This year the HIV conference has been dominated by presentations on anal cancer in men who have sex with men, particularly those living with HIV.

A/Prof David Templeton presented the interim findings from the SPANC study, which assessed the utility of cytologic screening for anal cancer.

Dr Jason Ong presented an interesting overview of what clinicians can do currently to screen for anal cancer, given how little evidence we currently have on the usefulness of screening.

Dr Amber D'Souza presented on the epidemiology of anal cancer

Ben Wilcox and Lance Feeney presented on community perspectives and education on anal cancer.

Brad Atkins gave a moving presentation on his personal experience of anal cancer.

Perhaps the key messages are:

- Modelling has shown that anal cancer screening by a digital anorectal examination has shown it to be cost-effective only for HIV-positive MSM over the age of 25. In that scenario, it is currently recommended to perform anorectal examinations annually. However, an argument could be made to offer screening also to those MSM who are HIV-negative.

- Cytologic screening is problematic, in that it lacks sufficient specificity, resulting in a very large proportion of referrals to high-resolution anoscopy.

- We need to offer HPV vaccination to all MSM under the age of 25, and whilst there is no evidence of benefit over the age of 25 it would be reasonable to offer is to those MSM also (keeping in mind the cost to the patient).

- Much more work remains to be done to determine the best strategies to screen for anal cancer in MSM.

As PrEP has now been used in the USA for about six years, Dr Jared Baeton compared PrEP to the developmental milestones reached by the average six year-old child.

1. At six years old, we begin to understand cause and effect relationships.

   1. If you take PrEP, it works. As in, if you have good adherence, then it is close to 100% effective at preventing HIV transmission. Interestingly, studies have shown that those individuals at greatest risk of HIV appear to have a greater HIV risk reduction from PrEP. This suggests that those individuals at greatest risk of HIV also have the greatest adherence to PrEP.

       

2. At the age of six, magical thinking fades quickly: PrEP is not perfect, and PrEP does not expect us to be perfect.

   1. PrEP is not perfect, but PrEP is safe. We have good data on kidney safety and bone safety for PrEP users. Also the risk of antiretroviral resistance appears to be limited to those who start PrEP in the context of an acute HIV infection, rather than those who seroconvert during PrEP use. He did not further expand on this thought, but perhaps those who seroconvert during PrEP use have such low adherence to PrEP that it does not result in the selection of resistant HIV variants.

   2. PrEP does not expect us to be perfect. In clinical trials, not everyone used PrEP, but those who did use it tended to be consistent users (Partners PrEP). Those who were not adherent at one month tended to never become adherent. Dr Baeton drew an analogy between PrEP adherence and flossing: Some of us floss every day, and tend to continue doing so, others rarely floss and never start flossing regularly.

       

3. The average six year-old starts to understand the feelings of others. As a medical community we’re starting to understand what PrEP users want out of PrEP. And PrEP use has been shown to be associated with:

   1. Decreased anxiey

   2. Increased communication, trust, and HIV status disclosure

   3. Increased self-efficacy

   4. Increased sexual pleasure and intimacy

Stigma remains a key barrier to PrEP use: This includes stigma about ARVs, HIV and stigma about being at risk of HIV.

4. Six year-olds become more flexible in their thinking:

• Success in PrEP adherence is achieved when PrEP is used during times of HIV exposure, this has been referred to as “prevention-effective adherence”. I think we need to develop some clear messaging around “prevention-effective adherence”, to assist people in

• STIs will occur in persons using PrEP. People who need PrEP are at hight risk of STIs.

• PrEP makes us think very differenctly about three decades of fear-based public health campaigns.

5. 6 year-olds start to understand more about his/her place in the world. PrEP is not a panacea, but it has the potential to form an important part of the toolbox of HIV prevention.

I think PrEP has come a long way over the last couple of years, including in Australia. In order to continue this trajectory, I think we need ongoing efforts to:

1. Obtain PBS-listing for PrEP

2. Prevent the emergency of PrEP-associated stigma, by framing the discussion around PrEP in a sex-positive manner.

3. Develop clear messaging around dosing regimens that do not involve daily PrEP. Some people do not need to be on PrEP continuously, and we need to have realistic conversations how these people can effectively manage their HIV risk without necessarily taking PrEP every day.

This morning we saw a series of presentations from the Monopoly Study, which is a national Australian study that looked at how gay and bisexual men think about and conduct their relationships. They looked at whether gay men have explicit relationship agreements with their regular partners, particularly around issues like monogamy. They also presented finding around why and when couples change their relationship agreements from monogamous to open and vice versa.

Some interesting points included:

• There is inconsistent classification of sexual partners in the literature. Generally in Australia partners are classified as either "regular" or "casual", but the definition of these categories is inconsistent. Particularly, they highlighted that "fuckbuddies" can be placed in either the regular or casual partner category, and perhaps clinicians and data collectors need to consider this group of partners as separate to either regular or casual partners.
• Young men have shorter relationships than their older counterparts.
• Young men tend to assume that being in a relationship means that the relationship is monogamous, so they don't tend to have explicit relationship agreements. There was some discussion on why this may be so. One thought was that these days young gay men tend to have more heterosexual friends than in previous generations, and hence they tend to have views on relationships that mirror their heterosexual counterparts. I think that perhaps this may also underlie the change in relationships amongst young heterosexuals, where it seems that young heterosexual couples now more often make explicit agreements around monogamy vs having an open relationship. Another possible contributor to the lack of relationship agreements among young gay couples is the ongoing marriage equality campaign. I think it's fair to say that the marriage equality campaign in Australia tends to promote monogamous gay relationships as being "the norm", and tend to ignore the many other possible types of gay relationships. Such campaigns may have altered the perception of young gay men on what is expected in a gay relationship, and hence they don't feel the need to have an explicit agreement.
• Older men tend to have explicit relationship agreements. The explanation offered was that many gay men over time come to the realisation that relationships are complex, and that the supposed "rules" dictated by social norms are not concrete. As such, they feel that it's important to discuss the needs of both partners, and that an agreement is reached, which is may subsequently be revised when the couple's needs change.

So what does all of this mean for clinicians?

1. It may be useful to ask patients about fuckbuddies when talking about their relationships, and to ask what agreements people have with their fuckbuddies. In the "casual" vs "regular" linguistic dichotomy, fuckbuddies may get lumped in the "casual" category, and thus not get the attention they deserve.
2. We must ask young gay guys whether they have explicit relationship agreements with their regular partners and fuckbuddies, as this data shows that they often assume that their relationships are monogamous. The assumption of monogamy may place them at increased risk of HIV and STIs.

Teddy Cook and Jeremy Wiggins gave a talk on the inclusion of transgender men in the HIV response, which provided much food for thought for healthcare practitioners and a call to action for health policy makers.

The presenters raised concerns that trans men generally report significant HIV risk, yet are overlooked in the HIV response. They highlighted some issues in data collection that may have resulted in trans people not being accurately represented in HIV data.

Particularly, they made the enlightening statement that "Transgender is not a gender identity". Trans men have very different experiences from trans women, and have different health requirements, including different sexual health requirements. 

Also, health data collection does not accurately capture data on transgender people. For example, the Victorian Department of Health HIV notification form gives the gender options of "male", "female" and "transgender". By lumping trans men, trans women and genderqueer people into the same category, health data loses nuances that are important for informing health policy and health promotion.

Also, they highlighted some case studies illustrating how this simplistic gender categorisation has resulted in miscategorisation of trans people in HIV statistics. One case described a non-binary trans masculine person who was assigned female at birth who has sex with men, who was categorised as a heterosexual female on her HIV notification form. Obviously, in order to develop an appropriate public health response to address HIV risk in the transgender community, we need data that accurately reflects what is happening in the trans community.

The presenters suggested the following two-question gender classification in order to overcome some of these issues.

• Question 1: What is your gender
• Question 2: What gender were you assigned at birth

On a lighter note, Jeremy pointed out that a recent HIV testing campaign from Victoria did include a trans man. It's a fun campaign, so have a look at the video below:

Professor Edward Gane from Auckland NZ gave a visionary plenary presentation on how we may be able to eradicate hepatitis C.

Background on the Hepatitis C epidemic

Global infected population consists of 80-100 million people, with about 250,000 people in Australia

The global mortality attributable to liver disease has increased 60% since 1990, making it one of the fastest rising causes of mortality. Most of this can be explained from liver cancer and cirrhosis due to hepatitis C.

Can vaccination eradicate hepatitis C?

There are many barriers to the successful development of a HCV vaccine:

1. HCV factors:

• HCV genomic diversity
• T cell exhaustion
• Impaired DC maturation
• HCV NS3/5A inhibits IFN

2. Patient factors:

• Host genomic diversity
• Aging population
• HIV co-infection

3. Other factors:

• The chimp is the only animal model for vaccine development
• Preclinical results do not translate to humans
• With new highly effective treatment, there is reduced interest in vaccine development

Can public health interventions eraticate hepatitis C?

Harm reduction strategies (needle exchange, opioid substitution programs) are moderately effective, modelling has shown that these strategies will reduce HCV prevalence in PWID by a maximum of 30% over 10 years. This is insufficient to eradicate HCV. These strategies do have other benefits, such as reductions in HIV transmission, reductions in crime and increased engagement with healthcare providers. 

Can treatment eradicate hepatitis C?

This slide demonstrates the current hepatitis C treatment cascade on the left, where about 1% of people living with hepatitis C achieve cure/SVR. If we only improve treatment with newly developed drugs, then cure rate will increase to 1.8% (middle cascade). Significantly driving up cure rates to 80% requires that 90% of people living with hepatitis C need to be diagnosed, and 90% of those diagnosed need to take up treatment.

I would think that with access to well-tolerated and highly effective hepatitis C treatment, there will be an increased drive for clinicians to test at-risk patients for hepatitis C, and there will be increased uptake of hepatitis C treatment by those who have been infected.

In Australia we are on the cusp of possibly being able to achieve a ramp-up in hepatitis C management, as the Pharmaceutical Benefits Advisory Committee (PBAC) has recommended the listing of several new hepatitis C treatments (see slide below) AND have recommended that these be available for treating people at any stage of liver disease AND that these treatments can be prescribed by general practitioners in the community, thus allowing for a large-scale rollout of hepatitis C treatment, potentially setting the scene for eradication of hepatitis C.

Iryna Zablotska gave a conservative estimate of the number of people in Australia who will be likely to start PrEP if it is approved by the TGA. She also highlighted some of the difficulties in making such estimates.

John de Witt gave two interesting presentations on data from the VicPrEP trial. His first presentation outlined their findings on "risk compensation" in those on PrEP. They found a modest decrease in condom use with casual sexual partners amongst VicPrEP participants. Reassuringly, they also found good self-reported PrEP adherence, so the reduction in condom use will hopefully not translate into an increase in HIV risk.

John's second presentation provided a summary of the experiences reported by people taking PrEP. Participants reported increased enjoyment of sex, but also reported some reluctance to inform sex partners that they were taking PrEP. The latter suggests the emergence of stigma, or perceived stigma, associated with PrEP use.

In this plenary session, Professor Myron S Cohen presented summary of the HPTN 052 study. This study assesses the risk of HIV transmission in couples where the HIV positive partner is either treated early, compared to couples where the treatment of the positive partner is delayed. Contrary to some medical media reports, the HPTN 052 study is ongoing, in 2015 some 1535 participants remain enrolled, and over 9000 years of follow-up have been completed. Participants are allowed to bring new partners into the study.

Prof Cohen reported an overall 93% reduction in the risk of transmission in those couples where the positive partner was started on ART early versus the risk in those couples where ART treatment was delayed. However, Prof Cohen stated that the actual risk reduction is probably closer to 100%, based on the following analysis of linked transmissions:

- In total 8 linked infections occurred after the index started ART

- 4 were diagnosed soon after the index started ART, raising the possibility that these transmission occurred before the index attained virologic suppression.

- 4 occurred after the index failed ART

- No infections were observed when HIV replication was suppressed.

Prof Cohen also shared his thoughts on starting ART during primary HIV infection (PHI), at the time of diagnosis. He argued that people should start ART immediately, whenever this is possible, citing the following reasons:

- If ART is commenced before people have a drop in CD4 number, then they are likely to have a healthy CD4 count in the long term.

- Starting ART immediately possibly reduces the latent reservoir, which could provide patients a better chance of cure if and when this becomes available.

- During PHI patients have extremely high serum viral loads, which possibly increases the risk of onward transmission.

Prof Cohen acknowledged that these points have been disputed by other HIV researchers, and the question of immediate treatment at the time of diagnosis has not yet been settled. Several studies are hoping to address this question over the next few years.