Efficacy of VHM After Treatment Interruption in Subjects Initiating ART During Acute HIV Infection

Study site:

This will be a single-center proof-of-concept study in which recruitment and follow-up of volunteers will be done at the Thai Red Cross AIDS Research Centre (TRC-ARC).

Subject Population:

Subjects aged 18-60 years old, who initiated ART during acute HIV infection and have maintained viral suppression (HIV RNA \< 50 copies/ml) for at least 28 weeks prior will be asked to enroll in the study. The subjects must have CD4 ≥ 450 cells/µl, and EKG and laboratory values within acceptable ranges.

Sample Size:

Fifteen subjects will be enrolled randomized 2:1 to VHM + ART (N=10) versus ART (N=5) only.

Study Design An exploratory, open label, randomized study of vorinostat/hydroxychloroquine/maraviroc (VHM) + ART versus ART only.

Study Drug Vorinostat will be administered at 400mg orally every 24h for 3 cycles, each of 14 days with an interim rest-period of 14 days between each cycle over a period of 10 weeks. Hydroxychloroquine (HCQ) will be administered at a dose of 200mg 2X/daily during the course of vorinostat administration for 10 weeks. Maraviroc will be administered at 600 mg 2X/daily on the same schedule as HCQ. This dose of maraviroc is based on its concomitant use with efavirenz. Dosing will be adjusted as appropriate should the subject be on an integrase inhibitor or a protease inhibitor instead of efavirenz due to intolerance to the drug or primary non-nucleoside reverse-transcriptase inhibitor (NNRTI) resistance. Any standard ART regimen may be used. However, it is expected that the majority of subjects will be on 2 nucleos(t)ide reverse-transcriptase inhibitors (NRTI) \[emtricitabine (FTC) and tenofovir (TDF) and 1 NNRTI \[efavirenz (EFV)\]. ART will be administered at the following doses: FTC, 200mg 1X/day or 3TC, 300mg 1X/day; TDF, 300mg 1X/day and EFV, 600mg 1X/day.

In subjects on NNRTI-based therapy, the NNRTI will be interrupted at week 8 and the rest of the regimens will be interrupted at week 10. In order to prevent NNRTI resistance, protease inhibitor replacement therapy with darunavir (900 mg 1X/day with ritonavir 100 mg 1X/day) will be given between weeks 8 and 10 and maraviroc will be reduced from 1200mg/day to 300mg/day.

Study Duration on Protocol: