AIDS: intermittent diet is as effective as daily treatment

To improve the tolerance of antiretroviral treatments in people living with HIV, as well as to reduce costs, the ANRS Quatuor project studied the taking ofa treatment four days a week instead of once daily, as a maintenance regimen (after the initiation phase of antiretroviral treatment). It’s the first randomized study to evaluate this strategy. This innovative approach has shown its non-inferiority after almost a year of follow-up in 636 patients – a non-inferiority trial aims to show that a new treatment has sufficient efficacy compared to the reference treatment.

This trial was conducted in collaboration with Inserm research teams and AP-HP clinicians under the direction of Dr Roland Landman (Bichat hospital – Claude Bernard AP-HP, University of Paris and Inserm), Dr Pierre de Truchis (Raymond-Poincaré AP-HP Hospital, University of Versailles-Saint-Quentin-en-Yvelines) and Lambert Assoumou (Institut Pierre-Louis d’Epidemiology and Public Health, Inserm, Sorbonne University, Paris). The main article of this study was published on February 2, 2022 in The Lancet HIV.

Improving the lives of people living with HIV is one of the current major areas of research and therapeutic relief is one of them. Several strategies aimed at limiting long-term drug toxicity and improving compliance with treatment are currently being explored, with for example the use of long-term injectable treatments duration of action, the transition to a dual therapy or dose reduction. This new study investigated the intermittent treatment route, with taking treatment four consecutive days a week, followed by three “pause” days. This trial builds on a previous pilot study conducted in 2017 which showed the therapeutic success of this strategy in 96% of patients after 48 weeks.

A lighter strategy, without the introduction of new molecules

This trial is the first randomized non-inferiority study to study the efficacy and safety of the intermittent regimen (four days of treatment and three days off) compared to a standard continuous regimen (taken daily). It included, between September 2017 and January 2018, in 59 hospitals in France, 636 adult patients infected with HIV-1under tritherapy antiretroviral, with viral load less than 50 copies/mL for at least 12 months, not presenting mutations of resistance to one of the drugs used and who had not changed treatment in the four months preceding inclusion.

” Unlike other simplification approaches, such as dual therapy studies, this strategy uses the same effective and tolerated combination already in use with the patient, without introducing a new molecule.says Dr. Pierre de Truchis. The therapeutic combinations studied in Quatuor are among the most used, in particular treatments comprising integrase inhibitors. »

The participants were divided into two groups: 318 in the “intermittent” group, 318 in the “continuous” group. They had to go to medical visits at inclusion, then at weeks 4, 12, 24, 36 and 48. After 48 weeks, the results show that the intermittent diet is not inferior to the continuous diet in terms of concerns the maintenance of virological suppression and tolerance.

In fact, 96% of patients in the intermittent group and 97% in the continuous group remained in virological success (viral load below 50 copies/mL). Only six patients (2%) in the intermittent group and four (1%) in the continuous group experienced virological failure (viral load greater than 50 copies/mL). From mutations Drug resistance appeared in three of six failing people in the intermittent group and one of four people in the continuous group. Severe adverse effects (grades 3-4) were observed in 9% of patients in the intermittent group and 12% of patients in the continuous group.

Towards an improvement in the quality of life of patients

In addition, the light strategy was not associated with a risk of increased viral reservoir, nor with inflammatory activation, as evidenced by the results of the sub-studies presented in the same article. The researchers also showed an improvement in compliance and acceptability of the intermittent regimen among study participants: 59% of patients in the intermittent group saw their quality of life improved, compared to 7% in the continuous group.

A notable benefit of this strategy is also the reduction of 43% in the cost of treatments antivirals, the average annual cost going from 7,207 euros in the continuous group to 4,127 euros in the intermittent group. This represents a strong saving, knowing that, for the Île-de-France region for example, in matter cost of treatments all pathologies taken together, that against HIV represents the second budget item. The adoption of an effective and less costly therapeutic strategy is also an important issue for low- and middle-income countries.

” The strategy evaluated by this trial represents an effective alternative for patients who take their treatments well and who use a combination that limits the occurrence of resistance.reports Dr. Roland Landman. With the aging of the population and the comorbidities associated, this intermittent diet is an avenue to explore in order to limit long-term drug toxicity. Additional virological and pharmacological studies, as well as longer-term efficacy (96 weeks) are being analyzed. Furthermore, the intermittent strategy is being studied in new studies, including with dual therapy strategies as in the ANRS Duetto study currently underway. »