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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This entertaining session presented a number of varying cases to highlight the promises PrEP may bring but also the pitfalls.

It emphasized the importance of "hearing the patient", as to their psychological and sexual needs.

In South Africa, Dr Abdool Karim expressed that women need PrEP type product that they can initiate themselves , independent from their partners knowledge , as a study of seroconversion rates still revealed 9.1%seroconversion in young women. She also reported an association between HPV acquisition and HIV acquisition.

Dr Raphael Landovitz from L.A. Introduced a new term "the dribble effect", which refers to lowering of serum levels of Truvada as some doses are missed , but those lower drug doses may still give some protection. It is still to be determined what the ideal treatment protocol is and also what are the lower serum levels that still offer some protection, before development of resistance may occur.

So far  Truvada toxicity has been minimal with most serum creatinines recovering  to normal.

a major issue will be cost as it is not yet funded in Australia.

 who will be keen to take it and how often it will need to be taken was explored in different scenarios which included the discordant MSM couple, the monogamous African woman, and the bipolar personality.

Dr  Landovitz stated the numbers were too low in the Ipergay trial to determine the efficacy of that regime.

we have lots to learn in the era of PrEP but it appears to be very promising as another way to prevent  further HIV seroconversions

Tagged in: IAS2015 PREP

I missed the START session as I was presenting and noticed there's no ASHM blog on what is a tremendously important study, hence thought I'd quickly rectify this. You will all recall the landmark SMART study published in NEJM in 2006 where they enrolled 5472 HIV-infected patients,  with a CD4 of >350 into an RCT with a a drug conservation arm (start when CD4 <250, stop when >350) and a viral suppression arm where they started ART immediately and didn't stop. The drug conservation arm was associated with increased risk of opportunistic infections, increased death from any cause and increased major cardiovascular, renal and hepatic diseases. We learnt then that drug holidays were unwise, and we needed to start ART earlier.   

Since then, we have had some strong observational data and implied data through basic science research suggesting starting at an even more robust CD4 was wise. Earlier ART not only reduces OI and complications but also improves CD4 recovery and reduces the HIV viral reservoir etc. The US for instance has been recommending for early ART in all patients for a number of years. We have been somewhat slow in adopting this.   

The START study now gives unequivocal data that all patients should start ART regardless of their CD4 count. In brief, they enrolled 4685 HIV-infected patients with CD4s >500 in 35 high-income and resource-limited settings. This study was stopped by the data and safety monitoring board in May 2015 as interim analysis showed their primary outcome had been met. The median VL was 12749, and median CD4 was 651. The composite primary end point (any serious AIDS-related event, serious non-AIDS-related event, or death from any cause) occurred in 42 patients in the immediate-initiation group (1.8%) as compared with 96 patients in the deferred-initiation group (4.1%); hazard ratio of 0.43. Frequency of TB, Kaposi, lymphoma, and cancer were lower in the immediate arm. The risks of a grade 4 event were similar in the two groups, as were the risks of unscheduled hospital admissions. You will find the full paper in this week's NEJM.

The TEMPRANO study, also published in the same NEJM issue, enrolled HIV-infected patients with a CD4<800 in Cote d'Ivoire. They examined the role of immediate vs deferred ART and isoniazid prophylaxis in comparison to WHO guidelines. They found that immediate ART and 6 months of IPT led to reduced rates of severe illness overall and also among those with CD4 >500. 

WHO will be publishing new guidelines recommending ART for ALL. We will need to reflect on how we can do this better (and quicker) in Australia. What is the lag time from acquisition to testing; from testing to diagnosis; from diagnosis to treatment?? San Francisco General Hospital is able to start ART within 24hours in patients with newly diagnosed HIV. The Thai group led by Dr Aranowich are able to start ART at acute HIV infection. The TEMPRANO group was able to do this is Cote d'Ivoire. How will we respond in Australia?????

 

 

 

 

Tagged in: IAS2015

Most of you may have already heard/ read/ watched Saez-Cirion's presentation on Monday 20th July where he presented data on a new post-treatment controller. To recap: 

Born at 37(+5d)/40 and mum on mono ddC since 13/40 with uncontrolled viremia 4.63M RNA copies, CD4 T-cells 81 and CD4/8 ratio 0.16. Baby was given ZDV prophylaxis immediate, RNA was undetectable at d3 and DNA ind at d3, d14 then positive at W4. ZDV was unfortunaelt interrupted at W6 and HIV-RNA reached a peak of 2.1x106 copies/ml at 3 months of age when cART (zidovudine, lamivudine, didanosine, ritonavir) was initiated. HIV-RNA was undetectable one month later and remained below assay-detection limits while on cART, except at 15 and 21 months of age. Between 5.8 and 6.8 years of age cART was discontinued by the family but HIV-RNA was undetectable when the child returned to clinical care at 6.8 years of age and cART was not resumed. HIV-RNA has remained < 50 copies/ml for more than 12 years except for 2 blips. This was not due to HLA type and raised the possibility if a defective provirus or an immune mediated phenomenon. 

Locally in Melb, we've seen a few unique post treatment controllers and elite controllers recently and are currently interested in exploring their immunological, virological and HLA features. You may have seen a few in your practice too and we'd be interested to hear from you. 

 

There was also some debate about the role of structured treatment interruption in this meeting. See also "ultrastop" data (Katlama). Should we risk-stratify? Do we know how to risk-stratify? Is it safe? How closely should we monitor? Is it necessary?

Tagged in: IAS2015
How Drug Policy Should Respond to the HIV Epidemic

Walking around Vancouver you can't help noticing the shops selling medicinal cannabis - the big cartoon weed pictures are so obvious!  So it was interesting to hear about the response to the IVDU problem here, and in yesterday's plenary Dr Evan Wood gave a summary of the main issues and how local authorities have worked to address them.

Dr Wood is a Professor of Medicine with an interest in HIV and drug addiction. He has been researching the impact of medically supervised safer injecting sites in reducing drug-related harm while increasing access to detox services for drug users. His research was the first to clearly demonstrate the positive impacts of safer injecting facilities for injecting drug users in Canada. This research has been instrumental in the development and continuation of Insite, a supervised injecting site in Vancouver that has saved many lives.  Dr. Wood pointed out that stigmatization of drug addiction is a major barrier, and he has been a voice for evidence based policies rather than ones based on negative perceptions of drug use.


He described the 4 Pillar approach to tackling drug use:

  1. Prevention
  2. Treatment
  3. Enforcement
  4. Harm Reduction

Vancouver had an explosion in HIV cases amongst its IVDU population in the 1990's, which at its height saw a fatal overdose occurring every day.  This prompted the city authorities to use a new approach.

The strategies employed included:

  • sterile needle provision
  • supervised safer injecting facilities (which prevents needle sharing)
  • methadone programs and other OSTs
  • treatment as prevention

Unfortunately, the 4 Pillars philosophy is not shared by the Canadian federal government, and a quick google search reveals that there is still much debate over the issue.  This is despite Dr Wood's claims that new HIV diagnoses in the IVDU community in Vancouver have dropped by 90% since the actions were implemented.

In stark contrast, at today's plenary I caught the last 10 minutes of the overview of the HIV situation in the Russian Federation, Eastern Europe and Central Asia, and was dismayed to hear that the situation there with respect to HIV in the IVDU population is very serious, largely driven by unsafe injecting although heterosexual transmission is also increasing. 

There are very few structured and recognized civil society and community-based organizations in most countries in the region.

The Russian Federation has some of the world's highest incarceration rates, with prisoners often waiting in overcrowded jails for months before trial.  Unsafe injection use, corrupt prison staff and high rates of unsafe sex and TB prevail.

Drug policies rely heavily on prohibition law enforcement, and methadone is illegal.

It is hard to see how a focused approach to the problem can be achieved under such circumstances.

 

 

 

 

 

Tagged in: IAS2015
MSM: The Global Perspective session began with a study examining testing behaviour in Thai MSM by Tim Holtz. This was followed by a presentation outlining the historical disparities in HIV incidence in Black MSM living in King County by Galant Au Chan. Ashley Grosso spoke about the potential issues associated with exclusion and inclusion of MSM aged under 18 years in epidemiological research. And finally Christen Khosropour and my colleague, Ben Bavinton spoke about seroadaptive behaviours in MSM in Seattle and in Australia, Brazil, and Thailand respectively.
 
Some findings of this session were:
- Only about one fifth of individuals attending a busy MSM clinic in Bangkok, Thailand met the current Thai national guidelines for HIV testing (every 6-12 months) Messages to improved repeat testing are needed.
- Historical examination of trends in HIV incidence showed HIV incidence increased in birth cohorts from 1940s to 60s then declined 65% but has since plateaued. These trends have been the same in both black and white MSM, and there is evidence of significantly higher incidene in black MSM almost since the beginning of the epidemic. Disparities and absence of progression in recent birth cohorts in concerning
- A significant proportion of MSM reported having had sex with a man under the age of 18yrs across different settings in Africa, estimates ranged from 15-65%. Most also reported non-disclosure of orientation to family and stigma experienced as a result of family members knowing their orientation suggesting that parental consent for <18 years of age is unlikely to encourage participation in this setting. We may be overlooking an important group of MSM in our epidemiological research, innovative ways of involving MSM under the age of 18 while considering ethical considerations in this group are required. 
-There is evidence that HIV testing frequency and ART use impacts sexual behaviour decision-making among MSM in Seattle. Results on incidence are not conclusive as there were few seroconversion however there was some suggestion  effects of this nuanced behaviour may lead to protection from HIV.
- HIV-ve MSM were twice as likely to have condomless anal sex when they perceived their partners viral load was undetectable in Australia, but not in Thailand or Brazil. Optimism about TasP were found to be associated with condomless anal sex in all three settings. 
 
Tagged in: IAS2015

Tuesday mornings Oral Abstract session was titled PreP: Demonstration for Implementation presented the initial findings from at least four studies into issues such as adherence and uptake. The studies examined some key affected populations. 

 

Of particular interest was an abstract from the U.S about PreP in Young MSM (YMSM) and transgendered women by the adolescent trials network (ATN) study 110. YMSM are at particularly high risk of HIV acquisition and remain relatively understudied with respect to PreP.

 

The ATN 110 study has some locally relevant points. 

 

ATN 110 was an open label study or once daily TDF/FTC across 12 U.S cities of men aged between 18-22. 

 

The primary objectives were to 

 

  • provide additional safety data on FTC/TDF use in YMSM
  • to examine the acceptability, patterns of use, rates of adherence and drug levels when YMSM are provided open label Truvada and 
  • to examine patterns of sexual behaviour when YMSM are provided PreP

 

The 200 enrolled participants had self-reported high sexual risk in the last 6 months and were HIV negative. 

 

The mean age of participants was 20 years, 78% identified as gay, more than 80% reported condoles anal intercourse in the last six months, almost 60% receptive anal intercourse and 22% were positive for an STI at screening. More then 50% were black.

 

There were very few adverse events but 25 discontinued primarily due to personal choice or a self perceived change in their sexual risk.

 

Study participants were incentivised $25 per visit and had study visits at weeks 4,8,12; then three monthly. 

 

There were 4 seroconversions by week 48. All four had undetectable levels of Truvada, None of them had drug resistant virus.

 

Generally, participants reporting higher sexual risk had higher levels of Truvada. This remained consistent though to week 48. The mean number of parterns and condomless sex acts was mostly unchanged. STI rates remained as high as there were at baseline.

 

Notably, adherence decreased for all participants over the 48 weeks. Adherence appeared to decrease as the study visits decreased in frequency. Some qualitative research will be done some time in the future. This could infer that YMSM may need more rigorous follow up or an ‘enhanced visit schedule’

 

 

Wednesday’s Plenary will further examine PreP

 

Some data from the Opposites Attract Study was presented by Ben Bavinton of the Kirby Institute this afternoon. Probably well known to most readers this longitudinal study is examining HIV transmission and viral load in serodiscordant gay relationships. This data continues to be collected and wasn’t presented today. What was shown was data relating to whether  seordiscordant couples were having condomless anal intercourse when the positive partner’s viral load was perceived to be undetectable. The study includes  couples in Australia, Brazil and Thailand. Most of the positive partners in Australia and Brazil are on treatment with an undetectable viral load.

 

Two thirds of  Australian couples and just under half of Brazilian couples were not using condoms.  There was a strong association in Australia between this behaviour and the perception by the negative partner that the positive partner’s viral load was undetectable. This association was not evident in Brazil or Thailand. There is evidence therefore that Australian couples are comfortable with the Treatment as Prevention message. Ben thought that the reason for the high association in Australia compared to the other two countries was very likely due to the widespread discussion in the community around the issue, better understanding of the new findings and good communication with healthcare workers ,etc.

 

Another really interesting study in the same session looked at another seroadaptive behaviour seen in Seattle MSM at a Sexual Health Clinic.Researchers sought to examine whether HIV negative men were having condomelss anal intercourse based on the timing of when their casual partner reported having their last test. 86% participants reported  asking when the partner had last tested. Two thirds of participants had then chosen not to wear a condom on the basis of the answer.

 

A similar number of negative men had reported asking potential positive partners about what their viral load was. 83% decided not to use condoms on the basis of this.Those who did ask their partner about testing were less likely to then test positive for HIV but the numbers who tested positive for HIV were very small in this study so I’m not sure of the siginifcance.

 

Tagged in: IAS2015

 It is known that combined  Antiretroviral therapy(cART) before 6 weeks of age results in low levels of HIV .

If treatment starts before 1 year of age, there is a median of 4 copies at 10 yrs of age.

Treatment within first 48 hrs(& first 4 days of life), most will clear the virus before 4 months. Most of the virus is in transient memory cells, rather than central memory cells. The Missisipi baby was infected in utero but treatment was initiated within 31 hrs and discontinued at 18 mths. This baby remained in remission for 28 mths off cART.

Very early cART alters HIV persistence in children. It limits pro viral and replication competent reservoirs.

In adults, we are still determining what undetectable HIV (when being treated with ART) really means., and how early is the ideal time to start treatment.

In HIV infection, there is a massive expansion of HIV in lymphoid tissue but with treatment it is undetectable in the bloodstream. There may be decreased intracellulardrug concentration in lymphatic tissue And this may be the site of clones that expand when cART is stopped or if there is poor adherence to ART medications for whatever reason

No impact of HIV on HEPC treatment outcome

95-97% cure rates even in co-infected

Improvement in quality of life occurs v. Quickly with new oral medIcations due to suppression of the Hep C virus.

If there is cirrhosis of the liver, treat for 24 weeks. De compensated cirrhosis may be reversible, but not always.

In Australia, HIV/HCV co infected numbers approx 2,500-3,000

 

Most cells infected with HIV are CD4's- what makes these cells persist long term.?

CD4cells have attributes of expanded cellular clones. The larger the cluster the older it is.

In HIV controllers, most are restricted to a particular tissue site.

Infected cells can traffick out into the blood and expand.

Can infected CD4cells capable of producing virus clonally expand in Vivo?

Where does virus replication occur in HIV controllers?Blood and lymphoid tissue are v. Different reservoirs.Rare sequences survived to traffick out of blood and into lymphoid tissue.

Are there any sequence similarities between lymph nodes at different sites?

The reservoir contains an archive of viral evolution

This was a poster presentation session focussing on new drugs and new strategies for the treatment of people living with HIV.  I will focus on results relevant to MSM populations.  

The first presenter was from Thailand.  T. Bunupuradah reported on results from a trial comparing 200 mg of boosted atavanavir  to 300 mg of boosted atazanavir in virologic suppressed HIV-infected Thai adults.  This was a randomised, open-label trial.  He showed that the lower dose atazanavir is non-inferior in terms of efficacy.  There was higher discontinuation due to intolerance in the 300 mg group.  there is difficulty extrapolating these results to other ethnicities though due to possible weight and genetic differences.  These results could not be generalised to treatment naive or those failing first line therapy either.

The second speaker was Tony Mills from California.  He presented data from a switching study which is at the 48 week mark.  This study switched patients from a tenofovir disoproxil fumarate (TDF)-based regimen to a tenofovir alafenamide (TAF)-based regimen.  The results are very encouraging for improved bone mineral density on the TAF based regimen.  Before switching, patients were on elvitegravir, cobicistat, FTC and TDF (stribild), or efavirenz, FTC and TDF (atripla), or boosted atazanavir and truvada.  They all had eGFR greater than 50.  Then they were switched to elvitegravir, cobisitat, FTC and TAF or continued on their TDF-based regimen.  I think this study was flawed however, given that in some patients the tenofovir component was not the only part of the regimen which was switched.  This introduced a confounding factor into the analysis.  Nonetheless, there was a significant increase in bone mineral density in the TAF group compared to the TDF-based regimens.  The TAF group also maintained virologic suppression and showed a significant improvement in proteinuria and other markers of renal function Compared to the TDF group.

J. Gatell from Barcelona presented data on a new NNRTI doravirine at 100 mg once daily with a truvada backbone compared with  efavirenz and truvada.  The study authors saw a need for a new NNRTI given the CNS side effect profile of efavirenz.  It was a double-blind study in ART-naive patients with HIV-1.  At the 24 week mark, the doravirine group had less CNS adverse events than efavirenz.  Furthermore, doravirine demonstrates similar viral suppression to efavirenz at the 24 week mark.  This study is ongoing.

Finally, C. Hwang from BMS presented data on a second generation HIV-1 maturation inhibitor called BMS-955176.  This was used in combination with boosted or unboosted atazanavir.  The need for another class of drug is clear given treatment emergent or transmitted resistance.  Newer drugs with fewer adverse events and less DDI's are still needed.  Maturation inhibitors maybe beneficial in this context.  BMS-955176 inhibits the last protease cleavage event between capsid protein p24 and spacer peptide 1 in Gag, resulting in the release of immature, non-infectious virions.  The inclusion criteria of this study include HIV-1 subtype B-infected subjects.  They were treatment naive or treatment experienced patients.  It was conducted over a 28 day dosing period to asses the safety and tolerability of 176 and the change in plasma HIV RNA levels From baseline.  176 was generally wel tolerated with no SAEs or AEs leading to discontinuation.  It also resulted in very good virologic response compared to standard of care.  A phase 11b study is now underway in treatment experienced patients.

 

Tagged in: IAS2015

At this morning's IAS plenary Professor Greg Dore from the Kirby Institute and St Vincent's Hospital in Sydney gave an excellent presentation on the exciting treatment options soon to become available for Hep C, and described some studies he is currently involved in.

The development of interferon-free HCV therapy provides one of the major advances in clinical medicine in recent decades. 

Major recent developments include:

  • There are now several highly effective IFN-free DAA regimens for genotype 1
  • HIV has no impact on HCV treatment outcomes
  • HCV resistance testing is of limited clinical relevance
  • Some treatment individualization may still be required (e.g. cirrhosis)
  • Decompensated cirrhosis is reversible, but not always
  • Shorter duration (6-8 weeks) pangenotypic regimens are in development

In the treatment of GT1, the presence of resistance mutation Q80K may compromise treatment response to simeprivir/sofosbuvir if cirrhosis is present, but treatment outcomes improve if the treatment period is increased from 12 to 24 weeks.

Treatment of GT3 will likely need combination with one of the NS5A inhibitors.

Professor Dore described "perfectovir", the ultimate therapeutic agent for Hep C, the holy grail which the pharmaceutical companies are striving to develop.  The attributes of "perfectovir" would be:

  • Extremely high efficacy
  • Well tolerated
  • Once daily dosing
  • Pangenotypic
  • Short duration (6-8 weeks)
  • Affordable

The cost of these new DAAs is the major barrier.  Broadened access to IFN-free HCV therapy would provide the foundation for HCV treatment as prevention.  This could be looked at in high risk populations such as incarcerated people and people on opioid substitution therapy programs.

Professor Dore went on to describe 2 interesting studies.

The STOPC study looks at HCV treatment as prevention in 5 Australian prisons.  The primary objective is to evaluate the impact of a rapid scale-up of IFN-free HCV treatment on HCV transmission.  The primary endpoint will be a change in HCV incidence from pre- to post- scale-up of IFN-free HCV treatment.  The baseline HCV prevalence in this community is 24%.

The CEASE study looks at co-infected populations, and again evaluates the impact of a rapid scale-up of IFN-free HCV therapy on HCV transmission among people with HIV, with the primary endpoint again being a change in incidence from pre- to post- scale-up.  This study is very much underpinned by the March 2015 recommendations of the Australian PBAC for use of the new DAAs sofosbuvir, ledipasvir and daclatasvir, with no restrictions based on stage of liver disease or injecting drug use.  The hope is that primary care S100 prescribers who currently manage co-infected HIV patients will start prescribing for HCV, and ultimately be able to provide this treatment for HCV mono-infected patients.

In summary, the arguments for IFN-free therapy access for all as presented by Professor Dore are:

  • IFN-free therapy is an enormous advance in therapy
  • HCV-specific QOL impairment in early disease, reversible
  • Potential HCV treatment as prevention benefits
  • Non-treatment = ongoing monitoring, potentially for decades
  • Drug price curve will continue downwards
  • Ability to cure empowering for entire hepatitis C sector

 

 

 

Tagged in: IAS2015

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

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

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

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

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

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

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

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

 

 

 

 

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

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

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

Day 2 of IAS2015, I attended a very full lunch poster discussion session entitled HIV Testing: The Gateway for Everything.

Sheri Lippman presented two posters. The first presented results from a cluster randomized controlled trial comparing the ‘one man can’ campaign in South Africa which aimed to engage men into testing through community mobilization. Community mobilization was found to be associated with higher testing uptake, though not equally for all CM domains. The main three domains which had the greatest impact were consciousness, concerns and collective action.

Sheri’s second presentation was on a pilot study examining feasibility and acceptability of self-testing in transgender women in San Francisco. 50 HIV-ve trans women were provided home HIV test kits and asked to utilized the tests once a month for three months, behavioral data was also collected at baseline and three months. 96% of study cohort had multiple recent partnerships and 80% had engaged in sex work, so as with other transgender communities, a pretty high risk population. Most found the test easy to use and would recommend to their friends (>90%), 68% would use the test again. The main reasons provided for not using again were around gaining access to counseling services that facility-based testing provided, and most participants had tested with a partner or a friend. A marketing strategy which provided two home-based tests aimed at testing with a partner could be an efficacious method for targeting this hard-to-reach population.

Laura Derksen from the London School of Economics presenting results from a cluster-randomized trial examining methods to reduce stigma in a community based setting in Malawi. 122 Malawi villages were targeting (60 intervention villages and 62 control) which reach two thirds of the target 15-49yrold population. In the control villages information was provided on the benefits of ARV including prolonging life and reversal of AIDS. While in the intervention villages, in addition to the control information, information regarding reduced likelihood of transmission in partnerships where the HIV+ve partner properly adhered to ARV was also propagated. The overall concept being that if they could reduce stigma, by showing that individuals who tested were in fact safer sexual partners then rates of testing would improve. The percent of the population having testing for HIV post-exposure was found to be  60% higher in the intervention arm compared to the control arm, and this was consistent for both genders.

Perhaps the most relevant to the Australian setting was a poster presented by David Katz, which examined self-testing as a method to increase overall testing frequency among high-risk MSM in Seattle. 230 HIV-ve MSM were randomized to have access to free HIV self-tests versus standard HIV testing for 15 months. The primary endpoint was the comparison of HIV testing frequency, secondary endpoints included non-inferiority in regards to behavioral markers of HIV risk acquisition. The mean number of test in the self-testing arm was 5.3 (4.7-6.0) compared to 3.6 (3.2-4.0) in the control arm, which was statistically significant (p<0.0001). Non-inferiority bounds were met for risk acquisition, which included difference in frequency of bacterial STI diagnosis at 15 months, likelihood of non-concordant anal intercourse at 3 months, and number of male non-concordant partners. However confidence intervals were wide for the secondary endpoints and the study not really adequately power to examine these associations.  

And finally the last two posters were presented by Sue Napierala Mavedzenge and Pius Tih Muffih respectively. Sue presented results of a feasibility study which examined the reliability of self-testing in both rural and urban settings in Zimbabwe. There was high sensitivity and specificity of interpreting self-test kits in both rural and urban settings, however slightly lower sensitivity in the rural setting, which was likely a result of lower literacy in this group. Some practical issues to encourage interpretation of the test (such as increased window size) were discussed.  Pius Tih Muffih provided the results of a very interesting study which examined integrating partner notification into Option B+ in Cameroon. Results looked promising with 823 women testing positive providing information on 840 partners of which 693 were notified, of whom 421 were tested for HIV and 139 new HIV+ve cases identified and linked to care. They had not observed any backlash in terms of violence to women as a result of the notification but this was highlighted as an issue which needs to be carefully monitored.

 

 

 

 

 

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

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

 

 

Just to add to Bk’s post…. In each site for HPTN 062   qualitative research in the form of in depth interviews were carried out with some participants. Rivet Amico found that in Africa, women’s adherence very much had to do with their trust/mistrust of the study drug. When they were suspicious they had low adherence. When they had confidence the drug worked, when  they felt they had ownership  of the study they had good adherence. Stigma played an important role in adherence in Bangkok and Harlem. Participants were viewed as either being HIV infected or sexually promiscuous if seen taking the drug. On the other hand for some participants it greatly relieved the anxiety of HIV acquisition and gave them a sense of freedom. One participant who had come of age during the AIDS epidemic commented that this was the first time in his sexual life he had ever felt truly free. This freedom from anxiety has been something which many of the participants on the Prelude Study that I have met have commented on also.

 

In addition to the PK data BK presented there were interesting differences in the PK data between rectal and vaginal mucosa. Concentrations of TDF-DP were 10-100 times greater in the rectal tissue compared with vaginal tissue after a similar dosing period. Time to reach peak concentration was also slower in the cervix compared with rectum. The reason for lack of protection in the studies such as FEM-PREP was explained by lack of adherence but perhaps this also has something to do with it.

 

Francois Venter from South Africa gave a great plenary yesterday about Biomedical Interventions : Contrasting Implementation Changes. He called for less moralising from politicians in his country and more accountability when it comes to the issue of young women in his country being infected by older men. Stop talking about the morality of it and act by keeping the girls at school- an intervention which has shown makes  a difference.

 

Tagged in: IAS2015 PREP

 

No HIV practitioner can avoid the onslaught of PrEP. Whether you like it or not, you'll be facing it head on from fellow doctors and patients alike. Yet there are too many vital questions unanswered. Today's session on "How would you like your PrEP" introduces HPTN 067 or ADAPT study that attempts to address the question of optimal dosing and schedule of daily vs "time driven" ( 2 tabs a week + post exposure dose) and "event driven" ( one before and one after). Equally important is the question regarding how to start and stop PrEP ie how many days after starting and stopping PrEP is an individual protected from acquiring HIV.

 
ADAPT STUDY or HPTN 067
 
were conducted in Harlem (US), Silom (Bangkok, Thailand) and Cape Town (South Africa), designed to measure the coverage of sex events, number of tablets (required and taken) and self reported side effects and secondarily, adherence, safety and HIV infections. In other words, it is designed to identify dosing schedules that participants are more likely to follow and if these schedules "influence healthier sexual practices".
 
Apart from the U.S. site, the speakers concluded that Truvada PrEP "coverage" were comparable across the arms although daily dosing proved to produce better adherence. It is important to note that " comparable coverage" in this context does NOT equate to "comparable efficacy". If proven efficacious it will provide easier/cheaper alternative to daily dosing.
 
 
IPERGAY PK SUBSTUDY
 
12 participants received a single double dose TDF/FTC followed by PK sampling of plasma, PBMC, DBS and saliva done at T0, 0.5, 1, 2, 4, 8 and 24 hours.
10 participants had 2 rectal biopsies (including T0) and 2 participants had rectal biopsies at the above time schedule. 
Rectal biopsies were then exposed overnight to CCR5 tropic HIV 1 virus.
 
High concentrations (comparable to ART drug levels) of FTC were detected early at around T0.5 and for TDF at around 24 hours after dosing. However, although all the rectal biopsies were "infected" at baseline this compares to 6/10 of infected biopsies taken after dosing. Unfortunately there were no rectal PK and "infectivity" analysis done with additional post exposure doses to determine the protection conferred by the second and 3rd doses in the Ipergay PrEP regimen.
 
CELL PREP
 
This study extrapolates PrEP protective intracellular concentrations from STRAND and iPREX. 
Participants were given daily TDF/FTC for 30 days to 19 volunteers and bloods taken at days 1,3,7,20,30 and 35,45,60.
Estimated risk reductions were found to be
After dose 1 - 77%
After dose 2- 89%
After dose 3 - 98%
After dose 4 - 98%
Stop +1d - 97%
Stop +3d - 96%
Stop +5d - 93%
Stop +7d - 90%
 
Putting all these together, I believe that we should continue to advocate for daily dosing as it encourages better adherence and good coverage. Patients should continue to use condoms for at least the first 3 doses.
 
However, stopping PrEP continues to be unclear. IPrex rectal PK substudy showed 6 out of 10 "infected" samples after 24 hours despite CellPrEP showing 96% risk reduction up to 3 days after stopping daily dosing. I guess the question remains as to what the period of infectivity is after a mucosal exposure/inoculum.
 
 
Tagged in: IAS2015

 

For those of you who see HIV affected couples who are considering pregnancy I attended an excellent symposium on the subject  yesterday.

 

Pietro Vernazza from Switzerland gave an overview on the science of safe conception strategies. Data from HTPN052 has obviously really transformed the information we can now give patients. We shouldn’t underestimate the power this news has for couples who believed they could never have a family or felt they were taking great risks if they tried.

 

 Nelly Mugo from Kenya spoke about her experiences in a study of close to 2000 serodiscordant couples using PrEP (Tenofovir and TDF/FTC). The study found no differences in pregnancy indcidence, preterm birth or infant growth in the first year of life when comparing the PrEP group with placebo. It is an important option for those women who’s partner has not yet started ART. Pietro Vernazza thought it was an unnecessary addition however for those women whose partners were on treatment even given the fact that these men may ocassionally have viral blips.

 

Elaine Abrams from Columbia University then discussed Unanswered Questions about ART and Pregnancy.  There were 1.5 million HIV infected pregnant women in 2014, with 1.3 million of those in subSaharan Africa. 73% of them were receiving ART. Important points were that since the change in WHO Guidelines in 2013 regarding the use of Efavirenz as first line ART in pregnant  women ( including those in the first trimester and women of child bearing age) there has been no subsequent uptick in the rates of congenital anomalies . This is reassuring and significant given the  hundreds of thousands of women who have taken it in the last couple of years.

 

Also, there have been approximately 18 large studies looking at ARVs and preterm birth. There does seem to be some association with prematurity but it is not severe. It appears to be mostly associated with PI use and if it is started preconception it seems to be associated with increased risk.

 

Can I bring to your attention the following website www.hiveonline.org. . Shannan Weber, the director of HIVE, a clinic in San Francisco which cares for HIV infected pregnant  women, gave a really inspiring and personal talk about some of the people she has assisted in having families. There are some great resources for patients on the website including a really practical one about Home Insemination.

 

TasP and PrEP have radically changed the experiences of those couples affected by HIV who want to have children. How great it is to be able to offer them such positive information.

 

 

 

Tagged in: IAS2015

Monday afternoon Bridging session: The present and future of combination prevent for HIV sexual transmission. 

 

Thanks to the ’How do you like your PreP’ session in the neighbouring room, this session was poorly attended but highly interesting and relevant.

 

Five speakers gave different perspectives on HIV prevention strategies amongst varying populations. 

 

The overarching message was about a paradigm shift in HIV prevention away from an ‘insufficient’ ‘condom protection (CP)’ based message to a more ‘realistic’, nuanced and individualistic combination-prevention model which should demonstrate flexibility and adhere to cultural and community ethics (a bit vague… but prioritise making the prevention relevant to the person/population you are treating) 

 

A stand-out and, perhaps, more locally relevant talk was  given by Andrew Grulich. 

 

He specifically discussed the combination prevention strategies ‘TasP’ and ‘PreP’  in MSM. 

 

He reminded the audience that HPTN 052 included only 2% MSM and there are yet to be ‘published’ findings on ‘TasP’ in sero-different MSM couples. Despite this, in HPTN 052, no index-to-partner transmissions were observed if viral suppression was achieved. 

 

The “PARTNER” study and “Opposites Attract” will ultimately aim to quantify this in MSM and the preliminary results appear at least as promising as HPTN 052 (zero linked transmissions to date in Opposites Attract).

 

PreP however has clearly demonstrated very high efficacy in MSM in iPrex, PROUD and Ipergay. Andrew proposed PreP as being a ‘missing link’ in the combination prevention intervention strategies and highlighted this with an example of new HIV diagnoses across three comparable MSM populations in Sydney, London and San Francisco. PreP is readily accessible in SF and less readily available as a prevention strategy in Sydney and London. 

 

Whilst the number of HIV diagnoses may not necessarily represent a true increase in HIV incidence, San Francisco is the only setting to see a substantial decline in HIV since the introduction of PreP. 

 

This decrease is  despite increasing rates of condomless anal intercourse in MSM and increasing rates of and STIs in San Francisco compared with Sydney and London. 

 

 

Tagged in: IAS2015

Please join us for a memorial event celebrating the life of one of Australia’s leading HIV advocates, Levinia Crook… https://t.co/N7dof5xaGa

ASHM ASHM