Australian Herpes Management Forum

Herpes Breakfast Forum: Questions and Answers

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The AHMF presented a Breakfast Forum at the recent Australasian Sexual Health Conference in Melbourne. During the forum, audience members posed a number of questions to a panel of experts. Here are the answers they gave, both on the day and with extra amendments added later.

Questions Answered at the Forum

1. Is there a correlation between viral load when someone has a clinically evident lesion as compared to asymptomatic shedding?

Professor Suzanne Garland:

We tend to say if there is a lesion there is a lot more virus there, perhaps Dominic would you like to comment?

Dr Dominic Dwyer:

I think in general terms Suzanne there is a strong correlation with the amount of virus shed form a clinical lesion compared to asymptomatic shedding and there is also a time factor – how long the clinical lesion has been present also influences what the viral load is like.  So in other words when the lesion is fresh the viral load is high and it drops, but it is worth saying that people can still have shedding at quite high viral loads in the absence of clinical diseases.

2. How can you explain the risk difference of HSV-1 between men and women?

Professor Adrian Mindel:

I think that is a really interesting question. The data would suggest that women are receiving oral sex more commonly than men are. Whether that is true or not I honestly don’t know, we haven’t got those data to back that impression from the serology up. I think it’s a really interesting question and something we need to do further studies on. We know so little in terms of adolescence sexual behaviour in real detail that it is something certainly worth studying. So, good question, but I can’t answer it.

3. Is there any data on interaction between HSV and HIV in pregnancy?

Associate Professor Cheryl Jones:

I am not aware of any data but it is a good thought in terms of risk of transmission. I think that data would be available but I haven’t seen it published.

Addendum post meeting by Associate Professor Cheryl Jones:

There is not published data on the association between HIV infection and perinatal HSV transmission. However there has recently been a retrospective analysis published which suggested that clinical diagnosis of genital HSV infection during pregnancy is a significant independent predictor of perinatal HIV transmission (adjusted odds ratio 4.8, 95% confidence interval 1.3–17.0; P = .02). Chen KT et al. Obstetrics & Gynecology 2005;106:1341-1348

4. What do you recommend for management of HSV-1 and HSV-2 seropositive gay males who are HIV+ or HIV-? Lifelong suppressive antivirals?

Dr Darren Russell:

It should be seen as a potential risk factor of both viruses HSV1 and HSV2 obviously, but also HIV. So if a gay male is HIV + and also has antibodies to HSV1 and HSV2 that should be seen as a potential risk factor, and that person be at higher risk of transmitting. And if that person is in a serodiscordant (that is an HIV serodiscordant) relationship that person may want to consider suppressive therapy. The problem we have in Australia is that if the person is asymptomatic it would be very hard to get that on the PBS.   

I think that lifelong suppression is not something that most people take up, but there will be a place for those who could be at high risk of transmission. We don’t really have the data that reducing that risk (reducing HSV2 reactivations) will reduce the risk of contracting HIV.  Those studies are ongoing, but at a client/patient level it is something to consider.

Dr Dominic Dwyer:

I think it is reasonable to have a high index of suspicion of using suppressive therapy in HIV infected people with a clinical history of genital herpes, and particularly if the CD4 count is low.  It is worth reflecting back on some very difficult data from years ago, before antiretrovirals were widely available and people were using high doses of acyclovir as a kind of management tool in stage HIV and there was some clinical benefit which was probably related to treatment of the herpes rather than treatment of the HIV.

5. With regard to shedding, is PCR too sensitive? Do we really know what constitutes an infectious dose?

Dr Dominic Dwyer:

If you go back to the clinical issue, we know that the bulk of herpes transmission is from asymptomatic people who are shedding, so therefore detection of shedding is important.  What you don’t know, is how little virus, or how much virus, do you need to shed to cause infection. So I think actually unlike a number of other diseases I would have thought that PCR detection of shedding is important.

6. Some patients never seroconvert to fully developed Western Blot. How often does this happen?

Dr Dominic Dwyer:

It does happen. I think that the type specific serology in general is actually a little bit more difficult from the lab point of view than one might be able to express in talks.  As you know with HIV, or any other situation where Western Blot is used, it is a complicated serologic technique.  It is generally less sensitive than perhaps your ELISA based techniques, but is often more specific for the disease of interest. Given all that, there are Western Blots that don’t fully evolve to be a true positive, and it is also dependent on the quality of the Western Blot produced, whether they are commercial or in house or so on.  There are a number of lab issues that make Western Blot tricky but it would be reasonable to say, at least in our hands, 10 percent of Western Blots are tricky to interpret, so then you are sort of stuck with …. as I had in one of my slides, trying to interpret that in the context of the clinical disease that you are managing.

Professor Suzanne Garland

It probably depends a bit when you are bleeding the patient relative to their outbreak because it can take a while for western blot to become positive.  And certainly when I was working in Steve Sacks department working with a cohort of pregnant women we found the occasional person who was culture positive who  9/12 months down the line had never made a positive Western blot.  But that’s pretty uncommon , and that was with Roeder Ashley’s Western Blot.

7. Is there a role for PCR screening for HSV – routine STI screens – to pick up asymptomatic shedding? Or is serology a better screening assay?

Professor Adrian Mindel:

I think the answer is no, because it is so intermittent that you are very unlikely to, on any particular day, pick up a positive PCR.  The question of routine serology I think was addressed very adequately by Dominic Dwyer.  There is potently some place and one needs to think fairly carefully as to whether or not that is part of a routine sexual health screening but as yet I think the jury remains out on that one as well.

The difficulty of course is if you get a positive test it has implications, you then need to counsel the patient, they may need to then talk to their sexual partner/s.  There are questions about who they have acquired it from. There are questions about who they might have given it to.  And so it becomes quite complex. And I think that it is not as simple as ‘okay, here is your test, see you later’.  We need to consider that carefully, but certainly in the sexual health context, PCR as a routine test has no place but serology might have a place.

8. C-section within 6 months of rupture of membranes if there are active lesions at the time of delivery

Comment: This is based on limited and old data.  The Americans have recommended c-section with longer duration of ROM because lesions may be vulval and not cervical.

Professor Suzanne Garland

I think I made the comment yesterday that in some situations you do need to individualize.  If it is a woman who has got ruptured membrane, say for 6 hours or 7 hours, is she a multi is she a prime eb? is she likely to go into labour quickly etc, so it is all about relative risks.  Cheryl you may want to comment further.

Associate Professor Cheryl Jones

It is hard to go through all of the nuances within a 10 minute talk and so that’s actually a very fair comment. I think that for any woman you must individualize your decision based on the site and severity of lesions. It is actually also quite true that the data about the 6 hour cut off is from some data in the mid 1970’s by Nahmius et al.  And when you look at the data, it is not that good, so that time point is arbitrary. It is currently what we are recommending but you should review it with each individual case.

9. Can you use genotyping (for HSV) to look at the source of transmission?

Professor Suzanne Garland:

I am thinking specifically here for use in a sexual abuse case?

Dr Dominic Dwyer:

You can do genotyping for herpes simplex. Genotyping tends to work. Genotyping in the sense of trying to work out relatedness between viruses or who gave what to who, is tricky. With RNA viruses such as HIV and Hepatitis C and so on, the inherent genetic variability of those viruses makes it easier to do genotyping to work out the origins of an infection or a group of infections.  With DNA viruses such as herpes simplex and CMV and the like, it is much more difficult because there is a lot less genetic variation that allows you to sort of work out subtle differences. Despite that, you can do it - and people have done it to look at outbreaks of herpes infections in unusual situations and so on.  It can be done by a range of methods from sequencing the virus or looking at restriction enzyme digests the viral DNA and so on.  So it can be done – but there are implications in trying to sort out who gave which virus to which person.

Questions Answered Subsequently

1. Now that most women with HIV who are on HAART will be delivered vaginally, do we need to increase our threshold for caesarian section if HSV-2 positive to protect against neonatal HSV (or HIV transmission)

Associate Professor Cheryl Jones:

We don’t yet have data to answer this. However, if HIV viral load is suppressed sufficiently by HAART such that a decision is made that an infants can be delivered vaginally, the risk of HSV and HIV interactions at the site of infection and on immunity generally are removed from the equation. As such, the decision to deliver the infant vaginally at the time of delivery should then be based on HSV alone (ie the presence of absence of significant lesions after careful speculum examination, avoidance of invasive monitoring, and forceps or vacuum assisted delivery of the infant where possible).

2. Please discuss management of HSV infection diagnosed by screening of HIV

Dr Darren Russell:

If HSV-2 is diagnosed at screening and the patient has no symptoms, then treatment of herpes is unlikely to be warranted. The screening (if positive) does allow insight into the nature of some anogenital symptoms, and counselling about the risk of transmitting HSV-2, and a possible increased risk of transmitting HIV, can be discussed.

3. If we are screening our HIV patients for HSV-2 – what are your thoughts in suppressive HSV-2 treatment for the asymptomatic HIV patient?

Dr Darren Russell:

This may sometimes be warranted. We know that asymptomatic individuals still shed HSV-2, often as much as those who actually have HSV-2 symptoms. If an individual does not wish to transmit HSV-2, then taking suppressive antiherpes medications will reduce the risk of sexual transmission. It is also possible that taking antiherpes medications will reduce the risk of transmitting HIV, but as I said in my talk, this is yet to be confirmed in rigorous studies.

Dominic has already reminded us that in the pre-HAART era, aciclovir was used to as a treatment for HIV itself, with some reasonable evidence for its efficacy in reducing mortality rates. Whether this still holds true in the days of HAART is unlikely, though in individuals with very low CD4 cell counts, say less than 100, it may be worth using an antiherpes medication in this way.

4. Treatment of recurrent genital herpes in pregnant women.

There has been some concern expressed about neutropenia in the babies of mothers taking aciclovir during pregnancy. Are you following these babies in prospective studies?

Associate Professor Cheryl Jones:

We are not specifically following this infants up after maternal antiviral therapy in either a research or clinical capacity.  Parenteral acyclovir is well tolerated by both term and preterm infants. Neutropenia has been reported after sustained oral suppressive therapy has been prescribed to HSV infected neonates. However, data from RCTs of maternal acyclovir during pregnancy, from the Aciclovir in pregnancy registry, and from foetal and neonatal PK studies have not suggested that this is a significant problem after maternal therapy (see review by S.L. Laurie, Clin Obstet Gynecol 1999, 42: 134-148). The recent RCT of valaciclovir to prevent recurrent disease in pregnancy did not show neonatal neutropenia as a secondary outcome. Sheffield et al, O&G, 2006; 108: 141-7.