Triple therapy three days a week

Could anti-hiv treatments be prescribed only two to three days a week? While the regularity of the catches – at fixed times seven days a week – is presented as an essential factor in preserving the effectiveness of the combinations of antiretrovirals, Dr. Jacques Leibowitch (Raymond Poincaré Hospital, Garches) is carrying out a pilot exploration with “intermittent” outlets. Its goal: to demonstrate that the undetectability of the viral load, a major objective of triple therapies, can be maintained with reduced protocols.

The daily dose of antivirals does not change, it is the number of weekly doses that decreases. “We started three years ago by treating 6 days a week, then gradually we went to 5, 4, then 3. At three days a week and with one to two years of hindsight, there was no virological failure, ”explains the doctor who continues to reduce the number of weekly doses, currently two. “I explore the antiviral lowlands,” he translates, insisting on extremely close virological checks (every fortnight) in the volunteers.

Who are they ? Consenting and motivated patients, whose virus had been undetectable for at least six months, says Dr. Leibowitch. But it is impossible to obtain more precise data on the number of workers, since this is a pilot experiment. “I hope to be able to do a systematic exploration, with an official clinical trial within a few months,” says the doctor. It remains to be seen how this initiative by Dr Leibowitch will be received.

“Intermittent catches, why not. But for the moment, no strategy for interrupting treatment, over a week or over a month, has proven to be effective, ”notes Professor Gilles Pialoux, head of the infectious diseases department at Tenon hospital (Paris ). In fact, in the last report on the management of people infected with HIV (Delfraissy report 2006), intermittent treatments are classified as “not recommended strategies”. The protocols referred to are quite different from the strategy explored in Dr. Leibowitch’s department.

These are either interruptions for varying durations depending on the level of CD4 lymphocytes, or interruptions of predetermined duration, for example two months every four months. Whatever the modalities, the objectives of these intermittent therapies are threefold, specifies the report: to reduce the cumulative duration of exposure to antivirals, the occurrence of undesirable and toxic effects of the treatment and the cost of these therapies. However, the results are not there.
Regarding intermittent treatments guided by the CD4 count, “two randomized clinical trials that included a large number of patients (…) recently showed a higher frequency of opportunistic infections and deaths in the“ intermittent treatment ”arm than in the“ intermittent treatment ”arm. “continuous treatment” arm, observe the authors of the report. Moreover, in another trial of CD4-guided intermittent treatment, SMART, the frequency of cardiovascular and metabolic complications was not lower in patients treated with intermittent treatment than in others. As for the other treatment attempts with interruption “at predetermined periods”, “they have so far not shown any immunological or virological benefit compared to virological treatment”. Sandrine Cabut

Questions to Dr Jacques Leibowitch, Garches hospital

The noose loosens In the world of AIDS, this immunologist is considered a maverick, who works alone. Jacques Leibowitch, he considers that he is right well before the others, as on the subject of the undetectable viremia, which he presents as a therapeutic requirement for ten years whereas the consensus on the question is very recent. His methods and the character annoy many, but his intuitions are also recognized. Will the future prove him right about the possibility of reducing triple therapy? In terms of AIDS, major upheavals seem in any case in preparation.
The idea that triple therapies, by reducing the risk of infection, could be a means of prevention is increasingly important in public health discussions. The National AIDS Council should give an opinion on this subject before the summer.
The Swiss go even further. Recently, the Swiss health authorities have bluntly recognized that patients whose viremia has been undetectable for several months are no longer contagious. Clearly, wearing a condom is no longer imposed on them to protect their partners. If the situation is not so clear in France, these new data are widely present in the minds of practitioners who help serodifferent couples to conceive.
SC