Trial Outcomes & Findings for Therapeutic Intensification Plus Immunomodulation to Decrease the HIV-1 Viral Reservoir (NCT NCT00976404)

NCT ID: NCT00976404

Last Updated: 2014-09-12

Results Overview

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 28 participants
• Primary outcome timeframe: 56 weeks
• Results posted on: 2014-09-12

Participant Flow

Participant milestones

Measure	ART Intensification: Maraviroc + Raltegravir ART Intensification (addition of raltegravir and maraviroc) to suppressive ART for 56 weeks	Maraviroc + Raltegravir Plus DNA + HIV-rAd5 Vaccine ART Intensification (addition of raltegravir and maraviroc for 56 weeks) PLUS immunomodulation therapy with DNA prime vaccine (Weeks 8,12,16) + HIV-recombinant Ad5-based vaccine (Week 32)
Overall Study STARTED	14	14
Overall Study COMPLETED	14	14
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Therapeutic Intensification Plus Immunomodulation to Decrease the HIV-1 Viral Reservoir

Baseline characteristics by cohort

Measure	ART Intensification: Maraviroc +Raltegravir n=14 Participants ART Intensification (addition of raltegravir and maraviroc to suppressive ART for 56 weeks)	Maraviroc + Raltegravir Plus DNA + HIV-rAd5 Vaccine n=14 Participants ART Intensification (addition of raltegravir and maraviroc for 56 weeks) PLUS immunomodulation therapy with DNA prime vaccine (Weeks 8,12,16) + HIV-recombinant Ad5-based vaccine (Week 32)	Total n=28 Participants Total of all reporting groups
Age, Continuous	49 years n=5 Participants	50 years n=7 Participants	50 years n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Sex: Female, Male Male	14 Participants n=5 Participants	14 Participants n=7 Participants	28 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	3 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) White	11 Participants n=5 Participants	9 Participants n=7 Participants	20 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
CD4 cell count	686 cells per mm^3 n=5 Participants	563 cells per mm^3 n=7 Participants	636 cells per mm^3 n=5 Participants
Time on antiretroviral treatment (ART)	13 years n=5 Participants	13 years n=7 Participants	13 years n=5 Participants
Adenovirus 5 antibody	18 titer n=5 Participants	12 titer n=7 Participants	12 titer n=5 Participants
HIV DNA	97 copies per 10^6 PBMC n=5 Participants	228 copies per 10^6 PBMC n=7 Participants	170 copies per 10^6 PBMC n=5 Participants

PRIMARY outcome

Timeframe: 56 weeks

Outcome measures

Measure	ART Intensification: Maraviroc +Raltegravir n=14 Participants ART Intensification (addition of raltegravir and maraviroc to suppressive ART for 56 weeks)	Maraviroc + Raltegravir Plus DNA + HIV-rAd5 Vaccine n=14 Participants ART Intensification (addition of raltegravir and maraviroc for 56 weeks) PLUS immunomodulation therapy with DNA prime vaccine (Weeks 8,12,16) + HIV-recombinant Ad5-based vaccine (Week 32)
Change From Baseline in HIV DNA in PBMCs at Week 56	0.00 log^10 copies per 10^6 PBMCs Interval -0.29 to 0.16	0.04 log^10 copies per 10^6 PBMCs Interval -0.11 to 0.19

SECONDARY outcome

Timeframe: Week 56

Outcome measures

Measure	ART Intensification: Maraviroc +Raltegravir n=7 Participants ART Intensification (addition of raltegravir and maraviroc to suppressive ART for 56 weeks)	Maraviroc + Raltegravir Plus DNA + HIV-rAd5 Vaccine n=6 Participants ART Intensification (addition of raltegravir and maraviroc for 56 weeks) PLUS immunomodulation therapy with DNA prime vaccine (Weeks 8,12,16) + HIV-recombinant Ad5-based vaccine (Week 32)
Change From Baseline in HIV DNA in Rectal Tissue at Week 56	0.08 log^10 copies per 10^6 cells Inter-Quartile Range 0.27 • Interval -0.06 to 0.22	-0.02 log^10 copies per 10^6 cells Inter-Quartile Range 0.37 • Interval -0.02 to 0.41

SECONDARY outcome

Timeframe: Week 56

Outcome measures

Measure	ART Intensification: Maraviroc +Raltegravir n=14 Participants ART Intensification (addition of raltegravir and maraviroc to suppressive ART for 56 weeks)	Maraviroc + Raltegravir Plus DNA + HIV-rAd5 Vaccine n=14 Participants ART Intensification (addition of raltegravir and maraviroc for 56 weeks) PLUS immunomodulation therapy with DNA prime vaccine (Weeks 8,12,16) + HIV-recombinant Ad5-based vaccine (Week 32)
Change From Baseline in CD4+ T Cell Count at Week 56	-1 cells per mm^3 Interval -144.0 to 151.0	23 cells per mm^3 Interval -100.0 to 114.0

SECONDARY outcome

Timeframe: 36 weeks

HIV-specific immunity: Interferon gamma ELISpot response to Env (clades A) at week 36 (one month after rAd5 boosting)

Outcome measures

Measure	ART Intensification: Maraviroc +Raltegravir n=14 Participants ART Intensification (addition of raltegravir and maraviroc to suppressive ART for 56 weeks)	Maraviroc + Raltegravir Plus DNA + HIV-rAd5 Vaccine n=14 Participants ART Intensification (addition of raltegravir and maraviroc for 56 weeks) PLUS immunomodulation therapy with DNA prime vaccine (Weeks 8,12,16) + HIV-recombinant Ad5-based vaccine (Week 32)
HIV Specific T-cell Response to Env	28 response per 10^6 PBMCs Standard Deviation 50	86 response per 10^6 PBMCs Standard Deviation 235

SECONDARY outcome

Timeframe: 56 weeks

Grade 3 or 4 serious adverse events related to study treatments (raltegravir, maraviroc, or HIV-recombinant Ad5-based vaccine)

Outcome measures

Measure	ART Intensification: Maraviroc +Raltegravir n=14 Participants ART Intensification (addition of raltegravir and maraviroc to suppressive ART for 56 weeks)	Maraviroc + Raltegravir Plus DNA + HIV-rAd5 Vaccine n=14 Participants ART Intensification (addition of raltegravir and maraviroc for 56 weeks) PLUS immunomodulation therapy with DNA prime vaccine (Weeks 8,12,16) + HIV-recombinant Ad5-based vaccine (Week 32)
Serious Adverse Events Attributed to Study Treatments	1 serious adverse events	3 serious adverse events

Adverse Events

Maraviroc + Raltegravir Intensification

Serious events: 1 serious events

Other events: 0 other events

Deaths: 0 deaths

Maraviroc + Raltegravir Intens. Plus DNA + HIV-rAd5 Vaccine

Serious events: 3 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Measure	Maraviroc + Raltegravir Intensification n=14 participants at risk ART Intensification (addition of raltegravir and maraviroc to suppressive ART for 56 weeks)	Maraviroc + Raltegravir Intens. Plus DNA + HIV-rAd5 Vaccine n=14 participants at risk ART Intensification (addition of raltegravir and maraviroc for 56 weeks) PLUS immunomodulation therapy with DNA prime vaccine (Weeks 8,12,16) + HIV-recombinant Ad5-based vaccine (Week 32)
Musculoskeletal and connective tissue disorders creatine kinase	7.1% 1/14 • Number of events 1 • 56 weeks	0.00% 0/14 • 56 weeks
Cardiac disorders acute coronary syndrome	0.00% 0/14 • 56 weeks	7.1% 1/14 • Number of events 1 • 56 weeks
Renal and urinary disorders Renal failure	0.00% 0/14 • 56 weeks	7.1% 1/14 • Number of events 1 • 56 weeks
Vascular disorders deep vein thrombosis	0.00% 0/14 • 56 weeks	7.1% 1/14 • Number of events 1 • 56 weeks

Other adverse events

Adverse event data not reported

Additional Information

Baiba Berzins, MPH

Northwestern University

Phone: 312-695-5012

Email: baiba@northwestern.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place