A/Prof Mark Bloch

Mark has been working in the field of HIV medicine since 1983; he was a doctor at Sydney Hospital and Albion St AIDS clinic prior to being a director at Holdsworth House. He has completed his Masters in Medicine, HIV and Sexual Health from University of Sydney, and he is a past President of the Sexual Health Society of NSW. He is the director of clinical trials at Holdsworth House and actively involved in clinical research in HIV and STIs, co-joint lecturer at University of NSW, and a member of medical advisory boards.

Mark Bloch

Mark Bloch

Dr Mark Bloch is director and head of Clinical Research of Holdsworth House Medical Practice, a large HIV-caseload practice in inner-city Sydney and is a board member of ASHM. (Disclosure of Interests)

It’s amazing how far we have come in the potential of neutralizing monoclonal antibodies against HIV. John Mascola from the Vaccine Research Centre gave a great plenary on “Harnessing antibodies for HIV prevention and treatment.”

Antibodies have been used in infectious diseases for passive immunization eg RSV, zoster, hepatitis B.

Many potent broadly neutralizing antibodies have been discovered in HIV since 2009, which can bind to various sites on HIV gp41 and block viral entry into cells. These newly discovered antibodies are 500x more potent than previously and more are being found.

Studies in monkeys have demonstrated that passive immunization with these newer antibodies such as VRC01 can prevent SHIV infection.

There are early phase studies in humans. The treatment appears safe and well tolerated. Protective levels of antibodies remain in circulation for 2 months – this period can be extended by creating mutations in the Fc region that increase the antibody affinity.

Can antibodies protect against infection in humans? How much is required (as more potent antibodies are discovered, they will require lower doses and last longer, thus reducing cost. Lower dosage also means they can be administered subcutaneously rather than IV). There also needs a greater understanding of how and where exactly these antibodies work in the body.

A large scale HIV prevention study is planned using broadly neutralizing antibodies to provide antibody mediated protection in 2400 MSM in North and South America and 15000 women in Africa.  The goal – safe effective administration sc every 4/12 for PrEP.

There needs to be protection against wide variety of HIV strains – combining antibodies acting at different sites will achieve this.

Other potential roles for these neutralizing antibodies include preventing mother to child transmission intrapartum and with breast feeding – animal models show this is viable.

Neutralizing antibodies may also have a role in treating HIV infection – either alone, or complementary to ART. They may be able to reduce viraemia in primary infection, or in those with chronic infection, to treat HIV, and to assist in killing of infected cells by marshalling immune response.

So while there is work to do in translating this knowledge into viable HIV prevention and treatment options, there has been major progress in this area. Watch this space.

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Tagged in: CROI2016

In the Resistance and Topism session, Prof Jonathan Shapiro gave an excellent summary on HIV resistance titled: “Resistance: what’s new and on the horizon, and a time to teach old dogs new tricks?”

Professor Shapiro explained that assessing viral resistance enabled better choices for patients and better new drugs that provided more durable lines of treatment.

Resistance testing was developed because, in early ART, many patients were failing virologically and individual mutations helped to guide future treatment. The benefit of resistance testing over and above expert opinion based on previous treatment experience was shown by studies such as Viradapt, GART and Havana.

Over recent years there have been more drugs available, new drugs without class cross-resistance, newer drugs with better resistance patterns and tolerability and simpler regimens, better adherence.

The SPREAD study in Europe showed that acquisition of resistant HIV virus had increased 35% from 2003 to 2013, even though overall prevalence of resistance hadn’t.

There was concern with the roll-out and widespread use of ART in low and middle income countries, resistant rates could sharply increase, but in low and middle income countries, resistance has remained stable 5-15%.

These days there is a need for resistance testing to optimise NRTI use in 2nd and 3rd line therapy and fine tune use of PIs e.g. to use darunavir once or twice daily.

Also resistance can be helpful in patients failing raltegravir or elvitegravir and deciding on dose of dolutegravir to use.

There is new technology that can provide for point of care testing for resistance by looking at specific mutations. Depending on requirements, specific point mutations are provided in a tiered kit:  for Tier 1, mutations are suited for 1st time failure; Tier 2 guidance for suspected transmitted resistance; Tier 3 for NRTI choice in 2nd or 3rd line failure; and Tier 4 for PI resistance.

Laboratories providing resistance testing need to improve the format of reporting of resistance testing to make it more user-friendly and clinically relevant.

In the future, reporting will provide not only which drug are okay to use, but also what dose and how many active drugs are needed to be included in the regimen.

 

 

 

 

Tagged in: Glasgow2014

Posted by on in Public Health and Prevention

CROI Tues am (session 21 - Abs #71) plenary speaker Prof Chris Beyrer from Johns Hopkins gave a clear, evidence-based, passionate and excellent summary of HIV in MSM (Men who have Sex with Men) (see also Lancet special issue 2012)

This presentation is well recommended to view from CROI website.

Key points:

1. Globally in first, middle income and third world countries, Global burden of HIV is stabilising or declining in most populations - MSM in all these regions is the exception.

2. MSM are disproportionately affected - eg USA 2010 - MSM 1-1.5% of population - 60% of diagnoses

3. WHY? - even in this era of ART?
Higher prevalence drives risk of acquisition, untreated STIs, unprotected receptive anal intercourse 18x greater risk than vaginal sex
Also clustering of population, "bursts" of transmission in primary infection
Structural issues - stigma & discrimination affects access to treatment and care, leads to depression and substance use
(Ironically MSM contributed so greatly to development of HIV treatments and are in many cases denied treatment and care in too many countries)

4. Achieving the end of HIV for everyone has to include MSM in all countries

5. Take home messages - applicable for our care in Australia - we need to combine all these:
 - Treat all MSM with HIV (treatment as prevention)
 - Test for HIV and test frequently
 - Condom protection for anal sex
 - PrEP for some, PEP
 - Test, diagnose and treat STIs
 - Access to care that's culturally sensitive
 - Address homophobic stigma, discrimination (legal and social) - the responsibility of all of us as health care workers, at work and at home

 

Tagged in: CROI2013

Excellent session at CROI Monday 4-6pm "Cardiovascular disease and other non-AIDS events: Epidemiology and Pathogenesis".

This session (which will be webcast) very successfully pulled together different presentations to give an update on the heart and vascular disease as well as other SNAEs (serious non AIDS events) in HIV.

The key messages were

1. Adjusted risk of myocardial infarct for HIV+ was 80% higher than HIV- controls (VACS - Veterans Aging Cohort Study of 68,000 HIV- and 31,000 HIV+) with similar mean age of incidence

2. Plaque formation in coronary arteries measured on CT was 80% higher in HIV+ (vs HIV- at risk) MACS cohort

3. HIV+ patients more likely to have plaque but also more likely to have "vulnerable plaque" - i.e. plaque which is soft, lipid rich, monocyte rich, subject to remodelling and less calcified (spotty calcification) - these plaques less stable, more likely to rupture and cause myocardial infarct or sudden cardiac death

4. Vulnerable plaque associated with inflammation and in HIV+ this is monocyte-mediated as measured by soluble CD163 (and CD16)

5. So, in HIV+, there is the traditional risk factor (smoking, lipids, hypertension) coronary artery disease as in the general population. Additionally there is an inflammatory monocyte driven process which could partially account for higher CVD in HIV.

 

 

Tagged in: CROI2013

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