Kenya has the 4th largest HIV burden in the world with about 1.6 million people living with
HIV. Of these, just over 1 million are on antiretroviral therapy (ART). Current national
guidelines recommend a first line regimen composed of 2 nucleoside reverse transcriptase
inhibitors (NRTI) plus an integrase strand transfer inhibitor (INSTI) or a non-nucleoside
reverse transcriptase inhibitor(NNRTI). Second line regimens are composed of 2 NRTI plus a
ritonavir boosted protease inhibitor(PIr). This is based on evidence showing good clinical
outcomes on this regimen. PIr are associated with side effects including an increase in
cardiovascular disease risk and, have significant drug to drug interactions that complicate
management of other conditions such as tuberculosis. INSTIs have been shown in one study to
be an alternative to PIr in second line regimens when combined with fully active NRTIs. It is
not clear if this would still be the case if the activity of the NRTIs was not known. The
investigators will evaluate the efficacy of switching from a PIr to a dolutegravir based
second line ART regimen.
Hypothesis: switching virologically suppressed patients from a PIr based second line to a
dolutegravir based second line is non-inferior to continuing on a PIr based second line.
Objectives: The primary objective will be to evaluate the non-inferiority of switching to a
DTG containing regimen relative to maintaining a PI/r containing second-line regimen in
virologically suppressed, INSTI-naive HIV-1 positive adults (≥ 18 years old) as determined by
having HIV-1 RNA ≥ 50 copies/ml at week 48. Secondary objectives will be to assess the impact
of such a switch on CD4 count, safety and tolerability.
Methods: Open-label, randomized, non-inferiority, multisite trial over 48 weeks, describing
the efficacy and safety of switching from a second-line ARV regimen containing a
ritonavir-boosted protease inhibitor (PI/r) plus 2 NRTIs to DTG plus 2 NRTIs in patients with
virological suppression (HIV-1 RNA < 50 copies/ml) for at least 12 weeks and with no prior
INSTI exposure. Adult participants will be randomized at baseline to remain on their
pre-enrollment PI/r or switch to DTG. Participants will continue the NRTIs from their
pre-enrollment regimen in both arms. A total of 766 participants(388 per arm) will be
recruited from 4 sites in Kenya Conclusion: This study seeks to inform guidelines around the
efficacy and safety of alternative second line regimens.
Phase:
Phase 4
Details
Lead Sponsor:
University of Nairobi
Collaborator:
ViiV Healthcare
Treatments:
Dolutegravir HIV Protease Inhibitors Protease Inhibitors