UK Community Advisory Board (UK-CAB)

UK-CAB 4 – Meeting Report


Members and attendees

Members attending

Paul Bateman
Hat Trick Group/Haemophilia Society
Christian Cassidy
Rainbow Project
Polly Clayden
HIV i-Base
Simon Collins
HIV i-Base
Steve Crewe
Yorkshire Mesmac
Richard Day
Yorkshire Mesmac
Jenni Fredriksson
Information Officer AVERT
Laurence Gibson
Positive Nation
Stuart Gregg
Emma Hudson
Begin Clinic, Wakefield
Richard Jackson
THT West
Jim Jewers
Globe Centre
Ben Hills-Jones
Information Officer AVERT
Robert James
Hat Trick Group/Haemophilia Society
Mohamade Jowata
Brent PCT
Andrew Lumsden
HIV i-Base
Susie McLean
National AIDS Trust
Mary Makarau
Phyllis Magombe
Joseph Ochieng
Christophe Palaggi
THT, London
Jo Robinson
THT, London
Marsh Rosengarten
UCL, London
Kapulu Simonde
Solas, Edinburgh
Minutes and reports
Andrew Lumsden and Simon Collins

1. Introduction

Simon Collins and Polly Clayden of HIV i-base welcomed those attending the fourth meeting of UK-CAB and Treatment Advocates Network and everyone introduced themselves.

For the fourth meeting’s opening session, Polly Clayden of HIV i-Base led a session on gender-related issues, repeatedly sidelined yet of accelerating global urgency.

The second training session, on Hepatitis C and coinfection, was organised by Babs Evans of the Haemophilia Society.

2. Women, HIV and research

An intensely followed discussion was assisted by information circulated in advance on gender-related articles from

Polly Clayden opened with the statistics. In 2002 women accounted for over 50% of new AIDS cases worldwide. In the US, AIDS is the leading cause of death among African American and Hispanic women between the ages of 25-44. Yet women provide only 12% of the participants in clinical research on pot ential treatments. And women are 33% more likely to die than men, because treatment for them begins much later, if at all.

Polly described some of the special factors, such as that in IV-drug use ‘boys go first’ so the likelihood is that far more women will be HIV-infected from needle-exchange than men. “Government publications tend to be ‘blind’ to women, so that for example the EMEA mentions gender twice in its guidelines whereas the Federal Drugs Administration (FDA) has a whole women’s division and in 1996 changed its rules to be a lot less paternalistic.

“Women tend to be started on treatment later than men. Women deemed to be of childbearing age were simply excluded from trials. Now women have more autonomy under US rules to say ‘I’m gay, I use barrier methods or I am in a monogamous relationship’. This is a treatment problem that’s not exclusive to H IV.”

Ques. These problems are getting increasingly stark when you realise that in the UK two women for every one man are being diagnosed with HIV. The inequity of leaving women out of research programmes is becoming greater every year.

Resp. Yes, male cohorts are ‘more convenient’, not having the same dependent-family problems. Over 30% women and over 50% non-white in a phase 3 protease inhibitor trials is the best balance so far. Drug companies are at least now making better noises about the problem. Until 1991 women were not allowed on ANY phase 1 trials because of their child-bearing potential. There’s more of this attitude still in Europe than in the US.

Ques. Can’t governments enforce a better gender-balance in trials?

Resp. The FDA has more clout, the EMEA doesn’t – it can only make recommendations. I agree it should have mandatory powers. I don’t know when or if change will come. We are lobbying the EMEA now.

Ques. An article in the recommended reading list suggested women may have lower viral loads at the same CD4 counts as men.

Resp. Yes, this received a lot of attention as it is one of the few differences that has been found. When guidelines for starting treatment were based more on viral load, it was also a concern that women should perhaps be started on treatment at lower viral load levels. Earlier use of HAART may have a beneficial effect on the risk of cervical cancer.

Ques. Another study, ‘Anal Sex Increases Risk for Heterosexual HIV Transmission’ suggests that in about 30% of AIDS couples in the US the woman contracted HIV anally. It suggests heterosexual couples having anal sex are much less likely to use protection than gay couples. There is also a ten times greater risk of HIV transmission with anal compared to vaginal sex. We need more studies of this.

Resp. Unprotected anal sex is a common Catholic form of contraception. So the anal infection figures are very high in Brazil. As an important gender-related matter, this subject is not sufficiently discussed at all. We have brought it up with pharma companies who are involved in research for microbicides and they were most disconcerted.

Ques. In the US the usual assumption is that 20% of sex is anal. Heterosexual studies often don’t even ask whether the infection was likely to be through anal or vaginal sex.

Resp. Unless it’s a gay study, it’s a big taboo.

Ques. Hepatitis C is seen as an IV-drug route issue only. There seems to be a widespread wrong assumption that it can’t be sexually transmitted. People should be automatically test for HepC at GUM clinics and not solely, as they do now, when they find you have HIV? I was shocked to find doctors aren’t giving any advice that it may/must be potentially sexually transmitted. No warning to have protected sex. This is not being taken seriously by the medical profession and there is definite evidence of transmission of HepC between sero-discordant gay coup les.

Other points covered in discussion included the apparent higher incidence of nevirapine rash among women, and the higher chance of hepatoxicity in women. Lipodistrophy, however, seems to affect the sexes equally, although earlier studies indicated that men were more likely to experience fat loss, and women to experience fat accumulation. Further studies are needed into whether HIV treatment worsens osteoporitis in women.

Polly Clayden spoke too of social factors affecting care. For example, “women are often less able than men to treat their doctor as a peer, but if they just have somewhere to put the kids they’ll talk more freely. AIDS doesn’t exist in a vacuum: anything that applies to a woman, will apply.”

Illustrating the pervasive difficulties encountered by women, she described her own entry into treatment advocacy. She had been at art-school, had gay friends, and about six years ago became a volunteer, doing photocopying and the like. She found it a “very male environment” where “no-one was highlighting the needs of children, who wer e receiving treatments that would be unacceptable in adults”, and “conferences weren’t answering my friends’ questions.”

Things are changing, if not fast enough. Polly recently attended a ‘Sex and Gender Issues in HIV’ conference in Washington, organised by the Forum for Collaborative HIV Research, another on ‘Fertility Regulation and Systemic Hormones in HIV-infected and At-risk Women’ organised by the National Institutes of Health.

Just before the UK-CAB meeting she had been in Botswana at an international workshop on ‘HIV-1 mother-to-child transmission’ and in line with the warning sounded by Dr Karen Beckerman at UK-CAB in October it was shown that single-dose nevirapine to mother and infant led to resistance in 20%-30% of people. When the child got a second d ose as a defence during breast-feeding, resistance rocketed.

“Nevirapine monotherapy”, said Polly Clayden, “is not allowed in Brazil. They make their own generics and have 120,000 people on combination therapy. This is a great model, I think.”

Ques. Are there any contra-indications when oral contraceptives are taken alongside HIV treatment?

Resp. Even though these are very commonly used drugs, o-one knows what strength of contraceptive should be taken. It’s incredibly frustrating.

Ques. It has been found that when African men won’t use protection, the women try oral conception for themselves and still conceive.

Resp.The choices are appalling. Ruandan research has shown that men with an HIV-positive partner will use condoms, but otherwise they usually won’t.

Ques. Also, African men frequently use contraception with girlfriends, when they don’t use them with their wife.

Summing up the first session, Polly Clayden said that according to UNAIDS figures, just over 50% of PWAs globally are women and in some countries young women are twice as likely as young men to contract HIV. It is estimated that in Western Europe 25% of the reported 560, 000 persons living with HIV are women.

“A recent literature analysis showed that the usual medical construct of an HIV-positive person when it comes to exploring the efficacy of treatment is: male, white, middle-aged gay, North American or Western European and treatment-experienced. The bottom line is, keep bugging the professionals!”

3. Living with multiple conditions

The second session of the morning began with an at times painfully funny presentation by Paul Bateman of Hat Trick Group/Haemophilia Society, Notts, who is also a member of the editorial team of the newsletter for Birchgrove, the forum for people with haemophilia and HIV.

His subject, delivered with unfailing good humour despite the infuriating circumstances he encounters, was the lack of co-ordination between the medical services for co-infected people.

There are only three actual co-infection clinics, respectively at the Royal Free and the Chelsea & Westminster hospitals in London and one in Edinburgh.

Paul himself was born with haemophilia, contracted HIV in 1985 through infected Factor 8, and was diagnosed with hepatitis C in 1992 – although told not to worry about hepatitis because ‘ HIV will kill you first!’. “I live in a rural part of the country and when I mention all three to my doctor he just looks as if he wishes I wasn’t there. While my care involves seeing several specialists about each of my conditions, there is never an appointment with all three at once.

“There’s no blood-test co-ordination. I don’t want more blood-tests than I have to. I cherish my veins after a lifetime of IV drug use for haemophilia. I’ve lost two veins. And as it happens I hate this subcutaneous business of pinching a fold of skin. That’s just me. “No-one looks at me from a holistic perspective. Tell them about what’s going on in your one body.”

He’s waiting to choose his moment to join a trial at his local hospital of the hepatitis C treatment pegylated interferon/ribavarin made by two pharmaceutical companies,

Scherring-Plough and Roche (subject of the afternoon’s presentation by Roche’s Dr Colin Hayward). It has been undergoing trials for several years, mainly among people without HIV.

Given the side effects related to HCV treatment he is postponing this decision for several months “If I’m going to be suffering from insomnia” (one of the wide range of side-effects reported) “I’d rather it wasn’t in the winter. So I said I’d wait.”

4. HIV and hepatitis C co-infection

Slides from this session are posted to the i-Base website in the section related to this meeting:’s presentation.ppt

Dr Ranjababu Kulasegaram of Guy’s and St Thomas’s hospitals in London then spoke on co-infection with HIV and Hepatitis C (HCV). Reported cases of HCV worldwide are 170 million or 3% of the world’s population, against 42 million reported cases of HIV.

In Europe as a whole there appear to be seven cases of HCV for every one of HIV. It is estimated that 30% of HIV patients are co-infected with HCV, though in some countries this is higher, eg Spain, estimated at 45%. It is estimated that mother-to-child transmission occurs in 6% of CTV cases, but in the case of co-infected mothers this rises to 15%-20%. Estimated prevalence of HCV s 200,000-400,000 people (only 30,000 diagnosed) and is found in 0.04% blood donors and 0.4-0.6 % ante-natal clinics in London.

Mono-infected HCV patients can estimate 25 years till the HCV becomes life-threatening, though much less if alcohol is taken. Pressed by questioners, Dr Kulasegaram said ‘as low as you can’ and qualified this as that two or three glasses of wine a week might be about the safe limit. With co-factors of continued alcohol consumption, or co-infection with HIV, the time to progression of liver disease accelerates to about 15 years.

Although further studies are needed it is now believed that HCV accelerates the progression of HIV and limits the CD4 response to HAART. Viral load is approximately 1 log higher in plasma and liver in coinfected compared to mono infected HCV patients. CD4 count is also important. A coinfected person who doesn’t drink alcohol and has a CD4 count over 200 has the same risk of progression as a mono-infected person.

Unlike HIV, HCV is potentially curable, because the virus does not integrate itself into cellular DNA. After infection, about 20 percent of people infected with HCV clear the virus by themselves. Also, unlike HIV, HCV viral load does not predict risk of disease progression. Given the opportunity there are many reasons why it might be better to treat HCV first, before going on to HAART.

Diagnosis is with HCV IgGAb test, followed by EIA-3 RIBA to confirm false positives. If positive screening and vaccination for Hep A and Hep B is recommended.

As neither HCV viral load, nor blood tests (ALT etc) are predictive markers of disease progression, biopsy in the only reliable test to assess fibrosis. This is both invasive and carries a small risk of complications. Unless cirrhosis is present treatment is not recommended.

HIV treatment is with interferon plus ribarivin. Recently pegylated interfon has been developed which requires only once-weekly administration rather than three times a week dosing – and resulting in better constant drug levels.

Both treatments can have “horrible” side-effects of fatigue, depression and irritability – so those about to take it must have good mental-health backup, but they should not necessarily take anti-depressants.

Primary aim of treatment is eradication and this is measured as SVR (sustainable viral reduction) – ie undetectable HCV viral 24 weeks after the end of treatment. However viral suppression itself is also associated with improved histology, delayed cirrhosis, end stage liver disease (ESLD) and liver cancer.

Whether on interferon alone or combined with ribavirin, people co-infected with HIV should not use AZT, d4T or ddC if possible, because ribavirin stops these drugs reaching optimum levels, although one recent study didn’t show a difference in clinical efficacy. Ribavirin can increase levels of ddI and is similarly not recommended. While taking ribavirin – and for six months afterwards, both men and women should avoid conception till six months after completion of t he treatment. 40% of those taking interferon and ribavirin in combination for 48 weeks clear their HCV virus.

Ques. What about transplants for people with coinfection?

Resp. The prognosis is not encouraging compared to transplants for alcohol induced liver failure alone, but this is being reported now.

Ques. What about the question of sexual transmission of HCV?

Resp. Less than 2% of HCV infections are associated with sexual transmission. There does seem to be a higher chance of HCV infection where there is co-infection with HIV.

Ques. In Bristol they say they don’t have funding so won’t test for HCV.

Resp. This is a Health Service problem in many areas. National guidelines may help, but other than travelling to a different clinic I’m not sure what else to suggest.

Ques. What about the risk of mother-to-child HCV transmission?

Resp. A French study has shown that elective Caesarean may be indicated because HCV can easily be transmitted during pregnancy.

Advantages of treating HCV before HIV is that is can reduces chance of future hepatotoxicity of HIV drugs, fewer drug interactions, easier adherence and better chance of good immunological response to HAART when it is used later.

Transplantation is an option in coinfected patients although this is a relatively new area. Response is much poorer with HCV infection compared to HBV, and coinfection with HIV doesn’t stop a referral.

5. 48 weeks of interferon and ribavirin – a personal view

Robert James of the Haemophilia Society, living in Brighton, concluded the morning session with a personal account of taking pegylated interferon with ribavirin as a person co-infected with HIV and HCV.

“I started in October 2001. I was already on HAART. I’m HCV genotype 5 and sought a year’s treatment.”

Like Paul Bateman he found the sub-cutaneous injections very difficult, though the pen injection has now been introduced. “There were massive fluctuating side-effects including headaches, joint and muscle pain, shivers, cold fingers, a cough, excessive snot without a cold, night sweats, insomnia, fatigue, diarrhoea (from IFN) and constipation (from RBV), weight loss and light sensitivity – you feel a berk in sunglasses on a cloudy day.”

The oddest effect he described was that his hair straightened from being naturally tight and curly, which he said he didn’t mind at all.

There was weight-loss and some lipoatrophy, “so I changed HAART and everything doubled – side effects, pills and injections included, for ten weeks. I was dehydrated, itched, had spots, the full teenage experience: manic and obsessive and so grateful when people were nice that I burst into tears.

“I finished in November 2002. I returned to alcohol and tea, coffee, alcohol and spicy food. Life is better and I felt really good. So did it work? Well the first set of blood results have gone missing so I don’t know… I expect I’ll find out one day.”

6. Roche and Hepatitis C

In the afternoon the CAB met with the Dr Colin Hayward from the hepatitis medical department of Roche. He works on Pegasys, the Roche pegylated interferon treatment for HCV .

Dr Hayward described how the hepatitis C virus was isolated in 1989. It comes in different genotypes, 1,2,and 3, and 4-6, of which genotype I is the most prevalent, accounting for 40%-50% of cases.

About 0.4% of the population in England and Wales and about 0.6% in Scotland are thought to have it in the blood, though this could be an under-estimate because of lack of screening. About 50% of IV-drug users have HCV. Age (over 40), male gender, alcohol, HIV, all appear to be factors in a more rapid acceleration of hepatitis C to cirrhosis of the liver, though it is not clear if smoking accelerates.

Ques. Can’t the companies reduce the cost of an HCV test (about £40) as many people can not get this easily?

Resp. Maybe we as a company should support that.

click on either slide for a larger view

Pegasys is a once weekly injection taken with ribavirin tablets. Ribavirin lasts six months in the body and is toxic to foetuses, hence the warnings against conception till six months after the end of treatment. Pegasy is a 40kD interferon (compared to the 12kD Peg Interferon produced by Schering Plough, called PegIntron). PEG stands for Polyethylene Glycol and these primers allow for a much long half-life in the body allowing once weekly injections (rather than three-times weekly).

Response rates from Pegasys are better than regular IFN+RBV across most population groups including for people with genotype 1 or 2/3,4,5, with higher viral load, with cirrhosis stage and lower age (<40 years). [see slides 25-30]

Safety and side-effects:

click on slide for a larger view

Ques. Are there mutations in the Hepatitis C virus?

Resp. Yes, quasi-species, very slight and not enough to change the genotype. A Roche study is looking into whether haemophiliacs have a winder range of Heptatis C virus than others.

Ques. Are there any differences in male/female responses to pegylated interferon?

Resp. No difference between the sexes has been found. And none for weight either.

Duration of treatment

New studies are providing information on the duration of treatment for different groups. Response rate at 12 weeks can given an indication of benefit of continued treatment which may reduce the time using an ineffective treatment for some people which is important given the toxicity – and provide additional success rates in other people when treated for 48 weeks.

click on slide for a larger view

In this, genotype makes a large difference to risk of success or failure.

click on either slide for a larger view

NICE are likely to recommend 24 week treatment, with a further 24 weeks available for genotype 1 if responding.

Ques: There is a reluctance to prescribe antidepressants, and this leads to higher discontinuations.

Resp: Treatment should ideally involve multidisciplinary teams that could improve this.

Ques: How many people are currently on treatment?

Resp: We estimate about 1500 currently in the UK and this will increase to 2000 this year.

Dr Hayward presented a summary of all current Pegasys studies, including the following issues in the UK:

  • Liver transplants
  • Co-infection (APRICOT)
  • Cirrhosis
  • Genotype I

The Roche APRICOT (Aids Pegysys Ribavirin International CO-infection Trial) trial includes 800-900 patients, 81% male, who are taking pegylated interferon as either the Roche Pegasys, or the Schering-Plough Peg-intron, or taking one of these plus ribavirin.

Ques: Are you looking at the effect of specific HAART regimens?

Resp: There are too many different combinations for this to have much significance when the study is analysed.

Ques: What about the role of complementary therapy?

Resp: Yes, people receiving more support are likely to do better but there is little data.

Other studies

Two slides [slides 61 and 62] were shown showing results of Pegasys for HBV, which given the toxicity, is likely to be more important for people infected with both HCV and HBV, rather than as a regular treatment for HBV alone.

click on either slide for a larger view

New drugs

Finally, the meeting concluded with a brief reference to Roche’s pipeline drugs for HCV which include Roches Ribavirin (CoPegus), combinations (CellCept – mycophenolate; and amantadine – an approved drug for Parkinsons disease that costs much less than interferon/PEG and which has been studies in HCV infected patients who failed to respond to interferon alpha-2b) and a new drugs levovirin (a second generation ribavirin candidate).

For early reports of CellCept and amantadine, see:

For and levovirin see:

7. Internal – programme for 2003 meetings

There will be at least four meetings this year – approximately every three months. The date for the next meeting will be confirmed with more notice than the January meeting, provisionally this will be Friday 9th May.

One of the training sessions could be on policy-related issues and after discussion, the subject of treatment access problems of asylum seekers might be a considered at the next UK-CAB.

8. Appendix

Preliminary reading material, together with powerpoint slides from all the presentations are available on the web page for this meeting.