Paul Kidd is the Chair of the Victorian HIV Legal Working Group. 

In this session, Paul discussed the definitions of laws in Victoria which involve Human Endangerment and PLWH. POAR Guidelines are in place to intervene to protect Public Health. The focus of these guidelines are to achieve behavioural changes to protect human rights. The problem Paul stated is that once a HIV positive individual has had allegations of Human Endangerment made against them, their privacy is lost forever, and they are publicly shamed.

Paul discussed prosecution when intent and HIV transmission occurs. For ths to happen, it has to be shown that sex occurred, there was appreciable danger and HIV was subsequently transmitted. 

Unfortunately HIV is stigmatised as a "Dread" disease and unfortunately stigmatism is alive and well in the Courts. Jurors ignore scientific evidence because of stigma in the media. Stigma drives stigma.

The key points taken from this session are that we may be winning the battle with HIV for effective treatment and prevention, but not for stigma. Policy changes are needed for more just and compassionate treatment of people with HIV before the Law Courts.

Hello Everyone

Cant wait to get to Brisbane on Tuesday and join at the ASHM Conference Wednesday

See You Then

Jeffrey

John Brooks presented two papers on behalf of the Indiana Dept of Health and CDC which described the recent HIV outbreak in a small town in Indiana and then looked in more detail at the molecular epidemiology of the events. This is a truly shocking story. Some of you may have been following it on HIV list serves, but these two papers eloquently and emphatically demonstrated just what can go wrong and how quickly. This should be essential viewing for many politicians and policy makers, particularly those who oppose harm minimisation strategies or question the need for surveillance.

The location is a small town in Indiana late last year 3 new HIV diagnoses were made in one month. Previously only 8 diagnoses had occurred in town. A surveillance office saw this and look into it.  It became apparent that they were connected through a common vector and were all injected oxymorphone (morphine prescription tablets) 8 additional cases were identified and an outbreak notified to the CDC.

Subsequent contact tracing has revealed 170 infections (as of 14 June) where the data was analysed and a further four cases have been identified since then. The outbreak has plateaued.

There is a very high level of injecting prescription morphine pills in the town. Many families have 3 generations injecting, unemployment is high, until recently NSP was illegal in Indiana. There was no HIV education and education levels low. Many people were not registered for Medicaid. There was very low HIV literacy, and little education there was no school based HIV education program. People thought injecting "at home" or "with the family" protected from HIV.

Philogentic testing had been performed on about 60 samples. These showed 2 groups one of three individual and all the rest in one amorphous mass. These are the clearest clusters i have ever seen. When HCV sequencing was performed on the same samples it revealed a number of clusters and a great many unrelated cases. What this shows is that HCV had entered this community over time from many different sources and that the HIV  outbreak is an actual outbreak. Once HIV came into the community it spread like wildfire.

The response has been excellent. It took a little while to get into full swing. But this was put done to the need for confidentiality and to initiate contact tracing in a confidential and privacy sensitive manner. Indiana has passed a law allowing NSP (perhaps just in this location) and they have mobile as well as a fixed site. People have been registered for Medicade, tested for a range of STI and BBV, vaccinated where needed and available. Linked to care and encouraged into treatment. 70% are in care and of those 40% are on treatment and this is being actively pursued.

There are billboards promoting HIV prevention and public campaigned promoting safety. Ryan Whites mother has addressed a public meeting in the town, in an attempt to curb discrimination. A number of people are on PrEP and even more are asking for it as awareness about it grows.

As was commented in the session. It is terrible that this is occurring now in a developed country. NSP should be universally available. The costs associated with this outbreak will keep on costing. What is scary is just how quickly this occurred. They were recent infections and so highly infectious. Injecting provided a very efficient route of transmission. If those 3 people had not been identified late last year would it even have been noticed now. But even more scary, could this be happening elsewhere.

In this session, 4 different speakers discussed the chronic inflammatory state that persists despite effective viral suppression with current ART regimens.

The first speaker (G Marchetti, Milan) highlighted that there is a persistent depletion of CD 4 cells in the gut despite normalisation in the peripheral blood.  There is also persistent damage to the gut tight epithelial barrier despite ART.  The altered gut tight epithelial barrier maybe a driver of inflammation.  This speaker also highlighted the fact that no matter which ART regimen is employed there is a similar reduction of T cell activation with effective viral suppression. 

The second speaker (P. Hunt, San Francisco) focussed on immune activation as a predictor of morbidity/mortality during ART.  As we know,age associated morbidities are increased in treated HIV infection.  Inflammatory markers are higher in treated HIV disease compared with HIV sero-negatives when adjusted for demographics and CV risk factors.  Chronic immune activation may also cause lymphoid tissue fibrosis.  He showed a graph which demonstrated that a single measurement of IL 6 or D-dimmer predicts morbidity or mortality over the next decade.  This indicates that some people are more susceptible to the inflammatory state of HIV than others.  However, bio markers that predict disease most strongly are not necessarily the best interventional targets.

The third speaker (N. Sander, Texas) looked at the role of interferon 1 in chronic treated HIV.  A lot of the data was based on nonhuman models.  Overal, type 1 interferons can improve protection against infection but because of immune system activation may not be suitable long term as adjuvant therapy.  This raised the question of whether there maybe a benefit of selective activation or blockade of the different pathways induced by IFN-1.

Finally, I. Pandreas (Pittsburgh) discussed approaches to reduce microbial translocation as a means of reducing immune activation.  These were with sevelamer and rifaximin.  However, in the presence of profound gut damage, these approaches are unlikely to have significant benefit.  She then examined other interfering factors on gut function such alcohol and fatty diets.  These results were based on nonhuman models.  Probiotics were shown to have benefit for gastrointestinal immunity in SIV-infected macaques.  This highlighted that lifestyle factors should be taken into consideration when designing clinical trials as they may all impact on immune system activation.  This also highlighted that therapies which target the underlying cause of immune activation and inflammation may be more effective than those aiming at reducing various bio markers increased during HIV infection.

All of these presentations highlight how complex and confusing the immune activation and inflammation process is in HIV infection!

Ebola - not a retrovirus but an international emergency

Ebola did in months what HIV took years to do. There were over 23,000 cases and more than 9,000 deaths as of last week.  The emergency medical coordinator for Ebola in Liberia, Dr Gilles Van Cutsem, of Medecins Sans Frontieres (MSF), described the response to the challenge.  

Ebola is a RNA virus in the same family as Marberg and Lassa fever. The incubation period is 2-21 days with an early febrile stage, then overwhelming GI symptoms, shock and death or recovery.  

The case fatality rate is 30-90%, severity is related to a high viral load at presentation. Transmission is from human to human, via contact with infected fluids. It is not airborne. The animal host is thought to be bats.  

This epidemic is different from previous Ebola epidemics with more cases than all other epidemics combined; previous epidemics have been confined to rural or remote areas and gradually burned out. Now there are massive outbreaks in cities. 

The index patient was a three-year-old child probably infected by a bat in Guinea in December 2013. All family members died rapidly then it spread to distant family and other villages. The first epidemic spread through 500 km.

In March 2014 the second outbreak occurred with rapid spread through neighbouring countries of Liberia and Sierra Leone.  Then there was a third wave of epidemic involving the cities of Monrovia and Freetown and further spread. The hIghest risk of transmission is thought to be later in disease progression; a small infectious viral load only is needed. Five hundred health care workers in Liberia have died. 

The Lagos outbreak was well handled by the Nigerian Ministry of Health. The interventions were based on community education/mobilisation with distribution of protective kits, case/outbreak investigation and contact tracing (which must be rapid), home disinfection, safe transport of patients (for isolation and treatment) and safe burial (it takes six people many hours to ensure decontamination).  One hundred percent of cases on contact lists were traced in Liberia but this is much less in the surrounding countries; in Guinea, 16% of contacts are traced and there the incidence is not falling. 

Current case fatality has been estimated at 51% but the death rate is declining over time in most centres.  A decreased VL on presentation for care has become more common.  The reason for this is unclear; perhaps decreased viral fitness or perhaps a lower infective inoculum in cases because of behaviour change.  

A pregnant woman about to deliver presented to a MSF care station. She was otherwise  asymptomatic and was accepted into the unit only because delivery was very close. She was checked for Ebola because it was routine and found to have a high viral load.  She remained asymptomatic for 3 days.  

Health system closures mean that people are dying from other disease. MSF isolation capacity has been close to full and people died waiting outside the centres. WHO declared a public health emergency only in August 2014 despite several earlier calls for MSF for a response.  MSF had actually called for civil and military biohazard response - unusual for MSF, and the response is still slow and not coordinated. There is a real difficulty balancing patient care and outbreak control.  WHO called for coordination and community organisation on 18 February 2015.   

There is no functional global response to epidemics in countries with fragile health systems. The decreasing incidence in Liberia is largely due to the quality of the response.  The national case manager from Liberia spoke of the country's response - they trained all their HCW and provide training to those who come to help. If there is any next time, the situation should not repeat. 

There was a standing ovation.  

Prevention and Treatment

Prevention and treatment were discussed by H. Clifford Lane from the National Institute of Health.  The NIH was involved following a direct government to government invitation.  

Ebola represents HIV compressed into a couple of months.  Ebola is different from HIV in that  survival means immunity but there is no clear correlate of protective immunity.  There are two current vaccine candidates: recombinant VSV and recombinant chimpanzee adenovirus.  There are the usual vaccine side effects including transient reactive arthritis.  Antibody induction post vaccination has been demonstrated.  

He proposed a trial of a vaccine candidate with probable 50% efficacy and assuming a 1% incidence in Liberia, initially focussing on people at higher risk such as contacts, HCWs and burial teams.  A clinical endpoint study is feasible because of the relatively high mortality and short clinical course. 

Potential therapeutic approaches are neutralising antibodies, nucleoside or nucleotide analogues and agents related to cellular cytotoxicity. Currently there is a monoclonal antibody focused on glycoprotein, a drug called brincidovir, convalescent plasma and an antisense compound. 

An adaptive trial of an investigational intervention would be added to supportive/standard of care. If the experimental arm is effective, then it becomes SOC.  The fatality rate means only 

small sample numbers. Historical controls may not be effective because of changes in the virus over time (74% morality in mid 2014, now at 25%).  The FDA have agreed to easing their licensing  process in this situation.       

Dr Lane emphasised "doing things the right way" and not just "doing something"; compassionate studies muddy the water and complicate subsequent decision making.  Rigorous research programs by extension enhance the local healthcare systems and may improve coordination of the various countries and organisations working in Ebola affected areas.