Trial Outcomes & Findings for Live Zoster Vaccine in HIV-Infected Adults on Antiretroviral Therapy (NCT NCT00851786)

Last Updated: 2021-11-04

Results Overview

Although the study was designed as a randomized trial, it was not powered to detect safety related differences between treatment arms. The safety of ZOSTAVAX was determined by comparing the number of subjects from the active arm who experienced safety endpoint to the number from a pre-specified decision rule, which was calculated based on a similar population and calibrated using the number of safety endpoints observed from the placebo arm. The pre-specified decision rule is that ZOSTAVAX would be considered to have acceptable safety if no more than 18 subjects experience a study-defined composite safety endpoint.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

395 participants

Primary outcome timeframe

During the 6 week study period after receipt of any dose of ZOSTAVAX

Results posted on

2021-11-04

Participant Flow

The first person was accrued on 04/29/2009. Accrual in the high CD4 stratum was closed in 02/2010 (n=203; 152 on ZOSTAVAX and 51 on placebo). Accrual to the low CD4 stratum proceeded more slowly with the last subject enrolled on 06/30/2011 (n=192; 144 on ZOSTAVAX and 48 on placebo). All 43 participating sites enrolled at least 1 subject.

Enrollment took place in two stages: Stage I were to enroll 48 subjects (24 in the low CD4 stratum and 24 in the high CD4 stratum). Subjects were randomized 3:1 to receive ZOSTAVAX or placebo. Stage II were to enroll approximately 352 subjects who would be randomized and stratified according to the same schedule.

Participant milestones

Participant milestones
Measure	ZOSTAVAX Participants with CD4 cell counts of 200 cells/uL or greater in Stage 1 and 2, stratified by CD4 cell counts (200-349 cells/uL vs. \>=350 cells/uL), will be given one dose of ZOSTAVAX (Zoster Vaccine Live) at Day 0 and Week 6 and will be followed for at least 42 days after each vaccination after which a safety assessment will be conducted.	Placebo Participants with CD4 cell counts of 200 cells/uL or greater in Stage 1 and 2, stratified by CD4 cell counts (200-\<349 cells/uL vs. \>=350 cells/uL), will be given one dose of placebo at Day 0 and Week 6 and will be followed for at least 42 days after each vaccination afer which a safety assessment will be conducted
Overall Study STARTED	296	99
Overall Study COMPLETED	291	97
Overall Study NOT COMPLETED	5	2

Reasons for withdrawal

Reasons for withdrawal
Measure	ZOSTAVAX Participants with CD4 cell counts of 200 cells/uL or greater in Stage 1 and 2, stratified by CD4 cell counts (200-349 cells/uL vs. \>=350 cells/uL), will be given one dose of ZOSTAVAX (Zoster Vaccine Live) at Day 0 and Week 6 and will be followed for at least 42 days after each vaccination after which a safety assessment will be conducted.	Placebo Participants with CD4 cell counts of 200 cells/uL or greater in Stage 1 and 2, stratified by CD4 cell counts (200-\<349 cells/uL vs. \>=350 cells/uL), will be given one dose of placebo at Day 0 and Week 6 and will be followed for at least 42 days after each vaccination afer which a safety assessment will be conducted
Overall Study Withdrawal by Subject	0	1
Overall Study Protocol Violation	0	1
Overall Study Lost to Follow-up	1	0
Overall Study Incarceration	1	0
Overall Study Site Closure	1	0
Overall Study Cannot Adhere to Protocol Requirement	2	0

Baseline Characteristics

Live Zoster Vaccine in HIV-Infected Adults on Antiretroviral Therapy

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	ZOSTAVAX n=296 Participants Participants with CD4 cell counts of 200 cells/uL or greater in Stage 1 and 2, stratified by CD4 cell counts (200-349 cells/uL vs. \>=350 cells/uL), will be given one dose of ZOSTAVAX (Zoster Vaccine Live) at Day 0 and Week 6 and will be followed for at least 42 days after each vaccination after which a safety assessment will be conducted.	Placebo n=99 Participants Participants with CD4 cell counts of 200 cells/uL or greater in Stage 1 and 2, stratified by CD4 cell counts (200-\<349 cells/uL vs. \>=350 cells/uL), will be given one dose of placebo at Day 0 and Week 6 and will be followed for at least 42 days after each vaccination afer which a safety assessment will be conducted	Total n=395 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	285 Participants n=5 Participants	94 Participants n=7 Participants	379 Participants n=5 Participants
Age, Categorical >=65 years	11 Participants n=5 Participants	5 Participants n=7 Participants	16 Participants n=5 Participants
Age, Continuous	49 years n=5 Participants	49 years n=7 Participants	49 years n=5 Participants
Sex: Female, Male Female	44 Participants n=5 Participants	18 Participants n=7 Participants	62 Participants n=5 Participants
Sex: Female, Male Male	252 Participants n=5 Participants	81 Participants n=7 Participants	333 Participants n=5 Participants
Race/Ethnicity, Customized White Non-Hispanic	141 participants n=5 Participants	44 participants n=7 Participants	185 participants n=5 Participants
Race/Ethnicity, Customized Black Non-Hispanic	90 participants n=5 Participants	26 participants n=7 Participants	116 participants n=5 Participants
Race/Ethnicity, Customized Hispanic (regardless of race)	60 participants n=5 Participants	27 participants n=7 Participants	87 participants n=5 Participants
Race/Ethnicity, Customized Asian, Pacific islander	1 participants n=5 Participants	1 participants n=7 Participants	2 participants n=5 Participants
Race/Ethnicity, Customized American Indian, Alaskan Native	2 participants n=5 Participants	1 participants n=7 Participants	3 participants n=5 Participants
Race/Ethnicity, Customized More than one race	1 participants n=5 Participants	0 participants n=7 Participants	1 participants n=5 Participants
Race/Ethnicity, Customized Unknown/missing	1 participants n=5 Participants	0 participants n=7 Participants	1 participants n=5 Participants
IV drug history Never	244 participants n=5 Participants	86 participants n=7 Participants	330 participants n=5 Participants
IV drug history Previously	52 participants n=5 Participants	13 participants n=7 Participants	65 participants n=5 Participants
Nadir CD4	197 cells/µL n=5 Participants	178 cells/µL n=7 Participants	188 cells/µL n=5 Participants
Screen CD4	373 cells/µL n=5 Participants	353 cells/µL n=7 Participants	372 cells/µL n=5 Participants
Entry CD4	399 cells/µL n=5 Participants	362 cells/µL n=7 Participants	394 cells/µL n=5 Participants
HIV-1 RNA	1.68 log10 copies/mL n=5 Participants	1.68 log10 copies/mL n=7 Participants	1.68 log10 copies/mL n=5 Participants
Prior History of AIDS Yes	288 participants n=5 Participants	97 participants n=7 Participants	385 participants n=5 Participants
Prior History of AIDS No	8 participants n=5 Participants	2 participants n=7 Participants	10 participants n=5 Participants
History of Chickenpox >5 years	219 participants n=5 Participants	77 participants n=7 Participants	296 participants n=5 Participants
History of Chickenpox Zoster/no Chickpox	17 participants n=5 Participants	7 participants n=7 Participants	24 participants n=5 Participants
History of Chickenpox None	60 participants n=5 Participants	15 participants n=7 Participants	75 participants n=5 Participants
History of most recent Zoster 0-1 year	2 participants n=5 Participants	1 participants n=7 Participants	3 participants n=5 Participants
History of most recent Zoster >1-2 years	13 participants n=5 Participants	1 participants n=7 Participants	14 participants n=5 Participants
History of most recent Zoster >2-5 years	23 participants n=5 Participants	7 participants n=7 Participants	30 participants n=5 Participants
History of most recent Zoster >5 years	65 participants n=5 Participants	22 participants n=7 Participants	87 participants n=5 Participants
History of most recent Zoster None	193 participants n=5 Participants	68 participants n=7 Participants	261 participants n=5 Participants
Duration from Historary Retinal Necrosis >5 years	2 participants n=5 Participants	0 participants n=7 Participants	2 participants n=5 Participants
Duration from Historary Retinal Necrosis None	294 participants n=5 Participants	99 participants n=7 Participants	393 participants n=5 Participants

PRIMARY outcome

Timeframe: During the 6 week study period after receipt of any dose of ZOSTAVAX

Population: Subjects who received at least one dose of study vaccine/placebo

Outcome measures

Outcome measures
Measure	ZOSTAVAX n=295 Participants Participants with CD4 cell counts of 200 cells/uL or greater in Stage 1 and 2, stratified by CD4 cell counts (200-349 cells/uL vs. \>=350 cells/uL), will be given one dose of ZOSTAVAX (Zoster Vaccine Live) at Day 0 and Week 6 and will be followed for at least 42 days after each vaccination after which a safety assessment will be conducted.	Placebo n=97 Participants Participants with CD4 cell counts of 200 cells/uL or greater in Stage 1 and 2, stratified by CD4 cell counts (200-\<349 cells/uL vs. \>=350 cells/uL), will be given one dose of placebo at Day 0 and Week 6 and will be followed for at least 42 days after each vaccination afer which a safety assessment will be conducted
Number of Participants With Composite Safety Endpoint of the Occurrence of Serious Adverse Events (SAEs) or Division of AIDS (DAIDS) Grade 3 and 4 Signs and Symptoms, Excluding SAEs Related to Trauma	15 participants Interval 0.029 to 0.082	2 participants Interval 0.003 to 0.073

SECONDARY outcome

Timeframe: Within 6 weeks following one or two doses of ZOSTAVAX

Population: Subjects with both baseline gpELISA result and at least one post vaccination gpELISA result available

VZV antibody titer measured by gpELISA after one or two doses of ZOSTAVAX/placebo

Outcome measures

Outcome measures
Measure	ZOSTAVAX n=280 Participants Participants with CD4 cell counts of 200 cells/uL or greater in Stage 1 and 2, stratified by CD4 cell counts (200-349 cells/uL vs. \>=350 cells/uL), will be given one dose of ZOSTAVAX (Zoster Vaccine Live) at Day 0 and Week 6 and will be followed for at least 42 days after each vaccination after which a safety assessment will be conducted.	Placebo n=96 Participants Participants with CD4 cell counts of 200 cells/uL or greater in Stage 1 and 2, stratified by CD4 cell counts (200-\<349 cells/uL vs. \>=350 cells/uL), will be given one dose of placebo at Day 0 and Week 6 and will be followed for at least 42 days after each vaccination afer which a safety assessment will be conducted
VZV Antibodies as Measured by gpELISA Baseline	5.68 log gpELISA antibody titer Standard Deviation 1.03	5.52 log gpELISA antibody titer Standard Deviation 1.26
VZV Antibodies as Measured by gpELISA 6 weeks after 1st ZOSTAVAX/Placebo	6.28 log gpELISA antibody titer Standard Deviation 0.92	5.57 log gpELISA antibody titer Standard Deviation 1.27
VZV Antibodies as Measured by gpELISA 6 weeks after 2nd ZOSTAVAX/Placebo	6.27 log gpELISA antibody titer Standard Deviation 0.87	5.52 log gpELISA antibody titer Standard Deviation 1.27

SECONDARY outcome

Timeframe: Entry, Week 6, Week 12

Population: Number of participants with ELISpot results available at entry and at the post-entry week (week 6 or week 12, respectively).

VZV-specific cellular immune responses in peripheral blood mononuclear cells (PBMC) were tested by ELISpot assay in a subset of participants pooled across CD4 strata. GMFR is the geometric mean of the ratios of Week 6 or Week 12 post-vaccination antibody to the pre-vaccination antibody.

Outcome measures

Outcome measures
Measure	ZOSTAVAX n=56 Participants Participants with CD4 cell counts of 200 cells/uL or greater in Stage 1 and 2, stratified by CD4 cell counts (200-349 cells/uL vs. \>=350 cells/uL), will be given one dose of ZOSTAVAX (Zoster Vaccine Live) at Day 0 and Week 6 and will be followed for at least 42 days after each vaccination after which a safety assessment will be conducted.	Placebo n=18 Participants Participants with CD4 cell counts of 200 cells/uL or greater in Stage 1 and 2, stratified by CD4 cell counts (200-\<349 cells/uL vs. \>=350 cells/uL), will be given one dose of placebo at Day 0 and Week 6 and will be followed for at least 42 days after each vaccination afer which a safety assessment will be conducted
Geometric Mean Fold Rise (GMFR) in VZV ELISpot Responses Week 6 GMFR	1.8 fold rise Interval 0.8 to 3.7	0.4 fold rise Interval 0.2 to 1.1
Geometric Mean Fold Rise (GMFR) in VZV ELISpot Responses Week 12 GMFR	3.8 fold rise Interval 1.8 to 8.0	1.1 fold rise Interval 0.3 to 3.4

Adverse Events

ZOSTAVAX

Serious events: 15 serious events

Other events: 98 other events

Deaths: 1 deaths

Placebo

Serious events: 7 serious events

Other events: 15 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	ZOSTAVAX n=296 participants at risk Participants with CD4 cell counts of 200 cells/uL or greater in Stage 1 and 2, stratified by CD4 cell counts (200-349 cells/uL vs. \>=350 cells/uL), will be given one dose of ZOSTAVAX (Zoster Vaccine Live) at Day 0 and Week 6 and will be followed for at least 42 days after each vaccination after which a safety assessment will be conducted.	Placebo n=99 participants at risk Participants with CD4 cell counts of 200 cells/uL or greater in Stage 1 and 2, stratified by CD4 cell counts (200-\<349 cells/uL vs. \>=350 cells/uL), will be given one dose of placebo at Day 0 and Week 6 and will be followed for at least 42 days after each vaccination afer which a safety assessment will be conducted
General disorders Injection site erythema	11.5% 34/296 • From study entry to study exit, approximately 24 weeks.	0.00% 0/99 • From study entry to study exit, approximately 24 weeks.
General disorders Injection site pain	17.6% 52/296 • From study entry to study exit, approximately 24 weeks.	4.0% 4/99 • From study entry to study exit, approximately 24 weeks.
General disorders Injection site swelling	5.4% 16/296 • From study entry to study exit, approximately 24 weeks.	0.00% 0/99 • From study entry to study exit, approximately 24 weeks.
General disorders Pyrexia	4.4% 13/296 • From study entry to study exit, approximately 24 weeks.	8.1% 8/99 • From study entry to study exit, approximately 24 weeks.
Musculoskeletal and connective tissue disorders Pain in extremity	5.7% 17/296 • From study entry to study exit, approximately 24 weeks.	1.0% 1/99 • From study entry to study exit, approximately 24 weeks.
Nervous system disorders Headache	6.1% 18/296 • From study entry to study exit, approximately 24 weeks.	4.0% 4/99 • From study entry to study exit, approximately 24 weeks.

Additional Information

ACTG Clinicaltrials.gov Coordinator

ACTG Network Coordinating Center, Social and Scientific Systems, Inc.

Phone: (301) 628-3313

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee In accordance with the Clinical Trials Agreement between NIAID (DAIDS) and company collaborators, NIAID (DAIDS) provides companies with a copy of any abstract, press release, or manuscript prior to submission for publication with sufficient time for company review and comment. The publication/other disclosure can be delayed for up to 30 additional business days for manuscripts and five (5) business days for abstracts, to preserve U.S. or foreign patent or other intellectual property rights.
Publication restrictions are in place

Restriction type: OTHER

Measure	ZOSTAVAX n=296 participants at risk Participants with CD4 cell counts of 200 cells/uL or greater in Stage 1 and 2, stratified by CD4 cell counts (200-349 cells/uL vs. \>=350 cells/uL), will be given one dose of ZOSTAVAX (Zoster Vaccine Live) at Day 0 and Week 6 and will be followed for at least 42 days after each vaccination after which a safety assessment will be conducted.	Placebo n=99 participants at risk Participants with CD4 cell counts of 200 cells/uL or greater in Stage 1 and 2, stratified by CD4 cell counts (200-\<349 cells/uL vs. \>=350 cells/uL), will be given one dose of placebo at Day 0 and Week 6 and will be followed for at least 42 days after each vaccination afer which a safety assessment will be conducted
Cardiac disorders Atrial fibrillation	0.00% 0/296 • From study entry to study exit, approximately 24 weeks.	1.0% 1/99 • From study entry to study exit, approximately 24 weeks.
Cardiac disorders Atrial flutter	0.00% 0/296 • From study entry to study exit, approximately 24 weeks.	1.0% 1/99 • From study entry to study exit, approximately 24 weeks.
Cardiac disorders Myocardial infarction	0.34% 1/296 • From study entry to study exit, approximately 24 weeks.	0.00% 0/99 • From study entry to study exit, approximately 24 weeks.
Gastrointestinal disorders Pancreatitis acute	0.34% 1/296 • From study entry to study exit, approximately 24 weeks.	0.00% 0/99 • From study entry to study exit, approximately 24 weeks.
Infections and infestations Bronchitis	0.00% 0/296 • From study entry to study exit, approximately 24 weeks.	1.0% 1/99 • From study entry to study exit, approximately 24 weeks.
Infections and infestations Bronchopulmonary aspergillosis	0.34% 1/296 • From study entry to study exit, approximately 24 weeks.	0.00% 0/99 • From study entry to study exit, approximately 24 weeks.
Infections and infestations Cellulitis	0.34% 1/296 • From study entry to study exit, approximately 24 weeks.	0.00% 0/99 • From study entry to study exit, approximately 24 weeks.
Infections and infestations Herpes zoster	0.34% 1/296 • From study entry to study exit, approximately 24 weeks.	0.00% 0/99 • From study entry to study exit, approximately 24 weeks.
Infections and infestations Osteomyelitis	0.00% 0/296 • From study entry to study exit, approximately 24 weeks.	1.0% 1/99 • From study entry to study exit, approximately 24 weeks.
Infections and infestations Pneumonia	0.34% 1/296 • From study entry to study exit, approximately 24 weeks.	1.0% 1/99 • From study entry to study exit, approximately 24 weeks.
Infections and infestations Urinary tract infection	0.34% 1/296 • From study entry to study exit, approximately 24 weeks.	0.00% 0/99 • From study entry to study exit, approximately 24 weeks.
Injury, poisoning and procedural complications Gun shot wound	0.34% 1/296 • From study entry to study exit, approximately 24 weeks.	0.00% 0/99 • From study entry to study exit, approximately 24 weeks.
Injury, poisoning and procedural complications Ligament sprain	0.34% 1/296 • From study entry to study exit, approximately 24 weeks.	0.00% 0/99 • From study entry to study exit, approximately 24 weeks.
Musculoskeletal and connective tissue disorders Osteonecrosis	0.00% 0/296 • From study entry to study exit, approximately 24 weeks.	1.0% 1/99 • From study entry to study exit, approximately 24 weeks.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) B-cell lymphoma	0.34% 1/296 • From study entry to study exit, approximately 24 weeks.	0.00% 0/99 • From study entry to study exit, approximately 24 weeks.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Hepatic neoplasm malignant	0.00% 0/296 • From study entry to study exit, approximately 24 weeks.	1.0% 1/99 • From study entry to study exit, approximately 24 weeks.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Lung carcinoma cell type unspecified recurrent	0.34% 1/296 • From study entry to study exit, approximately 24 weeks.	0.00% 0/99 • From study entry to study exit, approximately 24 weeks.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Malignant melanoma	0.34% 1/296 • From study entry to study exit, approximately 24 weeks.	0.00% 0/99 • From study entry to study exit, approximately 24 weeks.
Nervous system disorders Migraine	0.34% 1/296 • From study entry to study exit, approximately 24 weeks.	0.00% 0/99 • From study entry to study exit, approximately 24 weeks.
Psychiatric disorders Bulimia nervosa	0.34% 1/296 • From study entry to study exit, approximately 24 weeks.	0.00% 0/99 • From study entry to study exit, approximately 24 weeks.
Psychiatric disorders Delirium	0.34% 1/296 • From study entry to study exit, approximately 24 weeks.	0.00% 0/99 • From study entry to study exit, approximately 24 weeks.
Psychiatric disorders Depression	0.34% 1/296 • From study entry to study exit, approximately 24 weeks.	0.00% 0/99 • From study entry to study exit, approximately 24 weeks.
Renal and urinary disorders Renal failure acute	0.00% 0/296 • From study entry to study exit, approximately 24 weeks.	1.0% 1/99 • From study entry to study exit, approximately 24 weeks.