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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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It was the final day of this  truly wonderful global congress. 

Chloe Orkin of the Department of Infection and Immunity at the London Hospital co-chaired the opening session of the day and discussed some great advances in HIV research this year including:

. Phase 3 TDF v TAF trials

. Injectable PrEP

. ?generic 3TC/TDF

. New delivery methods

. New molecules

Sheena McCormack of the MRC clinical trials unit at University College London provided us with PrEP updates and effectiveness, highlighting:

. the overwhelming evidence of its efficacy

. Population effectiveness not compromised by resistance

Based on the evidence, she concluded that moving into the future, there will be more drug choices for PrEP, different regimen choices (episode driven) and a multitude of delivery methods (vaginal rings/injectables).

One of the day's most thought provoking presentations was delivered by Keith Rawlings from Gilead Sciences medical affairs. He reported that despite a steady increase in PrEP use since 2012, data showed there was a huge discrepancy in those who accessed it. He stayed that it was heavily weighted towards middle class caucasian MSM.

This was despite an increased lifetime risk of HIV acquisition of:

. 1:20 for African American males

. 1:48 for African American women

. 1:48 Hispanic males

 

 And when broken down further:

. 1:2 African American MSM

. 1:4 Hispanic MSM

as compared to 1:11 in Caucasian MSM

FTC/TDF for PrEP has been disproportionately low in the higher risk populations in the USA.

It was recommended that to effectively decrease new HIV infections, messaging and services need to be more focused on those populations with the greatest disease burden. 

It's been an incredible 4 days here in Glasgow which has sadly come to an end. I look forward with great anticipation to the next Glasgow HIV Drug Therapy Congress 2018 and anticipate further advances will continue globally in HIV management thanks to the many innovative and brilliant researchers working in the field.

 

 

On Day 3 of the Glasgow Congress, Dr Teymoor Noori from the ECDC in Sweden spoke about his organisation’s efforts to increase HIV testing rates among MSM during European HIV Testing week in 2015 and 2016 using pop-up messages on mobile phone apps.  In the EU, MSM account for over 40% of all diagnosed cases of HIV, and it is the only group where increasing HIV rates are being observed.  

 

The ECDC rolled out push messages for a one-week period on commonly-used hook-up apps – Hornet, Planet Romeo and Grindr – which linked to the AIDSMAP website where users could locate their nearest HIV testing facility.  In the week of 23-29 November 2015, they had over 70,000 page views, although it was not possible to track whether this led to increased testing.  In 2016 they are planning to expand the message to include viral hepatitis and STI testing sites. 

 

This intervention was large scale and was free, due to the enthusiastic support of the CEOs of the app companies approached for improving public health initiatives.  There are plans to work together with app owners to creatively embed test finders in their apps.  A lot of work has been done in this area by the Terrence Higgins trust and SOAIDS in Sweden, who are developing guidelines for sexual health and HIV organizations to cover issues related to promotion, education and marketing via social media, mobile apps, and the internet. 

 

Tarandeep Anand from the Thai Red Cross AIDS and Research Centre, Bangkok, gave a fascinating presentation on the use of the internet and public apps to address the HIV epidemic in Thailand, where 1 in 3 MSM are HIV positive.  Studies have shown that MSM and transgender people in Bangkok spend an average of 7-8 hours per day online, and are accessing the internet on average once every two minutes.  The website Adam’s Love is being used as an electronic health record portal to screen high-risk populations for PrEP, book clinic appointments (using the Eventbrite system), provide free online counseling, and provide test results and customized daily reminders to take tablets for PrEP.  Tarandeep commented that there has been more success adapting already-popular websites to provide these services rather than custom-build health websites or private apps. 

 

Later in the morning, Dr Francois Houyez, from the European Organisation for Rare Diseases in Paris, spoke about the use of medical apps and privacy issues.  He stated that medical data is high in the list of favoured information targeted by hackers, according to IBM, and legislation related to the use of new technology in this area is evolving and is still “catching up” to new uses.  

 

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. 

Enjoyable last day, great morning sessions discussing PrEP and The way forward. I managed to sit through all presentations as I felt that I may pick up on some information which I found interesting and I could take home. I have truely enjoyed this conference and feel I have learnt so much and can't wait to share to anyone who will listen.

I feel I could make a difference in Refugee Health as I would like to commence education on my return. Where and how could I commence this? Currently, I believe NSW refugee nurses aren't discussing Sexual Health to the extent it needs to be discussed. I am going to talk about HIV and STI's at my initial nurse assessment and would like to talk about this conference to other Refugee nurses. Humanitarian refugees have already had a HIV test prior to coming to Australia. Depending on the country of origin, depends on the clients sexual health knowledge and from experience, I have found that most refugees and the CALD populations have had no sex education prior to coming to Australia. 

I would invite other organisations such as FPA and the Sexual Health service to help with education. Another possibility would be to educate at my outreach clinic at TAFE Newcastle. I am unsure of the numbers of NESB clients living in the Newcastle area with HIV. Don't forget to use interpreters for NESB's and give houndouts in their first language.

My role will now include discussion around safe sex, sexual health, informing clients of services which can provide testing, online websites and Apps and to provide this information in their first language if they are literate. 

2017 celebrates 30 years of ART's and I look forward to immersing myself in new literature and research. Very exciting research and clinical trials looking at durable remission/cure which may also include the 're-building of the immune system'.

Thankyou to ASHM for this scholarship which has made me so excited and full of energy to go and educate Refugee nurses around Australia in all that is offered regarding sexual health. There are so many exciting trials happening around the world and I am optimistic that someone will find a cure. I also want to look into the App world more to see how we can use the tool for research. Since HIV has been classed as a chronic illness, I wonder how clinicians are keeping their clients on a happy, healthy pathway since the clients are living longer? This is a discussion that we should have later. It is difficult to motivate clients to continue medication regimes when they feel well and we see this in psychiatry and clients with diabetes. Just 'food for thought' . Cheers Karinne

 

One of the focuses of Day 3 of the HIV Drug Therapy Glasgow Congress was co-morbidities and HIV management, and how this affects patient care.

Dr Edouard Battegay from the University Hospital in Zurich presented in the morning on multimorbidity in HIV infected people as they age.  He stated that multimorbidity (the presence of multiple concurrent medical conditions) often occurs in clusters, and the complexity of managing the conditions, including potential drug-drug interactions, increases exponentially with each additional condition.  Common clusters in HIV–infected people include hypertension and dyslipidaemia, and pain and depression. 

 

The EACS guidelines for 2016 are one of the first sets of guidelines to systematically address comorbidities in DDIs in a specific disease.  Dr Battegay’s presentation prompted discussion of the relative and overlapping roles of HIV specialists, primary care physicians and specialists in managing these multiple conditions as the focus often shifts from the HIV infection, which is often stable, to management of the individual’s comorbidities.

 

Expanding on this exploration of the needs of the ageing HIV-positive population, Dr Charles Cazanave from France spoke about the results from a cross-sectional analysis of the ANRS CO3 Aquitane cohort.  He described the evolution of chronic non-HIV related disease and their risk factors in 2,138 patients included in this cohort between 2004 and 2014.  The mean age of the cohort increased from 42 to 52 years and the majority (71%) were male. 

 

He found that there was a significant improvement in HIV markers over the ten-year period, but also an increase in renal and cardiovascular risk scores, with rates of dyslipidaemia increasing by 40%, and rates of hypertension increasing by 37%.  There was also a high rate of smoking in this cohort (40%), reinforcing the importance of addressing lifestyle factors in comprehensive HIV management.  One of the limitations of this analysis was that there wasn’t a HIV-negative control group for comparison to see what happens to the rates of these conditions in the general population over a similar ten year period.

 

Is HIV-related lipodystrophy associated with an increase in the risk of morbidity and mortality?  Dr Estaban Martinez’s 20 year longitudinal cohort study asked this question and found that, contrary to their initial hypothesis, lipodystrophy or lipoatrophy (but not lipohypertrophy alone) was associated with a reduced risk of death in the group studied.  This was thought to be due to the fact that in the cohort studied, the presence of lipodystrophy is a proxy for effective viral suppression with antiretroviral medication.  LA, LD and LH were, however, all associated with an increased risk of hypertension and diabetes. 

 

Finally. Dr Davide de Francesco reported on results from the POPPY study in UK and Ireland, which showed that the HIV-positive people studied exhibit poorer cognitive scores when compared to controls, and there is a correlation with increased scores on depression-rating scales.  He concluded that reduced cognitive function may be mediated by depression or the two conditions may in fact be related to the same, as-yet unelucidated, pathophysiological process.   

 

 

Day 4 started with a session on PrEP in High Income Settings with a panel from USA and Europe and Jean -Michel Molina from France where PrEP has already been implemented.

It was interesting to listen to the discussion - everyone was in agreement of the value of PrEP and no-one had concerns about resistance or side-effects. There was debate about daily PrEP or on demand PrEP and how the choice will improve uptake and adherence.

There was concern about the cost of PrEP and who will access it and Keith Rawlings from Gilead in USA gave an excellent presentation on the demographics of the HIV positive population in the USA and the demographics of the PrEP accessing population - those that need it most do not access it.

There was also an interesting presentation about delivery modes - tablets, long acting injectables or slow release preparations - a Dapivirine vaginal ring.

Should treatment for Rectal Gonorrhoea and Chlamydia include PrEP??

The most surprising statement that was made today was in the last session of the day by Dong Wie from Nanjing China. In China, they only have access to six antiretroviral drugs. I found that difficult to believe but made me appreciate the range of drugs that we have in Australia.

Day 3 started with an excellent Symposium " Helping the Patients Stay on Course"

The session started with the importance of adherence to treatment and the barriers to this - the most common one being depression. 45% of cases of depression do unrecognised in HIV clinical care so if we are to look at the 90 90 90 target we need to make sure that we address the Mental Health needs of our patients to start to attempt to address this but more important is the fourth 90 - the quality of life.

Moises Agosto is a PLWHIV who is a Public health Physician and he gave a very personal account of the patient aspect and the doctor aspect. He also addressed the ageing of the HIV epidemic and the impact of comorbidities becoming more important after the age of 50 years.

The second session was  "Comorbidities and HIV management"and looked at the needs of HIV patients today and 10 years ago - particularly cognitive function and neuropsychiatric events - in particular looking at discontinuation of treatment due to adverse drug interactions and side effects.

During the lunch break there was a very interesting session on APPS and New technology in the Management of HIV infection and using social media to get the messages out to the target audience.

There was also discussion about medical APPS and privacy issues - should we be worried about confidentiality?? Should the medical APPS be developed by clinicians or IT gurus? 

Andri Rauch presented a very interesting session on HCV therapies and the remaining challenges - the take home message for me was that an SVR reduces the risk of HCC but does not eliminate it - do not forget the HCV treatment successes because they may not be a long term success.

 

Day 2 was amazing

The day started with the Lock lecture delivered by Julio Montaner from British Columbia. The overwhelming messages were:

Treatment as Prevention to prevent morbidity and mortality

ART is 100 % effective in preventing vertical transmission

While the end of the pandemic may be in sight, we need to be vigilant as there are problematic clusters of HIV emerging all the time and there is potential for the fire to be rekindled.

Jens Lundgren from Copenhagen provided a convincing argument for early vs deferred treatment but warned that CVS risk protection was not convincing with early treatment.

Cheryl Johnson from WHO Geneva provided a very insightful talk on the barriers to HIV testing and it is very apparent that this is the area that we need to improve upon if we are to meet the 90 90 90 target. The identification of the positive patients is the most important part of the cascade and we are still failing to identify them.

There was some controversy over HIV self testing and "At Home" STI screening but it was a suggestion to be able to test more people and reducing the stigma of having to go to a test centre and have the test. Also need to look at the accessibility of testing to patients - hours of opening and outreach centres.

Also discussed was differential ART delivery and the number of times per year that a stable patient needed to see a doctor.

There were a few Interactive cases which were very practical and could have been adapted to suit the practice of most of the clinicians in the audience.

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.

 

Andri Rauch, Bern University Hospital and University of Bern, Switzerland presented on the achievements and remaining challenges of Hepatitis C treatment.

We have all been fortunate to witness the breakthrough in HCV treatment from interferon-based regimens to DAAs:

  • Interferon acts by unspecific activation of innate and adaptive immune responses.
  • DAAs are specific and highly efficient in inhibition of the HCV life cycle.

The improvements in treatment efficacy in SVR genotype 1 infection:

  • by HIV status:
    • HCV SVR (cure) in both HIV/HCV co-infected, as well as HCV-monoinfected patients used to range from ~40% clearance in HIV/HCV co-infected patients to ~50% in HCV-monoinfected patients using PegIFN/RBV alone
    • Treatment with DAAs are now showing cure rates over 90% (and in some cases even up to 100%) in BOTH the co-infected and monoinfected patient
  • by cirrhosis status:
    • Cure rates of just over 30% have been observed in patients with cirrhosis who underwent treatment with PegIFN/RBV alone. The numbers were slightly better for patients with no cirrhosis at ~50% SVR on the PegIFN/RBV regimen
    • Treatment with DAAs are showing cure rates of ~95% and over.
  • by IL28B status:
    • SVR in IL28B risk allele were ~30% when PegIFN/RBV was used, compared to ~75% in IL28B protective allele carriers on the same regemine
    • Again, different DAA combinations show cure rates very close to 100%

Thus, DAAs achieve high cure rates irrespective of host and viral characteristics.

Changing from complex to simple treatments resulted a few (very welcomed) changes within the past 5 years:

  • Single tablet regimens
  • Treatment durations of 8; 12 or 24 weeks (depending on HCV genotype, cirrhosis status and past DAA failure)
  • No requirement for response-guided decisions
  • Minimal monitoring required

Andri discussed the remaining challenges:

  1. Difficult to treat: cirrhosis, NS5A RAS, GT3
    • lower SVR in GT3, cirrhotics and those with NS5A RAS
  2. Difficult to treat: renal impairment eGFR <30mL/min or haemodialysis
    • Suggested options for GT 1 and 4:
      • ombitasvir/paritaprevir/r +/- dasabuvir
      • grazoprevir/elbasvir
    • Other genotypes:
      • use sofosbuvir-based regimens with caution
      • close monitoring of renal function
  3. Drug-drug interactions:
  4. Events after SVR if therapy is started too late:
    • clinical improvement moderate in patients with decompensated cirrhosis with SVR
    • SVR does not eliminate risk of HCC
    • deferring treatment increases risk of liver-related events:
      • persistent metabolic risk factors
      • co-infections
      • liver toxicity due to drugs alcohol or co-medication
      • genetic predisposition to accelerated liver fibrosis
      • reversion of liver fibrosis/cirrhosis is frequent but not universal
  5. New epidemics and reinfections
  6. The cascade of care: comparing HCV with HIV (following the 90:90:90 targets). Increase of treatment rates to reduce prevalence by 90% in 2030.
  7. Affordability and reimbursement restrictions
    • Due to cost the DAAs are not readily available in many countries
    • The costs of treating all patients with hepatitis C would be equal to at least a tenth of the current annual cost for all medicines.
  8. Treatment-as-prevention and risk behaviour
    • Stabilisation in high-risk behaviour combined with an increase in treatment uptake is required to curb the HCV epidemic among HIV-infected MSM.
    • If this can be achieved, treatment-as-prevention can reach to HWO elimination targets (90% reduction in new cases by 2013)

In summary:

Goals of HCV therapy: achievements and challanges.

  • Cure HCV infection
  • Minimise adverse events
  • Provide universal access to therapy
  • Prevent HCV transmissions

 

Speaker: Edouard Battegay from the Centre for Competence Multi-morbidity (MM) at University Hospital Zurich.

Between 20–30% of the population and about 90% of inpatients hospitalised in General Internal Medicine have multiple concurrent acute or chronic diseases.

 He spoke about most prevalent triads seen at their out patient clinics such as combination of hypertension, dyslipidaemia, with chronic back pain/ osteoarthritis/diabetes mellitus or coronary heart disease, in people living with HIV. 

There are limited evidence-based guidelines for MM, be it without or with HIV, even for more prevalent forms of MM and frequent interacting combinations. This leaves MM care heavily reliant upon clinical guidelines intended for the treatment of single diseases.

He informed the audience about the new version of EACS guidelines (released 3-4 days ago) with new additions on managing MM.

The link to new edition of EACS guidelines;

http://www.eacsociety.org/files/guidelines_8.1-english.pdf  

Speaker - Brian Pence from the University of North Carolina 

His talk addressed a very common barrier to HIV care and treatment - mental health concerns, discussing  previous publications in the early years of the epidemic about responding to psychological crisis of HIV/AIDS. It is still a challenge faced by many of us, more than 30 years later. He gave an overview of psychological trauma and the heavy burden of stressful life events of many people living with HIV leading to chronic mental health issues in addition to stressful risk behaviours, immune suppression and side effects of antiretroviral therapy.

He showed data on depression and mortality in modern ART era from the WIHS cohort (in press) as well as in the early ART era from HERS cohort (Ickovics et al.JAMA 2001) where chronic depressive symptoms were reported commonly in patients with CD4 <200. 

Barriers to addressing mental health concerns among people living with HIV;

  • Lack of mental health expertise in HIV care settings
  • Stigma around mental health services
  • Access to specialty metal health services
  • Fragmentation of care

The concept of depression care managers where a nurse, social workers or a medical assistant is trained to assess and help clients with depressive symptoms under the supervision of psychiatrists,helping the HIV care providers to deal with mental health concerns of patients was a highlight in his talk.

The ways to move forward - it is necessary to think of,

  • How best to integrate evidence-based mental health approaches into HIV care
  • How to engage patients in mental health services
  • How best to address multiple psychiatric co-morbidities
  • How best to integrate mental health treatment with other adherence/retention support strategies

 

 

The weather has been very kind to us and has been very un-Glasgow like since the start of the congress. For the second consecutive day, a piper welcomed us to the SECC.

It's truly humbling to be in the presence of all these wonderful researchers and inspiring to see all the advances being made in the management of HIV. The focus of many of today's presentations was on HIV and ageing, associated co-morbidities, co-infections, malignancies and mental health. The need for improved screening programs was a recurring theme.

We were again reminded of the 2020 goals which aim for 90% of people with HIV being diagnosed, 90% diagnosed on treatment and 90% on treatment with an undetectable viral load. 

Highlights of the day for me included an interesting presentation on 'ARV Optimisation to meet patient needs' by Mark Nelson from the Chelsea and Westminster Hospital. He referenced a questionnaire/survey conducted by Redlin in 2014 comparing what health care providers and patients considered important when it came to HIV care and ARV therapy. Interestingly, efficacy of treatment was ranked highest and cost ranked lowest by both arms. 

The day was concluded by Fiona Mulcahy of St James Hospital who presented a complex case study of a young immigrant woman with a new HIV diagnosis who was planning pregnancy with her new partner of unknown HIV status. Disclosure was certainly an issue and the consensus was that he should be tested as soon as possible and that she should commence ART. The various options for reducing transmission of HIV to the male partner were discussed, including PrEP. There was some debate and conflicting opinion on how the couple should proceed, though the presenter suggested she would recommend natural conception as long as her viral load was undetectable. 

The congress sadly concludes tomorrow. There are some  exciting presentations to look forward to, including, but not limited to PrEP, the future of ARV's, drug interactions and new drugs. 

 

Tiring but another interesting day at the conference. I am noticing two interesting themes which are coming from most presentations and that is - as the HIV population become older, more co-morbidities are occurring like cardiac, psychiatric, renal, bones, pain and all the issues that become apparent as we grow older. The presenters have pushed the message for these clients to be seen by the specialities that care for each complex issue and that all specialties communicate between each other. 

The second theme was the fact that the younger generation are becoming infected with HIV and how do we engage this cohort in taking care of their health? Tandeep Anand from Thailand gave an interesting talk and statistics are as follows, 1 in 3 in Thailand have HIV and the majority use their mobiles between 7 - 8 hours per day and a high proportion monitor their health needs via their phone. Jennifer Whetham from Brighton, UK had also stated that >90% of 16-24 year olds have mobile phones. Reminders and Adherence is currently what Apps are used for and we must continue looking at ways Apps can be better utilised for health information.  Francois Houyez from France spoke about privacy issues for medical Apps which was also interesting. He asked, do health Apps loose real contact?, Apps shouldn't replace face to face consults and probably could be used for the stable client and not to forget that our "data belongs to business". I am really enjoying soaking up all the evidence and research that is being done from around the world, this conference has been a real eye opener and one that I look forward to discussing with my peers on my return.  Cheers Karinne

Day 3.

 

This morning’s session was largely about psychosocial issues in people living with HIV.

 

Moisés Agosto-Rosario (an educator and advocate for people living with HIV) spoke about communication and ways in which we can improve this. He emphasised that it must be patient-focused, and must consider the sensitivities of those “key groups” at risk of HIV (sex workers; MSM; PWID; trans people; CALD people). He finished by stating that by 2020, 70% of people living with HIV will be >50yo (I imagine that this was a US statistic, but he didn’t specify), so we must be prepared for the increase in comorbidities that’ll come along with an ageing population living with HIV.

 

David Stuart (from Dean Street Clinic, London) spoke about the change in culture of the MSM community, with specific reference to:

-       The social scene (hookups often through apps as opposed to in person)

-       The drugs used (crystal/GBL/mephedrone in London)

-       Risk-taking behaviour

Of the HIV-infected patient group they see, several have died in the past 12 months – but all were from drug-related issues (not from HIV/AIDS), highlighting the importance and risk of drug use in this population. He also emphasised the importance of doing “well-being” checks at each visit, including social and emotional well-being.

 

Changes in morbidity/mortality/HIV care – a cohort study over 10 years in France.

Charles Cazanave spoke about research they’re doing in Aquitaine, France, with the ANRS CO3 cohort, to assess how the needs and morbidity of people living with HIV change over time. They had a cohort of n=2138 that they recruited in 2004 and followed until 2014, following their HIV-related characteristics, as well as other patient factors and co-morbidities.

-       71% male (40% MSM)

-       52% were over 50 in 2004 (and obviously 62% in 2014)

-       91% had HIV VL<50 in 2014 (compared with 51% in 2004)

-       72% had CD4>500 in 2014 (c/w 44% in 2004)

-       ART regimens changed little between 2004 and 2014 (except integrase inhibitors being used in 6.5% in 2014).

-       Dyslipidaemia rates increased by 40% and hypertension by 37% over the 10 years

-       Cardiovascular (increased by 6.1%) and CNS adverse events increased over time; rate of people with EGFR<60mL/min increased by 5.1%; those with Framingham score indicating high risk increased.

Unfortunately there was no control group with which to compare these increases. However they concluded that monitoring for and management of co-morbidities is imperative in an ageing population with HIV.

 

Effect of lipodystrophy on morbidity/mortality.

Esteban Martinez presented research on the connection between lipodystrophy on risk of morbidity and mortality – their hypothesis was that lipodystrophy may increase the risk of comorbidities/mortality in people living with HIV.

They studied a population (n=494) that began CART between 1996 and 1999 – this CART initially involved 2 x NRTIs and at least 1 PI. 76% were men; 28% were MSM; 39% IVDU. Follow-up was until Dec 2015 or death (14%) or loss to follow-up (21%).

-       24% had lipoatrophy

-       4% had lipohypertrophy

-       18% had lipodystrophy (both lipoatrophy and lipohypertrophy)

Analysis of death rates, morbidity and lab testing by the end of Dec 2015 revealed:

-       Fewer AIDS events and fewer deaths in those with LA/LD, however no association with lipohypertrophy (however note the small number of people with lipohypertrophy).

-       Less hepatic decompensation in those with LA/LD.

-       Hypertension/diabetes rates increased in those with LD/LA/LH.

Conclusions were, unsurprisingly, that lipoatrophy was a proxy for effective CART and viral suppression, so morbidity/mortality overall less in this group.

 

Dolutegravir and cessation due to neuropsychiatric effects.

Michael Sabranski presented an analysis of all those beginning integrase inhibitors in Germany between Jan 2007-April 2016. All discontinuation reasons, start and stop dates were analysed.

-       In those that took dolutegravir, other covariables were analysed.

N=1704

The study found that:

-       The discontinuation rate of dolutegravir due to neuropsychiatric adverse effects was almost 6% within 12 months – this rate was higher than that reported in RCTs (and higher than for raltegravir/elvitegravir)

-       Women, older patients and patients who simultaneously initiated abacavir had a 2-3 fold higher risk of DTG discontinuation due to neuropsychiatric adverse events.

-       Such adverse events were reversible and not severe.

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It was acknowledged that a higher rate of people ceased DTG in 2016 (after research had already come out linking DTG with neuropsych side-effets. However even when those patients were removed, the relationships listed above were still significant.

Posted by on in Testing and Treatment

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.

The session . On. HIV and cancer  was a rapid overview anD quite  focussed on the French experience -

HIV and cancer - DR Jen Philippe Spano -france 

RIsk factors- Age, HIV, oncogenic infections (HPV, EBV, HCV, HBV, HHV8), smoking, inflammation, sun (melanoma), low CD4
 
cART relative risk -non AIDS cancer with inc risk - inc Hodgkins 19 RR, anus and liver and lung - often occurs at YOUNGER Age  than HIV neg counterparts (Not inc risk of breast ca, prostate or colon ca) 
 
SMOKING is the trigger for the oncogenic viral infections to have their effects; 
-HIV contributes to inc risk of non aids cancer when adjust for smoking and oncogenic viral infections cf the general population;
 
LUNG cancer-in HIV pos pt in France, this is the highest ca diagnosed; 
Screening in the Gen pop- - CT scan- false positive nodules, may lead to false pos, used for diagnosis;
One study showed (not specifically HIV pts) annual low dose CT scan was better than CXR and resulted in reduced mortality 
 
-in France did a study in HIV pos smokers , low dose CT annually, 400 pts, 10 pts were diagnosed with lung Ca, mean CD4 high, problem  is the high  rate of other pulmonary comorbidities and false pos rate and biopsy, anxiety etc to investigate these further 
 
SKIN malignancies- eg BCC, SCC - should have regular annual examination;
RFx -Sun , FH, aging 
 
IN France, all patients in Gen population diagnosed with these cancers recommended to have HIV test . 

PrEP case jean michel Molina

I  have  been  enjoying the  conference very much. a short session  on
PrEP- with 2 cases-
CASE 1 Discordant  couple HIV pos male, neg female wanting to be pregnant- him not yet on ART-
-enc partner to start ARV (This is more effective than PrEP) and cont using condoms, consider PrEP for her-PrEP-TDF alone risk reduction in women 71% in discordant couples when pos partner NOT on ARVs; if drug found in plasma, then inc efficacy to 80%; TasP more effective wth 96% reduction in linked transmissions.
 
HIV incidence was  0.2 per 100 yrs per person yrs when TasP and PrEP  used together 
Consider using condoms too;
 
-If they want a baby - and partner started on ARV but not yet fully suppressed- 
 could start PrEP-let them know that not yet fully studied in pregnancy, in real life, they present already pregnant' -does she need it? If partners VL is down to 60 copies/ml- depends on the risk they are prepared to take.
May take a bit longer til his VL undetectable and use PrEP
 
If parter has UDVL for 6 months, may not need PrEP to prevent infection, but if pt needs reassurance then can use PrEP 
 
HPTN 052 now has 5 yr follow up -93% reduction in incidence of linked transmissions. 
8 linked cases of linked infections- most early on day 35-84 after starting ART, no linked infection when HIV stably suppressed to <400copies/ml 

Christian Callebaut, Clinical Virology, Gilead USA, presented the findings of their clinical trial GS-US-292-0119.

Virologically suppressed, treatment-experienced patients on complex multi-tablet regimens were randomised to either switch to a simpler, more convenient antiretroviral regimen or remain on their current optimised ART.

After 48 weeks:

  • The regimen consisting of E/C/F/TAF DRV demonstrated maintained viral suppression in 94.4% of patients.
  • In the DRV-containing “Stay on Baseline Regimen” arm, maintained viral suppression was 76.1%

All patients had documented resistance to 2 classes of antiretroviral (ARV) agents at baseline. Detailed ARV regimens and the resistance profile of the study population are described.

Study methods:

The Stanford HIVdb algorithm version 8.01 was used to calculate genotypic susceptibility scores (GSS).

For each drug, a 5-point scale was used:

  • Susceptible = 1
  • Potential low-level resistance = 0.75
  • Low-level resistance = 0.5
  • Intermediate-level resistance = 0.25
  • High-level resistance = 0

 The total GSS for a given regimen was calculated as the sum of the scores for each individual drug. 

Results:

A total of 94.8% had documented resistance to 2 classes of ARVs, including:

  • protease inhibitors: 34.8%
  • non-nucleoside RT inhibitors: 88.1% and
  • NRTIs 94.8%.

The most common resistance associated mutations (RAMs) were:

  • Protease Inhibitor RAMs: L90M (15.6%) and V82A/F/L/S/T (14.8%).
  • NNRTI-RAMs: K103N/S (63%) and Y181C/I/V (19.3%) and
  • NRTI-RAMs: M184V/I (83%) and K65R (23.7%).

Thymidine analog mutations (TAMs) were present in 42.2% of patients (59.6% with one or two TAMs and 40.4% with three TAMs). 

The distribution of GSS at study entry was similar across treatment groups.

Patients in the E/C/F/TAF DRV arm maintained virologic suppression similarly, regardless of the DRV dosage received before switching (33/33 and 51/56 with treatment success in the 600 mg BID and 800 mg QD groups, respectively).

In the E/C/F/TAF DRV arm,

  • 11/89 patients (12.4%) had GSS <2,
  • 51/89 patients (57.3%) had GSS ≥2 and <3, and
  • 27/89 patients (30.3%) had GSS ≥3.

Within each treatment group, patients maintained virologic suppression similarly regardless of their GSS at study entry.
 

Conclusions:

  • Despite the high incidence of pre-existing resistance in this population, including resistance to ≥2 classes of ARV agents and presence of K65R or ≤3 TAMs, strategic simplification to E/C/F/TAF DRV was statistically superior to staying on the baseline regimen.
  • Patients benefited from switching regimen regardless of their prior DRV dose and their GSS.
  • Treatment with E/C/F/TAF DRV offers a simpler and more convenient option for treatment-experienced patients on complex multi-tablet regimens.

Details of the study can be found here: https://clinicaltrials.gov/ct2/show/study/NCT01968551

 

 

 

 

96-week data from ATLAS – M trial – a multicenter, open labeled, randomized trial on simplification to atazanavir/ritonavir and lamivudine versus maintaining atazanavir/ritonavir with 2 NRTI (Triple therapy) in virologically suppressed HIV infected patients was presented by Roberta Gagliardini, Catholic University from Rome, Italy.

  • A total of 266 patients (78%males with a median CD4 of 603 cells, 79% of them had Tenofovir in their treatment regimen) were enrolled in this trial.
  • 96 week data were available for 254 (126 in dual therapy arm and 128 in triple therapy arm).

At 96 weeks, the proportion of patients free of treatment failure were 77.8% (95% CI  70.5 – 85.1) in the dual therapy arm compared to 65.6%  (95% CI  57.4 – 78.3) in the triple therapy arm.

Virological failure was observed in two patients (1.6%) randomized to dual therapy arm and eight (6.3%) patients in the triple therapy arm (p=0.056).

  • Data demonstrated non-inferiority of treatment simplification to dual therapy in virologically suppressed patients.
  • Additionally, switch was associated with improved renal function but with increased total cholesterol and bilirubin levels in dual therapy arm. 

ANRS 12286/MOBIDIP trial investigator Laura Ciaffi from France presented 96-week data to show that dual therapy with a boosted protease inhibitor plus lamivudine is an effective maintenance strategy in patients on second-line antiretroviral therapy in Africa. 

  • This randomised, open-label, clinical trial was conducted in Cameroon, Senegal and Burkina Faso.
  • Recruited HIV-1 positive patients on stable protease inhibitors plus NRTIs as second-line Antiretroviral therapy.
  • All patients had HIV viral load below 200 copies/mL, CD4 above 100 cells/mm3 and adherence was ≥90%.
  • Two arms of the trial compared monotherapy with the ongoing protease inhibitor/ritonavir(PI/r): darunavir (DRV/r) or lopinavir (LPV/r) with the same PI/r associated with lamivudine 300 mg in the dual therapy arm.
  • From March 2014 to January 2015, 265 patients were randomised (133 in mono-therapy arm and 132 in dual therapy arm).
  • Most patients were women (73%).
  • At failure of first line, 96% had the M184V mutation.

At 48 weeks, Data Safety Board instructed to stop mono therapy arm.

In the ITT analysis, 3.0% (95% CI 0.8–7.6) in the dual therapy arm and 22.6% (95% CI 15.8–30.6) in the mono- therapy arm had virological failure (p<0.001).

  • Median time to failure was 24 weeks.
  • All failing patients, except one, re-suppressed to less than 200 copies/mL in a median time of 12 weeks after reintroduction of the NRTI backbone.
  • Increase in CD4 was significantly higher in the dual therapy arm (48 vs 7 cells/mm3).
  • No differences in adverse events were observed.

Investigators concluded that

  1. after viral suppression with PI/r plus NRTIs in second-line therapy, maintenance with PI/r plus lamivudine is associated with a high rate of success despite the presence of M184V.
  2. PI/r mono therapy cannot be recommended.

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