HIV-1 Infected Patients, Phase II Trial, Dual Combination Doravirine/Raltegravir Open Label
Status:
Recruiting
Trial end date:
2022-10-30
Target enrollment:
Participant gender:
Summary
The objective of antiretroviral therapy (ART) is the maintenance of HIV viral suppression,
the optimal condition to prevent disease progression, to optimize immune restoration, to
prevent the development of viral resistance and to reduce viral transmission. Antiretroviral
therapy has to be maintained long life over decades in the absence of strategies for HIV
cure. This is why the long-term cumulative toxicity of ARV drugs is a major issue. Indeed as
a consequence of potent ART strategies, in 2011 over 88% of patients on ART in the French
Hospital database (ANRS CO4 FHDH) achieved viral suppression with HIV-RNA plasma viral load <
50 copies/mL and nearly 60% had CD4 > 500/mm3. As a consequence of massive reduction of
mortality and morbidity related to HIV, infected patients are aging with 40% of patients over
50 years of age in the ANRS CO4 FHDH.
The current standard-of-care for antiretroviral therapy consists in a triple drug combination
with two nucleoside reverse transcriptase inhibitors (NRTIs) plus either a non-nucleoside
reverse transcriptase inhibitor (NNRTI), a protease inhibitor (PI), or an integrase inhibitor
(INSTI). NRTIs and PIs have been associated to cumulative long-term toxicity such as bone and
renal disorders related to tenofovir and increased cardio-vascular risk with PIs. In general
population, aging is associated with well-known comorbidities such as bone demineralization,
increased incidence of cardio or cerebrovascular disease, diabetes, renal dysfunction. HIV
infected patients are at a greater risk for such abnormalities. Another crucial concern is
the high probability of drug-drug interactions in HIV-infected patients, between ART and
comedications.
Alternative strategies are needed, which must address the following questions: how to
maintain the control of HIV viral replication while minimizing the occurrence of long-term
clinical and metabolic complications, and minimizing the risk of drug-drug interactions?
This study is an open label, randomized, switch study over 96 weeks in which virally
suppressed patients on a stable combined ART regimen will be randomized (2:1) to an immediate
switch to doravirine/raltegravir (immediate switch group) or to the maintaining of their
current ART followed by a switch to doravirine/raltegravir at W48 (delayed switch group).
Patients will be followed during 96 weeks.
Phase:
Phase 2
Details
Lead Sponsor:
Centre de Recherches et d'Etude sur la Pathologie Tropicale et le Sida