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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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. 

Tagged in: 2017 IAS Conference

This was an interesting oral abstract session regarding community knowledge and approaches to pre-exposure prophylaxis.  PrEP was discussed in detail and covered topics like barriers to uptake of PrEP, preferences for prevention technologies, measuring adherence in PrEP users and how the health system and study designs of PrEP trials can facilitate rapid enrolment of those at high risk of HIV acquisition.

The first speaker was Adeline Bernier from France.  Although PrEP is already available in Norway and France through government subsidised programmes it has not been widely taken up in the rest of Europe.  She presented results from The Flash! PrEP in Europe (FPIE) online survey.  This was a community-based research study aiming to assess interest in and barriers to PrEP uptake amongst respondents from 11 European countries.  They found low knowledge of PrEP amongst at-risk groups, high interest in PrEP but low uptake.  Most commonly cited barrier to taking PrEP was fear of side effects.

Darrell Tan presented results from an MSM survey conducted with those undergoing routine HIV testing.  They asked questions regarding preferred method of PrEP delivery (oral, injectable, topical) and whether the reliability of different technologies would influence their decision on which method to use.   The results were many and varied.  Further analysis is required to understand what influences each individual’s preference for PrEP.

James Ayieko from Kenya presented results from the ongoing SEARCH trial, 18% of 4,064 participants took up the offer of PrEP within 30 days.  Participants’ perception of own risk did not always match that from a risk score.  This indicates further community-based education regarding risk is required for those considering PrEP.

Edwina Wright presented data from the Melbourne cohort of the PREPX trial. Recruitment to the PrEP trial was facilitated by a high community PrEP awareness and involvement of GPs and Pharmacists who were remunerated for their services.The high PrEP awareness in Australia contributed to the high enrolment of the ongoing PrEP study.

Rupa Patel presented data from a US study which found a good correlation between adherence measured by 3-month MPR (medication possession ratio) and 7-day self-report with TFV-DP (tenofovir diphosphate) blood levels in DBS (dried blood spot) of MSM taking daily oral PrEP.  The good correlation of the 3-month MPR and 7-day self-report with biological measures of adherence in PrEP users suggests that this could be ideal for measuring adherence in the clinic setting.

Hanne Zimmermann from the Netherlands presented data from a longitudinal semi-structured interview in MSM using PrEP.  This revealed that MSM switched between daily and event-driven PrEP use or even stopped PrEP based on their personal situation and risk exposure.  Individuals made decisions on PrEP use based on perception of their own risk.  The authors concluded that in order to successfully support future PrEP users, a tailored approach, addressing choices for PrEP regimens as a continuum of flexible and changeable choices, is essential.  Appropriate education would be an essential part of this strategy.

As if there weren’t enough treatments for Hepatitis C already, results of another Hepatitis C treatment trial were presented on Monday at IAS 2017.

Karine Lacombe of Saint-Antoine Hospital in Paris presented findings from AbbVie's phase 3 EXPEDITION-2 trial, which evaluated an 8-week regimen of glecaprevir/pibrentasvir for people with both HIV and hepatitis C.

Glecaprevir is an HCV NS3/4A protease inhibitor and pibrentasvir is an NS5A inhibitor. Both are pangenotypic, or active against all HCV genotypes. The two drugs have been co-formulated in a once-daily combination pill, to be marketed under the brand name Maviret.

Studies in the DAA era have shown that HIV-positive people generally do as well on interferon-free regimens as those without HIV – though it is important to take into account the potential for drug interactions between DAAs and antiretrovirals – and they are no longer considered a "special population." Yet European and US HCV treatment guidelines currently do not recommend shorter treatment for people with HIV and HCV co-infection.  A shorter course of treatment could potentially improve adherence and reduce cost.

EXPEDITION-2 enrolled 153 HIV-positive people with chronic hepatitis C in Europe, the United States and Russia. More than 80% were men and the median age was approximately 45 years. About two-thirds had HCV genotype 1 (mostly with harder-to-treat subtype 1a), followed by genotypes 3 (17%) and 4 (11%); a small number had genotypes 2 or 6.  People with Hep B co-inbfection were excluded.

Sixteen participants (10%) had liver cirrhosis, and most of the rest had absent or mild fibrosis. Nearly 20% were previously treated with interferon and ribavirin, and three had also used sofosbuvir (Sovaldi).  Study participants had well-controlled HIV infection with a median CD4 count of nearly 600 cells/mm3.  All but nine were on antiretroviral therapy, and about three-quarters of treated people were taking the integrase inhibitors raltegravir (Isentress) or dolutegravir (Tivicay), which were shown to have minimal interactions with glecaprevir and pibrentasvir.  They had variable backbones including TDF, FTC, TAF, lamivudine.  I’ve included the drug-drug interaction profiles out of interested, as presented at the session.

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Participants without cirrhosis received glecaprevir/pibrentasvir for 8 weeks, while those with cirrhosis were treated for 12 weeks. Everyone received the study drugs and there was no placebo arm.

 Treatment was highly effective, with 98% having continued undetectable HCV RNA at 12 weeks post-treatment (SVR12). The cure rate rose to 99%, with no virological failures, for people without cirrhosis who were treated for 8 weeks.

A single patient with HCV genotype 3 and cirrhosis, who reported less than complete (85%) adherence, experienced virological failure during treatment. Another participant had missing data at 12 weeks post-treatment, but returned for care at 24 weeks post-treatment and was found to be cured.

 Glecaprevir/pibrentasvir was generally safe and well tolerated. Adverse events were similar to those seen in studies of HIV-negative people. One participant with cirrhosis stopped treatment early due to an adverse event that was not considered drug-related (stroke and brain haemorrhage). The most common adverse events were fatigue, nausea, headache, and nose and throat inflammation.

 "These results suggest that the glecaprevir/pibrentasvir regimen could be the first 8-week, pangenotypic treatment option for HCV/HIV-1 coinfected patients without cirrhosis," the researchers concluded.

This could be a bonus for co-infected patients but caution with drug-drug interactions is still an issue.  However, given the short duration of therapy these may or may not be significant.

 

Greetings from the 9th IAS Conference on HIV Science in Paris, France. As usual the content is broad, but (as the new branding signals) science dominates the agenda. On this occasion there is no great breakthrough or advance that might electrify the event and set tongues wagging.

From a global access to care point of view it is clear that funding is at best flat-lining (and this has been the case for the past 7 years) and in some cases falling as we move well beyond the Millennium Development Goals and firmly into the era of the Sustainable Development Goals.

It seems unlikely that the Trump administration will increase U.S. President's Emergency Plan for AIDS Relief (PEPFAR) funding and most likely will withdraw funding during this Presidency. According to UNAIDS. 19.5 million people are now receiving ART around the world. However it is estimated that 40% of all those infected are unaware of their HIV-status and that for every 1 person dying from AIDS every year 2 become HIV-infected. Thus, while the UNAIDS 90-90-90 goals are commendable, we are a long way from getting even close to achieving them. In this context the goals are in danger of being perceived as an impossible dream.

 

Such musings inevitably focus attention on the critical need for an effective vaccine to truly augment efforts to eradicate the HIV pandemic. Unfortunately there is little news on this front and we need to be realistic and understand that this may be a task beyond us given our current understanding of HIV pathogenesis. This is also the case with the cure, which despite intensive investigation over the past decade has little to show for all the effort. As with the HIV vaccine, a true advance will most likely come from a profound and unpredictable (and unfundable) paradigm shift in our understanding of HIV pathogenesis and immune protection. Let’s hope that occurs in our lifetime, but if I were a betting man…

Better news comes from the fields of therapeutics and PrEP

PrEP rollout is going well but is to a large extent restricted to those countries in which the research has been conducted – France, USA and Australia. Efforts are being made to introduce PrEP into Africa, but a major drawback is the lack of efficacy often seen in younger women (16-24 yo) with oral TDF/FTC. This may be overcome with the use of injectable long acting ART agents like cabotegravir and rilpivirine, and also possibly intra-vaginal rings containing ART (e.g. Doravirine). These rings could also be impregnated with other pharmaceuticals (e.g. oral contraception, anti HSV products, antimicrobials). We await the science.

This conference also saw the presentation of the phase 2b RCT of 2 drug maintenance of initial triple therapy induced virological suppression with long acting injectable cabotegravir and rilpivirine. Over 2 years in the once monthly injection group no virological failures were observed. This once monthly strategy is now enrolling participants in pivotal phase 3 RCTs. Joe Eron (UNC, USA) who presented the data at the conference said that the 2-monthly strategy is also still under active consideration. The result was reported by a few media outlets including the BBC.

See Injections 'next revolution' in HIV - study by James Gallagher:

http://www.bbc.com/news/health-40703336

 

 

The conference was also the venue for the public presentation of Phase 3 RCTs of Gilead’s unboosted once daily InSTI ‘Bictegravir’ versus Dolutegravir. The results of 2 Phase 3 placebo-controlled, double-blinded RCTs were presented; one with a backbone of TAF/FTC in both arms and one with BIC/F/TAF versus DTG/ABC/3TC. Non-inferiority was demonstrated in both cases with good tolerability across all groups. Importantly, no resistance was seen in the rare virological failures in both studies, consistent with what we have seen with DTG to date in trials and clinical practice. It is expected that the BIC/F/TAF fixed dose combination product will be licensed in the USA by Q4 2017 and most likely be listed on the PBS by Q3 2018 in Australia.

Tagged in: 2017 IAS Conference

This IAS 2017 session was dedicated to addressing HIV in 4 main populations that have been identified as “key” around the world, including migrants, sex workers, men who have sex with men and people who inject drugs.  The studies presented had varied countries of origin which helped to demonstrate that key populations vary worldwide.

 

The first presentation presented data from the aMASE study to determine the rate of migrant acquisition of HIV in Spain. This was a multi-centre cross sectional study that collected data from both patient questionnaires and clinical notes in 6 regions around Spain of patients who had been diagnosed with HIV in the preceding five years and had lived in Spain for a minimum of six months at time of diagnosis.  A range of information was collected including socioeconomic, behavioural, migratory, previous HIV testing, CD4 and viral load levels and resulted in a statistical analysis to determine most likely time and place of acquisition.

 

Of 710 participants, there was sufficient data to estimate time of acquisition for 685.  77% of the analysed respondents were men and 60% were MSM, 20% heterosexual women and 14% heterosexual men.  Median age was 35 years and median time in Spain was 9 years.  The region of origin were Europe 17%, Latin America 64%, Sub Saharan Africa 13% and others 6%, this trend is reflective of the large numbers of Latin American people migrating to Spain and so mirrors broader population trends.  A total of 72% of the sample were estimated to have acquired HIV whilst living in Spain.  Factors associated with post migratory acquisition were Latin American origin, younger age and increased duration of stay in Spain and the proportion was also higher in MSM.  This highlights 2 key populations that are being failed with regards to prevention, migrants (especially Latin American) and MSM and suggests who needs targeting in national prevention strategies, such as PrEP.

 

The second presentation presented data collected on transactional sex in MSM from Vancouver, Canada and has been blogged about by one of my colleagues, so I will only briefly touch on this presentation as it has been covered more extensively elsewhere.  The motivation for this study was to ascertain whether transactional sex in MSM is a causative factor in HIV transmission.  The study objectives were to determine prevalence of transactional sex events and evaluate temporal trends and consequences such as HIV risk or acquisition in a prospective cohort study.  Results of 690 participants and 8990 sexual events revealed that transactional sex was rare with 2.4% reporting receiving, 1.2% reporting giving, 0.3% reporting both giving and receiving.  To assess HIV risk, the investigators focussed on condomless anal sex and HIV concordance, discordance and unknown status and there was no statistically significant difference between these groups and whether they engaged in transactional sex or not.  Factors that did increase the risk of transactional sex included low income, loneliness, substance use of the partner (GHB and methamphetamine) and meeting online.

 

A third presentation of a study nested into France’s Ipergay study presented data about the suitability of on demand PrEP for chemsex participants.  The objectives of this sub study were to better characterise chemsex participants and study the association between engagement in chemsex and PrEP use.  Chemsex participants were found to be more likely to use anxiolytic medications, be sensation seeking and have increased numbers of sexual encounters.  They were also more likely to have condomless anal sex, hardcore sexual practices and perceive themselves to be at higher risk of HIV.  What was notable was that they were also more likely to use PrEP perhaps due to their justifiably perceived higher risk.

 

Fourth was a study from south Africa on health outcomes of children of female sex workers, who have about a 60% HIV prevalence rate.  This was undertaken in the form of a cross sectional study at sex work venues and mobile health centres from September 2015- February 2016.  The mothers completed a questionnaire and HIV testing.  The children were also tested for HIV and growth parameters measured.  Results demonstrated maternal HIV prevalence at 67.5% and ART at 63.6% and overall HIV prevalence in their children was 3%, rising to 4.5% in HIV positive mothers.  Full vaccine coverage decreased as the children got older and 27% of children’s growth was stunted, a reflection of their nutritional status.  This study really highlighted that health services for sex workers would be well placed to expand into caring for the children of their key population as well.

 

The Vietnamese DRIVE-IN study presented data on HIV and HCV incidence and risk in people who inject drugs in a longitudinal follow up of 204 eligible participants.  Of the 204, 105 were HCV positive only, 94 were negative for both HIV and HCV and 5 were HIV positive only.  No HIV seroconversions occurred during the 1 year follow up period but 18 HCV seroconversions occurred.  Factors associated with HCV seroconversion included more injections and being arrested. This data supported the perception that HIV was low in this population but also brought to light that HCV needs to be addressed as a priority for this population.

 

Finally, data from a Kirby institute run, multi-site Opposites Attract trial presented more data to support treatment as prevention in male serodiscordant couples.  A total of 358 couples enrolled worldwide and the total couple year follow up was 591 years.  During this time, 3 seroconversions occurred.  All 3 seroconversions reported condomless anal sex outside the principal relationship and phylogenetic analysis of the seroconverted participants and their principal partner demonstrated overwhelmingly that there were no linked transmissions.  The data demonstrated that in over 12,000 acts of condomless anal sex with a virally suppressed HIV positive partner and a HIV negative partner not on PrEP, there were no transmissions of HIV.

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This symposia session was the only session in the conference focussed entirely on women's health. It was a fantastic introduction for me to the management issues of HIV positive women from adolescence to menopause as I have had minimal exposure especially to adolescent HIV. Yesterday we heard from Associate Professor Darren Russell regarding the increase in HIV diagnoses in Aboriginal and Torres Strait Islanders in Northern Australia and I am concerned that being based in this region I unfortunately will be involved in more cases of adolescent HIV in the near future. Globally two thirds of new HIV infections are in adolescent girls.

I was surprised when I learned the epidemiology of HIV in women.

HIV is the leading cause of death among women aged 30-49 years globally. 

In hundred thousands:

HIV 241.9

Ischaemic heart disease 150.5

Maternal conditions 148.4

Stroke 139.5

Breast cancer 130.9

Tuberculosis 96.4

and the third cause of death globally for those aged 15-29 years.

Does ART modify hypertensive disorders in pregnancy? Or obstetric haemorrhage? Data is inconclusive.

But the take home message is there is more to antenatal care than prevention of mother to child transmission.

There was a slide regarding the global burden of disease in adolescents. As a GP I feel I am in an ideal setting to screen for many of these issues as I see a higher proportion of young females. These include vaccine preventable diseases, under nutrition, sexual health, violence and injuries, mental health and substance use disorders.

 

 

 

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Is there a role for treatment intensification with Maraviroc in addition to a standard cART for naïve patients with low CD4 counts, and will it decrease the risk of progression to AIDS? (ANRS 146 – GeSIDA OPTIMAL)

There is no clinical evidence that of successful treatment intensification by the addition of a 4th antiretroviral agent; despite numerous trials.

This double-blinded trial in France , Italy and Spain compared Maraviroc (+cART) to placebo (+cART).   Over 400 naïve, HIV-1 infected patients with an AIDS defining illness or CD4 cells < 200cell/mm^3 were enrolled.

The primary endpoint was the occurrence of a severe morbidity (AIDS, SNAE, IRIS, Death or other HIV related disease). Baseline characteristics were comparable.

In the 72-week follow up period; treatment intensification made no impact on the risk of infections, serious events, mortality, virilogic control or on CD4 count recovery. A post hoc analysis suggested Maraviroc might demonstate benefit on the occurrence of clinical events in the first 6 months of treatment, however this benefit “subsequently disappeared”.

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Peripheral Arterial Disease. 

HIV infection and the risk of peripheral arterial disease; an observational, longitudinal cohort of HIV positive U.S. Veterans matched 1:2 with HIV- uninfected veterans matched for age, race, ethnicity and site.  The sample was greater than 90,000.

The investigator presented data from 7 years of observation of this very large cohort. The participants were followed for peripheral arterial disease (PAD), death or their last follow up date.

Cumulative incidence of PAD was calculated and adjusted for confounders. A regression model was used to examine the association between HIV positivity, CD4 count and PAD after adjusting atherosclerotic risk.

In this study, the HIV positive veterans had significantly higher rates of peripheral arterial disease when compared with HIV uninfected veterans.

The speaker encouraged checking for ankle/feet pulses as PAD is often not diagnosed – this seems like a extraordinarily simple ‘practice-changing’ intervention for primary care.

An absence of a pulse should prompt vascular referral. Smoking cessation obviously remains a vital health intervention. A low CD4 cell count was also a strong predictor of PAD, with almost a 2-fold increase in the risk. Importantly, a CD4 count of greater than 500 showed no increase in risk. Lipid lowering treatment will be part of a future analysis and was not examined in this paper.

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This was an oral abstract session focusing on some novel approaches to HIV treatment and modifying treatment in special risk groups.

Jean-Michel Molina presented some switch data from the EMERALD study, a randomized (2:1), open-label, international, multicenter, parallel-group, non-inferiority, 48-week study.  Virologically suppressed individuals were switched from boosted-protease inhibitors (PI/r)+emtricitabine/TDF to darunavir/cobicistat/emtricitabine/tenofovir alafenamide (TAF).  This showed good virologic efficacy and better bone and renal profile at the wk24 interim analysis.

Jose Gatell presented data from an elegant study focused on virologically suppressed individuals with high cardiovascular risk.  They were aged 50 years or older and had Framingham cardiovascular risk greater than or equal to 10 percent.  They switched from PI/r-based to dolutegravir-based regimen and showed non-inferior virologic efficacy with improvements in lipid profile at wk48.  Other outcomes from this ongoing trial are awaited.

Laura Ciaffi showed data from a switching study.  After viral suppression with second-line PI/r+NRTIs, maintenance with PI/r+lamivudine showed virologic efficacy at wk 96 despite the presence of the M184V mutation.   This study was conducted in Africa.  This is an example of the increasing number of dual therapy studies presented at IAS this year.

Kathleen Squires presented data comparing a fixed dose combination of doravirine/lamivudine/TDF to efavirenz/emtricitabine/TDF in treatment-naïve adults with HIV-1 infection.  It showed non-inferiority at week 48 regardless of the baseline HIV RNA.  Doravirine also showed superior neuropsychiatric and lipid profile in these results of the Phase 3 DRIVE-AHEAD study.  A useful extension of this study would be a co-formulation of doravirine with FTC/TAF to reduce the renal and bone effects well known with TDF.

Micheal Aboud presented week 24 interim data from the DAWNING study.  This looked at individuals with first-line NNRTI-based regimen failure.  The superior efficacy of dolutegravir (DTG) plus 2 nucleoside reverse transcriptase inhibitors (NRTIs) compared with lopinavir/ritonavir (LPV/RTV) plus 2 NRTIs in second-line treatment was demonstrated.

Finally, Trevor Crowell presented data from a study using one of the newer approaches to HIV treatment, broadly neutralising antibodies.  In virologically suppressed individuals who initiated ART during acute HIV infection, VRC01 was well-tolerated.  However, VRC01 monotherapy was insufficient to maintain viral suppression.  This is an early setback but this will benefit future research in this area.  Broadly neutralising antibodies are being used in a growing area of research to assess alternative approaches to therapy besides daily oral therapy.  On a more reflective note, another theme from the conference this year was to start treatment as soon as possible to reduce the potential viral reservoir which we know is concentrated in lymphoid tissues.  This is likely to enhance prospects of cure or functional cure when future therapies become available.

 

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From HIV and the Liver: Co- infection and Complications  

Nikoloz Chkhartishvilli presented an overview of the co-infection care cascade from Georgia, a country which has a high disease burden of HIV/HCV co-infection. Despite the differences in our countries political and presumably health care systems, the roll out of their HCV elimination program recalled similar population priorities to the Australian model.

During 2011- 2015, the Global Fund supported Georgia to reduce the disease burden of HCV by offering PEG/RBV to people living with HCV. From 2015, in partnership with Gilead Sciences and U.S. CDC to launch their National HCV Elimination Program and DAAs became available. Similar to the Australian model, there was no cost to the patients and current injection drug use was not a barrier to accessing treatment.

The care cascade is described as follows: 1) HIV/HCV co-infected; 2) Diagnosed for both HIV & HCV, 3) Treated for HCV, 4) Achieve SVR . Data were obtained from the national AIDS health information system

Results: Among 3300 co-infected individuals, 2201 (67%) were not aware of their HIV status, 1099 (33%) were diagnosed with both HIV/HCV, and of those 1099 (33%) persons, 697 (63%) were treated with either PEG/RBV or DAAs. 480 (69%) of those treated attained SVR with 44% for PEG/RBV and 89% with DAAs. So of the 697 (21% of the original cohort) individuals treated, approx. 480 achieved SVR, this being 69% of the treated cohort and 15% of the original co-infected cohort.

A gap in care was identified from time of diagnosis to time of treatment as the major contributor to the low uptake and completion of treatment, calling for tighter systems to support the elimination plan. Highlighted that it’s not just free or subsidised treatment availability, but also the systems and infrastructure required to support programs such as this.

 

Nadine Kronfli presented on trends in cause- specific mortality in HIV/HCV co- infected patients in Canada 2003- 2016 and the impact of early HCV treatment.

Liver related deaths (ESLD & viral hepatitis) account for 20-25% of deaths in Canadian co-infected population. Mortality rates have decreased since introduction of DAAs achieving SVR>85% and opportunity to reverse fibrosis, decrease sequelae.

Looking at which modifiable risk factors may contribute to excess mortality in co-infected population to help prevent potentially preventable deaths in an already high risk population (lifestyle, exposures related to IDU in co-infected pop).

They used the Canadian Co-infection Cohort which is a prospective multicentre cohort of 1695 co-infected patients from 19 sites in Canada (resulting in 6675 person- years follow up from 1477 eligible patients). Deaths were classified using a ‘coding of cause of death in HIV’ protocol. Event rates per 1000 person- years before (2003- 2009) and after (2010- 2016) the availability of widespread effective treatment stratified by age 20-50, 50-80 yrs were calculated.  

75% of the cohort were current smokers at baseline, 84% taking ART, 64% HV VL <50 copies/ml, 81% HCV treatment naïve, 21% APRI > 1.5, 9% prior ESLD dx.

Overall and cause specific mortality, with cause of death divided into 5 categories: ESLD (20%), smoking related (17%), drug OD (16%), other- including AIDS/infections/ cancer/ trauma/ suicide (22%), unknown (25%).

20- 50 yrs: 2003- 2009: 26.04 (13.91, 48.75); 2010- 2016: 19.29 (11.59, 32.11)

50- 80 yrs: 2003- 2009: 56.61 (28.09, 114.1); 41.97 (28.2, 62.46)

Key point from deaths- most had poorly treated HIV and did not achieve SVR as higher deaths on ‘non- ideal’ patient population (CD4 <350, APRI > 1.5, HIVRNA>50).

Concluded that all cause mortality decreased in both age groups over time, explained by a reduction in mortality from a variety of competing causes, no significant decrease in ESLD deaths overall however ESLD appears to be declining in 50-80 year olds, or those who have been successfully treated; immediate impact of HCV therapy most profound among those with fibrosis, and targeting modifiable risk factors such as smoking may confer the highest benefit.

 

Maud Lemoine presented ‘metabolic syndrome and obesity are the cornerstones of liver fibrosis in HIV monoinfected patients: results of the METAFIB study’

Metabolic syndrome and its hepatic manifestation, NAFLD, have emerged as new concerns for PLHIV (prevalence 25% and 35% respectively).

METAFIB study proposed to assess the impact of metabolic syndrome on the proportion and severity of liver fibrosis and analyse association between met syndrome, liver fibrosis, markers of adipose tissue and macrophage activation.

METAFIB is a single centre exposed- non exposed cohort of HIV monoinfected individuals without excessive alcohol consumption, viral hepatitis, or other causes of CLD.

Fibroscan used to measure liver stiffness.

Results from 405 participants (203 with metabolic syndrome, 202 without). Patients with met syndrome were older and 49% had insulin resistance, risk factors for fibrosis: Obesity with BMI >30, T2DM, elevated GGT and leptin.

Liver transaminase levels, ART exposure or HIV parameter levels were not associated with liver fibrosis.

Take home message was that HIV monoinfected patients with metabolic syndrome are at risk of liver fibrosis irrespective of transaminase levels and should be systematically screened. Mass fat measured by BMI and circulating leptin is strongly associated with fibrosis independent of HIV parameters or ART exposure. Adipose tissue, insulin resistance and macrophage activation are likely key players in the development of fibrosis.

There was an audience question regarding impact of some ART in regards tocausing/ association with insulin resistance. Answered that the cohort was older, and treatment experienced, however patients with good virological control were selected so didn’t feel the results could answer that question.

Recommendation to screen all PLHIV with metabolic syndrome regardless of LFTs for fibrosis using fibroscan cheap, easy, non-invasive.

 

Hugo Perazzo Pedroso Barbosa presented data from the PROSPEC- HIV study looking at predictor factors associated with liver fibrosis and steatosis in a monoinfected population.

Cross sectional study from a cohort of 4000 patients who have been followed from 1990. Exclusion was viral hepatitis co-infection and ART naïve.

 

Heavily pre- treated population inc. AZT and other early ART.

Clinical evaluation including alcohol assessment, fasting bloods and fibroscan was used.

 A total of 348 HIV mono-infected patients [61% female, median (IQR) age=44 (34-52) years, BMI=25.4 (23.0-29.3) kg/m²] were included. Median (IQR) time under c-ART and under the current c-ART regimen were 7.3 (4.1-12.8) and 4.3 (1.9-7.5) years, respectively. LSM and CAP were unreliable in 6% and 12%. Liver fibrosis and steatosis prevalence were 9% (n=30/326) and 33% (n=102/305). In age and gender adjusted multivariate analysis, factors associated [OR (95%CI)] with liver fibrosis were: age > 45 years [2.91 (1.19-7.15); p=0.020]; CD4 count < 200 cells [5.00 (1.38-18.21); p=0.014] and type-2 diabetes [3.04 (0.97-9.55); p=0.056]. Male gender [5.69 (2.68-12.04); p< 0.001]; dyslipidemia [2.86 (1.46-5.60); p=0.002]; type 2 diabetes [6.00 (2.08-17.28); p=0.001] and central obesity [10.24 (4.11-25.50); p< 0.001] were independently associated with liver steatosis.

Concluded that low CD4 count was independently associated with presence of liver fibrosis, metabolic syndrome features were independently associated with steatosis by CAP, higher duration of ART especially AZT as a backbone was associated with steatosis independently of metabolic factors.

 

 

Take home message from session: Importance of reducing modifiable risk factors to improve patient’s health outcome, especially smoking and factors contributing to development of metabolic syndrome. 

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Summary of the Report from the IAS HIV Cure and Cancer Forum

In its 15th year, the IAS initiative Cure Towards an HIV Cure, held its forum prior to the IAS conference. This year the forum expanded its attention to Cancer given the similarities between the fields and limited formal collaboration. Many immunological therapies used for Cancer treatment may also have a role in HIV Cure. As our HIV patients age with suppressed HIV viremia they are experiencing more cancer. Cancer and Persistence of HIV share many features and goals of treatment so that a shared approach to research will only enhance outcomes for both groups and especially for HIV patients with cancer. This latter group are currently serving as an “observational cohort” as we try to understand the effects of immune checkpoint blockers – both efficacy and adverse effects, short and long term – in people living with HIV and its associated additional immune dysfunction. Cell surface marker CD32a on CD4 cells has now been recognised as a potential marker for HIV DNA levels. The concept of measurement of residual disease burden after treatment is being borrowed from oncology to aid in the understanding of achieving durable remission. Focus on the change in approach to treatment of cancer from drugs targeting cancer cells to the approach now of targeting the host’s own immune cells to kill the cancer cells. Understanding of how anti-cancer drugs affect the HIV reservoir was progressed, as was comparisons of the effects of immunotherapy for cancer and in HIV. The class and availability of different “immune checkpoint inhibitors” is exploding in cancer treatment, and as HIV patients with cancer start to receive these drugs for their cancer, the effects on latency reversal of HIV are being carefully documented. Interferons are being revisited, effects of stem cell transplants and gene therapy to improve the immune response to cancer are also being explored – but all early days and case reports in the main. One of the most important sessions was a round table discussion on clinical trial design once the safest better candidates have been identified – protocols with a common trial design, agreed endpoints (most likely composite) and biomarker measurement, need to be established. Access has been identified as a major consideration, community engagement vital, understanding of how analytical treatment interruptions will be used and viewed by participants and the financial “toxicity” of HIV Cure were identified. We continue to make strides towards our ultimate goal.

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Is “on-demand” PrEP a suitable tool for MSM who participate in Chemsex?  From ANRS-Ipergay.

This was in an IPERGAY sub-study of 331 participants during the open-label extension (OLE) phase of the study who reported drug use during at least one sexual encounter.

 2 monthly data was collected regarding drug and alcohol use, sexual behaviors and PrEP adherence during the participant’s most recent sexual encounter(s) and analyzed with a multivariate regression model. PrEP use was self-reported by participants.

Among the MSM participants, 29% reported Chemsex at least once during the follow up period and16% reported chemsex at all visits.

Socio-demographics between those labeled chemsexers were not different from those labeled non-chemsexers, other than a higher use of anxiolytics in chemsexers.

 After adjustment, chemsexers were found to be more likely to use PrEP (OR (95% CI = 2.18 (1.04; 4.49)) and less likely to use condoms (p< 0.001)

Of note, when MSM reported chemsex during their most recent sexual encounter there was a grater likelihood of receptive anal sex, hardcore sexual practices, casual sexual partnerships and a higher perception of risk. All p-values <0.001

This important and interesting sub-study suggests that PrEP may therefore be a suitable tool for HIV prevention people practicing chemsex.

 

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Day 3 of the conference and PrEP of course has been the 'hot topic'

This oral abstract session was a reminder that there is more to prevention than antiretrovirals however.

First up, Kelly Kilburn gave evidence from the HPTN 068 study in South Africa where a third of women experienced physical violence by a partner. And there are direct correlations between this and HIV transmission.

The experiment involved 2,533 women between the ages of 13 to 20 years. They were randomly assigned to one of two groups where one group of girls (or their parents) received approximately $10 USD if they attended at least 80% of school days in the past month. Participants then completed a self interview and HIV and HSV-2 test each visit and at 12, 24 and 36 months following. The questionnaire was able to distinguish between sexual and physical intimate partner violence (IPV). 

The conclusion was that the conditional cash transfers had no significant effect on sexual IPV, HIV or HSV-2 acquisition. There was however a significant risk reduction for physical IPV by 34%. It was interesting to note that there was 95% attendance in both arms of the study and that the cash payment had no effect at all on school attendance but may have given the young person the independence from a violent intimate partner. 

I took a few interesting points from Shona Dalal of the World Health organisation that will be useful to my practice. She presented a systematic review of HIV partner notification services. Assisted versus passive notification where there were varying types of active notification - contract, provider or dual referral approaches. Contract is where the HIV positive client enters into a contract to disclose their status within a certain time frame and advise their partner to have HIV testing. Provider is where the provider confidentially contacts the HIV positive clients partner and offers voluntary testing. Dual referral is where the provider accompanies the HIV positive client to assist whilst they disclose their status and voluntarily offer HIV testing services.

With all types of notification if it didn't occur within a week it was less likely to occur. There were very few reports of harm and there was increased linkage to care and treatment among partners.

There was a talk from Sean Allen regarding a change in the policy of syringe distribution in Baltimore, MD from 1 syringe given for 1 returned to as many given as required. The number of syringes distributed doubled but the average number of HIV infections per month reduced. 

Also covered in this session were male circumcision and its effect on transmissions to women of sexually transmitted diseases. And also community based distribution of oral HIV testing kits aiding the early diagnosis and treatment of men in Zambia. 

Phew - what a session!

 

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IAS2017 Tuesday 11 am 25/7/2017

 

This session provided updates from various oral, topical and long-acting injectable PrEP clinical trials.

Sheena McCormack presented long-term PROUD study data from 2-4 years post enrolment.  This indicated that reduction in HIV incidence was sustained, and confirmed high adherence and durable effectiveness of PrEP in the study population.  However, as suspected rectal chlamydia and gonorrhoea and syphilis diagnoses remained high re-iterating the need for structured regular followup of these high risk patients.

A qualitative analysis exploring PrEP perceptions among PROUD participants, found that most viewed PrEP as a temporary HIV prevention option. Participants described psychosocial benefits in terms of reducing fear and providing relief when taking PrEP.  They didn’t discuss some of the stigma that still persists in the community about people who take oral PrEP however.  Acceptability seems to be increasing however.

Guillemette Antoni presented data from a double-blind, randomised sub-study of IPERGAY which found a significant reduction in HIV infection risk with on-demand TDF/FTC vs. placebo, in MSM having infrequent sex.  Oral PrEP with tenofovir/emtricitabine is now subsidised in France.

Sharon Hillier presented data from the completed FAME study.  This study found that FGT and plasma drug levels of dapirivine were not affected by Lactobacillus or G. vaginalis microbiome.  Tenofovir levels in FGT and plasma however are adversely affected by vaginal disbiosis (bacterial vaginosis). The potential influence of vaginal microbiome on topical and plasma PrEP drug levels emphasises the need for HIV prevention products that work in women with vaginal dysbiosis.

Ian McGowan from the USA presented data from the MWRI-01 multi-dose Phase I study.  They found long-acting IM rilpivirine to be safe. Drug accumulation was significant in plasma, rectal, and female genital tract (FGT) tissue.

Finally, Raphael Landovitz presented data from HPTN077, a double-blind, randomised, placebo-controlled tolerability and pharmacokinetics trial.  They found LA cabotegravir was well tolerated at 800mg/600mg doses in HIV-uninfected low-risk males and females.

Updated safety, acceptability and pharmacokinetic data on LA IM rilpivirine and cabotegravir provides hope for the viability of long-acting injectable PrEP formulations and circumvention of the adherence challenges associated with oral or topical PrEP.

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Presented as part of the mixed bag "Co-chair's Choice" session this study aimed to assess dolutegravir (DTG) in pregnancy. There are many benefits to DTG as treatment, highly effective, well tolerated, once daily with high barriers to resistance.  However, despite being a drug with many desirable qualities, the lack of data in pregnancy have resulted in DTG not being recommended in pregnancy by the WHO.  This study addresses some of the research shortfalls and compared pregnancy outcomes from patients who used EFV/TDF/FTC between August 2014 and August 2016 and those who used DTG/TDF/FTC from November 2016 to April 2017 

 

Much of the groundwork for this study was laid out by the Tsempano study, which demonstrated that EFV/TDF/FTC was associated with lower rates of any adverse birth outcomes as well as lower rates of severe adverse birth outcomes compared with other ART regimens (NVP/TDF/FTC, NVP/ZDV/3TC, LPV/r/TDF/FTC, LPV/r/ZDV/3TC).  A similar framework was adopted for the comparison of DTG/TDF/FTC with EFV/TDF/FTC in women who commence ART pregnancy.

 

Maternal demographics were well matched in both groups for age, employment, parity, gestational age at presentation, previous pregnancy losses and smoking and alcohol consumption.  They were also well matched with regards to the gestational age at which ART was commenced as well as their CD4 counts.

 

Outcomes were startlingly similar as listed below:

 

Total and severe adverse birth outcomes 34% in the DTG/TDF/FTC group, with 11% being a severe adverse birth outcome.

 

Total and severe adverse birth outcomes 35% in the EFV/TDF/FTC group, with 11% being a severe adverse birth outcome.

 

 

 

Birth at less than 37 weeks gestation 18% and less than 32 weeks gestation 4% in the DTG/TDF/FTC group

 

Birth at less than 37 weeks gestation 19% and less than 32 weeks gestation 4% in the EFV/TDF/FTC group

 

 

 

19% small for gestational age and 6% very small for gestational age in the DTG/TDF/FTC group

 

19% small for gestational age and 7% very small for gestational age in the EFV/TDF/FTC group

 

 

 

2.1% stillbirth in the DTG/TDF/FTC group

 

2.3% stillbirth in the EFV/TDF/FTC group

 

 

 

1 major congenital abnormality in the form of skeletal dysplasia in the EFV/TDF/FTC group

 

This preliminary data suggests that DTG may well be considered safe in pregnancy at some point but further research is needed in the following areas:

 

Birth outcomes associated with exposure to DTG from conception

 

Combination with other backbones eg ABC/3TC

 

Maternal viral load at delivery

 

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An important group of presentations today on STIs, a somewhat neglected area of discussion in HIV, despite evidence that people with higher rates of STIs are at increased risk of HIV and vice versa.

 

First presenter was Darren Russell from Australia presenting some background on the epidemiology of STIs.  First and foremost, the point was made that, if you do not test for it, you will not find it and then you cannot treat it (much like the first 90 with HIV!)  and that in contrast to HIV, testing, reporting and surveillance of STIs is inconsistent throughout the world, making STIs the “poor cousins“ of HIV. Given the international nature of the conference, epidemiological data from around the world was presented for STIs.  One slide demonstrated that in the early 20th century, as many people died from syphilis as did from HIV/AIDS at the height of the epidemic in the USA.  The incidence of syphilis from late last decade throughout the USA, Canada, Germany, Sweden, France, The United Kingdom and Australia was noted to have risen significantly in all countries and a special mention was made of the syphilis epidemic in Aboriginal and Torres Strait Islanders, a group in which we must try to do better if we are to close the gap.  This presentation ended on a high note with a success – the roll out of the HPV vaccine and the dramatic decrease of genital warts in vaccinated Australian women and eventually men.  I thought that ending on this information really served to demonstrate to the sexual health community what is really needed to stop epidemics – vaccine development.

 

Next Presenter was Scott McLelland from the United States who presented on STIs and susceptibility to infection.  We have known for some time that STIs place people at risk of HIV and vice versa but elucidating exact mechanisms has been challenging and interventions have not been as successful as previously hypothesised.  Yet more recent data has demonstrated significantly increased risk of HIV acquisition with HSV2, vaginal dysbiosis (bacterial vaginosis) and HPV due to the immune response.  For example, the site of HSV lesions has been shown to have high numbers of CD4 T cells and dendritic cells as does HPV infected mucosa, providing increased target cells for HIV virus.  How we use this information as a basis for further research, treatment and ultimately health policy remains to be seen.

 

Next was Connie Celum, also from the United States who presented on STIs in the era of TasP and PrEP.  One of the first and very important points made was that there is no evidence to indicate decreased efficacy of PrEP in users who have an STI – demonstrated in both iPrEx and Partners PrEP studies.  One caveat was that bacterial vaginosis may impact the efficacy of topical vaginal tenofovir.  The possibility of PrEP programs actually leading to a long-term reduction in STIs was brought up and the role of regular STI screens as part of PrEP use as well as the potential for STI PEP using doxycycline, presented as part of the ipergay study at CROI in early 2017 were both put forward as mechanisms to reduce the burden of STIs in PrEP users.  The model of STI testing, treatment and follow up was also addressed with reference to the Dean Street Express clinic in London with changes in service delivery proving effective in testing and treating more people in a shorter space of time and as mentioned previously – if you don’t test for it, you can’t treat it!

 

Last but not least was Cecile Bebear from France who gave a presentation called “should we fear antibiotic resistance for STIs?” with a focus on 4 bacterial STIs – Chlamydia trachomatis, Neisseria gonorrhoea, Treponema pallidum and Mycoplasma genitalium. For Chlamydia trachomatis, the concern for antimicrobial resistance (AMR) is low with the organism remaining sensitive to tetracyclines, macrolides and quinolones and only very rare cases of macrolide resistance being reported, so as Chlamydia trachomatis remains the most common bacterial STI, it also remains very easy to treat. Neisseria gonorrhoea is the complete opposite however, with resistance to almost every agent ever used against it since about the 1930s.  First line treatment with combined antibiotics of two classes has held Neisseria gonorrhoea at bay, but for how long?  Extended cephalosporin resistance rates in this organism, where there is resistance monitoring range from 0.1% to 30 % in various parts of the world (up to 5% in Australia).  Azithromycin resistance ranges from 2-8% across the world, fluoroquinolone resistance 30%- 50% and tetracycline resistance more than 50%.  New treatments are in development pipelines but the ideal way to tackle this organism would be through a vaccine.  Syphilis remains relatively easy to treat with penicillin or doxycycline but does have a high prevalence of azithromycin resistance (84% in Australia).  Finally, the new kid on the block, somewhat of a problem child, Mycoplasma genitalium, tetracyclines demonstrate poor levels of eradication but no resistance characterised, macrolide resistance is widespread, between 43% and 63% in Australia and there is acquired resistance to the agreed upon second line treatment moxifloxacin, ranging from 4.5% in the UK to 47% in Japan.  Unfortunately, this problematic organism did not generate much discussion nor were potential third line agents for consensus discussed.  Certainly more research needs to be done in regards to this organism and consistent guidelines on management are required.

 

Tagged in: 2017 IAS Conference

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