The French MONCAY study recruited adults with fully suppressed
viral load (< 50 copies/ml for at least 12 months) on a regimen of
and no history of AIDS-defining illness or nadir CD4 cell count below 100
Participants were randomised to continue their existing
three-drug single-tablet regimen (n = 80) or simplify to dolutegravir 50mg once
daily (n = 78).
The primary outcome of the study was the proportion of
participants with viral load below 50 copies/ml at week 24.
Study participants had been on antiretroviral treatment for
a median of 8 years in the dolutegravir arm and 9.4 years in the three-drug
arm, having taken a median of four regimens in the dolutegravir arm and five in
the three-drug arm. Seventeen per cent of those in the monotherapy arm had
prior exposure to another integrase inhibitor, either raltegravir or elvitegravir.
No information on drug resistance or prior virological failure was reported.
The week 24 analysis of the study showed that dolutegravir
monotherapy was non-inferior to three-drug treatment; 94% of participants had a
viral load below 50 copies/ml in the monotherapy arm compared to 96% in the
three-drug arm by intent-to-treat analysis. Two cases of virological rebound
above 50 copies/ml had occurred by week 24 in the dolutegravir arm compared to
none in the three-drug arm (both participants subsequently resuppressed viral
load after returning to three-drug treatment and did not develop integrase
inhibitor resistance mutations).
One participant in the three-drug arm discontinued the trial
drugs at week 4 due to drug-related mood disturbance. The remaining
participants not counted as virally suppressed at week 24 comprised four
people who withdrew from the study and one protocol violation.
However, the week 24 results provide an excessively
optimistic picture of the effectiveness of dolutegravir monotherapy.
Participants were followed for a further 24 weeks and during that period a
further five cases of virologic rebound occurred in the monotherapy arm,
leading the study’s Data and Safety Monitoring Board to halt the study in
In two of the five cases, participants developed new
integrase inhibitor resistance mutations. In one case a participant reported
100% adherence to study treatment at week 4, but at week 36, experienced a
viral rebound to 46,300 copies/ml.
Participants who experienced virological rebound were
significantly more likely to have a low nadir CD4 cell count (p = 0.004), a low
CD4 count at study screening visit (p = 0.027) or a positive PCR signal (i.e.
viral load was detectable but too low to quantify) (p = 0.026).
The DatAIDS research group has shown previously that a
positive but unquantifiable viral load is associated with a greater risk of
viral rebound in people with viral load below 50 copies/ml. In this study,
multivariate analysis showed that participants with a positive but
unquantifiable viral load were eight times more likely to experience viral
rebound on dolutegravir monotherapy (OR 8.2, 95% CI 1.4-68.6).
Low CD4 count at screening was also associated with
virological failure (OR 1.70, 95% CI 1.1-2.8).
Ten per cent of participants in the three-drug arm and 8% in the monotherapy arm experienced drug-related adverse events.
The study investigators concluded that dolutegravir
monotherapy is not safe enough to be used as a management strategy in any
patients – but went on to question whether a study of the strategy in patients
with high CD4 cell counts and optimal virological control might still be