UK-CAB 20 – Meeting Report

London HIV commissioning — renal toxicity — Gilead

26 January 2007
Programme for the meeting
Background reading
Background to speakers

Post Meeting Report

Members attending
1. Renal Toxicity
2. London Specialised Commissiong Group
3. PI monotherapy study
4. Gilead
5. Any other business

Members attending:

Bonita de Boer
AVERT

Paul Clift
UKC

Simon Collins
i-Base

Ben Cromarty
North Yorkshire AIDS Action
Christian Decle
KVN Forum

Paul Decle
Westminster HIV Services Users Forum
Russell Fleet
Medical Foundation for AIDS and Sexual Health

Bernard Forbes
UKC

Haydn Forde
UKC

Rena Greifinger
Body&Soul

Mohamade Jowata
Brent PCT

Robert James
UK CAB

Simonde Kapulu
Waverley Care

Mary Lima
THT

Mary Makarau
UK CAB

Badru Male
UK CAB

Michael Marr
Waverley Care

Christophe Pallagi
EATG

Jax Shapter
UK CAB

Jack Summerside
UKC

Tracy Swan
Treatment Action Group

Carmen Tarrades
ICW

Caspar Thomson
NAM

Mathew Williams
UK CAB

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Welcome

The chair (Mark McPherson) welcomed participants

1. Renal Toxicity

Speaker: Simon Collins, HIV i-Base

Relevant research is summarised on the UK CAB website.

Kidney toxicity is a concern for individuals taking tenofovir because this drug is cleared by the kidneys and a similar drug (adefovir) was stopped as an HIV treatment because of kidney problems at high doses. Studies indicate that kidney impairment is not common among patients taking tenofovir (less than 5%), occurring at about the same rate or only slightly more often than among individuals taking other nucleoside reverse transcriptase inhibitors. There appears to be a very modest decline in kidney function on starting tenofovir compared to other nucleosides.

Starting ARV therapy often improves kidney function on its own and is important if you are diagnosed with HIV associated nephropathy (HIVAN).

Studies consistently find that the risk of tenofovir kidney toxicity is higher among patients with a history of pre-existing kidney impairment. Female sex, older age, lower CD4 cell count, and use of other kidney-toxic drugs are also consistent risk factors. This includes drugs by people who have had more advanced HIV disease (ie IV pentamadine for PPCP, and foscarnet, ganciclovir and cidofocir for CMV).

In people with reduced kidney function, dose reduction of tenofovir is recommended (with the dose dependent on level of dysfunction).

Given these results, people should have their kidney function assessed before starting tenofovir and monitored regularly during treatment. This is noted in the prescribing information, and some clinics now routinely monitor kidney function via urine tests as well as blood tests to estimate creatinine clearance.

Q: If impairment happens, how long does it take to develop?

A: Generally, it happens slowly, and usually reverses on ceasing the use of tenofovir.

Q: Are Africans at higher risk?

A: Yes, studies show Africans are at higher risk – this may be related to higher risk of kidney disease in HIV-negative African people

Q: Is it possible not to have laboratory indicators of kidney dysfunction but still have kidney damage?

A: Monitoring tests (calculating creatinine clearance form a blood test) will pick up most problems, and regular monitoring should pick up any indication that function is changing. How closely you look determines what you find, and more sensitive tests (analysing urine collected over 24 hours) are used to confirm norderline results. There is not currently concensus on one standard way of measuring or assessing the clinical markers for kidney dysfunction in HIV positive patients, and develoing guidelines on this will be important.

Reply to SC: a personal experience – I was just feeling ill, a general feeling, various causes were discussed; when I stopped tenofovir I felt better (no specific clinical indicators of kidney dysfunction).

Q: What about hepatitis co-infected patients?

A: Differences, if any, are not well studied yet. Should be on our agenda to push for those kind of studies.

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2. London Specialised Commissiong Group

Speaker: Mark Creelman, North West Sector Lead for HIV.

Mark Creelman (MC) outlined the historical arrangements for HIV treatment information commissioning and NHS bureaucratic and conceptual drivers for the quickly-drafted (not by him) commissioning intentions put out to consultation recently.

There was a vigorous response to the proposals. In short, the outcome of this exercise is:

  • current contracts rolled forward for 6 months
  • a new proposal to be drafted and put out to consultation with a view to letting new contracts in October 2007 (3 year contracts)
  • The bespoke integrated database of service contacts will be abandoned

Questions and comments largely covered the extensive discussion on the UKCAB email list, especially the importance of HIV treatment information being part of a multidimensional approach to support and care with a particular emphasis on the peer-level information provision and hence meeting more in-depth the needs of the PLWHA and improve the treatment results, quality of life, etc.

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3. PI monotherapy study

Nick Paton (Clinical Trials Unit, MRC) presented an outline for a PI monotherapy study. Further details will be circulated on the UKCAB list for detailed comment. If the study goes ahead, UKCAB will be invited to be represented, including on the DSMB.

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4. Gilead

Speaker: Geraldine Reilly, Medical Science Liaison, UK and Ireland

Geraldine Reilly outlined a number of studies on Atripla and its component drugs, efavirenz, tenofovir and emtracitabine, including studies showing bioequivalence for the 3-in-1 formulation. This included some thought-provoking but unexplained data on non-emergence of M184V mutations for people using emtracitabine in combination with efavirenz and tenofovir compared to lamivudine.

Gilead is the lead company for patient assistance programmes for access to Atripla.

A number of questions were put to the meeting about aspects of Atripla’s forthcoming European release and the trials data, but the company had little more information about the process until the EMEA complete their review.

This was followed by a reprise of studies on tenofovir and renal toxicity, notably Gilead 903 and 934. These studies are widely reported on the web eg:

Gilead 903 – www.natap.org/2003/Retro/day48.htm
GIlead 934 – www.aidsmap.com/en/news/CC754D1C-9F1C-4A59-B32C-8D6D450B7EAA.asp

Follow-up on renal toxicity has now been for 7 years. No-mild kidney damage is noted on close inspection except in a very small percentage of people. Generally, more serious kidney damage occurs only in patients with underlying renal dysfunction prior to commencing treatment with tenofovir. There are questions about which diagnostic test, and which degree of kidney function impairment, indicates it is timely to switch to a different drug.

Different tests are summarised online at the National Kidney and Urologic Diseases Information Clearinghouse
kidney.niddk.nih.gov/kudiseases/pubs/yourkidneys/index.htm

There is some concern about tenofovir’s long-term effect on bone density. Registrational studies show a small early drop in the first year, that has not been associated with any clinical events (ie no increased freactures in the tenofovir groups) and there doesn’t seem to be any further loss in bone densitiy with continued use (over the 2nd, 3rd and 4th years).

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5. Any other business

The UK-CAB is working on election procedure for the situations when we are invited to have a representative.

5.1 Future meetings

Mark Creelman should be invited to come to the next meeting in July. Merck will be invited to the meeting in July. The next two meetings will cover Africans and treatment + testing (diagnosis and diagnostics). Ideas for topics for future meetings should be sent to the UK CAB list. The MHRA should be invited to talk at a future meeting, especially about the Yellow Card scheme.

Next meeting: Firday 18th April – focusing on African-specific treatment issues.

5.2 BHIVA conference community slot

Gus Cairns will report the outcome of topic choice in the very near future.

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Edit
Published: January 26, 2007
Last edited: January 6, 2011