Supplemental Digital Content 1. Pictorial PK Result Tool
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Legend: The pictorial PK result tool was developed through expert consultations with PrEP researchers and site staff
and pilot-tested at each site. The tool was designed to serve several purposes: (1) to provide graphic representation of a
potentially complex concept using well-recognized, locally relevant objects (tea cups and tea pot), and to simplify specific
average drug detection levels (e.g., 18%) into five broad categories (TFV never detected, TFV detected in 1-49% 50-74%, 7599%; and 100% of plasma samples, respectively); and (2) to minimize the likelihood of feeling judged by providing participants
with their categorical adherence level rather than a point estimate of their individual result.
Tea cups represent detection of TFV in plasma at a given visit. Tea cup rows represent pattern of use; by design,
presentation was not specific to individual results. For analysis purposes, women were classified at 3 PK levels: low
(0% of plasma samples with drug detected), inconsistent (1-74% of plasma sample with drug detected) and high (75100% of plasma samples with drug detected).
Supplemental Digital Content 2. Rank ordered statement cards: by PK level, by product group, and
overall (N=68 IDIs)
PK level
High
(n=20)
Health services
Tablet
(n=32)
Side effects
Product
Gel
(n=36)
Side effects
Card
ranking
1
Low/Inconsistent
(n=48)
Side effects
Total
(n=68)
Side effects
2
Harm
Side effects
Health services
Harm
Harm
3
Health services
Harm
Harm
Health services
Health services
4
5
6
7
8
9
10
11
12
13
14
15
16
Support
Can’t prevent HIV
Boring
Challenge to take
Too busy
HIV stigma
Told not to take
Peer influence
Partner disliked
Family/friends
Had to hide
Not interested
Living situation
Told not to take
Peer influence
Not at risk
Had to hide
Boring
HIV stigma
Can’t prevent HIV
Reimbursements
Challenge to take
Support
Too busy
Partner disliked
Sexual pleasure
Challenge to take
HIV stigma
Support
Told not to take
Boring
Peer influence
Can’t prevent HIV
Family/friends
Not interested
Had to hide
Didn’t need
Too busy
Living situation
Too busy
Can’t prevent HIV
Support
Partner disliked
Boring
Told not to take
Peer influence
HIV stigma
Had to hide
Not at risk
Challenge to take
Living situation
Family/friends
Support
Told not to take
Boring
Can’t prevent HIV
HIV stigma
Challenge to take
Peer influence
Too busy
Partner disliked
Had to hide
Family/friends
Not at risk
Not interested
17
18
19
20
Not at risk
Didn’t need
Sexual pleasure
Reimbursements
Family/friends
Not interested
Didn’t need
Living situation
Partner disliked
Reimbursements
Not at risk
Sexual pleasure
Sexual pleasure
Not interested
Reimbursements
Didn’t need
Living situation
Didn’t need
Sexual pleasure
Reimbursements
Legend: Following an open-format discussion, interviewers used a set of cards listing 20 predetermined statements intended to
elicit additional information about study participation and adherence challenges. The statements were selected by the research
team from previous qualitative research and recorded on a series of cards. Participants were asked to select the statements that
were salient to them from their experience during VOICE and relative to their product adherence challenges (pile sorting), and to
rank these in order of relevance. Cards were assigned a score according to ranking. A card ranked as most relevant was
assigned a score of 20, a card ranked as second most relevant was assigned a score of 19, and so on. Non-relevant
cards were assigned a score of 0. Average scores for each card were calculated and are presented in descending
order, from most to least relevant. Participants were given an opportunity to indicate additional challenges during the exercise
if they desired, though these were not scored. The following key provides the full text of each card: Boring  It was boring to
take the products daily; Can’t prevent HIV  The products cannot prevent HIV; Challenge to take  It was challenging to
swallow big tablets/insert a gel in my vagina; Didn’t need  I didn’t need to take the products; Family/friends  My
family/friends disliked the products/VOICE; Had to hide  I had to hide when taking my products; Harm  The products may be
harmful; Health services  I joined the study for health services provided by the clinic; HIV stigma  Others would think I have
HIV if I took the products; Living situation  The place where I lived made it hard to take the products; Not at risk  I wasn’t at
risk of getting HIV; Not interested  I was not interested in using the products; Partner disliked  My partner disliked the
products/VOICE; Peer influence  [I heard that] other participants were not taking their products; Sexual pleasure  The products
decreased sexual pleasure; Side effects  I experienced or was worried about side effects; Support  I didn't have enough support
from others to take the products; Told not to take  Someone told me to not take the products; Too busy  I was too busy to take
products every day; Reimbursements  I joined the study for the reimbursements.
Supplemental Digital Content 3: Comparison between characteristics of VOICE-D stage 2 and
VOICE participants not enrolled in VOICE-D at same sites (in Durban, Kampala, and
Chitungwiza)
Characteristics
VOICE-D stage 2
Sample
Non-stage 2 VOICE-D sample at
same sites
pvalue1
(N = 131)
%
(N =1311)
%
Age 25 or younger
77
59%
633
48%
0.03
Completed secondary school or more
46
35%
626
48%
0.006**
At time of VOICE trial enrolment
Earns an income of her own
88
67%
840
64%
ns
Parity (0-1 children)
59
45%
570
43%
ns
Married
59
45%
546
42%
ns
Had multiple sex partners in previous 3 months (ACASI)
43
33%
358
27%
ns
Used a condom at last sex (CRF)
93
71%
875
67%
ns
Current injectable contraceptive (CRF)
92
70%
848
67%
ns
Current oral contraceptive (CRF)
30
23%
298
23%
ns
Baseline behavior in VOICE
Legend: 1Fisher’s exact test; **Chi-square test no longer significant when stratified by site/country
CRF, Case Report Form; ACASI, Audio-Computer Assisted Self-Interviewing
Supplemental Digital Content 4. Participants’ reactions to PK results and illustrative quotes
Accepted PK results (high, inconsistent and low PK groups)
I: Now, the results that came back from your blood showed that for most of the time your blood was checked,
the product was found to be in your body and that you fall in line “A”
R: Ehh and yet I used to miss? [laughs] Okay, that happened in the beginning but towards the end we had
understood it well and it was swallowed daily.
I: You could no longer forget?
R: Yes, but that happened in the beginning and [then] we were given a calendar. (IDI, Uganda, high PK, Tablet)
I: When we tested your blood, we found that you had been using the product because it was found in your
blood. You fall under category "B". [..] What was your experience? What would you say helped you use the
product even though your partner didn't like it?
R: I would say that I'm the kind of person who cares about her health. It was important to get tested and know
my status. We did PAP-smears and we had our blood drawn for testing. Some people continued in the study but
others stopped. Luckily I was among those who continued. That motivated me a lot... I told myself to use the
product because it might help me.” (IDI, South Africa, high PK, Gel)
I: What this shows is that your blood samples show that you had traces of the
product in your blood at times and sometimes you had none. […]What do you think
about your results?
R: Yes, that’s correct since on some days I would forget. That’s correct. (IDI, Zimbabwe, inconsistent PK, Gel)
I am disappointed. Because I have been found out that I hadn’t been using the gel. (IDI, South Africa, low PK, Gel)
We weren’t faithful. We weren’t honest enough to use the products (IDI, Zimbabwe, low PK, Gel)
Did not accept initially and/or challenged PK results (all low or inconsistent PK groups)
Initial reaction:
R: Maybe something happened, they made a mistake with the results.
I: Why do you say we made a mistake on your results?
R: Ah because how can you not find the drug at all when I was using my tablets?
Later in IDI:
R: I feel guilty..[..] Sometimes I would forget [laughs]; other times I took them. (IDI, Zimbabwe, low PK, Tablet)
Initial reaction:
I: Now, they are informing you that you belong to Category E and not D as you had thought. Most of the time,
there were no products in your blood
R: I am not sure
I: Why aren’t you sure?
R: Because I used to use.
Later in IDI:
I: You used to insert the gel but why do you think the results came back like this?
R: I don’t know doctor [referring to interviewer]. Maybe when they tested, that is what they found. You cannot
argue and insist on it when they did not find any products. (IDI, Uganda, low PK, Gel)
I became less motivated to take the products, as time went by. But I did use the products for a while. Because
why are there no traces of the product at all, in my blood sample in the initial stages? We knew that there would
be checks for product use, so I used the product a bit. So I am failing to comprehend why there was no evidence,
whatsoever, of the product in my blood? I do not understand at all. [..] It looks like I did not use the product at
all, but I did use it sometimes. That is what made me upset. (IDI, Zimbabwe, low PK, Gel)
Denied results; some provided alternative explanations (all low or inconsistent PK groups)
I feel bad because I used it [the tablets]. [..] I swear to God I never did [have a problem]. I would drink it
whenever I was listening to a Xhosa story which starts at 19:15. (IDI South Africa, low PK, Tablet)
I used to take a lot of tablets. Some for headache, chest pain and ulcers. I was swallowing tablets all the time. In
my opinion, I think that might have led to the inability to detect the medication in my blood. (IDI, Uganda, low
PK, Tablet)
I used to drink beer a lot, maybe my drinking distorted the results. In fact I was drunk on most of my visits. (IDI,
Zimbabwe, low PK, Tablet)
How were you able to tell from my blood that it was working [had the drug] when the one I got was a placebo?
[…]They will say to you, “you, the one that you were using didn’t have the active drug”. In my case I was told that
… (FGD, Zimbabwe, low PK, Gel)*
Legend: I= interviewer; R=respondent. Quotes from respondents are italicized to distinguish them from
statements by the interviewer. (*) we verified that this participant had been assigned to active gel during
VOICE and that she had been correctly informed of her study arm by staff after trial completion.
Supplemental Digital Content 5. Typology of product use patterns
Non-initiation
Discontinuation
Misimplementation
Temporary
Visit-driven use
Permanent
Variable taking
(e.g. missed set
time)
Adherence
Modified dosing
(e.g. extra or
partial dose)
Modified regimen
(e.g. intermittent
or episodic use)
Legend: Product use patterns reported in VOICE-D can be described by this typology, which includes
four major adherence behavior components (adapted from [14; 31; 32]: non- initiation (or nonengagement with drug regimen), discontinuation (temporarily or permanently), persistence with the
product regimen but mis-implementation (or poor execution) and adherence (i.e. using product as
instructed during the trial). Discontinuation and mis-implementation may or may not be intentional.
Mis-implementation can result from various behaviors including visit-driven use (or white coat
compliance); variable taking, when the product is not taken at the set time; modified dosing, when the
correct amount of product is not taken with each dose (over- or under-dosing), and modifying the
regimen or frequency of product use (i.e. non-daily, inconsistent, intermittent or episodic use).