E-DRUG: FDC ARV validated in Cameroon Clinical Trial
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[Just before the AIDS conference, some good news about FDC ARVs from Cameroon. First the MSF press release, then a comment by Andy Gray (South Africa), finally the Lancet papers. WB]
Dear E-druggers,
Please find below a press release issued by M�decins Sans Fronti�res
Switzerland, the Agence National de Recherches sur le Sida (France), the
Institut de Recherche pour le D�veloppement (France) and the Ministry of
Health of Cameroon, announcing the successful results of a clinical trial.
The study is published in today's Lancet.
The trial proves the safety and efficacy of the triple fixed dose
combination anti-AIDS drug, Triomune, from the Indian generic manufacturer
Cipla. This is the first ever clinical trial of a generic triple fixed dose
combination.
"Thanks to these findings it is now no longer possible to raise scientific
uncertainty as an objection to the widespread utilization of FDCs in the
developing countries".
The French original is first [suppressed, WB], with the English translation below.
Sean Healy
Information Officer
Campaign for Access to Essential Medicines
M�decins Sans Fronti�res
Geneva, Switzerland
tel ++41-22-8498 401
fax ++41-22-8498 404
mobile tel ++41-79-239 9271
sean.healy@geneva.msf.org
www.accessmed-msf.org
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PRESS RELEASE
An advance for HIV/AIDS treatment access in the developing countries
A fixed-dose combination of generic antiretroviral drugs is validated in a clinical trial
Combination therapy with three generic antiretroviral drugs in a single
tablet has been validated for the first time in an open clinical study in a
developing country. Follow-up of 60 patients treated in Yaound�, Cameroon,
has demonstrated the excellent efficacy and safety of a generic fixed-dose
combination. The results of this clinical trial (ANRS 1274) have been
published in The Lancet by a team of researchers from the Institut de
recherche pour le d�veloppement (IRD), Cameroon and M�decins sans
Fronti�res (MSF) Switzerland.
Generic fixed-dose combinations (FDCs) of antiretrovirals are a key factor
in access to treatment of HIV/AIDS infection in the developing world. FDCs
combine three antiretroviral drugs in a single tablet and have the twofold
advantage of being simple to use and substantially cheaper than brand name
drugs.
Lack of scientific evidence for the efficacy of FDCs has until now caused
some international AIDS donors to refuse to fund the use of these
treatments, even though they have recently been prequalified by the WHO.
ANRS 1274 is the first trial to provide scientific evidence for the
efficacy and safety of an FDC in a clinical study. The results were
published in the 3 July 2004 issue of The Lancet.
ANRS trial 1274 was conducted in two hospital centers in Yaound� (Central
Hospital and Military Hospital) within the framework of the Cameroon AIDS
Control Program by a team of researchers from the IRD, Cameroon and
MSF/Switzerland. Of the 60 HIV-infected patients included, 92% had
full-blown AIDS. The patients were treated with Triomune�, an FDC combining
generic versions of three antiretroviral drugs from two different classes:
lamivudine, stavudine and nevirapine. The treatment regimen was one tablet
morning and evening.
Triomune� is produced by the Indian pharmaceutical company Cipla. This
generic combination is now one of the most used in first-line treatment in
the developing world.
"This trial demonstrates in a perfectly rigorous manner that FDCs can be
prescribed in first-line treatment in the developing countries ", explained
Eric Delaporte of the IRD/University of Montpellier, who coordinated the
study with Sinata Koulla-Shiro of the Central Hospital and Eitel
Mpoudi-Ngole of the Military Hospital of Yaound�. The results recorded
after six months of follow-up showed that viral load was undetectable in
80% of patients. Immune reconstitution was significant, with a median
increase of 83 CD4 lymphocytes/mm3 after six months. Treatment safety was
excellent, with a single discontinuation of therapy due to adverse drug
reactions.
A pharmacological study showed that plasma antiretroviral concentrations
were fully satisfactory and equivalent to those observed in patients
treated with brand name drugs.
"This generic fixed-dose combination gives results comparable to those seen
in the developed world using triple-drug therapy comprising brand name
drugs", noted Eric Delaporte. "Thanks to these findings it is now no longer
possible to raise scientific uncertainty as an objection to the widespread
utilization of FDCs in the developing countries ". Nevertheless, "the study
must be pursued to confirm these excellent results over the longer term"
commented the Minister of Public Health in Cameroon, Mr. Urbain Olanguena
Awono.
In Cameroon, where antiretroviral therapy is state-subsidized, the monthly
cost of Triomune� treatment is 20 US dollars, compared with 35 dollars for
equivalent triple-drug therapy with brand name drugs. Cost differences
could vary by as much as 100% in other countries. The demonstrated efficacy
of generic FDCs means that from now on more HIV-infected people should be
able to access to treatment.
Source : Laurent1 C., Kouanfack2 C., Koulla-Shiro3 S., Nkou�3 N.,
Bourgeois1 A., Calmy4 A., Lactuock4 B., Nzeusseu2 V., Mougnutou3 R.,
Peytavin5 G, Li�geois1 F., Nerrienet6 E., Tardy2 M., Peeters1 M.,
Andrieux-Meyer4 I., Zekeng7/8 L., Kazatchkine9 M., Mpoudi-Ngol�3 E.,
Delaporte1 E. for ANRS 1274 study group, Effectiveness and safety of a
generic fixed-dose combination of nevirapine, stavudine, and lamivudine in
HIV-1-infected adults in Cameroon : open-label multicentre trial, in The
Lancet 2004, 364, pp.29-34
1 Institut de recherche pour le d�veloppement (IRD)/Universit� de
Montpellier, France
2 Central Hospital, Yaound�, Cameroun
3 Military Hospital, Yaound�, Cameroun
4 M�decins Sans Fronti�res, Gen�ve, Suisse
5Laboratoire de Toxicologie et de Dosage de M�dicaments, Centre Hospitalier
Universitaire Bichat Claude Bernard, Paris, France
6 Centre Pasteur, Yaound�, Cameroun
7 Laboratoire de Sant� et d'Hygi�ne Mobile, Yaound�, Cameroun
8 National AIDS Program, Yaound�, Cameroun
9 Agence nationale de recherches sur le sida, Paris, France
Research contacts:
Eric Delaporte Sinata Koulla Shiro
Eitel Mpoudi-Ngole
IRD/Montpellier H�pital Central
de Yaound� H�pital Militaire de Yaound�
T�l : 04 67 41 62 97 T�l : +237 223 38 97
T�l : +237 222 62 58
E-mail : eric.delaporte@mpl.ird.fr E-mail :
koullasinata@yahoo.fr E-mail : empoudi@yahoo.uk
Press contacts:
ANRS IRD
MSF
Marie-Christine SIMON B�n�dicte ROBERT Emma
Amado
T�l : +33 (0)1 53 94 60 30 T�l : + 33 (0) 1 48 03 75 19
T�l : +41 (0) 22 849 84 77
marie-christine.simon@anrs.fr presse@paris.ird.fr
emma.amado@geneva.msf.org
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Hi all
Here's media coverage (from Sunday Times, as "fair use") as well as the abstract of the Lancet article about a clinical trial with Cipla's Triomune (d4T, 3TC, NVP) - the full article is accessible free (as is the whole issue, which focuses on HIV issues). This trial is sure to be criticised - the number of patients was relatively small, the trial was open-label in design, the "undetectable" viral load was high by developed country standards (cf. <50 copies/ml using more modern equipment).
The Lancet also has a very useful commentary on this paper and the whole issue of standard treatment guidelines and the use of generics.
regards
Andy
Andy Gray MSc(Pharm) FPS
* Senior Lecturer
Dept of Experimental and Clinical Pharmacology
* Study Pharmacist
Centre for the AIDS Programme of Research
in South Africa (CAPRISA)
Nelson R Mandela School of Medicine
University of KwaZulu-Natal
PBag 7 Congella 4013
South Africa
Tel: +27-31-2604334/4298 Fax: +27-31-2604338
email: graya1@ukzn.ac.za or andy@gray.za.net