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Thursday, November 23, 2017

an excellent article

This was originally published here, in French. We provide this translation for your convenience, practical aspects may differ where you live.

An excellent article by Carole Petit

Brought to you and commented by Charles-Edouard!

Note added 08 Jan. 2018: the Conversation has since published an English version

HIV: soon the end of daily treatment for HIV-positive people?

By Caroline Petit, École Normale Supérieure (ENS)

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A pillbox (photo illustration). Shutterstock

Most HIV-positive people in France take daily treatment for life. But the possibility of easing this constraint is looming for patients on triple therapy, i.e. more than 100,000 people (France). A major trial began in September 2017 [translator's Note: English here] to confirm, in the continuation of a smaller trial, that patients can skip several [Note: consecutive] days of treatment in the week without risk to their health.

In France, some 300 patients have already switched to a "intermittent short-cycle" treatment method. For years, they have taken their medication four [Note: consecutive] days a week, instead of the seven days as per official protocol. And they are doing well.

The new trial, named Quatuor, was launched by ANRS, the French Agency for Research on HIV / AIDS and Viral Hepatitis. It aims to show that there is a benefit for the patient to take his triple therapy only four days out of seven, compared to seven days out of seven. 640 volunteers are being recruited [translator's Note: English here] in the 65 public hospitals involved in France, including the Caribbean. Dr. Pierre de Truchis, infectiologist at Raymond Poincaré Hospital in Garches (Hauts-de-Seine), is the principal investigator of this trial.

It can be assumed, however, that physicians will not wait for the results of this study to suggest to some of their patients remove three days of medication per week. The prescribing recommendations published in May 2017 [translator's Note: English here] for the medical care of people living with HIV, under the aegis of the National AIDS and Hepatitis Council (CNS) and the ANRS, go in this direction. "On a case-by-case basis, under conditions similar to those of the studies carried out, a strategy of intermittent take four or five days out of seven can be considered," say - cautiously - the experts. It should be emphasized that such a change implies a rigorous medical follow-up, with close biological examinations.

Fifteen years in favor of treatment four days a week

There is now a 15-year expertize in the safety of intermittent aleviated maintenance therapy. The main experiment is conducted since 2003 as part of a protocol called ICCARRE, an acronym for "intermittent in short cycles, anti-retroviral remain effective". This program was initiated by Dr. Jacques Leibowitch, a known figure in the fight against HIV / AIDS. He was the instigator, in France, of tritherapy which, in 1996, transformed a mortal pathology into a chronic affection.

Patients followed by Dr. Leibowitch and his colleagues at the Raymond Poincaré Hospital have thus gone from seven to five days of treatment a week, then to four. In spite of this, their viral load remained below the detection level. These results for 48 patients were considered sufficiently robust by the international scientific community to be published in 2010 in the Faseb Journal. The same experiment led to a second publication in 2015, with a greater number of patients (94, precisely) and more years of hindsight.

That year, the direction of Assistance Publique-Hôpitaux de Paris (AP-HP) and Versailles Saint-Quentin University, the two employers of Dr. Leibowitch, jointly invested in the filing of two international patents , one for so-called "maintenance" tritherapies at four days a week and less [translator's Note: English Patent_US20120283177], and the other for the use of innovative quadruple therapies for this purpose[translator's Note: English patent_US20120270828].

A first clinical trial nationwide

Convinced by the first results of the Iccarre protocol, ANRS launched in 2014 a two-year clinical trial conducted in 17 centers in France, named 4D (English, four days). The doctors received many applications to participate in this trial, to the point that they had to refuse, as entrusted to me by Professor Christian Perronne, the principal investigator. The findings were presented at the 2016 International AIDS Conference in Durban, South Africa [translator's Note: English poster]. They indicate that 96 of the 100 patients in the trial who followed the dosing regimen with four consecutive days out of seven did so successfully. 3 patients had a new detectable viral load by the fourth week of the study. It has become undetectable again, with the return to a daily treatment regimen. 1 patient left the study.

The results encouraged the ANRS to continue in this direction with the Quatuor trial. The new study has, this time, a "control" group consisting of patients who will continue to take their treatment seven days out of seven for 48 weeks, to allow for a comparison. This methodology meets the requirements of health authorities for the level of evidence to be provided before a change in their prescribing recommendations.

"Quartuor seeks to demonstrate that the four-day-seven strategy is non-inferior to the seven-day-seven strategy, in other words that at equal effectiveness, patients in the Aleviation group will get secondary benefits from this protocol. 'side effects, better compliance ...)', said the ANRS on September 1 on its website.

Daily treatment, sometimes badly perceived

In fact, the stress of taking a daily treatment can be a bad experience. Many patients are less regular in their dosings after several years of treatment - a problem for many chronic diseases. It is very risky for patients to reduce their own treatment without medical supervision. [Translator's Note: this is a statement which we oppose]

In addition, the use of anti-retroviral drugs is sometimes accompanied by side effects such as nausea and diarrhea, as well as fatigue. Dosing reduction can be accompanied by a reduction in these effects.

Switching to four [Note: consecutive] days a week is the equivalent of five months without medication for the patient.

What will happen now? It is only after the results of the Quatuor trial, at the earliest in 2019, that the practice of four days out of seven can officially be recommended in France. [Translator's Note: it is, in fact, already recommanded - Morlat 2016 - at time of this translation] Abroad, it has not drawn much interest. Not even in the United States, the country that initiated first, in 2001, a path to Short Cycle that Dr. Jacques Leibowitch had followed.

It is surprising that this reduction in treatment is still, more than fifteen years later, at the experimental stage.

It must be said that in France, the historical patients associations in HIV / AIDS have not grasped this issue. They focused on other priorities such as preventive treatments, pre-exposure prophylaxis (PreP). On the other hand, patients of Dr. Leibowitch following a lighter treatment created an association, The Friends of Iccarre, under the impetus of artist Richard Cross. It aims to promote intermittent therapeutic aleviation for all [translator's Note: English abstract].

The doctor free to prescribe according to the code of medical ethics

Only a few AIDS clinicians in France have begun to aleviate their prescriptions. Article 8 of the code of medical ethics allows them: "Within the limits fixed by the law and taking into account the acquired data of the science, a doctor is free of his prescriptions which will be those which he considers the most appropriate in the circumstance".

The persistence of the seven days a week regime can be explained, in my opinion, by a resistance to change - which is not unique to physicians - and by the difficulty of challenging a long-standing rule in the medical community. One can imagine that other factors at play: obviously, patients prudence and of doctors before a level of proof considered as insufficient according to the standards in force; the fear of doctors regarding the judiciarization of medicine; or the influence of the pharmaceutical industry on the strategic choices by medical authorities.

Seven to four days of treatment represents 42% fewer drugs. This would result in savings of around 500 million euros for the French health system each year (based on 100,000 patients on treatment, with an average cost per patient and per month of 1,000 euros on average). Globally, the issue of cost meets ethical and humanitarian concerns at a time when 22 million HIV-positive people still do not access triple therapy.

For his part, Dr. Jacques Leibowitch pushes further the alleviation of treatments, in accordance with the code of medical ethics, and for patients who so wish. It reduces medication, depending on the case, to three, two or a day only a week. With this new protocol called "big" Iccarre, he pursues the goal of finding for each patient the right dose, both necessary and sufficient. In accordance with The principle: Primum non nocere ("first do no harm") which was dear to Hippocrates?

Caroline Petit, Biologist, CNRS researcher at IHEST, École Normale Supérieure (ENS)

The original version of this article was published on The Conversation.

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