavir (oral HIV attachment inhibitor with Phase 2 results soon to be released)

2 Ibalizumab (monoclonal antibody given parenteral, binds to CD4 receptor/works as HIV entry inhibitor)

 

2 New classes of HIV Rx being developed:

1 HIV Maturation Inhibitors

2 HIV Capsid Inhibitors

 

Newer approaches to safety and tolerability in the future ART include:

Using lower doses of drug eg (EFV 400mg vs 600mg). Other studies in progress are ATV 300mg, DRV 400mg

Newer drugs eg tenofovir alafenamide(TAF). Switching TDF to TAF improved renal/bone markers

2 Drug regimes: PI/r+3TC (or FTC), PI/r+ integrase inhibitor, NNRTI +integrase inhibitor , DTG+3TC/Paddle Study(results showed VL all suppressed by 8 wks)

Less frequent dosing eg RAL daily formulation

New co formulations eg ATV/c and DRV/c

New injectable drugs RPV LA, Cabotegravir

 

Latte 2 study is looking at IM CAB +IM RPV with conclusions showing IM is comparable to PO and well tolerated. Phase 3 studies are evaluating IM q4wks.

 

Dr Gulick concluded by saying that future ART Rx will involve greater use of sub dermal implants and injections with potentials for dosing going from weekly up to every 1-3 months. Costs will radically decline and affordability improve. Convenience will also continue to improve. We have already seen the dosing levels of 20 tablets a day reduce to one a day in the last 10 years. Interestingly life expectancy in ART uses from recent studies in US, Canada and UK were showing higher figures than for the average population!  Presumably regular medical intervention can be a good thing for our species!

 

 

Tagged in: EACS 2017 HIV

The single-most incredible presentation at the conference.  Dr Kedar Narayan presented on some amazing new technology which is allowing us to view HIV in a completely different light.  He somehow managed to explain what is clearly a very complex principle in simple terms, and with plenty of humour sprinkled in.

 

  • traditional electron microscopy only provides a 2D image of the cell
  • focuses ion beam scanning electron microscopy (FIB-SEM) allows a 3D image
    • the tissue is embedded in a block, with the side face open to the EM scanning
    • the FIB laser is used to slice the tissue (like a deli slicer/cutting a loaf of bread) to reveal the next layer of the tissue
    • the EM can then image the 2nd layer
    • this is repeated 1000s of times to obtain a stack of images (like a CT scan)
    • computer software can generate a 3D image of the tissue, including all the internal structures
  • FIB-SEM can be applied to HIV
    • HIV virons actually use small tunnels from intracellular vesicles to the extracellular surface to escape the cell
      • this explains why other studies have found that the pH of vesicles were less acidic than expected (i.e. because they were actually connected to the extracellular membrane)
    • virological synapse
      • the dendritic cell actually “hugs” the T cell
        • rather than individual projections from the cell, the DC actually has lasagne like sheets (veils) to connect with the T cell
        • this excludes all drugs since the synapse is covered by the “hug”
      • often thought that the T cell is passive in receiving antigen presentation
        • not so - they can reach into the DC to sample for virus

 

What an exciting start to the day (following on from the excellent trainee sessions this morning), and the rest of the session proved equally as informative...stay tuned

Day 4- Increasing the demand for HIV testing

Mark Stoove discussed innovative ways to improve HIV testing.  50-70% of HIV transmission among GBM are attributed to undiagnosed infection. There were policy and regulatory changes in 2012, which revolutionised HIV testing in Australia. Rapid HIV testing was introduced and there was an increase in HIV testing in community settings. The uptake of rapid HIV testing has been modest. Barriers may include funding, lack of government subsidy and some services feel testing can be time and resources heavy. The majority of HIV testing continues to occur in primary health care settings using serological laboratory testing

Community based HIV testing services such as ACON provide a comfortable, peer based service which clients find very acceptable.  ACON in Sydney provides a peer based testing model, which is supported by nursing staff. Peer based clinics have successfully attracted first time testers that were classified as ‘high risk’. Rapid HIV testing has increased testing in urban areas but more needs to be done for those living in rural areas. We need to expand the geographical reach of HIV testing. The Terence Higgins Trust provided funding to increase testing in the UK. In a 14-month pilot study over 17,500 testing kits were posted and 10,410 specimens were returned. There was a positivity rate of 1.4% and this testing was welcomed by participants with 97% reporting that they would test this way again. Self-testing kits are available in the UK and the uptake has been excellent with over 27,000 units sold between April 2015 –Feb 2016. Half of the test kit users have never had a HIV test before.

Key messages

-We need to ramp up HIV testing

-Self testing kits should be available in available

-Funding may be a barrier for services offering HIV testing. Government subsidies could improve rates of HIV testing

 Vickie Knight spoke about the effect a[TEST] clinics has had on HIV testing among gay and bisexual men. It was found that the clinic on Oxford Street in Sydney has increase testing and also increased the frequency of testing. Factors that make this clinic user friendly include short wait times, the service is free, CASI is used which means intrusive sexual health histories are not taken by health professionals.

 

Key messgaes

This model works and has increased testing among GBM.

 

Roy Gulick, from the Division of Infectious Diseases, Weill Cornell Medical College, New York City, gave answers to the question "What next for ARVs?" during his presentation today.

But before we talk about the future, let's pause and look at ART in the year 2016:

  • When to start:
  • Currently 29 approved drugs:
    • From five broad mechanistic classes:
      • EI, NRTI, NNRTI, PI & INSTI
  • We currently have up to 10 recommended first-line regimens:
    • 1 standard strategy: 2 NRTI + [NNRTI, PI or INSTI]
  • Properties of ART:
    • Virologic activity
    • Safety and tolerability
    • Convenience
    • Access and cost
    • Life expectancy

 

Newer strategies, formulations and investigational ARV agents:

  • Long acting compounds under investigation:
    • Injectable formulation of the NNRTI, Rilpivirine LA (long acting)
    • Injectable formulation of a new INSTI, Cabotegravir
  • Formulations of implantable devices that provide sustained release of ARVs
  • A new NNRTI, Doravirine (DOR):
    • Active agains drug-resistant strains
    • In vitro active against viral strains with K103N, Y181C, G190A, E101K, E138K or K103N/Y181C
  • A new INSTI, Bictegravir:
    • In vitro active agains viral strains with integrase resistance
  • Two new mechanistic classes under investigation and in clinical development:
    • An oral CD4 attachement inhibitor, BMS-663068:
      • BMS-663068 is a prodrug of BMS-626529 an inhibits CD4 binding to gp120 
    • HIV maturation inhibitor (MI), BMS-955176:
      • Binds tightly to HIV GAG
      • In vitro active agains strains with polymorphisms and PI resistance

There has also been a lot of talk at the conference about two-drug regimens and Dolutegravir monotherapy, but until we have conclusive data to support the efficacy, three-drug regimens remain the current gold standard.

Conclusion:

Currently, we can control HIV infection long-term with potent, safe and convenient ART that leads to prolonged healthy survival in our patients. The development of newer drugs and new drug classes opens up options for patients with multiple resistances. 

We have just heard from 7 speakers on the status of PrEP across Euro and North America. There is considerable support for PrEP and incredible consistency across the regions in both trends and challenges a s well as interest.

Clearly there is no debate about the efficacy of PrEP, thought there remain differences in choice about daily or on demand PrEP. There seems to be considerable comfort in the level of resistance, side-effects and toxicities, while these may be appearing they are at such low levels as to no impact support for PrEP.

There is also a very generalised concern about cost of PrEP, but a growing confidence that cost issues will be addressed. How to implement PrEP is where the differences are most striking. Many people are indicating that PrEP must be resourced by cutting back in other areas. Cost effectiveness remains linked to the cost of the drug ad the level of risk, but a number of speakers also introduced location or background prevalence into that assessment.

PrEP access, at least in a number of settings, does not match HIV transmission risk. One presenter gave a detailed account of where PrEP is accessed and by whom. Overwhelmingly PrEP access in the USA favours white MSM, yet black and hispanic MSM and women are at much greater risk. This is s strong take home message. We will need to make sure that PrEP can be assessed by at risk populations and communities at greater vulnerability.

 

Talk by Professor Ian McGowan on long-acting ARVs (LAARVs).

 

-       Research from NYC (MSM) indicates high rates of willingness, and that a majority would prefer an injection.

-       Research from Africa (women) indicates that injection/implant/vaginal ring (as PrEP) would be preferred.

 

Current development of LAARVs is both for treatment and prevention.

 

Requirements for LAARVs as injection:

-       Infrequent dosing (every 2-3 months)

-       Practical injection volume (<4mL)

-       Doesn’t require cold-chain storage

 

Rilpivirine and cabotegravir most likely candidates of current generation of medications.

-       Have only been evaluated in the context of clinical trials (phase 1 and 2); adherence data likely to vary in the real world (and depending on whether being given as PrEP or treatment)

-       Tolerability good; patient satisfaction overall good

-       Efficacy signal in cabotegravir (animal studies)

-       Injection-site reactions reasonably frequent over time (highest at first injection)

-       Long-acting rilpirivine detectable in tissue (plasma/endocervical and vaginal fluid) up to >500 days (!) later – which is concerning for risk of resistance. Therefore cabotegravir more promising for use as long-acting PrEP (and phase 3 studies planned) – cabotegravir involves 4 week oral lead-in then Q8 weekly injection.

 

Novel NRTI “EFdA” also promising based on animal modelling; currently at phase 1 studies in humans. Animal models indicate that long-acting formulation could be effective up to 1yr.

 

As mentioned elsewhere – TAF silicone tubing implant and biodegradable implants both promising for use as PrEP.

 

Main challenges with LAARVs:

-       Safety (need oral lead-in)

-       Acceptability (needs real-world data)

-       Adherence

-       Resistance

-       Pharmacokinetics

-       Delivery

African Vaccine Dreams

Everyone's intrigued by it, every country is keen for it, apparently even the CIA wants it. The room brimmed with academic excitement as we gathered to hear a panel discussion on the prospects of an HIV vaccine and how "vaccines are needed to conclusively end HIV/AIDS and TB".

Six major trials have been conducted in the past, looking at potential HIV vaccines, but so far the results have been disappointing. The most successful vaccine trial was the RV144 study in Thailand, but this vaccine was only modestly protective against HIV infection.

The HVTN 702 trial is due to commence in South Africa towards the end of 2016, but scientific research is expensive and a phase three vaccine trial costs approximately $135million.

It's proving difficult to produce a vaccine for HIV. There are not only challenges with the science, but also with policies, politics and funding. We need international collaboration if we're ever going to create an HIV vaccine that works.

We already have a vaccine for Tuberculosis but it's more than 95 years old and not very effective. There's been little interest, investment or pharmaceutical support for a new TB vaccination and the research already performed has only yielded disappointing results.

Ruth Labode (Parliamentarian of Zimbabwe) was asked if politicians are growing cynical of ever getting an HIV vaccine and is this affecting TB and HIV research. She responded that when she hears a church minister saying "let's pray that we find a vaccine for HIV", she thinks the minister should be praying “for those who are on treatment, to stay on treatment".

She has a point. It’s important to plan for the future, but remember we already have medication that works - let's use it.

Ruth Labode stated “African countries need to come together as an informed community to collaborate with their international partners”. Her opinion is that Zimbabwe is not investing enough money into scientific research and development. “We always worry about money, but at the end of the day the epidemic is not in recession".

The panel was asked their opinion about how to get people excited about a vaccine, but continue to have a measured scientific approach. Peter Godfrey-Faussett (UNAIDS) passionately responded by saying “everyone’s talking about the UN's 90/90/90 targets for HIV, now even TB has a 90/90/90 target, but sometimes we don't quite understand what we're talking about. When we're talking about HIV we really need three ZEROS - zero HIV-related deaths, zero new infections and zero HIV-related stigma".

"Our current 90/90/90 targets relate to HIV treatment and it's working because we're seeing that the number of people dying from HIV is reducing. Some countries are nearly at 90/90/90 targets. Australia has recently announced that they're already at 90/90/90, but in some areas of the world HIV diagnoses are going up. 90/90/90 is a popular catch phrase, but people forget that it's only one of 10 targets the UN has mentioned. Millennial goals have become sustainable goals, but now we need a specific target for TB".

Peter Godfrey-Faussett continued “Where does research and development come into this? Domestic governments are putting money into it and domestic resources are going up. Economists talk about "discounting" - would you rather have 50 Rand today or 100 Rand in 20 years time? Do we deal with things today or do we invest in things for the future? Of course we need both and we need to balance this".

He proposed "We need more than just treatment. A quarter of funds should be put into prevention.” A successful mosaic vaccine is more likely to arrive sooner if countries collaborate and share the load.

But vaccines don't just come in a syringe. Condoms, male circumcision and PrEP all decrease HIV transmission. PrEP is especially effective at preventing HIV but we're still not promoting it as well as we could be.

Glenda Gray (South African Medical Research Council) was asked what African-led science would look like in the future. Her response was simply that African governments don't fund enough science. "Until African countries see the value of funding medical research, we will always be behind. Our budget is puny compared to other organisations like the Bill and Melinda Gates Foundation" she said. "We need our government to support science. Science is slowly emerging in South Africa, but it's still not good enough. We need to see a renaissance of science in Africa. If you want a healthy country, you need to invest in Research and Development."

Mark Feinberg (International AIDS Vaccine Initiative) was asked to reflect on the pharmaceutical industry. He stated that people still think the pharmaceutical industry "only gets involved when there is a payback, but industry is evolving [to a place] where collaborative efforts can go ahead and answer big questions. Scientific challenges and the challenge of scientific partnerships is an area where there is incredible potential. Organisations need a pathway and direction to take them to a much greater scale". He stated that we all learnt a lot from the international efforts with Ebola and this has shown us a much different way of dealing with these big issues in a collaborative way.

Countries respond very differently to dealing with TB and HIV. Fragmented systems of care exist where health professionals are either concentrating on TB or HIV, but we need to be treating both. The general population doesn't equate TB with death like they used to do many years ago and there's currently a lack of engagement from the community. We don't provide aggressive case management and we lose patients to follow up. We have incredibly rigorous surveillance with our HIV patients, but we need to have the same approach with TB.

The panel was asked if scientific research and development funding would increase as we continue our search for an HIV vaccine. Glenda Gray replied "South Africa does fund HIV vaccine research, but the funding from the National Institutes of Health (NIH) is a thousand-fold more than what South Africa is funding. It's like South Africa isn't serious about its funding towards an HIV vaccine. We've been able to improve South Africa's life expectancy by 9 years due to aggressive antiviral therapy, but to fuel our economy we need to fund research & development." She continued “We need to harness an economy of knowledge, but we are short-sighted in our vision. We need science like we need clean water."

Dr Anton Pozniak (my new professional man-crush) stood up from the audience, took the microphone and addressed the panel. “There's currently a gross inequity between HIV and TB. Regarding vaccines, seven times the amount is spent on [research for] an HIV vaccine compared to a TB vaccine." We don't need to make it a competition, but it's a matter for the TB community to step up. "The TB community needs activists to show that a TB vaccination is important."

Anton continued "It's extraordinary that we don't give people more Isoniazid. There's a lot of evidence regarding TB and HIV (showing) that people do better when we put them on Isoniazid, but people aren't taking it." We need a continuous dialogue between organisations to decide where funding is most appropriately needed. "We have people talking about Zika, but we have people dying every day from TB. In Ethiopia the AIDS association is taking funding on behalf of TB." Money is eventually getting to Tuberculosis, but an answer may be to integrate health services.

“[We've just had the] TB Pre-conference and there are some signs of change, but it is nowhere near fast enough. There have been SIX trials for an HIV vaccine, but only ONE trial for a TB vaccine. We need to think about these issues together. We need to 'leap-frog" innovation and science by making an HIV/TB think-tank. Science is the driver of development. We need to see a lot less people dying from TB. We need people to know their HIV status and use antiretroviral (ARV) treatments. If they're using ARV, then they're less likely to die from TB infection."

The panel discussion came to a conclusion, but not before Dr Anton Wozniak dropped the mic saying that after all this discussion about TB and HIV “it's important to put it into perspective that non-communicable diseases kill far more people compared to infectious diseases” - but I don’t think we have a vaccine for that yet either.

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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