Clinical Trial DOMONO

Clinical Trial DOMONO

This paper was originally published here, in French. We provide the google translation for your convenience. Proper translation will come soon. Some practical aspects may differ where you live.



See project description

abstract can be found publication of abstracts: HIV-glasgow 2016:

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Switching from cART to dolutegravir (DTG) maintenance monotherapy in virologically suppressed HIV-1 infected adults: a randomized multicenter, non-inferiority clinical trial (DOMONO) Ingeborg Wijting ... Bart Rijnder

Here is the abstract:

Introduction: DTG-containing cART showed equal or superior viral suppression when compared with raltegravir-, efavirenz- or darunavir-containing cART and is one of the preferred regimens in current treatment guidelines. As short- and long-term side effects of cART remain a concern, maintenance HIV therapy with fewer drugs is an attractive goal. Given the high genetic barrier to resistance, DTG is a potential candidate for maintenance monotherapy.

Materials/methods: In a randomized, open-label, multicentre study, we compared DTG maintenance monotherapy (50 mg QD DOLUDOLUMONO) with continued cART (con-cART). After 24 weeks, the con-cART patients switched to DOLUMONO as well (‘delayed switch’). Eligible patients were on cART and suppressed (B50 c/mL) for 6 months, had a CD4 nadir 200 cells/mL, HIV RNA zenith B100,000 copies/mL, no history of virologic failure and HBV immune. The primary endpoint was the proportion of patients with virologic suppression at 24 weeks defined as a viral load (VL) B200 copies/mL in the on treatment population. With an anticipated viral suppression of 95% on con-cART, 104 patients were needed to demonstrate non-inferiority of DOLUMONO (delta 0.12, power 80%, alfa 0.025). Predefined secondary endpoints were (1) proportion with a VL B50 copies/mL after 24 weeks of DOLUMONO versus con-cART and (2) proportion with a VL B200 copies/mL and B50 copies/mL after 12, 24 and 48 weeks of DOLUMONO in the entire study population ( immediate delayed switchers combined). The study was registered as NCT02401828.

Results: The 104 patients included were predominantly male (89%), had a median age of 45, a HIV RNA zenith of 21,840 copies/mL (IQR 7045 59,550), CD4 nadir of 345 cells/mL (IQR 270 500) and on cART for 40 months. One patient discontinued DTG at 12 weeks (with VL B50 copies/mL) for disturbed sleep. Of 103, 102 patients had a VL B200 copies/mL at week 24: 98% (49/50) on DOLUMONO and 100% (53/53) on con-cART. DOLUMONO was therefore noninferior to con-cART (delta 2% with exact 95% CI 12 5%). The single patient on DOLUMONO with virologic failure had a VL at 4 weeks of 70,000 copies/mL despite 100% compliance by pill-count and therapeutic DTG plasma levels of 1.3 mg/L. Integrase sequencing on stored pre-cART plasma and at DTG failure did not reveal resistance-associated mutations. At 24 weeks, more patients on DOLUMONO had low level viraemia (VL of 50 200 copies/mL in 3/49 vs. 0/53, p 0.12). Week 24 results of all 104 patients on DOLUMONO ( immediate and delayed switchers combined) will be presented.

Conclusions: In a carefully selected HIV-1 population on suppressive cART, DTG monotherapy was well tolerated and noninferior to cART. Although these results are promising, longer follow-up is needed as more patients on DOLUMONO had low-level viremia.