The lessons learned with CCR5-inhibitors

This drug belongs to a class of ARVs which has brought about much expectation, with little debate, and in at least one case (that of Pfizer's candidate) a sometimes harshly toned controversy.

The expectation comes from the fact that CCR5-inhibitors are part of a new treatment strategy which consists in stopping the replication of HIV by blocking the entry of the virus into the cell. Up to now, this had only be possible with T–20. By acting on the cell surface it is expected, as with T–20, that the systemic effects will be less than with ARV drugs working intercellularly. The advantage of CCR5-inhibitors is that, by being taken orally, they would not have the inconveniences of T–20.

The debate has come about from limited knowledge, contradicting studies and biased readings on the role that the distinct co-receptors, concretely CCR5 and CXCR4, have on the progression of HIV infection.

The controversy springs from the differences in opinion on when is the correct moment during the investigation process to test these new drugs in people with no prior treatment experience and who are immunologically weakened. These differences are not only seen between companies, such as Pfizer, and activists, but also among activists themselves.

The EATG, as you know, has defended that currently it does not make sense to expose people with low CD4 counts and no prior treatment history to unnecessary risks when other options are available. We therefore believe that the inclusion of these populations in these types of studies should be limited to the more advanced phases.

It was recently made public that the Drug Safety Monitoring Board (DSMB) for the Phase II/III study of maraviroc, Pfizer's investigational CCR5-inhibitor, did not find any element related to efficacy or safety in these trials that could lead to their suspension. The DSMB gave its green light for the study to continue.

This fact, which is good news for the HIV community in terms of advances in the search of future new therapeutic options, is nevertheless not in contradiction with the heart of our argument: there was no safety issue with maraviroc, but it could have been the case, as it has happened with aplaviroc. Had it been the case, including HIV-positive people with a damaged immune system and no prior treatment experience into this stage of investigation would have exposed them to an unnecessary risk.

But this is not about showing that aplaviroc case proves the EATG right or wrong. The real point is that, ten years after the general use of protease inhibitors has begun, there still needs to be a composed and joint reflection by all the different actors (activists, regulatory agencies, doctors, pharmaceutical companies) on what the clinical standards are on the development of new antiretroviral drugs and drugs with new mechanisms of action.

This reflection would serve to look for a clear-cut agreement that secures both biomedical advances and the protection of people living with HIV who contribute to these advances.

This new EATN issue includes several articles that offer elements to contribute to this reflection from different perspectives. We hope you shall enjoy them.

EATN - European AIDS Treatment News, Volume 14, II – Autumn 2005

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