| HVTN505 {HVTN505} | R Documentation |
dat.505 contains Week 28 immune response biomarkers (Janes et al. 2017, Fong et al. 2018, Neidich et al. 2019) and clinical covariates (age, racecc, bhvrisk, and BMI are always adjusted in the aforementioend manuscripts) for 150 vaccinees and 39 placebo recipients.
var.505 and score.505 contain metadata for immune response biomarkers.
var.505 is for individual immune response biomarkers with higher than 20 percent positivity rates.
For IgG/IgG3/IgA measurements, both baseline subtracted and unsubtracted variables are included. The baseline unsubtracted version is named as, for example, IgGw28_xxx, while the baseline subtracted version is named as, for example, IgG_xxx.
score.505 is for composite/summary scores. The scores include PC1 and mdw scores for groups of vaccine-mismatched markers with more than 1 member, as well as COMPASS for T-cell responses
For each continuous immune response marker, a dichotomized version, with suffix _bin, is also created using the function dichotomize.505.
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Clinical covariates in dat.505
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Abbreviations
dx = diagnosis = HIV-1 diagnosis
dxdt = date of (HIV-1) diagnosis
pd = post-dx = post-diagnosis = any time on/after the HIV-1 diagnosis date
prewk10 = pre-week-10 pd (see Notes for definition)
ART = Anti-retroviral Therapy
Variable information:
NAME LABEL
trt Treatment Assignment: 1 = Vaccine, 0 = Placebo
MITT Indicator of MITT status (2496 have MITT=1, 8 have MITT=0)
week28 Indicator that ppt is part of Week28+ cohort - meaning that they either
have a neg HIV test (draw-date) at/after study day 196, or else their
first positive HIV test (draw-date) was on/after study day 196
perprot Indicator of per-protocol status, requires:
(a) Receipt of all 4 vaccinations in-window
(b) No study-product-administration-errors reported
(c) On study through/past day 196 post-enrollment
(Last condition added to make the per-protocol cohort
a subset of the week28 cohort)
casecontrol Indicator of inclusion in the case-control cohort
case 1 = Case, 0 = Control. Only defined for the case-control cohort (casecontrol = 1), missing for all others
control Opposite of case
sitenum Numeric ID of site at which the participant enrolled in the study
site Name of site at which participant enrolled in the study
age Age (in years) at randomization
gender Self-identified gender: male/female/male transgender/female transgender
race Derived Race/Ethnicity variable:
1 = ( Race=White and non-Hispanic),
0 = ( (Race notequal White) or Hispanic=Yes)
racefull Old Race category - previously (incorrectly) labeled as "NIH Race category":
1 = 'White'
2 = 'Black or African American'
3 = 'Hispanic'
4 = 'Asian'
5 = 'Hawaiian/Pacific Islander'
6 = 'Native Am./Alaska Native'
7 = 'Other Race'
8 = 'Multi-racial'
9 = 'Missing'
racecc Three-level race catgory for use with case-control (cc) analyses
The ppt.s in the cc data are all either White, Black or Hispanic
(based on racefull variable values).
The values for 'racecc' are:
"White", "Black", "Hispanic/Other"
white Indicator of White race
black Indicator of Black/Afr. American race
asian Indicator of Asian race
hawpi Indicator of Native Hawaiian or Pacific Islander
natam Indicator of Native American or Alaskan Native race
otherrace Indicator of other race (ppt. specified)
hisp Indicator of Hispanic ethnicity
BMI Body Mass Index: (Weight in Kg)/(Height in meters)**2
BMIcat Body Mass Index - categorized for reporting
bhvrisk Baseline behavioral risk score
DNA1 Indicator of receipt of 1st DNA vaccination = 1st study vaccination
DNA2 Indicator of receipt of 2nd DNA vaccination = 2nd study vaccination
DNA3 Indicator of receipt of 3rd DNA vaccination = 3rd study vaccination
Ad5 Indicator of receipt of Ad5 vaccination = 4th study vaccination
lastvac Number of the last vaccination received (1=DNA1, 2=DNA2, 3=DNA3, 4=Ad5)
SPAerr Indicator of study-product-administration (SPA) error:
Wrong product given, vaccination administered outside of
visit window, or incorrect dosage/volumne received by ppt.
SPAerroutwin Indicator of SPA-error due to vaccination administered outside visit window
SPAerrdoseprod Indicator of SPA-error due to incorrect dosage received by ppt
SPAerrvisit Visit at which the SPA-error occurred
DNA2days Days b/t enrollment vaccination and 2nd DNA vaccination
DNA3days Days b/t enrollment vaccination and 3rd DNA vaccination
Ad5days Days b/t enrollment vaccination and Ad5 vaccination
lastvst Visit number of the participants most recent schedule 1/schedule 4 visit.
Does not include missed visits or infected-track visits
HIV Indicator of HIV-1 infection diagnosis (before month 24)
HIVall Indicator of HIV-1 infection diagnosis at/before the month-48 visit
HIVwk28 Indicator of HIV-1 infection diagnosis on/after study week28 (day 196)
HIVfu Follow-up time (in days) for HIV infection diagnosis endpoint, measured
from randomization to one of the following dates:
(1) diagnosis date (dxdt): for MITT ppt.s dx at/before the month 24 visit,
(2) latest specimen drawdt (at/before the month 24 visit) whose testing
for HIV produces a negative result: for all other ppt.s
NOTE: non-MITT ppts will have no negative specimen drawdt. We set it to
be their randomization date so that their HIVfu equals 0
HIVallfu Follow-up time (in days) for HIV infection diagnosis occuring through
the month-48 study visit. For use with event indicator 'HIVall'.
Other details as given in 'HIVfu' description
HIVwk28fu Follow-up time (in days) for HIV-1 infection occuring on/after study-day
196 (i.e. time origin is study-day 195). For use with event indicator
'HIVwk28'. Other details as given in 'HIVfu' description.
<NOTE - The following three indicators do not have associated follow-up time variables.
They should only be used to identify pre-unblinding infected ppts >
HIVpreunbl Indicator that 'HIV'=1 and 'dxdt' <= Unblinding Date (22Apr2013)
HIVallpreunbl Indicator that 'HIVall'=1 and 'dxdt' <= Unblinding Date (22Apr2013)
HIVwk28preunbl Indicator that 'HIVwk28'==1 and 'dxdt' <= Unblinding Date (22Apr2013)
HIVwk28preunblfu
HIVpreunblfu
dropout Indicator of dropout prior to HIV infection
dropoutfu Follow-up time (in days) from enrollment until the earliest of:
dropout, HIV-infection (dxdt), completion of the month 60 visit
dropout48 Indicator of dropout before the month 48 visit and prior to HIV infection
dropout48fu Follow-up time (in days) from enrollment until the earliest of:
dropout, HIV-infection (dxdt), last-visit before/at month 48.
dropout_postunbl Indicator of termination date after the date of unblinding (22Apr2013)
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Variables pertinent to T cell immune responses measured by ICS in case-control cohort
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tcellsub TCell subset (CD4+ or CD8+)
cytokine Cytokine subset (e.g. IL2 and/or interferon-gamma)
antigen Antigen
response positive response call assessed by comparing HIV-1
peptide stimulated and unstimulated negative control data
scoretype COMPASS (Combinatorial Polyfunctionality Analysis of
Single Cells) scoretype (Functionality, Polyfunctionality,
or revised scores ending in "Rev"). The functionality score
(FS) is defined as the estimated proportion of antigen-specific
subsets detected among all possible ones. The polyfunctionality
score (PFS) is similar, but it weighs the different subsets by
their degree of functionality, naturally favoring subsets with
higher degrees of functions, motivated by the observation that
higher degree function has been correlated with good outcomes in
certain vaccine studies.
logpctpos log10 of pctpos_adj, which is net
pctpos_adj_ind binary pctpos_adj variable, indicator of below/above median by tcellsub,
cytokine, antigen. Median is calculated among vaccinees (cases and
non-cases)
score COMPASS score magnitude
score_ind binary COMPASS score, indicator of below/above median by tcellsub, cytokine,
antigen. Median is calculated among vaccinees (cases and non-cases)
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HLA class I data, for the case-control cohort
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hla Class I HLA category (Protective: HLA-B*27, B*57 and B*58:01); Unfavorable: HLA-B*35:02, B*35:03, B*35:04, B*53:01 or homozygous in at least one locus; or Neutral, all others)
hla.num Numeric HLA variable (0 = Neutral, 1 = Protective, 2 = Unfavorable)
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Derived variables for analysis of post-infection data, HLA data, and T cell immunogenicity data
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exclude Indicator of exclusion from post-infection analyses, based on HIV infection diagnosis after ARV initiation
cc_cohort
hg_cohort Indicator of eligibility for case-control sampling
hg_strata Stratum for case-control sampling. Sampling strata were defined based on treatment assignment, race/ethnicity, and BMI. Eg Vacc/White/[25, 29.8) is the subset of participants eligible for case-control sampling who were assigned to the vaccine group, White race, and 25 <= BMI < 29.8
stratuminds sampling stratum number for participants in case-control cohort
in.subcohort Indicator of being a control in the case-control cohort
wt inverse-sampling weights, for the case-control cohort, used for cumulative incidence plots
stratuminds_vaccs sampling stratum number for vaccinees only (need counts to start at 1 for
tps() function in R)
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Notes:
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(1) For our purposes, the 'diagnosis date' is considered to be the date of
the first specimen-draw whose testing produces to a redraw-request
(a request for follow-up confirmatory testing) that leads to a
confirmation of HIV-1 infection by the HVTN Diagnostic labratory.
(2) The variables whose names include the 'prewk10' (pre-week-10) suffix
are computed based on data from the time interval beginning at
"week 0 post-diagnosis" (i.e. the diagnosis visit, 'dxdt') and ending
at (but *NOT* including) the week-10 post-dx visit. So the data used
is all strictly *pre* (before) the week-10 visit. The week10 post-dx
visit is considered to happen on day 74 (the end of the week-10 pd
visit window) for purposes of the 'prewk10' variables, for
participants that miss their week-10 pd visit.
(3) The variable 'evaluable' will tell us whether the observation can be used in
the VL analysis - meaning does it have the requisite information to run the
method. This is *NOT* an indicator of having complete data or anything like
that, just does it have either of the following:
(1) >= 1 pre-ART VL from the week 10-20 PD (post-dx) period
(2) no pre-ART set-point VL data *and*
non-missing values for the "prewk10" LVL and CD4 variables *and*
one of the following:
- initiated ART prior to the week-10 PD visit
- dropped out prior to the week-10 PD visit
- is past the week-10 PD visit but has not dropped-out/initiated ART
(4) An "undetectible" results means that the result of the RNA viral load test was
"negative" - i.e. if there is any RNA present, it is below the limit of
detection. Tests with negative results still have their 'viral load' field
populated, and show "<40" (where 40 is the lower-limit of quantitation for the
kit). PLEASE note that the converse is not true, a viral load of "<40" does
*NOT* imply that the test result is negative. The "<40" result is also used
when there is detectible RNA but the level is too low to accurately quantify.
The 'undetectible' indicator is set to 1 iff (if and only if) the variable
'result' in the source HIV dataset has a value of '2' (the code for negative).
Janes, H. E., et al. (2017). Higher T-cell responses induced by DNA/rAd5 HIV-1 preventive vaccine are associated with lower HIV-1 infection risk in an efficacy trial. The Journal of infectious diseases, 215(9), 1376-1385.
Fong, Y., et al. (2018). Modification of the Association Between T-Cell Immune Responses and Human Immunodeficiency Virus Type 1 Infection Risk by Vaccine-Induced Antibody Responses in the HVTN 505 Trial. The Journal of infectious diseases, 217(8), 1280-1288.
Neidich, S. D., et al. (2019). Antibody Fc-effector Functions and IgG3 Associates with Decreased HIV-1 Acquisition Risk, Journal of Clinical Investigation, in press.