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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Anthony Fauci from the National Institute of Allergy and Infectious Diseases (NIAID) & National Institute of Health (NIH), Bethesda, USA, presented an excellent keynote lecture on ending the HIV/AIDS pandemic.

He started by taking us through a timeline of HIV infection. Starting in the 1980s, when the mean life expectancy of a newly diagnosed 20 year old (not on ART) was ~12 years. We followed the science through time and today, over 35 years later, the mean life expectancy of a newly diagnosed 20 year old (on ART) is ~53 years.

What we've learned since the 1980's regarding the etiology, virology, pathogenesis, treatment and prevention have given us a better understanding on how all these advances should continue to be used in conjunction in order to end the HIV/AIDS epidemic.

We've discussed treatment as prevention (TasP) and looked at a traid of pivotal ART studies regarding the treatment of individuals with HIV infection:

  • The SMART study showed that episodic ART is inferior to continuous ART
  • The HPTN 052 study showed that early ART reduces HIV transmission to uninfected sexual partners by 93%
  • The START study showed that early ART reduces serious illness or death by 57%

 

We are all aware of the continuum of care when our patients have a positive HIV test results, but we should also be very proactive in the continuum of prevention in those who test negative.

Despite our 90/90/90 targets, the numbers of newly diagnosed HIV infection have plateaued globally since 2009.

Continuing to improve access to ART and HIV prevention strategies, such as pre-exposure prophylaxis (PrEP) could dramatically decrease HIV-related deaths and the rate of new HIV infections.

The efficacy of PrEP has been proven in multiple studies and most recently the San Francisco Strut PrEP program showed no new HIV infections in >1200 men on PrEP in nurse-lead intervention over nearly 1.5 years. There were 82 new infection at that clinic among men not enrolled in the PrEP program.

The two main remaining scientific challenges for HIV identified are:

  • Addressing HIV persistence
    • eradicate the reservoir - classic "cure"
    • control viral rebound - sustained virologic remission
  • Development of a safe and effective preventative HIV vaccine 

Towards a HIV vaccine:

  • The first signal of efficacy (31%) in a HIV vaccine clinical trail - RV144, was seen in: Vaccination with ALVAC and AIDSVAX to prevent HIV-1 infection in Thailand. S Rerks-Ngarm, et al. For the MOPH-TAVEG investigators. N Engl J Med 2009; 361:2209-2220. Dec 3, 2009
  • Additional work since this study has lead to a large-scale HIV vaccine trial that will launch in November 2016 in South Africa: HVTN 702 modifeid RV144 prime-boost regime
  • More work is also being done on Neutrolising Monoclonal Antibodies, discovered since 2009.

 

Conclusion:

Treatment + non-vaccine prevention + vaccine = durable end of the HIV/AIDS pandemic

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.

 

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

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

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

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

Treatment to Prevent HIV: Opening Plenary HIV&AIDS 2015

Prof Myron Cohen, the lead investigator of the multinational HPTN052 trial kicked off today's Plenary clinical presentations with Treatment to Prevent HIV: Does timing matter?

Great overview mentioning that risk of transmission is explicitly related to viral load. 

His breaking news: HPTN052 trial has found an overall 93% risk reduction of contracting HIV in ITT analysis of sero-discordant couples. And even better news was that the 8 linked partner infections that occurred whilst their partner was on ARTs occurred either before ART was commenced or when the partner was actually failing ART therapy (i.e. had a detectable viral load).

This means NO infections were observed when the partners' HIV replication was suppressed. 

He then highlighted that a significant proportion (19-52%) of HIV transmissions occur during early/ acute infections, adding much weight to the argument for very early ART treatment.  

His message was applauded and was loud and clear to "Start ART Now!" 

Tagged in: HIVAIDS2015 TasP

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.

 

 Greetings from Day 1 of IAS 2015,

Treatment as prevention (TasP) and the UN proposed ambitious 5-year treatment target of 90% of HIV+ve individuals being diagnosed, 90% of those diagnosed on efficacious treatments and 90% of those treated virally suppressed equating to 73% of all HIV+ve individual’s being virally supressed was the topic of discussion at the pre-conference workshop UN 90-90-90 Target Workshop: Lessons from the field.

There were four sessions spanning the day. After an opening speech by Michel Sidibé, Session One starting with RCT evidence to support immediate versus standard of care (SOC) ARV population-based roll out interventions and it’s utility to achieve the 90:90:90 target (SEARCH, HTPN071 (POPART), ANRS12249 and the Botswana Combination Prevention Protocol(BCPP). There was also some evidence reported for the utility of financial based incentives (FIs) to encourage linkage to care (HPTN065) and some discussion of acceptability of immediate ARV in sero-discordant couples (HPTN052) though 1-year follow-up results of HPTN052 will be presented Monday 2:30pm. The take home messages of session one included:

  • Largely testing rates, linkage to care and viral suppression levels achieved in SEARCH, POPART, ANRS12249, and BCPP were all high, around the 80% mark, however the big question of the impact of early ARV on HIV incidence in all of these trials is yet to be determined. Results so far look promising.
  • There still remain some pockets of the HIV+ve population which seem consistently hard to reach, primarily migratory young men in Africa. However while there were some gender disparities in linkage to care, once in care outcomes seemed similar for both genders. More social behavioural data from SEARCH, POPART and ANRS12249 to come.
  • There was evidence to support that immediate ARV does not have detrimental impacts on adherence to treatment i.e. HIV+ve people who feel healthy still seem to be good at take their drugs
  • The multi-disease approach undertaken by SEARCH, grouping testing for HIV with hypertension and diabetes was an encouraging approach
  • Financial based incentives did not show significant improvements in linking known HIV+ve individuals into care in the US, however they did show some efficacy in specific sub-groups, suggesting possibly that FI should be a target rather than a broad roll out. Some discussion over the ethics of FIs and the difficulty in implemented these strategies was highlighted in the discussion

Session Two largely covered evidence from cohorts. Evidence in achieving the 90-90-90 targets was presented for HIV cohorts in rural Malawi, Swaziland, KwaZulu-Natal and Rwanda, and evidence from the new cohort AFRICOS was presented. Lessons from this session included:

  • Results from rural Malawi where MSF task shifted ARV roll out from doctors to nurses which was later subsumed into the national program look very promising, 77% diagnosed, 84% on treatment and 91% of those virally suppressed. Again young men are those not linking to care.
  • The Early Access to ART for All (EAA) Study in Swaziland provided evidence for scalability feasibility and acceptability of the 90-90-90 target approach. Results supported initiating ARV on the same day as testing to avoid LTFU. While this may be difficult to implement if GART for first line is part of the recommended national guidelines in most of the developing world it is not.  Further lessons from KwaZulu-Natal presented by Frank Tanser showed barriers to care were distance from treatment centres (even in non-centralised settings) and gender.
  • The cascade of care in Rwanda looks close to the 90-90-90 target, with the epidemic now moving into older aged groups.

Session Three covered field implementation initiatives in China, Brazil, Thailand, and San Francisco. The ability for faith based organisations to engage people into care was also presented as well as some interesting results from a phylogenetic monitoring system that has been set up in British Colombia. Take home message from this post lunch, slightly jet-lagged session were:

  • In many settings described in this session, patients still had a median CD4 at diagnosis of less than 350 so it’s not really a question of immediate or deferred ARV rather engaging people in testing and linking to care. HIV peer intervention testing and self-testing has found to have encouraging results in Brazil. While a mixed facility and community-based testing model has improved diagnosis and linkage rates in Thai MSM and Transgender populations.
  • San Francisco has surpassed the 90-90-90 target and is now aiming for zero new infections. The RAPID program which enlisted individuals in immediate same-day ARV initiation looked promising. The difficulties in reaching that last 10% of the HIV+ve population in non-generalised epidemics was highlighted. How to reach specifically transgender populations was also discussed in question time, online outreach methods and linking ARV services with hormone therapy services were some of the suggestions.

  • Finally a population-wide HIV resistance database in British Colombia has been used for phylogenetic monitoring of outbreaks in real time. Fascinating results but a real potential for huge legal ramifications (two Supreme Court appearances later, Art Poon and colleagues in British Colombia have managed to resist forced disclosure of individuals). What a shame we live in a world where criminalization of sex in HIV+ve individuals is still common place!

And finally the workshop ending with presentations from donors, PEPFAR and the Global fund, and agencies, CDC who highlighting the cascade in the US, and the WHO and IAPAC who discussed soon to be released guidelines. The main highlight of this session was the (unofficial) report by Gottfried Hirnschall that the new WHO ‘When to Start’ guidelines including PrEP recommendations will likely be released in September of this year. These will (unofficially) include ART initiation for all regardless of CD4 count, PrEP for individuals with substantial risk (to be defined…), Option B+ as the recommended SOC and some suggestions for dose reduction strategies.

So finally, my overall conclusions of the workshop are the 90-90-90 UN target seems a difficult target but potentially achievable in some settings. Primarily generalised epidemics where the health system can support such targets with UNAIDs strengthening the provision of ART and donors getting on board, or non-generalised epidemics where innovation methods are employ and large amounts of resources can be mobilised in support of such efforts.  It will, however, be a specific challenge in other setting where either there isn’t a national health system to support such a roll out or there isn’t the resources to achieve these target where the epidemic remains localised in particularly hard-to-reach populations. As suggested by one of the attendees, perhaps there should be a fourth 90, 90% of countries achieving the 90-90-90 UN target by the year 2020?

 

For details of the workshop see http://www.treatmentaspreventionworkshop.org, for a live stream of the workshop see http://flash-vs.cfenet.ubc.ca/cfestream1.html