Control of HIV infection: an alternative to daily treatment?
First results from the ANRS QUATUOR trial
While it is possible to control HIV infection, this has hitherto been achieved using daily antiretroviral (ARV) treatment. However, the ANRS 170 QUATUOR trial, led by Dr Pierre de Truchis (Hôpital Raymond Poincaré, APHP) and Dr Roland Landman (IAME, UMR 1137, Inserm, Université Paris Diderot, Sorbonne Paris Cité, Hôpital Bichat, AP-HP), is exploring a new de-escalation of treatment in patients successfully controlled by triple therapy. In 647 patients with HIV infection controlled by ARV treatment for over one year, the study sponsored by ANRS has shown the non-inferiority of treatment de-escalated to four days a week, compared with the same treatment administered daily 7/7. These results are presented today by Dr Roland Landman at the 10th IAS Conference on HIV Science (Mexico City, 21-24 July 2019).
Antiretroviral (ARV) treatments control HIV when the infection is detected before an advanced stage, but currently must be administered daily and are therefore subject to the attendant potential side effects and constraints.
The QUATUOR study shows that daily intake of ARVs may not be indispensable. This study follows on from the ANRS 4D pilot trial, which in 2017 showed in patients on effective ARV for more than one year that viral replication was still controlled (96% success) when treatment was de-escalated to 4 days a week.
Following these positive results, the open randomized study ANRS 170 QUATUOR was set up under the direction of Pierre de Truchis and Roland Landman, with assistance from the IMEA (Institut de Médecine et Epidémiologie Appliquée) and methodological support from the CMG directed by Lambert Assoumou (Institut Pierre Louis d’Epidémiologie et Santé Publique IPLESP, Inserm and Sorbonne Université). Following rapid recruitment of patients in 59 centers in France from September 2017 to January 2018, ANRS 170 QUATUOR compared two groups of 318 patients, one treated conventionally (every day, 7 days a week) and the second receiving ARV therapy de-escalated to 4 days out of 7, with a 3-day interruption each weekend.
QUATUOR showed that in patients with well-controlled HIV infection, with an undetectable viral load for 5.8 years on average, treatment for 4 days a week, irrespective of the triple therapy used, was statistically non-inferior to daily treatment. After 48 weeks of follow-up, 95.6% of the patients in the 4 days a week study arm had an undetectable viral load, compared with 97.2% in the daily treatment arm. Virologic failure was seen in only 6 patients in the 4 days a week study arm and in 4 patients in the daily treatment arm. In view of these results, we can envision de-escalation of treatment to 4 days a week in patients whose HIV infection has been controlled by ARV for several years.
Although no between-group difference in safety was seen at 48 weeks, such de-escalation of treatment constitutes a potential option for the management of patients with HIV infection controlled by triple therapy, and also substantially reduces the cost of treatment.
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