ASHM Report Back

Clinical posts from members and guests of the Australasian Society for HIV, Viral Hepatitis and Sexual Health Medicine (ASHM) from various international medical and scientific conferences on HIV, AIDS, viral hepatitis, and sexual health.

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African Vaccine Dreams

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

The Treatment Evolution: New Drugs, New Reality session on Thursday afternoon was the most important session so far at the conference from the point of view of therapeutics.  Of great interest was the 48 week data for injectable cabotegravir + rilpivirine.

 

At this session the 48 week results for the Cabotegravir + rilpivirine as long-acting maintenance therapy: LATTE‑2 week 48 results’ were presented by David Margolis (THAB0206LB).    This phase 2b study compared 4 week and 8 week injections vs oral therapy (CAB + ABC/3TC) to maintain viral suppression of HIV-1.

 309 patients ART-naïve HIV infected adults were treated during the 20 week induction period to reach a RNA< 50 c/mL with daily oral CAB 30 mg + ABC/3TC then were  randomized 2:2:1 to IM CAB LA + RPV LA every 4 weeks (Q4W), every 8 weeks (Q8W), or oral CAB + ABC/3TC (PO) in the Maintenance Period (MP).

 Key findings from this study were 

-          At Week 48, 92% (Q8W), 91% (Q4W), and 89% (PO) remained suppressed (ITT).  

-          More patients on Q8W (5%) than Q4W (< 1%) and PO (0%) had HIV-1 RNA >50 c/mL at Week 48. 

-          There were more discontinuations in Q8W (8%) and PO (9%) arms versus Q4W arm (1%).   

-          Injection sited reactions were common but resulted in < 1% withdrawal.  

-          Three subjects met criteria for viral failure during maintenance, one Q8W subject with emergent RPV and CAB resistance

 Q4W dosing resulted in lower rates of virologic non-response than Q8W so was selected for progression into phase 3 studies.  This treatment appears to be very effective and safe.   Questions remain about the acceptability of monthly injections in various clinical settings but this is a potentially the beginning of a whole new approach to HIV therapy.

 

Catherine Orrell  presented ‘Superior efficacy of dolutegravir/abacavir/lamivudine (DTG/ABC/3TC) fixed dose combination (FDC) compared with ritonavir (RTV) boosted atazanavir (ATV) plus tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) in treatment-naïve women with HIV-1 infection (ARIA Study)’.   (THAB0205LB) DTG/ABC/3TC was superior to ATV+RTV+FTC/TDF, with 82% and 71%, respectively, achieving HIV-1 RNA < 50 c/mL at Week 48.

Differences were driven by lower rates of both discontinuations due to adverse events (AEs) and virologic failures in the DTG/ABC/3TC group.  Of six DTG/ABC/3TC subjects who met protocol-defined virologic withdrawal criteria, none had resistance mutations, compared with 4 ATV+RTV+TDF/FTC subjects who met virologic withdrawal criteria of which one had an NRTI mutation, M184M/I/V. This study was very important in that it showed superiority and was female only.

 

 

 

Jean-Michel Molina  presented ‘Who benefited most from immediate treatment in START? A subgroup analysis’ (THAB0201).  In asymptomatic ART-naïve adults with >500 CD4 cells/mm3, immediate ART was superior to deferral across all subgroups.  People > 50, higher plasma HIV RNA level, lower baseline CD4 count, and higher Framingham risk had the greatest benefit.

 

Alejandro Arenas-Pinto presented ‘Increased risk of suicidal behaviour with use of efavirenz: results from the START trial’ (THAB0202). These findings suggest that participants using EFV in the immediate ART group had an increased risk of suicidal behaviour compared to ART-naïve controls. A prior psychiatric diagnosis increased the risk.

 

Michael Aboud  presented ‘STRIIVING: switching to abacavir/dolutegravir/lamivudine fixed dose combination (ABC/DTG/3TC FDC) from a PI, INI or NNRTI based regimen maintains HIV suppression at week 48’ (THAB0203).  Treatment experienced patients were randomized to continue current ART on Day 1 or switched to ABC/DTG/3TC.  The current treatment arm then switched at week 24.   In this switch arm 92% maintained viral suppression at 48 weeks (note the 24 week data has previously been presented).

 

 

 

Today there were a few other abstracts presented about Prep.

A Siegler presented a demonstration project about a home testing system for Prep in the US. This involved sending out kits for STI testing and taking a few drops of blood for tests as wel as a questionnaire. Interesting idea- parts of which might be useful for future planning of Prep systems. 

P-C Crouch presented a San Francisco implementation of non-physician based Prep program using nurse and peer support volunteers. This has been successful in delivering Prep to a lot of people there. Again, food for thought about how we may be able to do things differently, even though their model is really in response to the barriers in their health system which are different in Australia. Since November 2014, they have screened over 1250 people with 95.5% enrolment and 71% retention and no HIV seroconversions.

I Zablotska presented details of the EPIC- NSW Prep implementation - good to see this being presented on a world stage and we all await the results of this and the other state based programs.

R Heffron presented data about renal screening- comparing the 3 months screening in the Partner Prep study to the Partner demonstration project whi did it six-monthly. There showed no difference between the two, so it supported the US CDC guidelines of six month renal screening being recommended.

All in all, some things to think about as we use more Prep.

At the Prep symposia yesterday, here was discussion about microbicides research- which agents to use and wil there be a need with oral Prep proven effective, the long acting injectables and infuseable (VRC01) agents as a possible for the future, It was also mentioned the research around rectal microbicides, suppository being investigated, the idea of a douche that might deliver the agent and ongoing research in vaginal rings.

 

Overall a very informative an interesting conference- the best I have been to. There is a sense that the world is coming together demanding the best treatment and access for all. The program's being rolled out in developing countries can be very impressive which should inspire us to reach and exceed the 90-90-90 targets.

Tagged in: AIDS2016 PREP
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Tagged in: AIDS2016

Thursday 21.07.2016 -Hormonal Contraception and HIV: A Review of the Science and Research, and their implications for Research, Programme and Policy.

Some studies suggest an association between specific hormonal contraception methods and HIV acquisition.   DMPA has been mostly implicated.  Information has come from observational studies alone. 

Chelsea Polis, US, presented an updated systematic review,updating their previous 2014 review, Ten new and 21 studies from past review were included in the analysis. 

 

Patches, rings, Hormonal IUDs:  no data

Implants:  very limited data on LNG implants, does not suggest increased risk.

OCPs [Oral contraceptive pills]:  substantial amount of data, does not suggest increased risk.

DMPA [depot medroxyprogesterone acetate ]:  substantial amount of data, newer data are increasingly concerning and converging around 1.2 -1.6.  

NET-EN [norethisterone enanthate (NET-EN)  ]:  limited data; less concerning than 2014 review, still worthy of investigation.  

Questions were raised regarding the reliability of the results considering the nature of the studies, none being RCTs in particular relating selection bias. ie. Women at higher risk for HIV choosing DMPA.  

Another delegate stated that pregnancy per se increases risk of HIV acquisition by around two fold and there is a need for reliable contraception; hence findings of any small increases in risk of HIV acquisition with DMPA should be considered in context.

Jared Baeten, US,  Update on ECHO Multi Centre,  Open Label, Randomised trial on HIV acquisition among users of different hormonal contraception methods [DMPA, LNG implant, Cu IUCD].

 

N=7800 f/u , 12 sites in Kenya, South Africa (9), Swaziland and Zambia.   18 mths per women. Quarterly follow up with usual standard of care.

Started in 2015 and will go on for ~36 mths.

This is a very important study.

 

Janet Hapgood, SA, Biological/immunological mechanisms for an association between HC and HIV

Very interesting presentation with regard to progestogens: different doses, methods of delivery, duration, inter-individual variation,  differ in their off-target effects via different steroid receptors which predicts different side effects.   DMPA has activity like cortisol. 

Conclusion: Collectively, clinical, animal, and ex vivo studies are broadly consistent and show that DMPA increases permeability of the female genital tract and compromises select FGT and systemic immune responses.  This most likely leads to increases in HIV acquisition via multiple mechanisms more so in some individuals than others. 

 

Andy Gray, South Africa,  presented on Interactions between HC methods and ART- updated systematic review.  This review was to update the evidence on which the WHO guidance and local policy is bases.

ART and HC effectiveness

·         Efavirenz – most clinically significant interactions were with Efavirenz. 

Implant users:  pregnancy rates from 5-15 per 100 w-y.   (c.f 0-2 per 100 w-y)

Combined oral contraceptive pill:  13-15 per 100 w-y. 

DMPA: not impactecd.

·         Nevirapine – No significant impact.

 

 

HC and ART effectivenessNo significant effect noted.

 

DMPA and PrEP – no significant effect. 

Conclusions include:

·         Current published data do not support limiting access to any HC.

·         Full range of HC options should be made available

·         More well designed studies are required to study drug interactions

 

 

Tagged in: AIDS2016

Of the plenary session today what really stood out was Anton Pozniaks session ‘TB and Co-infections: the long game.  During the session he reminded us that TB is now the leading cause of death for people living with HIV.  He detailed steps to disease elimination for TB, hepatitis B and C – a very long game indeed.

In ‘The Living with HIV: Long-Term Effects’ Amanda Mocroft (PDB0101) examined renal function in patients in the START study.  eGFR was significantly lower in the deferred arm versus the immediate treatment arm. This finding reached significance in the non-adjusted analysis despite the use of potentially nephrotoxic drugs such as tenofovir.  Yet another reason to start ART early.

PrEP has been a major theme at this conference.  More good news was provided by Jean-Michel Molinain the extension arm of the Ipergay study  (WEAC0102).   This study used intermittent PrEP and previously reported the high efficacy of PrEP with TDF/FTC taken ‘on demand’ in high risk MSM – an 86% relative reduction in HIV-incidence in the TDF/FTC arm vs Placebo (95% CI: 40-98, P=0.002).  All participants were offered open-label TDF/FTC.  During 515 person-years only 1 HIV infection occurred giving a risk of HIV of 0.19 (0.01-1.08) per 100 per year.  This patient reported that he had ceased PrEP.

 Also continuing good news for HIV/HCV co-infection.  In the ‘Bad Bugs’ session Norbert Bräu  (WEAB0301) presented the results of the ASTRAL-5 study Sofosbuvir/velpatasvir was given for 12 weeks to 106 patients.  The genotype distribution was 62% GT1a, 11% GT1b, 10% GT2, 11% GT3, and 5% GT4. No patient experienced confirmed HIV virologic rebound (HIV-1 RNA ≥400 copies/mL).  SVR rates were 95% overall, and 100% with cirrhosis and 97% the previously treated.

As this combination will be widely used in Australia the next session was very relevant. AnnieLuetkemeyer (WEAB0302)  presented ‘Drug-drug interactions studies between HCV antivirals sofosbuvir/velpatasvir and HIV antiretrovirals’.  This was a Phase 1 study conducted in healthy volunteers to evaluate potential drug-drug interactions (DDIs) between SOF/VEL and HIV antiretroviral (ARV).

-       Increased TFV exposure (~40%) was observed with SOF/VEL when administered as TDF

-       Decreased velpatasvir (53%) when given with efavirenz

The author concluded that all study combinations could be used except efavirenz-containing ART.  This is an important finding given the number of patients taking Atripla.

And for the rare patients who does not achieve SVR with DAA therapy with sofosbuvir/ledipasvir (Harvoni)?  Well they can be retreated with…. Harvoni for 6 months combined with ribavirin.   Annie Luetkemeyer  (WEPEB060) presented data on 9 HIV/HCV who had not cleared with 12 weeks of Harvoni who were then retreated with 8/9 achieving a SVR.

 

 

 

 

 

"So, what are you doing about TB?"

There’s a particular gentleman at the AIDS 2016 Conference who causes a kerfuffle wherever he goes and I’ve witnessed his performance a number of times over the past few days.

At the end of every session he asks the lecturer “So, what are you doing about TB?”

It’s an AIDS Conference so most speakers are caught off guard when they don’t get a question about AIDS, but on Tuesday a speaker retorted “Well Anton, I didn’t know you were in the room, otherwise I wouldn’t have asked if there were any questions”.

I’m sure you’ll be pleased to hear that Dr Anton Pozniak finally got his own platform to speak in the plenary session.

He informed his captive audience that it’s all very good to treat HIV, but every year in Africa, Tuberculosis causes more deaths. He reminded us that our current TB vaccination is 95 years old and we need a new one.

Tuberculosis is diagnosed too late, with half the diagnoses made at post-mortem. HIV testing is improving, but we also need to be using a rapid test for TB. Whether it’s spitting in a pot or peeing in a jar, we already have the technology to test for Tuberculosis - but we need it to be quick, portable and affordable. 

We know Tuberculosis causes significant morbidity and mortality for people living with HIV (PLHIV). We also know that using Anti-Retroviral Therapy (ART) by itself is not sufficient to treat Tuberculosis. ALL patients co-infected with HIV & Tuberculosis need to be treated by a combination of ART and anti-TB medications.

We cannot shorten the duration of Tuberculosis treatment to any less than 6 months using our current anti-TB medications. New drugs are being trialled and some appear promising, but we’re even trialling old drugs to see if they might possibly work for Tuberculosis too.

Nelson Mandela once said “We can’t fight AIDS unless we do much more to fight TB”, but Anton isn’t keen to stop there. He not only wants to fight HIV and Tuberculosis, but he’s keen to eradicate viral hepatitis too.

Anton's dream is for everyone with viral hepatitis to be treated, but this dream comes with a price.

Hepatitis B treatment costs ~$15,000 in the USA, but the estimated true cost is $36. Hepatitis C treatment in the USA costs ~$84,000, but the estimated true cost is $62. Affordable medication can truly change the lives of millions of people around the world, but that's not yet happening.

Anton urged everyone to communicate and combine efforts to provide integrated health services for people in need. Testing and treatment should not only be for HIV, but also for Tuberculosis, Hepatitis B & Hepatitis C. 

We’re aiming to end HIV by 2030, but let’s aim to eliminate Hepatitis C and Tuberculosis too.

Anton closed his speech by saying that we need new 90:90:90 goals. We should aim for the cost of HIV treatment to be $90 per year, Hepatitis B treatment should be $90, and Hepatitis C cures should be $90 too.

NB - There was no kerfuffle at the end of his presentation as Dr Anton Pozniak wisely did not ask the audience if they had any questions. 

Delinkage of the cost of research and development from drug prices

James Love, Director of Knowledge Ecology International

This was a fascinating talk that proposed an alternative model for R+D of new drugs that would reduce the cost of new drugs and improve access for all.

Love outlines how the current drug patent and monopoly for funding the R+D of new drugs has many challenges. Pharmaceutical companies invariably set prices for maximum profitability and costs have risen dramatically even over the past 10 years. The current trajectory means that high and middle-income countries will likely limit access and impose restrictions on those who receive these treatments, and resource-limited settings will face further inequities.

Love proposes an alternative model that funds R+D by “delinkage” of the cost or R+D of new drugs, from the final price of the product.  Alternative funding models for R+D have been proposed; drug research grants and contracts, R+D subsidies, incentives and innovation prize funds.

Some of the above initiatives already exist. There are NIH and EU framework grants, R+D subsidies such as the Orphan Drug tax-credits which are funds available for R+D on drugs for rare diseases (apparently 47% of new US drug approvals in 2015 fell under this model).

Love proposes expansion of current incentives, and progressively switching from the current system of monopolies to alternative models of funding. Progressive delinkage mechanisms could be introduced by governments over time that sequentially move prices closer to the marginal cost of production of the drug.

Love talked about the $15 billion spent on HIV drugs in the US annually with the return of on average one new HIV drug per year. Recently Bernie Sanders in his US election campaign proposed that $3 billion of this money be set aside to fund R+D for new HIV drugs and at the same time eliminate monopolies. He also advocated setting aside funds to reward scientists and researchers who contributed to the development of a drug via open source platforms. 

There seems to be growing support for Love’s model with many seeing the current system as unfair and ridiculously expensive. Apparently several members of the European parliament have expressed interest in the delinkage model, the Human Rights Council has asked states to support the principles of delinkage, India and the World Health Assembly have endorsed the model, the CEO of GSK has endorsed the delinkage model in the context of expensive drugs for rare diseases and several companies have endorsed it for the development of new antibiotics.

This issue has repercussions the world over, and is pertinent at a conference being hosted in sub-Saharan Africa that addresses the HIV and viral Hepatitis epidemics. While we come from a relatively privileged position in Australia, we do face shortages in provision of access to many of the new cancer medications, and one wonders how our health budget will fund the escalating pharmaceutical costs in the future.  This talk outlined an elegant alternative model of funding R+D that would be more equitable and allow universal access to new drugs for all.

Everyone Loves Concert Tickets!

Nittaya Phanuphak (Thai Red Cross AIDS Research Center, Thailand) spoke at AIDS2016 on the topic 'Prevention Equity: How Innovations in HIV Testing and Prevention Technologies can Reduce Incidence Globally'.

She highlighted the inequality of health care in Thailand and outlined that the populations at highest risk for HIV have been missing out. She is involved in a 'Test and Start' program for MSM and Transgender Women in Thailand. The program provides clients with HIV rapid testing, with provision of PrEP (or ART) on the same day.

They have trained up MSM and Transgender Women to provide services for the LGBTI community through the clinic. By design, this creates a work force that is compassionate, caring and culturally aware of the target population.

Their clinic has enrolled over 300 patients in the PrEP Program so far, but they plan to roll this out to a further 3000 MSM and Transgender Women over the next 3 years.

They created the website www.adamslove.org to provide sexual health information and encourage clients to attend the clinic. Everyone loves tickets, so they provide online Eventbrite "concert tickets" that are exchanged for STI tests (Please note that a visit to the clinic is more important, but is much less fun than seeing a show).

Most clients have a phone or webcam and the clinic's sexual health nurse utilises this to conduct online medical consults, providing education in sexual health, counselling and guides patients through performing a home HIV screening test.

Nittaya Phanuphak gave a shout out to NSW in her talk, stating "NSW must be congratulated for their efforts to use PrEP. We hope to learn more from NSW in the next few years" - and we hope to learn more from you Nittaya. 

J-M Molina this morning presented the Ipergay extension study results. Participants of Ipergay were offered to go onto an open label extension study to remain on episodic use of Prep. Ipergay was the placebo controlled study of use of truvada 2-24 hours before and 24 and 48 hours after sex as Prep. Some new participants were also enrolled. There were 362 participants. There was 1 HIV seroconversion in a person who was not taking the Prep. The mean pills per month taken was 18, There was no significant increase in number of sexual partners. Self-reported adherence was slightly improved. There was a significant reduction in comdomless receptive anal sex, but the STI rate remianed the same. 

This study is very assuring for us in Australia as there are several such programmes that either have or about to begin. It is good to know that we should expect high levels of risk reduction with Prep, even though there is still active debate about episodic vs daily Prep. It would appear that episodic Prep is also very effective.

There were also many posters on Prep displayed today. INterestingly, there was a study from Amsterdam comparing acceptability of episodic versus daily Prep. 73% of participants preferred daily Prep. These men tended to be younge and had more sex. 

I think it would be good to have both options but I suppose patients may do it anyway.

Another poster from Thailand using Prep in MSM found it feasible as they were able to deliver Prep for USD1- which includes cost of their generic drug and associated services. I am to sure if this was a daily cost or per visit cost.

 

Many Prep posters about acceptability in many settings around the world- some in MSM, some in young females, some about newer topical methods, All ver promising for the future and nice to see many places taking Prep seriously as a method of eliminating new HIV infections

Tagged in: AIDS2016 PREP

The Lancet Special Theme Issue:  HIV, Viral Hepatitis, and TB among Prisoners

Lancet July 2016 issue has been dedicated to prisoner health, with more information online available from the Lancet website.  It is a sincere hope that this issue and discussions raised at this conference will influence the care of prisoners around the globe.

 

In this sessions the lead authors presented: a global review of the burden of HIV, viral hepatitis and TB among prisoners; clinical care among incarcerated women and men; best practice for prevention in prisons and jail; human rights and right to health access; and two region-specific presentations- on prisoners in Eastern Europe and Central Asia and Sub Saharan Africa.  Kate Dolan from UNSW presented on the Global epidemiology of HIV, HCV and TB in prisoners.

 

Annually 30 million people are passing through some form of detention.  These people are at high risk of acquiring and transmitting infections due to risk that are in play before and after incarceration.

Developed nations are not leading by example with US having the highest incarceration rates in the world, with blacks over represented  in the prisons.   Only eight countries have needle and syringe exchange programmes in prison.  The focus of incarceration should be rehabilitation. 

There is a moral and legal imperative to provide appropriate care to prisoners.  Only by including them and other marginalised populations in the global HIV/AIDS response, will the fast-tract to accelerate the fight against HIV and to end the AIDS epidemic by 20130 become a reality.

Recommendations:

  •  Reduce incarceration for key populations, especially people who inject drugs
  • Introduce and scale-up HIV prevention with Opioid Agonist Therapy, Needle Syringe programmes and Anti Retroviral therapy, including effective transitional programs post-release
  • Improve testing and treatment strategies (continuum of care) for HIV, HCV and TB.
  • Eliminate the gap between prison and community treatment and prevention services, including structural impediments for service delivery and continuity.
  • Integrate services given the high rate of medical and psychiatric co-morbidity.

The Standard Minimum Rules for the Treatment of Prisoners were first adopted in 1957, and in 2015 were revised and adopted as the Nelson Mandela Rules with eight substantive areas revised. By the UN General Assembly in December 2015.   

UN Standards on Treatments of Prisoners -- Mandela Rules (2015)

·         Prisoners must be managed in a manner to respect and protect the human rights and dignity of prisoners. 

·         Prison should be viewed as a place for preparation for reintegration of prisoners and society - minimise differences with outside world. 

Adequate space, food, sanitation.

No discrimination.

Health care to meet prisoner's needs throughout detention and linkage to public health.

Monitoring and accountability.

 

“It is said that no one truly knows a nation until one has been inside it jails.  A nation should not be judged by how it treats it highest citizens, but its lowest ones.”…………Nelson Mandela

Tagged in: AIDS2016

Day 1 plenaries continued the themes from the opening ceremony with great presentations on the epidemiology of the HIV pandemic from Steffanie Strathdee.  Alex Coutinho presented data on Universal Access, the stage beyond the 90:90:90 target set by WHO.  Some countries in Africa appear to be close to passing these benchmarks include Rwanda and Swaziland.  There were few dry eyes at the conference as Edwin Cameron, a South African judge described his life living openly as a HIV positive gay man since 1986.  He introduced his godson who has been living with HIV since his birth 22 years.

 

A Clinical highlight of the morning was the PrEP:New Drugs session.  Robert Grant (TUAC01) reviewed the risk of drug resistance versus the benefit of HIV prevention across 6 randomized clinical trials and one demonstration project. This study was of great interest to those doctors involved in PrEP studies in Australia so the take home messages are:

 

1)    FTC resistance occurred in 10 who received FTC/TDF PrEP, including 33% (5/15) with acute infection when starting PrEP, and in 3% (5/157) with established infection. 98 infections were prevented giving 10 (98/10) infections prevented for every FTC resistant infection.

2)    Tenofovir resistance occurred in 1 who received TDF PrEP, including 10% (1/10) with acute infection when starting PrEP, and none (of 90) with established infection. 53 infections were prevented by TDF PrEP giving 1 (53/1) infection prevented for every tenofovir resistant infection

3)    A screen for acute viral symptoms in PrEP assessments led to deferral of PrEP among 30 of 1603 (1.9%) of whom 2 (6.7%) were found to have acute HIV.  No acute infections were missed using this screen.

 

At the Late Breaker session K Rawlings presented data on the uptake of PrEP in the USA with almost 80 000 people started PrEP in the USA to end of 2915, 76% are men.  No data was available on longer term use of PrEP.

 

The highlight of the ‘Cancer and HIV’ program was a presentation by Andrew Grulich from Kirby Anal cancer in people with HIV  (TUSY0803).

To summarise.  Historically anal cancer is the third most common cancer in HIV +ve males after KS and lymphoma. In heterosexual males it is 10 x more common, in gay males it is 50 X more common than the general population with an incidence of up to 100 / 100  000. Following ART and CD4 recovery there has been a rapid decline in KS and lymphoma but only a slight decline in anal cancer incidence which remains high even with normal CD4.

In terms of primary prevention HPV vaccination results in a 75% reduction in high grade disease in young gay men but preliminary data did not show that it was effective in males older than 26 although further studies are needed.

In terms of secondary prevention – screening and treatment is complicated by the 75% prevalence of high risk virus with 30 – 40% high grade disease but there appears to be less progression to cancer compared with cervical disease.   Treatment pathways are currently uncertain. In comparison to colposcopy anosocpy requires much more training.

In terms of tertiary prevention detection of anal cancer remains controversial with some recommendations to perform annual PR examinations

In the epidemiology session Alison Rodger presented results from the PARTNER (TUAC0206).  This prospective, observational study enrolled 1166 HIV sero-discordant couples who reported condomless sex and HIV-1 RNA load suppressed to less than 200 copies/mL.  1166 enrolled couples, 548 heterosexual and 340 MSM provided had a median follow-up of 1.3 years. No HIV transmissions occurred within the studied couples.  11 infections occurred from ‘unlinked’ partners. This gave rate of within-couple HIV transmission of zero with upper 95% confidence limit of 0.30/100 couple-years, and for condomless anal sex 95% CI of 0.71 per 100 couple-years of follow-up. These results are very encouraging in terms of the tremendous value of treatment as prevention.

 

Central Demand of "Access Equity/Rights Now" Vocalised on Opening Day of AIDS2016 Durban

The IAS AIDS2016 Conference in Durban, officially opened Monday night local time, however multiple pre-conference meetings had already taken place in the days running up that, including the first MSM Global Forum to be held in Africa; the 1st IAS HIV Cure Symposium, TB, HIV/HCV co-infection, paediatric HIV sessions as well as funder meetings, and political activism, along with cultural and community events in the Global Village. It is 16 years since the conference was held in South Africa, in Durban and the current meeting's theme is "Access Equity/Rights Now" – a central demand is the need for world leaders to meet global goals they need to continue to support HIV treatment and prevention and stick to their funding commitments and goals as well as a call  to combat inappropriate criminalisation of HIV transmission (and recognising the current evidence base of very low HIV transmission risks in a treatment era) – something ASHM is working on through a Consensus Statement with expert stakeholders nationally.

 

MSM Global Forum points out critical issues

Chris Beyrer, President of the IAS opened the MSM Global Forum pre-conference day meeting, pointing out that the recent UNAIDS High Level Meeting on HIV/AIDS struggled to keep key populations on the agenda including MSM, and stigma remains a critical issue intersecting with very low funding (2% of global funding which is out of proportion to the burden of new infections among MSM), violence and criminalisation. An interesting angle taken by the Forum was considering the national economic costs of homophobia, based on a premise that if political leaders and decision makers do not listen to rights based arguments then the ‘dollar value’ impact of the consequences of homophobia on their respective government wallets might work better. Legal reform indicators need also to be included in UNAIDS global indicators.

 

"Know your epidemic means know your HIVDR"

At a well-attended pre-conference meeting, a WHO organised session on HIV Drug Resistance found speakers addressing an inherent potential paradox of a universal access or ‘Treat All’ global response and indeed PrEP scale up and the increased risk therefore of HIV drug resistance (HIVDR).  This session therefore focused on how to prevent the emergence and transmission of HIV DR and consequent risk of treatment failure, increase in drug costs, higher treatment complexity and lowered durability of 1st line regimens (i.e. if people need to switch to more expensive 2nd or even 3rd line regimens due to DR). Fast tracking of global treatment goals need to include the issue of HIV DR risk and this should be an integral part of delivering quality HIV services and be part of routine program management in terms of VL suppression across all the UNAIDS 90-90-90 goals. Presentations focused on strengthening surveillance with the inclusion of a new zero draft WHO Global Action Plan on Early Warning Indicators (EWI) for HIV DR.  This plan is intended to complement national HIV DR surveillance through for example indicators of possible emergence of DR such as monitoring ART prescribing practices, loss to follow-up at 12 months, retention on ART at 12 months, on-time pill pick up, on time appointment keeping, drug stock outs and their relation to VL suppression. VL monitoring is obviously also critically needed (as a proxy for possible patient HIV DR) but still unavailable in too many country contexts. Clinic level data from  55 countries have indicated high levels of appropriate prescribing but sub-optimal levels of loss to follow-up at 12 months, retention at 12 months on time ARV drug pick up and ARV stock outs – which could indicate emergence of HIV DR.

 

WHO seeks online public consultation on Global Action Plan on HIV Drug Resistance

WHO is consulting with global and regional stakeholders to inform the Global Action Plan  on HIV DR – of note to the region is a WHO Western Pacific/South-east Asia regional consultation in Bangkok, August 8th – 12th, 2016 with a plan finalised by end 2016 and full launch in early 2017.

A rather late (18:30-20:30) but very interesting session.

Richardo Garcia-Lema presented the findings of his study in macaques which investigated several different intermittent TDF/FTC schedules to cover teh vaginal exposure to SIV, including: two pills within 24 hours before and after exposure each; one pill 24 hours before and one pill 2-3 hours after exposure; one pill 2-3 hours before and one pill 24 hours after exposure; two pills each time within 24 hours before and 24 hours after exposure. While all schedules were protective, the latter was most effective. The study highlighted the importance of post-exposure dosing, which has to be taken as soon as possible after exposure. 

Jean-Michel Molina summarized the key findings of the French-Canadian IPERGAY study:

  • HIV incidence was above 6 per 100 person-years and was twice higher than expected;
  • the risk of HIV was reduced by 86%, which is some of the highest (if not the highest) levels of protection from HIV observed in clinical trials;
  • risk was reduced due to intermittent, not daily PrEP;
  • intermittent PrEP is highly effective in gay men who are frequently exposed to HIV, and 
  • intermittent dosing includes an inherent recommendation of how to start and stop PrEP (two pills before first exposure, one pill daily during ongoing exposures and one pill per day for two days after the last exposure). On that point, Bob Grant commented that he still struggles with the recommendation (or rather the lack of one) on how to start and stop daily PrEP.

Intermittent PrEP is now recommended in France, UK, Europe, and is up to be recommended in the new Canadian guidelines (which are being finalized now).

 

The discussion returned quite a few times to the importance of adherence to daily PrEP or strategic use of intermittent PrEP (strategic use seems to appear a new term to indicate correct use of intermittent PrEP). 

Another important point in the discussion was that appropriately conducted information and education of patients at the start of PrEP results in better adherence to PrEP and unilaterally in better prevention outcomes. 

 

 

 

 

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several prep presentations on Tuesday covering different aspects of prep.

Brocca-Cofano presented a study about using maraviroc on infant macaques as prep. The conclusion was that it offered no protection from SIV in infant macaques. This may be different in human populations.

Gulick then presented a phase II study on maraviroc tolerability in US women. There were 188 women in the study, 160 completed. This was a four arm double blind study comparing maraviroc, maraviroc + TDF , maraviroc + FTC , and TDF + FTC . This was a purely safety and tolerability study over 48 weeks and there was shown to be no difference between the four arms.

McGowan presented a study about the persistence of Rilpivirine after a single long acting injection. N=36, they compared plasma and genital fluid and rectal fluid  and compared either single dose, 600 or 1200mg vs 1200 every two months. In 7/7 of the participants who had 1200mg im single dose, there was Rilpivirine present in their genital fluid and plasma after 18 months. This raises issues about he use of this as prep due to concerns about development of resistance due to this long residual level of Rilpivirine . 

Grant presented a study about the benefits of prep relative to drug resistance. They showed that across all prep studies, the risk of drug resistance was very low 0.05% risk. Most of the resistance occurred in people who were HIV infected at entry into the trial. They concluded that the benefit of prep far outweighed the low risk of drug resistance. As this occurred mainly at the start of prep, it was important to exclude anyone who might have and acute vital illness from starting prep to ensure that it was not a HIV infection. It was also suggested that it might be important to do HIV Ag testing or dna before commencing prep.

Brown presented an interesting study about the use of dapavirine vaginal rings from the aspire study. The level of drug level in the ring after use gave an idea about adherence levels. After some stratification, they found that in the moderate to high adherence women, the risk reduction improved from 27% to 56-75% risk reduction.

late breakers

hosek presented data about the safety of prep in 15-17 yo msm in the US. The numbers were small -60 due to recruitemnt and consent issues but the conclusion was that it was are to use with no real differences. There is the bone data presented in the past that still needs clarification.

Rawlings presented data on prep use in the US between 2013-2015. This data was collected from prescription data with PEP and treatment prescriptions excluded. Almost 80,000 people used prep in this period, with a significant increase in men using prep in the last two years. The study also looked at seroconversion rates across multiple prep studies. They had about 8,500 participants and there was  a seroconversion rate of 1.03% in men, 0.25% in women.

The theme of access equality rights now is palpable. There is a mood of activism to overcome these barriers in HIV . Quite exciting to be around!

 

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Combating HIV drug resistance

 

With the rapid scale up of access to ART and with countries working towards the 90-90-90 and 2030 targets, this session seemed very pertinent in addressing the final tier of the cascade – that 90% of those on treatment should have an undetectable viral load. Meg Doherty from WHO discussed that this is particularly important in settings where access to viral load and drug resistance testing is limited.

Several low and middle income countries have reported levels of HIVDR at or above 10% in ART naive patients and up to 37% in those restarting ART with prior exposure to ART. *

The WHO speaker cautioned that a “one size fits all approach” would be a mistake and this was certainly evidence by presentations from certain countries with varying resistance rates. However access to viral load, not to mind genotypic resistance testing is lacking in many low and middle income resource countries and each country needs to collect this data to guide and tailor its own response.

Modeling suggests that the cost of inaction is a costly price to pay with increased morbidity and mortality, increased transmitted resistance, increased program costs with second and third line ARVs and increases in new infection rates.

WHO recommends that each country should have a HIVDR surveillance strategy that is based on 1) Early Warning Indicators which essentially reflect the quality of care of the program and include data on prescribing practices, loss to follow-up, ARV supply continuity, viral load etc, 2) National surveys of pre-treatment resistance, 3) National surveys of acquired drug resistance, and 4) Nationally representative surveys that measure drug resistance in <18month olds.

Other interesting comments from panel members at the session emphasised the importance of monitoring drug resistance in pregnant women returning to care with PMTCT option B+ and also in children and adolescents who have lower viral load suppression rates than with adults.

The Global Fund panelist talked about the important implications of HIVDR rates in reaching other targets such as 90% of people who have need of PrEP having access to it, and HIVDR rates being important for effective PrEP.

Dr Anna Flavia presented some of the drug resistant data from Brazil where pre-treatment Efavirenz resistance rates are 7%. This has prompted discussions about whether the national program should recommend routine resistance testing prior to ART initiation, or whether the country simply switch to including Dolutegravir in the first line regimen. All cost benefit analyses favour the switch to Dolutegravir rather than performing resistance testing on all commencing treatment.

The take home message from this presentation was that drug resistance is rising and if the target of ending AIDS by 2030 is to be achieved, then monitoring and responding to HIVDR will be a critical element and that each country is called to act and collect more and better data in order to tailor their response in terms of thinking about switching ART regimens and quality improvements to their HIV programs.

*The WHO draft of the Global Action Plan on Drug Resistance (2017-2021)

Tuesday Morning Sessions at AIDS 2016 Conference Durban - Plenary Session "Where are we now?" and "Hep C treatment in HIV infected patients".

A number of barriers to treatment and reduction in transmission were discussed. Of notable repetition was the barrier of cost. This was raised by the speakers as well as protestors at the sessions. A protestor raised the issue of pharmaceutical companies overcharging for medication such as Hep C treatment at $96K in the US. The speaker responded that this was expensive, but indeed cheaper than the cost of Hep C to the health system overall, and was therefore still cost effective. The protestor responded that people were selectively being treated in the US and were not getting equal access to treatment and therefore a cure. Whilst it may seem cost effective, governments need to be willing and in a position to fund these treatments. In Africa, there are many countries in which patients simply cannot afford any of the treatment options.

In Australia, we are quite fortunate in that that our health system has embraced treatment for Hep C and HIV treatment despite costs and can offer treatment to all residents. Currently Australia is involved in studies for PrEP to help provide a case for funding. We are certainly grateful to Pharmaceutical Companies who have developed effective treatments and cures but there is a need to advocate for lower prices so that we can more easily move towards our goal of zero transmission!

 

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Tonight was a very moving opening ceremony for opb2ap3_thumbnail_Charize.jpgening of the 21 st International AIDS conference.  Many speakers made reference to the World AIDS meeting in 2000 and the great achievements of the last 16 years.  From almost no access to treatment in Africa then, now more than 12 million people are receiving ART. 

 

Today is also the birthday of Nelson Mandela.  At the 2000 meeting he famously said "AIDS is caused by HIV".   Leading up to the 2000 conference and at the opening the then president of South Africa, Thabo Mbeki, denied the role of HIV as the cause of AIDS.

I attended the 2000 meeting so it is exciting to be back in Durban. I am very much looking forward to reporting on new developments in HIV and HIV/HCV co-infection.

But I will leave it to Charlize Theron.  Talking about a cure for HIV she said ".... we have to stop meeting like this..."

 

 

 

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An intro to AIDS2016 & Charlize Theron

It's my first time attending an International AIDS Conference and my first time blogging for ASHM. Over the past 18months I've been working as an HIV s100 prescriber, but it seems like there is a lifetime of learning to catch up on. 

I'm told by my colleagues that the AIDS Conference held in Durban 16 years ago was a turning point in our understanding and treatment of HIV/AIDS, but it's hard to believe that back in 2000 'AIDS denialism' was still a thing.

Nelson Mandela made his famous speech at the AIDS2000 closing ceremony, but Charlize Theron took centre stage at this year's opening ceremony, stating "HIV isn't just transmitted by sex. It's transmitted by sexism, racism, poverty and homophobia. And if we're going to end AIDS we have to cure the disease within our own hearts and within our own minds first". From what I understand Charlize is more intent on challenging psychological barriers rather than curing endocarditis or encephalitis - however I've noticed many people at the conference are very passionate about treating Tuberculosis.

Charlize Theron made an impassioned plea to end HIV by the year 2030, suggesting that we should only have another seven International AIDS Conferences before the next generation finishes off HIV for good. She proposed that the next generation should be called "Gen End It" and a new hashtag was born.

Get ready to see #genendit in your social media feeds over the next few years.

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My notes from the Thursday Morning Plenary

 

Professor Deborah Persaud – Paediatrics Johns Hopkins University School of Medicine. Known for the “Mississippi Baby”. Time magazine top 100 most influential people in 2013.

 

Children with HIV - 2.6 mil

New HIV in 2014 - 220 000

Deaths due to AIDS in 2014 -150 000

Decreasing number of mother to child transmission around the world due to treatment.

 

Early treatment of babies in the perinatal treatment allows a 99% survival at 6 years. Without treatment 50% die by age 2.

 

Effects of HIV in Children: Lipoatrophy, substance abuse, bone disorder, mental health issues, learning disabilities, abnormal lipids, STIGMA

 

Barrier to HIV -1 Cure

 

  • Viral Reservoirs. Sites that protected the virus from antiretrovirals. Within 2 weeks of cessation of treatment, the virus returns.

  • Exists in resting memory CD4 T Cells. Memory response after naïve cells are activated by initial HIV infection. Cells are present all over the body. High concentration in lymphoid tissue. They have a half-life of 3.6yrs. An Adult would need to take ARV for 78 yrs to get rid of 1000000 million memory CD4 Cells.

  • Treating a child for 10 years doesn’t change the rebound time of 2 weeks.

 

Goals of HIV -1 Cure

 

  • Eradicate latent reservoir (as in the Berlin patient)

    • Bone marrow transplants for those who need BMT for other conditions

  • Control viral rebound off ART (Sustained Virologic remission)

    • Early treatment to limit reservoir. Other immunosuppressive treatment.

 

Infant Immune System

 

  • Lower immune cell activiation. Slower memory cells. Less memory cells.

  • Unlike adults early treated children end up having a much lower number of infected cells/reservoir.

  • This shows that the reservoir doesn’t evolve over time.

 

 

 

Very Early ART at less than 48hrs of age (Mississippi Baby)

 

Baby was started on AZT 3TC and Neviripine. Started within 48hrs but not immediately after birth due to lack of resources at location of birth. Drug was ceased at 18 months. At this time there was no plasma viremia, no HIV antibodies, no latent reservoir. No protective genetic alleles. No evidence of immune response. The child however ended up having a vira rebound at 27 months.  Small latent reservoir can lay dormant for 1-2 yrs when child is treated very early.  No adverse effects of rebound and child was effectively treated after to viral suppression.

 

 Findings – early treated with ARV is feasible safe, and ideal.

 

AZT, 3TC, Nevirapine is the only current recommended treatment for immediate treatment. Kaletra can be used from 2 months.

 

Long acting injectables to neutralize antibodies early on to reduce reservoir in early infancy are currently being developed to last for 6 months.

 

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