Study to Evaluate the Efficacy of MONotherapy of TiviCAY® Versus a Triple Therapy in HIV-1-infected Patients
Status:
Terminated
Trial end date:
2018-06-23
Target enrollment:
Participant gender:
Summary
Triple antiretroviral regimens have greatly improved the prognosis of patients living with
HIV (PLHIV). Patients virologically controlled and having a good immune restoration can have
a life expectancy close or equal to that of people not infected with HIV.[1] However, this is
under the condition of a "lifetime" maintenance of an undetectable plasma viral load (pVL)
(<50 cp/ml). On the other hand it is well established that aging increases comorbidities
among PLHIV and the burden of co-medications.[2] This also has the consequence of frequent
drug-drug interactions. In this context it is important to decrease pills burden,
side-effects and drug-drug interactions, while maintaining undetectability.
Currently, there is a strong interest for medical research to validate lightened regimens
(i.e. bithérapies [3-7] and monothérapies [8,9], particularly in a maintenance strategy, with
the primary objective of reducing burden of pills and side effects. Several monotherapy
trials using a boosted protease inhibitor (PI/r) showed high level of viral suppression, even
if this proportion was not always non-inferior to maintaining a triple therapy. [8,9]
Fortunately, when virological failure occurred under monotherapy virologic suppression was
easily restored by the addition of two NRTI. Patients who are most likely to maintain viral
suppression under a reduced scheme are those that have a high nadir (> 100 CD4 / mm3), no
previous AIDS event and a sustained virologic suppression (>12 months).
Monotherapy is the option that best reduces the burden of pills and the risk of side effects
or drug-drug interactions. It must be considered using very powerful molecule that harbor a
strong binding to its ligand in order to minimize the risk of selecting resistant mutants in
the case of virologic failure. To be as simple as possible in its use, it must be a single
agent administered as a single dose once a day and not boosted if possible. The molecule must
have very good tolerance. Finally, to be effective in viral sanctuaries this molecule should
have a good (or sufficient) diffusion to ensure effective Cmin on wild viral strains.
Dolutegravir meets all these exigences.[10] In addition, our team recently presented results
of a pilot study showing that the switch of a successful combined antiretroviral regimen to
dolutegravir monotherapy maintained undetectable viral load (<20 cp/ml) after a median of 7
months (range 6.5-10 months).