I'm reporting from oral abstracts from the Australasian Viral Hepatitis Elimination Conference 2017 with speakers discussing Models of Care/What are the challenges ahead for hepatitis B and C elimination? 

A wonderful world-wind tour of current models of care for upscaling chronic hepatitis C treatment, mostly based around nurse-led models of care linked in with tertiary care settings. A very promising model that appears to have had great success in accessing marginalised populations who require intensive case management. Missing from the discussion however was how General Practitioners could be incorporated into this model, or indeed exploration of a GP led model of care for clients with a reduced need for support.

A particularly interesting speaker presentation was given by Dr Carla Treloar about the development of a tool to monitor the experience of stigmatisation for those engaged in the health care system - a much neglected area of research in understanding the barriers to patients seeking access to care. Clearly, all options need to be on the table if we are to reach the aspirational targets of elimination, as it is unlikely that one-model-fits-all will be sufficient to reach all of the populations concerned.

Link to the oral abstracts and speaker presentations here

I attended a collection of very interesting oral abstracts at the 2017 Australasian Viral Hepatitis Conference, each dedicated to addressing elimination of hepatitis outcomes in key population groups.

The first presentation by Timothy Papaluca involved a population group across 14 prisons in Victoria. It was a nurse-led HCV DAA program that evaluated the efficacy of the antiviral therapy delivered in the prison system using this model. After 17 months, 1180 prisoners had been assessed with 718 eligible for treatment and 633 prisoners having had treatment commenced. Per-protocol analysis achieved SVR12 of 95% but intention to treat analysis was only 68% with a percentage lost to freedom, highlighting the difficulties with follow up and adherence once they are out of the prison setting. With appropriate follow up and review through to SVR12 however, the prison setting provides an ideal scenario for implementing HCV DAA treatment based programs.

The second presentation by Marianne Martinello looked at HCV/HIV co-infection cohorts. An estimated 230,000 Australians live with chronic HCV and an estimated 2,700 of those have HCV/HIV co-infection. This cohort study evaluated HCV treatment uptake and outcomes of this cohort following DAA therapy. Annual HCV treatment uptake went from 7% in 2014 to 9% in 2015 before skyrocketing to 67% in 2016, while HCV RNA prevalence within the cohort fell from 79% to 74% and 28% in those respective years. Two key factors assisted in the dramatic uptake in treatment. Firstly, this cohort has a high proportion already linked in to HIV care and secondly, the introduction of broad based government subsidies for DAA therapy in 2016. SVR12 was 92% on an intention to treat basis and 96% among 159 individuals on a per-protocol basis, with one case of reinfection.

Phillip Read looked at ATSI patients at The Kirketon Road Centre, Sydney, an interesting look at their model of care for HCV. On a per-protocol basis where they were able to be followed up at 12 weeks, an SVR12 of 100% was achieved although a proportion were unable to be followed up at 12 weeks and modified intention to treat SVR12 was only 91%.

A remarkable achievement from a holistic program called “itha mari”, A Barkindji word roughly translated to “this way in the right direction”. With a patient-centred set agenda and activities such as lunches, workshops, art, storytelling, movies and food vouchers, KRC’s innovative program that is ATSI people led, showed quicker uptake than KRC’s non-indigenous patients and adherence. KRC’s commendable program with ATSI clients provides inspiration on improving follow up and outcomes not only for ATSI clients but the broader HCV demographic.

SIMPLIFY is an international open-label study that looked at DAA outcomes for specifically PWID group presented by Jason Grebely. It recruited participants who had recent (within six months) injecting drug use in 17 countries (19 sites) in 2016. Particiapnts received sofosbuvir/velpatasvir daily in a one-week electronic blister pack for 12 weeks. 96% completed treatment and SVR12 of 94% was achieved showing no difference between recent the PWID group and existing data for OST groups. Adherence to DAA was also highlighted in an informative pixel graph with green dots indicating compliance with daily medication while yellow dots showing missed doses, were surprisingly very low, with mean adherence of 89%. The simplified once daily regimens of DAA are more forgiving to patient adherence and the end points support the efficacy of DAA HCV treatment among recent PWID populations.

Darren Russell had incarcerated prisoners clamouring to be transferred to the Lotus Glen Correctional Centre (LTGC) near Mareeba in Far North Queensland once work spread within the prison community of their successful HCV treatment program for inmates. A total of 94 patients were treated with DAA therapy regimens and as of early 2017, no further existing patients at LTGC were known to have Hepatitis C in the prison.

Andrew Lee provided data in a prospective cohort study of patients treated by Cairns Hospital. Over a 13 month period, 481 received treatment for HCV. SVR12 results were available for only 77.8%. SVR12 results of those that followed protocol and not lost to follow up however, was 96%.

Greg Dore looked at HCV reinfection and injecting risk behaviour, following Elbasvir/Grazopevir treatment in patients on Opioid Agonist therapy (OAT). Of 296 patients in Co-STAR trial, 185 patients were enrolled in the follow up. Of the enrolled patients, 108 reported any drug use (injecting or non-injecting) while 47 reported injecting drug use in the past 6 months since follow up. Only 6 reinfections were found among this cohort suggesting HCV reinfection among patients on OAT following DAA therapy was uncommon despite ongoing drug use.

For more information on the abstracts and oral presentations visit the AVHEC17 website

On the first day of the 2017 Australasian Viral Hepatitis Elimination Conference, Benjamin Cowie from the WHO Collaborating Centre for Viral Hepatitis/Doherty Institute gave an inspiring summary of Australia's Progress in the management of Hepatitis B which challenges us to go further.

Figures from 2015 show 232,600 people in Australia expected to have Hepatitis B, 144,216 diagnosed, 36,534 in care and 14,636 being treated. More than 6,000 notifications for Hepatitis B were made in 2016. 

There is a marked variation within Australia of the percentage of people being managed for hepatitis B, with the Southwestern area of Sydney monitoring and treating where appropriate more than 30% of their patients with hepatitis B, but in some areas in Australia areas this figure is as low as <5%.

The challenge then is to work at screening. Asking where a person or their parents were born, or whether they identify as Aboriginal or Torres Strait Islander will help to pick up 2/3 of potential cases. Late diagnosis leads to a marked increase in decompensated cirrhosis and liver cancer.

If we fail to look for Hepatitis B in the appropriate places, we are doing our patients a great disservice, and a potential long term medicolegal disservice to ourselves.

Link through to A/Prof Ben Cowie's presentation here

Dr Maia Butsashvili discussed Hepatitis C elimination in Georgia. 

Of a total national population of 3.7 million inhabitants, the incidence of chronic Hepatitis C in Georgia is 5.4% (i.e. 150,000 people).

Hepatitis C is found in 3 population subgroups in Georgia - PWID, MSM and healthcare workers; with the peak incidence being men in the 30-49 age group.

Georgia underwent a period of political and economic upheaval in the 1990s with the collapse of the Soviet Union. Injecting drug use was at its peak and healthcare procedures were compromised. Blood transfusions, dental and obstetric procedures (especially terminations of pregnancy as a form of contraception) are thought to be the source of the health care related hepatitis C infections.

With the help of the CDC, Georgia is running a pilot program to eliminate Hepatitis C in  its population.The Georgian government has supported this initiative, and the pilot is aiming for 90% diagnosis, 95% treatment and 95% cure of its Hepatitis C population by 2020. Coupled with this aim are the strategies of harm reduction in PWID communities (needle syringe and OST programs) and preventing transmission of Hepatitis C in the healthcare setting.

The pilot was initially established at 4 sites in 2015, and telemedicine support for difficult cases was provided by Boston specialists. All results are reviewed by a committee before treatment was selected and commenced. Treatment was initially with a combination of Sofosbovir, Ribavirin, and Interferon and more recently Harvoni has been added to the treatment regime. There were initial concerns that the treatment provided would be sold as there are no treatment programs in surrounding countries; this has been limited by fortnightly dispensing.

To date, Georgia has treated 30,000 of its target group of 150,000 and has screened half a million people from 2015 to 2017.  SVR in 2015 was 85%, and has risen in 2016 to 95%- the difference being the introduction of Harvoni and the treatment of the sickest patients initially. SVR is missing in 25%. 

Georgia has extended the pilot to 28 centres, and is now targeting the PWID population to improve detection, prevention and treatment in this community.Georgia has established a treatment centre in a drug treatment clinic (OST) and is using peer workers help PWID clients access and attend healthcare providers.

Other plans to scale up screening include providing incentives to primary care providers and delivering a mass information campaign.  It doesn't sound like they are going to stop.

Link through to Dr Maia Butsashvili's Speaker Presentation here

This 1 hour lunch time poster session presented an overview of different studies presenting STI epidemiology amongst MSM & heterosexual populations. 

1. Florence Lot: STI co- infections at HIV diagnosis in France

Aim was to analyse the frequency of STIs in new HIV infections between 2012- 2015, using the mandatory HIV surveillance system which has, since 2012, collected data on bacterial STIs (CT, NG, LGV, syphilis). These had to be reported if detected at time of or in the 12 months prior to HIV diagnosis. 

Analysis by transmission group and trends. Reported as ‘HIV/STI co-infection’.

Result 1: 

Frequency of STI/HIV co-infections in adults by HIV transmission group & sex:  14.6% globally (26.4% MSM; 11.3% male & 5.8% females born in France; 5.1% male & 2.5% females born abroad; 7.2% male & 8.7% female IDU).

Result 2:

Frequency of STI/HIV co-infections in adults by HIV transmission group & year of HIV diagnosis: Significantly increased over time with 12.6% in 2012 to 18.3% in 2016. By transmission group, this increase was only significant for MSM from 22.1% in 2012 to 31.9% in 2016.

Result 3:

 Frequency of STI/HIV co-infections in adults by HIV transmission group and bacterial STI: Syphilis on the rise especially in MSM, heterosexual men were more often co-infected with syphilis and NG than heterosexual women who were more frequently infected with CT. Rectal LGV dx only in MSM. 

Conclusion:

HIV & STI co- infection has increased over time and affect almost 1/3 of MSM newly dx with HIV. Highlight importance of testing, treating index + partner. 

There was a question around testing frequency in France- was once per year and is now 3 monthly, including viral hepatitis screen (not sure if this had increased from yearly..). Another Q around high syphilis prevalence- confirmed that asymptomatic people are screened. 

A comment from a clinician from the UK regarding HCV, they are seeing a significant increase in acute HCV infections not associated with IDU amongst HIV negative MSM population, same in France? A- don’t have the data. 

1. Flavia Kiweewa Matovu: STI acquisition among women using a variety of contraceptive options in Uganda

LARCs are being widely promoted, not much data on STIs in LARC use. High risk female population in in Uganda, established STI increases risk of HIV transmission.

Prospective cohort study- ASPIRE study.

Results:

Analysis population: 2264 women (50.2% from Sth Africa). 817 cases of STIs detected over 3,440 person years of follow up.

CT: 408 cases/ incidence of 11.86/100 person years

NG: 196 cases/ incidence 5.70/100 person years

T.vaginalis: 213 cases/ incidence 6.19/100 person years

(No mention of HIV, syphilis etc).

Conclusion: 

Incidence of CT & NG were not different across contraceptive methods.

Incidence of T.vaginalis was significantly lower for DMPA (medroxyprogesterone acetate injectable contraceptive), implant and NET-EN (norethisterone enanthate injectable contraceptive) users compared to IUD. 

Significantly lower rates of T.vaginalis among users of progestin- based methods, likely due to hypoestrogenic states. 

Limited by lack of randomisation to contraception method. 

Question around extra- genital sites being tested- yes, serology and genital swabs. 

Another question around relative risks being adjusted for baseline sexual risk- yes, adjusted for baseline age, sexual risk. 

3) Jeffrey Parsons: Differences in biological and behavioural HIV risks before, during and after PrEP use among a national sample of GBM in the USA

PrEP & STIs- Does going on PrEP lead to increased condomless sex (CAS) and thus higher rates of STIs OR are the increases seen in STI rates due to the required quarterly testing…?

Limitations to these data: Predominately Caucasian, employed and well educated population. Half were in a relationship, half were single. The sample were also early PrEP adopters.

Results: 

Cross sectional between group analysis: the 823 PrEP naïve men had significantly lower STI infection rate (4.2%) than those 77 currently (10.4%) or 17 formerly (11.8%) on PrEP (p < 0.02), with men on PrEP also reporting more acts of CAS (p <0.001). 

Within- person longitudinal analyses of 181 men reporting PrEP use indicated a non- significant increase in the odds on an STI diagnosis while on PrEP  and after discontinuing (OR= 1.25, p= 0.55; OR= 1.43, p= 0.53 respectively), compared to before starting PrEP. There were also no significant changes in CAS while on PrEP (OR = 1.09, p = 0.76) or after PrEP discontinuation (OR = 0.48, p = 0.10) compared to pre-uptake levels.

Discussion:

Using between- subjects comparisons of all participants, some evidence was found that GBM on PrEP have higher levels of both behavioural and biological risks, though findings were mixed when examining multiple time points. 

Using within- subjects comparison over time among only those who had been on PrEP during at least one of the three visits, the rates of CAS increased while on PrEP but returned to pre- PrEP levels after discontinuation. They did not see a statistically significant increase in odds of STI infection. 

Comment:

Important not to lump all GBM into one category. Differences in behaviour, risk and motivation for accessing and using PrEP. 

Early adopters- so more study required to determine the behavioural differences in early and late PrEP adopters. 

Question from the audience regarding the sites tested for STIs- in NYC, only 50% of participants had completed a rectal swab which could affect the data. 

88% completed urine and serology test.. pharyngeal swab around 60% (sorry missed that comment). 

Highlights the importance of a complete STI screen to ensure both a public health and epidemiological perspective. 

4) Marie Suzan- Monti: Partner notification (PN) of STIs among MSM on PrEP: s sub- study of the ANRS- IPERGAY trial

In France, there are no PN specific guidelines, and scarce PN information. Data on 275 HIV negative men from the ANRS- IPERGAY PrEP trial who reported an STI were used. 

Results:

Out of 275, 250 reported at least one previous STI. Of the 250, 172 had informed their partner (138 their occasional partner and 83 their main partner). 

No significant socio-demographic difference between this who did and did not notify their partner. 

Less likely to notify their main partner when most recent sexual contact was through condomless sex with an occasional partner (aOR(95%CI) 0.31 (0.14; 0.68), p=0.03).

Older MSM less likely to inform occasional partners (aOR(95%CI) 0.44(0.21;0.94), p=0.03).

Those participating in chemsex at most recent sexual encounter were more likely to inform sexual partners (aOR(95%CI) 2.56(1.07;6.09), p=0.03). 

Discussion:

Condomless sex with occasional partners was identified as a barrier to PN, and chemsex a motivator for PN. 

Not measures if health care workers were notifying partners. 

Hopefully these data support the need for systematic PN services, support and information in France- highlights how well Australia (speaking from a Victorian perspective) undertake PN form a top down approach. 

5)  Kristin Wall: Predictors of genital ulceration in HIV negative sero-discordant couples in Lusaka, Zambia.

Genital ulcers are a known risk factor for HIV transmission, and little is known about the risk factors for genital ulcers, limiting early detection and treatment. 

Exposure data were taken from HIV serodiscordant heterosexual couples every 3 months at ART uptake or HIV transmission. Associations were evaluated between exposures measured during the visit prior to the presentation with an ulcer. 18 year longitudinal cohort study (1994- 2012).

Results:

1393 M+F- couples were followed for 2756 couple- years, and 1656 M-F+ couples were followed for 3216 couple- years.

Risk for genital ulcer in HIV- women was associated (p<0.05) with bilateral inguinal adenopathy (BIA) (aHR=1.9), genital inflammation (GI) (aHR=1.5-1.9), male partners non- STI GI (aHR=2.9) and increasing number of previous pregnancies (aHR=1.1).

Risk for genital ulcer in HIV+ women was as above (BIA- aHR=1.5; GI- aHR=1.5-2.0; male non- STI GI- aHR=2.0), as well as late HIV vs early HIV (aHR=1.5) and being pregnant (aHR=0.7).

Risk in HIV- men was associated with BIA (aHR=1.8), STI GI (aHR=2.9) and non- STI GI (aHR=1.4), female partners ulcer (aHR=1.7), and being uncircumcised (aHR=1.7). Being uncircumcised with foreskin smegma was independently predictive (aHR=3.2). 

Risk in HIV+ men was associated with STI GI (aHR=2.8), HSV-2 positivity (aHR=2.5), late HIV  vs early (aHR=1.7) and being uncircumcised with foreskin smegma was independently predictive (aHR=2.4). 

Discussion:

Ulcers were also tested for syphilis, prevalence of chancre 2-3%  

BIA & GI may be early indicators/ risk factors for genital ulceration. Uncircumcised men with foreskin smegma either HIV +/- were at increased risk of ulceration. 

HSV-2 positivity not a predictor once controlled for genital ulcers and only a predictor in HIV+ men. 

Suggest: Targeted screening amongst those with advanced HIV infection. 

 6) Cari van Schalkwyk: Are associations between HIV & HPV transmission due to behavioural confounding factors or biological effects? 

This presentation was a mathematical modelling study to assess whether confounding for behavioural factors and network effects sufficiently explain associations between HPV & HIV infection. 

MicroCOSM is a dynamic individual- based network model and was used to simulate epidemics of HIV & 13 oncogenic HPV types.

Results: 

The mean unadjusted hazard ratio of HIV acquisition after detection of an oncogenic HPV type is 3.2 (95% CI 2.6, 3.8); and the mean unadjusted hazard ratio for the effect of HIV on newly detected HPV is 3.7 (95% CI 3.4, 4.1).

Discussion:

The study results are similar to observational study unadjusted results, suggesting that observed associations between HPV & HIV transmission could be attributed to confounding by behavioural factors and network- level effects. The author concluded that primary prevention with the HPV vaccine may therefore not be beneficial in HIV prevention. 

There was also no further increased risk in the presence of cervical lesions. 

The study group have a proposal for a clinical trial using the HPV vaccine to determine if this decreases HIV transmission although no funding as yet.