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.

One of the sub-themes of this conference is how to reach the illusive 10%, or 20% or 40%. Those people who have HIV but are not diagnosed. Unfortunately, I have not yet heard the answer.

Five posters look at this and it has been the subject, at least in part of the IAS Symposium on Patient Centered Care and the the EATG symposium on new technologies and Apps. Suffice to say this conundrum of how to reach the unreached, or in settings where there have been big gains, how to reach the persistent residual of untested patients has been a focus of many presentation.

Unfortunately, there is not an answer. I am not looking for the panacea, but some greater or closer consideration of this issue is greatly needed. What I would like to hear and I think many of us could learn from is "what caused someone to test now". People who have established infection, and then come forward for testing must have made that decision for some reason.

Patrick Sullivan, Rollins School of Public Health, Emory University, talking on technology based and at-home testing and PrEP services, gave an example from one man, characteristic of what his group was hearing, namely that being able to order on line was the thing that finally pushed him into action. Is that common? Can we build on this.

The posters focus more on describing the late presenter but unfortunately do not investigate their motivations for eventually testing. We do find out that many people had had contact with health services and that these were viewed as lost opportunities. Almost 50% of recent enrolees in the Swiss Cohort had missed opportunities (P#341);  starting late had less favorable outcomes (P#340); 1 in 4 people in an Edinburgh study were not tested in line with Guidelines (P#342); in a Lisbon sample 56% had clinical symptoms,prior to testing (P#343) and a further Lisbon based study found late presenters were presenting in hospitals and on wards and questioned the targeting of campaigns to specific groups(P# 344), given the diversity of late presenters. NONE of theses studies asked the patient.

It seems that while a focus on Key Populations is vital, this needs to be matched to be complemented with some focus on non-priority groups. Julio Montaner, describing new infections in his British Colombia population,  used phylogenetic sequencing to describe a situation where about 30%-40% of new infections are related to two large clusters. The remaining infections are much-much smaller clusters with about half of those infections happening locally and about half outside of BC. This tells us it is vitally important to focus on more prevalent settings and in communities with high rates of infection, but equally effort needs to be made to access those who don't respond to those messages and are not members of key affected populations.

Good food for thought and hopefully we can get some interest in finding out what actually tips the balance for people to seek testing, to engage in prevention and to access care.

Julio Montaner has just presented his assessment on the roll out of 90:90:90 focusing on Canada but with global observations. The take home message is that transmission reductions are associated with greater roll out of therapy and higher rates of undetectable viral load. Achieving this is not easy and even in developed settings. People are now being explicit that 90:90:90 really means that only 73% of people with HIV are immune suppressed.

David Cooper has asked about what other strategies might be needed by countries with high rates, of treatment and viral suppression, to get incidence down. Julio, refereed to the the phylogenetic clustering work they are doing as a way of getting a better handle on this. He cautioned that PrEP may miss clusters.

Julio also discussed phylogenetic testing. Canada has high rates of prosecution for HIV transmission and they they are trying to change that. Changes in government may facilitate that. They got agreement form the Attorney General that data would not be used for prosecution. 

This has resulted in data being collected without the fear of prosecution. They are hoping to adopt the same process across Canada. It might be useful to look at this in Australia as jurisdictions and research groups look to increasing phylogenetic monitoring.

Glasgow HIV 2016 has just opened.

It was interesting to hear new-comers to this meeting reflect on the three excellent presentations in the opening: Clarity, different perspectives, and reflections mixed with predictions. The sessions will be up on the Conference website shortly.

Tony Fauci, giving the Joep Lange and Jacqueline van Tongeren Memorial Lecture. Ending the HIV/AIDS pandemic: follow the science, reflected on the changes that have come about since he entered the field in 1981, following the publication of seminal articles in the MMRW. Fauci indicated that this is when he decided to change his career trajectory and concentrate on the, as then un-named, phenomenon which would become HIV.

Fauci sprinted through 30 years of HIV to focus on the more recent research which has redefined ending HIV. Namely the recognition that treatment reduces virus which in turn reduces transmission and that knowing ones status allows for interventions. But he did not stop there. He went on to cast and eye to the horizon and identified two areas where science has significant contributions to make.

HIV persistence, or stopping persistence, is a holy grail. This comes in two forms, eradicating HIV where HIV is made dormant while treatment is administered, yet re-emerges when treatment is stopped or controlling rebound, where interference at binding or replication sites reduces proliferation. This individualised therapy has shown to be useful in this strategy in cancer treatment and it has potential in HIV.

HIV vaccines, whether therapeutic or preventative are of course what everyone is hoping for. Fauci presented some realistic steps which are being made to transition vaccines from 32% effective to more like 50% effective, a point which he suggested could make significant inroads in reducing transmission, particularly in endemic settings and in combination with other strategies. He also discussed a number of new vaccine initiatives.

He ended with neat summary of why vaccinologists have not yet been rewarded. This I thought was a poignant rationale for continuing with vaccine development in the absence of any hitherto prizes. Most vaccines mimic the actual process of disease and immune response. That is not the case in HIV, so the vaccinologist needs not to copy the virus, but be much smarter than it.

Andrew Hill

Spoke about the potential to improve treatment access through the greater use of generic drugs. I can’t help thinking every time I hear Andrew talk that he is simplifying something in the greater economics and practicalities of capitalism or financial markets. But his arguments are very compelling.

Interestingly Andrew inserted discussion about Australia’s funding for hepatitis C treatment. Having just come from the USA where I was asked about details of the same, it seems to me that there are very different mechanisms in place in different countries which can result in very different approaches to price setting.

Two years ago at this meeting Andrew suggested it might be in the interests of the NHS budget to make a two pill (rather than single pill) regimen available to the UK public through the NHS. This brought criticism from at least one senior Australian clinician and commentator who thought that it would be unacceptable to expect patients to take a less convenient regimen.

Linda-Gail Bekker

As always presented clearly and passionately about the current experience of HIV in Africa and was able to compare and contrast this to other global settings. She is able to mix population and locational differences and introduce a third dimension of how these interact.

Adolescents were for a long time not a priority in HIV prevention. Key affected populations, are largely characterised as being “the-non-majority population”. While recognising this, she introduced an emerged KAP in Africa and that is adolescent women.

Linda-Gail was able to focus on trends which demonstrated changes for the good. It was very interesting to see a map where Australia was pink (on a blue to red scale) for increasing or sustained new infections. While our numbers might not be big they seem to be somewhat intransigent. Many African states have seen dramatic improvements. While more developed settings seem to be finding it difficult to make changes to address persistent, comparatively low-level, new infections. Something which Fauci also recognised in the USA. It would be interesting to see Andrew Hill’s economic assessment of the cost of these different interventions.

A great opening session which augers well for the coming days.

Levinia

We came to this meeting in part to hold a round table discussion about the role of DBS sample collection. Excitingly for us, further exploration of DBS, including through multi-centre collaborations made it onto the list of 4 priorities coming from the meeting.

Dry Blood Spots are a simple way to collect a biological sample for analysis in the laboratory. You use a lancet to pierce the finger-tip and drip blood onto one or more target sites on a sheet of blotting paper. This sample is then dried, sent to the lab (through the mail or easily transported at room temperature) and then analysed in the lab. The spot is punched out of the blotting paper and eluted The lab can test for any number of things including the presence of antibody, molecular, and serological tests. Labs can use their own tests or test which are marketed through diagnostics companies using a variety of analysers.

In order to be approved (and rebated), a DBS claim needs to be made by a producer/supplier when the product is registered. This has been something which has held back DBS sample collection for some time. As tests became more sophisticated and analysers more mechanised, the operator-involved steps in processing a DBS sample probably seemed overwhelming.

But there are many factors which place a DBS sample in good light. Transportablity, durability and stability are all excellent in remote, hard to reach or poorly serviced areas. They also appear to provide an alternative for people who are, for whatever reason, avoiding testing through conventional means.

Two posters which also looked at DBS, both its use in one of the larger format analysers, and as an acceptable sample collection technique for consumers are below.

Validation of the GEN-PROBE^® APTIMA^® HIV-1 RNA Qualitative Assay for use with Dried Blood Spots.pdf

Diminishing Return on Increasing DBS Sample Quantity.pdf

The presentations from the HIV Diagnostics Conference have now been put on line. They are accessible at

http://hivtestingconference.org/2016-hiv-diagnostics-conference/oral-presentations/

You can access the full program from this link and simply click on the desired presentations.

Those who pay much attention to the HIV testing landscape in the USA will be aware that there was a long period where the testing algorithm was debated, discussed and reviewed, resulting in the 'New' algorithm coming into effect in 2014. At this conference it was suggested a number of times that the new algorithm should now be redrafted.

Largely the reason for this is the shift in treatment guidelines and the relationship between testing and treatment. The 'new' guideline was written against a background of selective CD4 and viral load based decisions about when to start treatment. Now, with the emphasis being on starting people on treatment as soon as feasible after diagnosis, the need for repeat testing was questioned. This is an important shift, where one can see treatment and clinical practice driving precursor testing. These issues are discussed in 

Session C: CDC/APHL Laboratory Testing Algorithm and 

Session D: CDC/APHL Laboratory Testing Algorithm (Part 2)

There was a very good round table discussion on Wednesday morning which looked at matching testing approaches to the HIV cascade. Joanne Steckler raised the issue about the large differential between people tested and people lost to follow-up. This comes from work in Washington state, where a great many people who were thought to be lost to follow-up were in fact legitimately in care somewhere else, often no longer in the county or state.  

At the same time, rapid tests, which have been widely used in the USA for many years as part of the testing strategy, particularly in community settings, but also in more remote areas (Alaska, Midwestern and north states) where laboratory access is limited, are becoming less popular.

One of the major reasons driving this is the problems associated with false negatives. As always there was some discussion about the amount of transmission associated with very early infection, and it was interesting that there was a greater linkage between efforts to get people to test, particularly very early after infection, and recognising the limitation of point of care or rapid tests in these contexts. 

Session F: Performance of CLIA-Waived HIV Tests and the session immediately before this examined some of these issues.

Testing was very much seen as the vehicle facilitating the linkage of patients to care. A presentation from Eugene Martin, New Jersey, demonstrated that high level linkage could occur with timely intervention.

The laboratory instrument providers also attend this conference. It seems that many of the analysts have the capacity to perform multiple tests (concurrently, but not yet necessarily all the tests we would like to see in the one run). But this really did seem the next step where the largest leap could be made. This particularly emphasised the need to link HIV testing with related testing in the STI and viral hepatitis areas.

The closing remark gives a good coverage of the scope of the meeting. It was thought there was ongoing need for the meeting and that it would have to, in the context of HIV PrEP, include STI in its agenda. 

The Conference opened with a broad based plenary looking at the new landscape in HIV, often referred to as the HIV Testing 101 Workshop. This is a two hour session which will be on line shortly and really is an excellent overview. It starts out with a glossary of terms and then moves through technology; performance; programs; surveillance and the relationship between laboratory and strategy.

I strongly recommend that anyone setting out into the world of testing watch this session. The slides will all be up on the website some time after the conference and we will advise when this happens.

The USA has recently introduced a change algorithm for HIV diagnostic testing. This raises practical issues for laboratories. But an equally important issue for this conference is how laboratories support initiatives to increase testing (and timeliness of testing) and improve the care continuum.

Details can be found on the website http://hivtestingconference.org  

Key HIV Testing Issues

Key issues in this meeting are how to get testing done early enough and also how to use the best test on an early-after-exposure sample. This will likely play out over the next few days. Clearly the cognitive distance between the laboratory and the clinic is narrowing here. Labs are trying to play a role in the clinical improvements that are sought in reducing the time between exposure and testing. Yet with the increase of self testing, and large scale community clinics with the capacity to perform more complex tests, the laboratory is coming much closer to the community.

With this comes the big question for me: How does one get this information to the person needing testing, at the time that they need it? The Achilles heal in any algorithm would seem to be the differentiation of the population upon which it is performed.

Joanne Stekler (Seattle) discussed this in the breakfast session today. Indicating that the greatest variation between yield on different tests is how differentiated the sample is.  Population-based screening is low yield in low prevalence settings and yield rises dramatically when more targeted testing is performed.

Increased infectivity during seroconversion and early in infection mean it is vitally important to get people to test during this period. Though this has not been discussed here yet, the role of PEP in this context should be reconsidered.

John Brooks from the CDC in Atlanta provided an update on the HIV outbreak first identified in Indiana in December 2014. I reported on his first update from the IAS Conference in Vancouver in July last year.

A couple of things are very noteworthy from these presentations. The response to the outbreak was dramatic, all be it very costly, and effective. What is hugely upsetting is that it could have been prevented with a good public health approach to HIV in the first instance.

A small cluster of HIV infections were identified in a rural county in Indiana. Case follow-up and contact tracing has identified 188 infections. The vast majority of these were identified in the first half of last year with only 11 being identified more recently, and of those the majority had been approached but declined testing previously.

A lot of features made this a perfect storm: no needle and syringe program; high levels of injecting (4 - 15 times daily and sharing with 1 - 6 partners) the reason for this is that the main drug injected was oxymorphone, which sells on the street for up to $140 per tablet, so people inject small doses, regularly to manage withdrawal. High levels of intergenerational sharing, with the belief that this was protective.

The county has the lowest socio-economic profile. Access to health care was limited, many people were uninsured and not registered for social security, unlicensed, not working and did not have common documents such as birth certificates.

This is an excellent presentation which show how a significant epidemic can occur in close knit community with limited access to resources, education and information. Viral sequencing has demonstrated that these were very recent infections and all linked. 

The plenary

http://www.croiwebcasts.org/console/player/29695?mediaType=podiumVideo&

and all of the slides amd MP3 are available at http://www.croiwebcasts.org/y/2016/25?link=nav&linkc=date

There was an HCV positive rate of >90%. But the HCV, unlike the HIV was well established in the cohort, coming from multiple sources over many years. A complementary presentation by Sumathi Ramachandran, Networks of HCV Transmissions Among Persons Who Inject Drugs: Indiana, 2015  looks at hepattiis C infection in this community can be found at http://www.croiwebcasts.org/console/player/29742?mediaType=slideVideo& 

There has been considerable discussion about the potential for outbreaks in rural and remote communities in Australia. This experience is one which should be viewed by all involved in the public health response to HIV and by all those involved in policy making which impacts public health.

This paper reviewed the increase in viral suppression and sustained viral suppression in USA adults on ART between 2009 and 2013.

Viral suppression increased in a linear fashion from 72 - 80% a significant 2% rise year on year. Sustained virological response followed a similar trajectory from 58% - 68% over the same time. This was not explained simply by an increase in number of people on therapy.

Women, 18-29 year old's, 30-39 year old's, African Americans all had a greater benefit than the overall. MSM were higher than the average at all time points.  There were two Guidelines introduced during the study period which actively promoted treatment and barriers and delays to accessing AIDS drugs. All suggesting that policy change is having impacts.

This is Oral paper number 53, in session O-5, if you want to have a look when the presentations go on-line. http://www.croiconference.org/

Sydney Rosen presented this SA randomised trial. Patients in South Africa were randomised to start ART on first visit or delay to standard guidelines (which require CD4 testing and behavioural visits, which can take up to 4-6 visits). Three quarters in the RapIT arm started on the first visit (TB was the main cause for delay in the RapIT arm). The RapIT arm had improved outcomes. It saw greater effect for young people, in primary care clinics and loss to follow up was very low.

The presentations should be on line shortly http://www.croiconference.org/ this one is #28 in Session Oral-2

This WHO consultation followed on immediately from the CDC. This was one of the data collection workshops aimed at feeding into the development of the new WHO resistance testing guidelines. I was the only person in the audience from South East Asia and the Western Pacific. But a survey can be completed on line Insert website.

What was important here is the trade-off between affordable therapy for most people versus switching (and abandoning 1^st line therapy). Willem Venter, from South Africa, cautioned against switching, and introduced the practicality that this would not be affordable, if 85% of people were benefiting from that therapy. Jonathan Shapiro questioned the 15% versus 85% assumption about resistance, and suggested there might need to be more consideration of this.

I raised the issue that there was no-one in the audience from ESA and the Pacific, including Australia. The consultation is open online and I was told consultation would come from the WPRO and SEPRO offices.

http://www.who.int/hiv/topics/drugresistance/en/ 

25^th HIV Drug Resistance Workshop

This is the second time I have attended this meeting. It was very different from last year. Considerable attention was paid to transmitted resistance in the context of PrEP. While this does occur, it does not appear to be persistent.

There were also a number of papers looking at the practical implications of resistance in treatment. A number of presenters reported that resistance may not render a regimen defective. There was discussion about the utility of testing and while resistance testing remains too costly for use in many settings, it was also suggested that many clinicians in developed settings perform resistance testing, but don’t use it in regimen selection. There was some suggestion that resistance testing is becoming less important in the context of newer therapies. One take home message was that the longer people are on treatment, the greater the likelihood to resistance.

Preserving 2^nd and subsequent line therapy was seen as the major reasons for not switching, even in the absence of resistance testing, particularly in low and middle income settings.

Sequencing virus for epidemiological purposes is becoming increasingly important. A number of papers looked at clusters. It was suggested that some virus may be becoming more durable. With 30 clusters in one sample accounting for 1500 infections, while 1300 infections were seen as singleton transmissions. In this study the resistant virus was seen to be as fit as wild type virus. At a practical level what this means a new population is getting infected with lower sexual activity and with a lower testing frequency. There was also an interesting paper looking at clusters among injectors. The abstracts can all be found on line at https://www.informedhorizons.com/resistance2015/pdf/RW2015_Book.pdf

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.

Daily dosing for PrEP seems to be taking precedence over other dosing schedules. This was cast into some doubt when the IPERGAY and PROUD studies were presented at CROI revealing and 86% reduction in transmission for both daily and event driven PrEP. But discussion about frequency of dosing remains. HPTN067 the ADAPT trial reported 2 of 3 arms comparing daily, twice weekly + one dose after event and one dose before and one dose after event dosing. The sites were Harlem and Bangkok. Daily dosing was best in both studies. Doses after sex event were most frequently missed. No risk compensation.

Less than daily dosing is probably effective at some level, but determining that level is the challenge. Having sufficient drug on board to maintain an effective therapeutic dose is the issue and this may be impacted by other host factors such as weight and metabolic rate. If 3 or 4 doses are sufficient to provide protection then this would provide significant cost savings against the cost of Truvada

On the topic of risk compensation, a passing comment was made that if anyone is going to see risk compensation and reduction in condom use it will be the Australians as they are the only people who use condoms.

The ground breaking HPTN052 trial was presented as a complete study yesterday. True to form, the data is compelling. Treatment prevents onward transmission. In a very small number of linked transmissions cause was attributable to not having drug on board, treatment failure and viral rebound, or transmission occurring very soon after treatment commencement, before viral suppression was achieved.

HPTN052 followed many thousands of patients in couples. Monitoring transmission ostensibly between partners. Unlinked transmissions, from a partner other than the study partner (who was on treatment) were more common than linked transmissions. Viral suppression is confirmed as the holy grail. Achieving this is the challenge.

Cindy Zahnd reported on data modeled from the Swiss HIV and hepatitis C Cohort. Specifically the considered the impact of deferring treatment initiation in HIV-HCV co-infected patients. There was not difference starting in a month or 12 months. But treatment outcomes were heavily impacted by fibrosis score at treatment commencement. Delaying till F3 doubled the risk of disease progression and delaying till F4 saw a five fold increase.

Interestingly patients with F4 were more likely to have a serious or fatal liver event even after having had an SVR on treatment. This is probably because even though the virus was cleared irreversible damage was sustained. A salient message for clinicians and patients who might be waiting for the next best drug to come along.

You can view this and other coinfection oral presentations from the http://www.croiwebcasts.org/ it was session O-12 Curing hepatitis C: Mission accomplished

This symposium provided a great analysis of some of the issues confronting prevention efforts. Julie Overbaugh gave a great overview of HIV biology, particularly that period of time known variously as HIV stage 0, pre-seroconversion and/or early infection. She emphasised that this was the period before viral-load peaks and a time where it is very difficult to study what is happening in humans as they are not aware they are infected. Macaques provide the study model, but given the complexity of this period even slight differences between the hosts and the viruses might introduce great variation. So with that caveat she explained that there is considerable dissemination of virus int he first 1 - 3 days and by days 3 - 7 the reservoir is establishing in gut and lymph nodes. The impact of prevention diminishes as the reservoir is established.

She also suggested that there is selective pressure not just from the dominant virus but that CCR5 is more common in transmission that CXCR4 virus, making R5 inhibitors logical for PrEP. CCR5 virus is also more resistant to interferon, which is produced in a storm during infection. She lastly she compared cell to cell infection and cell free virus, and suggested that infection may be facilitated to hindered depending on whether cell to cell or cell free viruses are the target. Meaning that what drives transmission in breast feeding for example may be very different from what is important in vaginal transmission.

Christophe Fraser discussed phylogenetics and gave a detailed analysis of comprehensive sequencing of virus in the Netherlands. He suggested that about 69% of new infections were originating from the undiagnosed and ~24% from diagnosed but not on treatment and only 7% from people on ART. Immediate treatment could be expected to result in a reduction of between 25-30% of transmissions. PrEP and treatment might result in a reduction of 50-60% of infections, summarising that there is a lot to do to push prevention beyond where we are now.

Richard Elion building on the this reviewed optimising ART and looked at Treatment as Prevention. He made the statement that "we can't just treat our way out." He suggested that we need to better know where infections are occurring in populations and compared the treatment cascade between a number of countries. But to illustrate this point he then dissected the 19% of people with HIV in the USA who are estimated to have suppressed virus a number of ways: 6% of people under 30 and 28% over thirty; 16% black MSM and 34% Caucasian. He also questioned some of the definitions within the cascade. and challenged what was meant by "in care" when 74% are in continuous care while 26% are in only sporadic care.  He ended his talk by looking at how to engage the unengaged and identified: stigma, delivery methods, integration of bio-medical approaches and resourcing as the critical issues. This led seamlessly into the last talk.

Jeffrey Crowley looked at HIV criminalisation and suggested that laws are not protective, even though law makers might want them to be. And in places with a high prevalence it is unrealistic to expect the assumption of negativity. He pointed out the important role of health care workers in educating about HIV and pointed out that provisions such as anti-discrimination legislation are not sufficient alone to remove stigma.

Australia was referred to in the questions. A country which has excelled in the response but which is still seeing sustained incidence. The strong take-home message from this session was the importance of biomedical prevention to interrupt the the establishment of infection. This will challenge many attitudes but it may, in combination with treatment and testing, be the only way to significantly reduce new infections, particularly in settings, such as ours, where retention in care, treatment and viral suppression are approaching their maximum potential. 

The session was symposium S-5 4.00 pm - 6.00 pm Wednesday Advancing HIV prevention. You can view it from the webcast http://www.croiwebcasts.org/

CROI formally opened yesterday evening. The format for the opening session of this conference is reliable and runs to its own format. Very little formality, straight into the science and accessible.

This year the first plenary, dedicated to Bernard Fields, was on Hepatitis C, a tiny bit of co-infection but largely monoinfection. It was given by Charlie Rice from the Rockerfeller. Hepatitis C has increasingly been making inroads into CROI and I think this is a great move. Rice commented on the prominence of HCV in this program. While it is not a retrovirus, it is a common opportunistic infection of HIV and we were told that globally about a third of people with HIV also have hepatitis C.

Like all good plenaries the lecture was general enough to be understood by a wide audience, covered the history, outlined some of the challenges and did some speculating. If you are looking for a comprehensive timeline for HCV science have a look at the earlier slides in this presentation. I found it very informative.

Hearing about the problems scientists have experienced in working with the virus were interesting, but I couldn't help thinking "they can't have been that difficult or you wouldn't have got to a cure so quickly." Charlie then went on to summarise the great leaps in treatment efficacy, which I think most of the Australians are familiar with.

In closing he revisited his comments about the difficulties in not have animal models and the practical issues this causes in looking at things like:

• why some people don't respond to treatment
• why others do or don't have improvement in their liver health, and
• why still other's go on to develop liver disease or cancer even if the virus is cleared.

At that stage I ate my words about cure.

The last few minutes of this talk were very poignant:

• about a trillion visions are produced each day,
• the drugs have the potential for resistance resistance, and
• efforts have been focused on treatment rather than vaccine development.

Lastly, accompanied by a photo of the lab dog, he summarised some of the potential animal models. I recommend that you have a look at the presentation. It is up on the CROI webcast site http://www.croiwebcasts.org

Plenary 1, Presented by Raphael Landovitz is available for viewing http://www.croiwebcasts.org/

The speaker address a number of the common concerns associated with PrEP:

• Decreased condome use, not being observed and high risk individuals self selecting for PrEP
• Resistance not emerging (at least in early data)
• Safety and adverse event (low and stop when PrEP stopped)
• Supporting adherence, needs to be multifaceted
• Optimal deployment is still to be determined

The big issue with all studies is that:

“Drugs don’t work in patients who don’t take them”

Interestingly Landovitz suggested that primary care providers are best placed to manage PrEP with their patients as they have long standing relationships and service negative patients. Specialists on the other hand see patients once they have HIV and may be in clinics which negative people avoid. He also suggested that generalists are least well equipped with information and education. This is a very interesting comment from the Australian perspective where so much HIV care happens in general practice.

He also suggested that optimal deployment will require a multi-pronged approach with information for health care providers, patients and from professional and clinical organisations and government providing clinical guidance. I recommend the talk, particularly for people wanting a comprehensive overview of contemporary PrEP science and implementation.

Three exciting and anticipated papers were presented in the Oral session #1 this morning.

Sheena McCormack (abst 22LB)presented the PROUD study, which was designed to see if previous results could be achieved in a "real world setting", 539 people were randomised to 2 years once daily dosing with Truvada and 545 to a one year delayed therapy arm. The study was stopped late last year due inferiority in the deferred arm. There was an 86% reduction in transmission in the treatment arm and the three seroconversions is this group were probably infected or sero-converting at the outset. There were few side effects and the study population was at high risk of HIV.

Jean-Michel Molina presented IPERGAY (abst 23LB) this study looked at "on-demand PrEP" to see if efficacy achieved in macacques treated before and after exposure could be achieved in a real-world setting. The regimen was 2 pills 2 - 24 hrs before sex, one after sex and a further pill 24 hrs after the first dose. If there was more than one encounter the daily PrEP was prescribed. The results were also an 86% reduction in transmission and transmissions were again observed in participants who were either infected at the start or who had ceased taking drug. This is a very important study as it provides an option for people who have only limited high risk exposures. Side effects were minimal and stopped when the drug was ceased. Importantly from a cost effective standpoint. 18 pills per year were required to avert and infection and the average was 16 pills per month or 4 pills per week. This study will require close further scrutiny and could be a game changer.

Bob Grant (abs #25), from the San Francisco AIDS Foundation looked at what would be required to achieve transmission reduction targets. He found a combination of PrEP, increased treatment and testing together had the greatest impact. Importantly he reported that people who were taking PrEP were at high risk. Other were interested in taking it or interested but wanted more information. These people were eligible and given access had the potential to drive down infection rates.

The talks are available on line at http://www.croiwebcasts.org/ I really suggest considerable attention is given to this important session.