HIV cure: An acceptability scientific agenda

Abstract

Purpose of review:
Recent years have seen major investments into HIV cure research, seeking a permanent cure or remission. The purpose of this review is to consider how this important research agenda could be broadened to include issues of acceptability and appropriateness for different populations.

Recent findings:
We discuss how the definitions of cure such as functional cure (remission) or complete cure (viral elimination) could be interpreted differently by various populations. We also discuss the different methods of cure and the importance of including Africa in cure research to ensure that emerging remedies could be trialled and utilized on the continent that bears the brunt of the AIDS pandemic.

Summary:
We propose that the social science research of HIV cure acceptability should be done concurrently with the basic and clinical sciences, to ensure that cure methods consider stakeholder preferences.

Full text

C
URRENT
O
PINION
HIV cure: an acceptability scientific agenda
Evelyn Y. Bonney
a
, Helena Lamptey
b
and George B. Kyei
a,b,c
Purpose of review
Recent years have seen major investments into HIV cure research, seeking a permanent cure or remission.
The purpose of this review is to consider how this important research agenda could be broadened to
include issues of acceptability and appropriateness for different populations.
Recent findings
We discuss how the definitions of cure such as functional cure (remission) or complete cure (viral
elimination) could be interpreted differently by various populations. We also discuss the different methods
of cure and the importance of including Africa in cure research to ensure that emerging remedies could be
trialled and utilized on the continent that bears the brunt of the AIDS pandemic.
Summary
We propose that the social science research of HIV cure acceptability should be done concurrently with the
basic and clinical sciences, to ensure that cure methods consider stakeholder preferences.
Keywords
analytical treatment interruption, HIV cure, HIV cure acceptability, HIV cure research
INTRODUCTION
Although antiretroviral therapy (ART) has been rev-
olutionary in transforming HIV from a death sen-
tence to a manageable chronic disease, it does not
provide cure [1,2,3
&
,4,5,6
&&
,7]. Patients must commit
to lifelong medications and deal with issues such as
incomplete viral suppression, social stigma, drug
resistance, medication side effects and unsustainable
costs. Therefore, an HIV cure is a highly desirable goal
for patients [8,9], the reason organizations like the
National Institutes of Health and the International
AIDS Society have made cure a top research agenda
[10– 12]. An HIV cure will eliminate stigma and
discrimination, reduce new infections and provide
sustainable financial solution for controlling the HIV
pandemic [13].
The main obstacle to an HIV cure is the persis-
tence of transcriptionally silent and immunologically
inert latent proviruses in quiescent memory CD4
þ
T
cells [4,14]. These cells serve as viral reservoir ready to
respond to antigenic stimulation and replenish the
virus if ART is interrupted [9,14]. On the basis of the
known characteristics of the HIV-1 provirus reviewed
by Cohn et al. [4], various methods are being inves-
tigated for an HIV cure. First, is the shock and kill
approach (latency reactivation), whereby small mol-
ecules are used to force proviral reactivation from
latency under the cover of ART. Induction of de-novo
virion synthesis isthen expected to result in cell death
from viral cytopathic effects or immune clearance,
after which ART can be discontinued [15,16]. Second,
the block and lock approach, wherein small mole-
cules will be used to modify the surroundings of the
integrated virusto send it into ‘deep latency’ such that
upon discontinuation of ART, the virus will not reac-
tivate [5,7,17,18]. Third, genetic methods that will
either completely excise integrated HIV-1 provirus
from the genome or produce mutations that will
render the virus inactive [19–21]. Fourth, immuno-
therapies such as the use of broadly neutralizing anti-
bodies or chimeric antigen receptors to suppress
reactivation or kill cells with reactivated virus [22].
Finally, combination approaches like shock and kill
with immunological approaches are also being
a
Noguchi Memorial Institute for Medical Research, University of Ghana,
Legon, Accra, Ghana,
b
Departments of Medicine and Molecular Micro-
biology, Washington University School of Medicine in St Louis, Missouri,
USA and
c
Medical and Scientific Research Center, University of Ghana
Medical Center, Accra, Ghana
Correspondence to George B. Kyei, Noguchi Memorial Institute for
Medical Research, Off Akilagpa Sawyer Rd, University of Ghana, Accra,
Ghana 00233. Tel: +233 55 1989937;
e-mail: gkyei@noguchi.ug.edu.gh, g.kyei@wustl.edu
Curr Opin HIV AIDS 2023, 18:12 –17
DOI:10.1097/COH.0000000000000771
This is an open access article distributed under the terms of the Creative
Commons Attribution-Non Commercial-No Derivatives License 4.0
(CCBY-NC-ND), where it is permissible to download and share the
work provided it is properly cited. The work cannot be changed in any
way or used commercially without permission from the journal.
www.co-hivandaids.com Volume 18 Number 1 January 2023
REVIEW

pursued [10,23
&&
]. Each approach may lead to treat-
ments that differ in the range and nature of side
effects, duration, intensity of treatment and type
and probability of benefit.
The value that patients place on various dimen-
sions of risks and benefits, in comparison with the
current ART, will determine acceptability in clinical
trials as well as ultimate public health impact in real-
world settings. Patients considering cure therapies
will therefore need thorough education and may
have to overcome substantial uncertainties in both
side effects and prospect of benefit. As all of these
interventions may carry substantial risks for people
living with HIV (PLWH) without any guarantee that
they will provide a cure, the research agenda must
also include questions such as: What does a cure
mean for patients most of whom have undetectable
virus on ART? Will patients agree to interrupt ART
during cure trials and under what circumstances?
What risks are patients willing to endure to achieve a
cure given that most are doing well on ART? How
applicable and acceptable are the cures being devel-
oped to patients in low-middle income countries
(LMICs)? There is an urgent need to answer these
questions in different geographical settings [24] to
ensure that interventions being developed will be
acceptable to patients around the world, especially
in Africa where most PLWH reside. These answers
could feed into the design of cure intervention to
assure maximum participation in future trials.
ACCEPTABILITY OF A FUNCTIONAL CURE
Understanding the concept of cure as far as HIV is
concerned is crucial to determining what will qual-
ify as cure. Researchers anticipate the two forms of
cure. The first, termed ‘eradication cure’ or ‘steriliz-
ing cure’ involves complete eradication of all repli-
cation-competent provirus from the infected
person, including removal of viruses in cellular
and anatomical reservoirs [2,3
&
,10,25,26]. The sec-
ond form is termed ‘functional cure’ or long-term
remission whereby the viral reservoir is depleted to
the extent that cessation of ART will not result in
immediate viral rebound [2,3
&
,10,25,26]. The gold
standard of infectious disease cure is elimination of
the pathogen; therefore, everyone will take eradica-
tion cure as the ideal. However, given the enormous
difficulty that eradication of HIV presents to research-
ers, a more likely scenariowill probably be some form
of functional cure. Indeed, methods such as shock
and kill, block and lock and immunological strategies
mentioned above are aimed towards some form of
functional cure. Will patients see a functional cure as
cure, as there is some risk of virus return even if it is
very low? A functional cure also presupposes that
patients will need periodic evaluation to ensure that
the virus has not come back. Will patients rather take
their ART once a day, insteadof subjecting themselves
to such uncertainties? Few studies have examined the
specific question of desirability of functional cure. In
a study involving 356 men who have sex with men
(MSM) in Hong Kong, Kwan et al. [6
&&
] showed that
although 58% of participantswere not aware of func-
tional cure, when it was explained to them, 90% were
willing to participate in long-term remission trials. In
qualitative interviewsdone in Australia, Netherlands,
South Africa or USA, participants envision cure as
being a virus-free state. Sustained remission is not
considered as cure because it does not take away
concerns such as stigma, fear of transmission and
potential future ill health [27,28
&
,29– 32]. These stud-
ies show that the concept of functional cure is not
intuitive to patients. More patient education and
studies are needed to determine the acceptability of
long-term remission as a form of cure. Ultimately,
researchers may need to abandon the term
‘functional cure’ and use the more appropriate term
of long-term remission, especially given the advent
of long-acting ARTs.
ACCEPTABILITY OF TREATMENT
INTERRUPTIONS
To evaluate the efficacy of any cure strategy, patients
may be asked to stop taking ART while being closely
monitored, a process called analytical treatment
interruption (ATI) [33
&&
,34
&&
]. Two types of ATI are
used to assess potential cure therapies: time to viral
rebound (TVR) studies and viral set-point studies
[34
&&
]. The TVR determines the time taken for viral
load to become detectable (50copies/ml) after partic-
ipants stop ART and the time takenfor the viral load to
reach the threshold for restarting ART (which can
range from 1000 to 10 000 copies/ml) depending
KEY POINTS
Basic and clinical science research alone cannot
provide all the evidence needed for the development
and deployment of HIV cure, collaboration with the
behavioural sciences is urgently needed.
Investigation is vital to determine how patients,
including those in Africa, will accept the risks and
benefits associated with the types of cures being
considered by researchers.
Education and advocacy are crucial to bring home the
message of HIV cure to all stakeholders, who should
participate and help design effective cure strategies
that will be acceptable to patients.
HIV cure: an acceptability scientific agenda Bonney et al.
1746-630X Copyright ©2022 The Author(s). Published by Wolters Kluwer Health, Inc. www.co-hivandaids.com 13

on the study [34
&&
]. Set-point studies evaluate the
participants’ immune systems’ control of HIV during
treatment interruptions. These are much longer stud-
ies with months of ART withdrawal during which
researchers allow participants’ viral loads to increase
to high levels (100 000 copies/ml) to determine if the
immune system can control the virus and decrease
the load to a level below the initial spike. Whichever
type is used in HIV cure trial, ATI is currently an
indispensable part of the process to evaluate the
efficacy and performance of HIV cure strategies
[35– 38]. Already, there are at least two reported cases
of sexual transmission during ATI for vaccine studies
[39,40]. Implementation of ATI during HIV cure-
related clinical trials is a necessity, yet the modalities
are complex and the outcomes unpredictable [41,42].
There are currently no biomarkers to predict viral
rebound, despite ongoing research [38,43,44]; there-
fore, frequent viral load measurements, often once
week, must be done to inform when ART should be
resumed [45]. This may inconvenience trial partici-
pants who must visit the clinic several times a week
during the trial [46]. Due to the complexity and
ethical dilemmas involved, expert groups have issued
guidelines for ATI, which will help streamline the
procedure in different trials [42,47].
Studies on ATI show that there may be sex and
regional differencesin acceptability. An international
online survey comprising mainly PLWH in Europe
and America found that patients were willing to take
substantial risks without guarantee of benefit includ-
ing 62% who would undergo ATI [48].Being an online
survey, motivated participants may have self-selected
to influence the results. This is because in almost all
qualitative in-depth interviews published from South
Africa, USA, Netherlands and other places, ATI is a
main concern for participation in cure trials
[42,46,47,49,50]. It is possible that in-depth face-to-
face interviews help participants to understand what
ATI really entails. In addition, most of these studies
recruit MSM who are the majority of patients in the
developed world. Few studies about perspectives of
patients and other stakeholders have been performed
in Africa where the majority of HIV patients live and
where the demographic of the disease has twice as
many women as men. In two qualitative studies
performed in South Africa, treatment interruption
was a major concern, as patients felt they may get
sick again [31,51]. In a survey of 251 patients living
with HIV in Ghana, although mostpatients expressed
enthusiasm about participating in cure trials, they
were not willing to take substantial risks [3
&
]. For
instance, most participants (87%) said ‘no or maybe’
to ATI with 67% saying a definite ‘no’ even if their
physician will follow up closely [3
&
]. This study did
not explore the reasons for such high resistance
to ATI, but it may have something to do with
fears of getting sick and distrust in the medical estab-
lishment.
It is important to emphasize that many stake-
holders in the fight against HIV do not fully under-
stand the modalities involved in ATI, the
implications and the risks associated [37,48], while
those who know about it have limited understanding
of the full implications [52].One mitigation factor for
ATI is when patients know their partners will be
protected from getting infected [47,52,53,54
&&
].
Therefore, there is the need to find ways to involve
trial participants’ partners and offer them preexpo-
sure prophylaxis (PrEP), as a way to assuage the fear of
transmission to sexual partners [53,54
&&
].
ACCEPTABILITY OF DIFFERENT CURE
MODALITIES
Cure strategies such as shock and kill, block and lock,
immunotherapy and gene therapy, may have differ-
ent side effects, time commitment for trial participa-
tion, length of trial and frequency of monitoring,
factors that may determine whether patients want
to participate. Few studies have examined stake-
holder preferences for specific cure modalities and
trial characteristics. The most extensive of these is
discrete choice experiment conducted by Protiere
et al. [55] among 195 virally controlled PLWH and
160 physicians from 24 French HIV centres. Partic-
ipants were made to choose and make tradeoffs
between cure types (immunotherapy, latency rever-
sal, gene therapy and combination therapies) and
trial characteristics, namely trial duration, consulta-
tion frequency, trial outcomes and moderate and
severe side effects. Overall, patients preferred immu-
notherapy, and trials that were less burdensome for
them in terms of time commitment and frequency of
physician evaluation. A recent focus group study to
determine preferences for gene therapy however
showed that most were not willing to participate in
potential gene therapy cure trials [56]. They felt they
were happy with their current treatment and health
status and unwilling to undergo a procedure that was
invasive, has unknown side effects and potentially
irreversible. A lot more research is needed to deter-
mine how patients feel about the different types
of cure being considered by researchers to help feed
patient and provider inputs into the design of these
therapies.
ACCEPTABILITY OF CURE TRIALS IN
AFRICA
Most of the studies conducted to determine the
acceptability of the cure agenda and risk of
Implementation: PrEP, ART and vaccines
14 www.co-hivandaids.com Volume 18 Number 1 January 2023

participation in cure related clinical trials were done
outside Africa where the greatestburden of HIV exists.
Therefore, it is not clear what people living in Africa
want from an HIV cure. Some of thestrategies such as
gene therapy, for example modification of T cell ex
vivo and reinfusioninto the patient, and some types of
immunotherapy such as chimeric antigen receptor
may not be feasible in Africa [2]. Although patients
everywhere may be hesitant to undergo ATI, PLWH in
Africa may have a lot more hesitation for unclear
reasons [3
&
]. We recently showed that patients in
Ghana may be more risk averse than patients in the
USA or Europe [3
&
] and this needs further study. In
addition, majority of PLWH in the USA are men and
most studies aimed at understanding perception of
PLWH regarding HIV cure trials were done among
MSM. Given that HIV affects mostly women in Africa,
it is imperative to engage PLWH in Africa, as the risk
perception and tolerability may be different from
those in developed countries [57].
HIV cure researchers must therefore engage and
work with affected communities, local scientists and
local HIV care advocates to define what is acceptable.
Engaging the communities is also critical in deter-
mining the type and levels of risk they are willing to
take during participation in HIV cure trials so that
trials are designed with participants’ specification.
ADVANCING THE ACCEPTABILITY CURE
AGENDA
The NIH strategic plan for HIV and HIV-related
research identifies ‘Cure Ethics and Acceptability’
as a priority research area for 2021–2025. To accom-
plish this goal will require deliberate collaborations
among basic scientists, economists, implementation
scientists, clinical trialists and social and behavioural
scientists. Collaboration is critical because true iden-
tification of patient cure preferences requires careful
experimentation using different approaches such as
mixed methods qualitative design, discrete choice
experiments (DCE), best worst scaling and human-
centred design (HCD). Although mixed methods will
deliver in-depth qualitative understanding of patient
choices, DCEs will allow stakeholders to weigh differ-
ent cure intervention characteristics, make trade-offs
and select appropriate options [58,59
&
]. The HCD
borrowed from economics and gaining grounds in
healthcare and HIV research is an iterative process
that narrows the gap between an intervention being
planned and end user preferences [60,61
&&
,62]. Thus,
bringing together scientists working on HIV cure,
patients, ethicists, economists and socio-behavioural
scientists could yield new ideas that can feed into
the design of cure interventions, and early termina-
tion of approaches that are likely to be rejected by
patients and caregivers. In addition, methods like best
worst scaling could help determine the extremes of
cure trial preferences for patients and caregivers
[63,64]. Although investigators from different back-
grounds could come together to performthese impor-
tant studies, the NIH and other funders could ‘force’
collaborations by issuing special FOAs for cure
ethics and acceptability that require cross-cutting
interactions.
CONCLUSION
As biomedical scientists workto find an effective, well
tolerated, affordable and scalable HIV cure, there is a
need to engage other stakeholders, including PLWH
and their healthcare providers, to determine their
acceptability of HIV cure and willingness to partic-
ipate in trials. Most studies show that patients and
caregivers know little about the HIV cure strategies
that are beingdeveloped [48,52]. Education andadvo-
cacy is therefore crucial to bring home the message of
HIV cure to stakeholders so they are involved in
proposing strategies and designs of cure that they
are willing to accept. The HIV cure field urgently
needs experts such as implementation scientists, eth-
icists, economists and social scientists to help bring
out patient and provider preferences more clearly.
Acknowledgements
None.
Financial support and sponsorship
This work is supported by the grant no. R01 AI155120-
01A1 from the NIH, and TMA2017SF-1955 from the
EDCTP. The funders had no role in the writing of this
review.
Conflicts of interest
There are no conflicts of interest.
REFERENCES AND RECOMMENDED
READING
Papers of particular interest, published within the annual period of review, have
been highlighted as:
&of special interest
&& of outstanding interest
1. Deeks SG, Lewin SR, Ross AL, et al. International AIDS Society global
scientific strategy: towards an HIV cure 2016. Nat Med 2016; 22:839 –850.
2. Abana CZ, Lamptey H, Bonney EY, Kyei GB. HIV cure strategies: which ones
are appropriate for Africa? Cell Mol Life Sci 2022; 79:400.
3.
&
Bonney EY, Lamptey H, Aboagye JO, et al. Unwillingness of patients in Ghana
to interrupt antiretroviral therapy for HIV cure research. J Virus Erad 2021;
7:100027.
One of the few quantitative survey studies in Africa on HIV patients’ perspective on
cure trials and associated ATIs. They reported that patients have different per-
spectives compared with those in developed countries.
4. Cohn LB, Chomont N, Deeks SG. The biology of the HI V-1 latent reservoir and
implications for cure strategies. Cell Host Microbe 2020; 27:519 –530.
5. Elsheikh MM, Tang Y, Li D, Jiang G. Deep latency: a new insight into a
functional HIV cure. EBioMedicine 2019; 45:624–629.
HIV cure: an acceptability scientific agenda Bonney et al.
1746-630X Copyright ©2022 The Author(s). Published by Wolters Kluwer Health, Inc. www.co-hivandaids.com 15

6.
&&
Kwan TH, Chan CP, Wong NS, Lee SS. Awareness of HIV functional cure and
willingness in participating in related clinical trials: comparison between
antiretroviral nave and experienced men who have sex with men living with
HIV. BMC Infect Dis 2022; 22:383.
This study assessed awareness of functional cure among MSM in Hong Kong and
their willingness to participate in related trials. It is the first study that specifically
asked about patient views on functional cure.
7. Kyei GB, Meng S, Ramani R, et al. Splicing factor 3B subunit 1, interacts with
HIV Tat and plays a role in viral transcription and reactivation from latency.
mBio 2018; 9:e01423-18.
8. Rokx C, Prins HAB, Vandekerckhove L, et al. Launching amultidisciplinary
European collaboration towards a cure for HIV: the EU2Cure Consortium.
J Virus Erad 2021; 7:100045.
9. Sankaranantham M. HIV: is a cure possible? Indian J Sex Transm Dis AIDS
2019; 40:1– 5.
10. Deeks SG, Archin N, Cannon P, et al. Research, priorities for an HIV cure:
International AIDS Society Global Scientific Strategy 2021. Nat Med 2021;
27:2085– 2098.
11. Deeks SG, Autran B, Berkhout B, et al. Towards an, HIV cure: a global
scientific strategy. Nat Rev Immunol 2012; 12:607 –614.
12. National Institutes of Health OoAR. Research toward HIV cure 2020. https://
www.oar.nih.gov/hiv-policy-and-research/research-priorities-overview/re-
search-toward-hiv-cure. [Accessed 12th October 2022].
13. Dybul M, Attoye T, Baptiste S, et al. The case for an HIV, cure and how to get
there. Lancet HIV 2021; 8:e51–e58.
14. Mendoza P, Jackson JR, Oliveira TY, et al. Antigen-responsive CD4þT cell
clones contribute to the HIV-1 latent reservoir. J Exp Med 2020; 217:
e20200051.
15. Archin NM, Liberty AL, Kashuba AD, et al. Administration of vorinostat disrupts
HIV-1 latency in patients on antiretroviral therapy. Nature 2012; 487:482–
485.
16. Spina CA, Anderson J, Archin NM, et al. An in-depth, comparison of latent
HIV-1 reactivation in multiple cell model systems and resting CD4þT.cells
from aviremic patients. PLoS Pathogens 2013; 9:e1003834.
17. Kessing CF, Nixon CC, Li C, et al. In vivo suppression of, HIV rebound by
didehydro-cortistatin A, a ‘‘Block-and-Lock’’ strategy for HIV-1 treatment. Cell
Rep 2017; 21:600– 611.
18. Mousseau G, Valente ST. Didehydro-cortistatin A: a new player in HIV-
therapy? Expert Rev Anti Infect Ther 2016; 14:145– 148.
19. Peterson CW, Kiem HP. Cell and gene therapy for HIV cure. Curr Topics
Microbiol Immunol 2018; 417:211–248.
20. Stone D, Kiem HP, Jerome KR. Targeted gene disruption to cure HIV. Curr
Opin HIV AIDS 2013; 8:217–223.
21. Wang CX, Cannon PM. Clinical applications of genome editing to HIV Cure.
AIDS Pat Care STDS 2016; 30:539–544.
22. Spencer DA, Shapiro MB, Haigwood NL, Hessell AJ. Advancing HIV broadly
neutralizing, antibodies: from discovery to the clinic. Front Public Health
2021; 9:690017.
23.
&&
Dube
´K, Kanazawa J, Dee L, et al. Considerations for designing and im-
plementing combination HIV cure trials: findings from a qualitative in-depth,
interview study in the United States. AIDS Res Ther 2021; 18:75.
This is an important study that generated broad views on ethical and practical
considerations of cure from biomedical researchers, people living with HIV and
their advocates, policy makers, funders and regulators.
24. Miall A, McLellan R, Dong K, et al. Bringing social, context into global
biomedical HIV cure-related research: an urgent call to action. J Virus Erad
2022; 8:100062.
25. Newton L, Necochea R, Palm D, et al. Revisiting the ’sterilising, cure’
terminology: a call for more patient-centred perspectives on HIV cure-related
research. J Virus Erad 2019; 5:122 –124.
26. Xu W, Li H, Wang Q, et al. Advancements in developing strategies, for
sterilizing and functional HIV cures. Biomed Res Int 2017; 2017:6096134.
27. Power J, Westle A, Dowsett GW, et al. Perceptions of HIV cure research
among people living with HIV in Australia. PLoS One 2018; 13:e0202647.
28.
&
van Paassen P, Dijkstra M, Peay HL, et al. Perceptions of HIV cure and
willingness to participate in HIV cure-related trials among people enrolled in
the Netherlands cohort study on acute HIV infection. J Virus Erad 2022;
8:100072.
This study assessed the perception of HIV Cure and willingness to partake in cure-
related trials among Netherlands Cohort on Acute HIV Infection, who started ART
immediately after diagnosis. They found that participants had limited knowledge of
cure trials.
29. Saberi P, Campbell CK, Sauceda JA, et al. Perceptions of risks and benefits of
participating in HIV cure-related research among diverse young adults living
with HIV in the United States: qualitative research findings. AIDS Res Hum
Retroviruses 2022; 38:649– 659.
30. Dube
´K, Willenberg L, Dee L, et al. Re-examining the HIV ’functional cure’
oxymoron: time for precise terminology? J Virus Erad 2020; 6:100017.
31. Moodley K, Staunton C, de Roubaix M, Cotton M. HIV cure research in South
Africa: a preliminary exploration of stakeholder perspectives. AIDS Care
2016; 28:524– 527.
32. Sylla L, Evans D, Taylor J, et al. If we build it, will they come? perceptions of
HIV cure-related research by people living with HIV in four U.S. cities: a
qualitative focus group study. AIDS Res Hum Retroviruses 2018; 34:56 –66.
33.
&&
Campbell DM, Dube K, Cowlings PD, et al. It comes altogether as one:’’
perceptions of analytical treatment interruptions and partner protections,
among racial, ethnic, sex and gender diverse HIV serodifferent couples in
the United States. BMC Public Health 2022; 22:1317.
This study is important because the authors interviewed a broad range of racial,
ethnic, sex and sex minority populations in the USA to understand their perspec-
tives about ATI. The participants saw ATI as contrary to the HIV treatment
adherence message and strongly advocated for partner protection measures
including PrEP during ATI.
34.
&&
Lau JSY, Cromer D, Pinkevych M, et al. Balancing statistical power and risk in
HIV cure clinical trial design. J Infect Dis 2022; 226:236– 245.
This study used mathematical models to explore how ATI study design can be
improved. The sample size proposed that ATI studies should make their findings
meaningful.
35. Dube K, Sylla L, Dee L. Reply to commentary: ‘‘Are HIV-Infected Candidates
for Participation in Risky Cure-Related Studies Otherwise Healthy?’’. J Empir
Res Hum Res Ethics 2018; 13:23–25.
36. Garner SA, Rennie S, Ananworanich J, et al. Interrupting antiretroviral treat-
ment in HIV cure research: scientific and ethical considerations. J Virus Erad
2017; 3:82– 84.
37. Lau JSY, Smith MZ, Allan B, et al. Perspectives on analytical treatment
interruptions in people living with HIV and their healthcare providers in the
landscape of HIV cure-focused studies. AIDS Res Hum Retroviruses 2020;
36:260– 267.
38. Li JZ, Smith DM, Mellors JW. The need for treatment interruption studies and
biomarker, identification in the search for an HIV cure. AIDS 2015;
29:1429– 1432.
39. Lelie
`vre JD, Hocqueloux L. Unintended HIV-1 transmission to a sex partner in a
study of a therapeutic vaccine candidate. J Infect Dis 2019; 220(Suppl 1):
S5– S6.
40. Ugarte A, Romero Y, Tricas A, et al. Unintended HIV-1 infection during
analytical therapy interruption. J Infect Dis 2020; 221:1740 – 1742.
41. Dube
´K, Eskaf S, Hastie E, et al. Preliminary acceptability of a home-based
peripheral blood collection device for viral load testing in the context of
analytical treatment interruptions in HIV cure trials: results from a nationwide
survey in the United States. J Person Med 2022; 12:231.
42. Julg B, Dee L, Ananworanich J, et al. Recommendations for analytical anti-
retroviral treatment interruptions in HIV research trials-report of a consensus
meeting. Lancet HIV 2019; 6:e259– e268.
43. Giron LB, Palmer CS, Liu Q, et al. Noninvasive plasma, glycomic and
metabolic biomarkers of posttreatment control of HIV. Nat Commun 2021;
12:3922.
44. Giron LB, Papasavvas E, Yin X, et al. Phospholipid, metabolism is associated
with time to HIV rebound upon treatment interruption. mBio 2021; 12:
e03444-20; https://doi.org/10.1128/mBio.03444-20.
45. Dube K, Agarwal H, Carter WB, et al. Participant experiences, using novel
home-based blood collection device for viral load testing in the HIV cure trials,
with analytical treatment interruptions. HIV Res Clin Pract 2022; 23:76 –90.
46. Dube K, Evans D, Dee L, et al. We Need to Deploy Them, Very Thoughtfully
and Carefully’’: perceptions of analytical treatment interruptions in HIV, cure
research in the United States: a qualitative inquiry. AIDS Res Hum Retro-
viruses 2018; 34:67– 79.
47. Peluso MJ, Dee L, Campbell D, et al. A collaborative, multidisciplinary
approach to HIV transmission risk mitigation during analytic treatment, inter-
ruption. J Virus Erad 2020; 6:34–37.
48. Lau JSY, Smith MZ, Allan B, et al. Acceptability, motivation, and the prospect
of cure for people living with HIV and their healthcare providers in HIV, cure-
focused treatment interruption studies. AIDS Res Ther 2020; 17:65.
49. Protiere C, Fressard L, Mora M, et al. Characterization, of physicians that might
be reluctantto propose HIV cure-relatedclinical trialswith, treatment interruption
to their patients? The ANRS-APSEC Study. Vaccines (Basel) 2020; 8:334.
50. Stecher M, Klein F, Lehmann C, et al. Systematic review of, the current
literature on structured treatment interruptions in HIV-infected patients,
receiving antiretroviral therapy: implications for future HIV Cure Trials. Open
Forum Infect Dis 2016; 3(Suppl 1):S64 –S65.
51. Moodley K, Rossouw T, Staunton C, Colvin CJ. Synergies, tensions and
challenges in HIV, prevention, treatment and cure research: exploratory con-
versations with HIV experts in, South Africa. BMC Med Ethics 2016; 17:26.
52. Sylla L, Patel H, Louella M, et al. Community HIV clinicians’ perceptions about,
HIV cure-related research in the Northwestern United States. HIV Res Clin
Pract 2022; 23:61– 75.
53. Dube K, Kanazawa J, Dee L, et al. Ethical and practical, considerations for
mitigating risks to sexual partners during analytical treatment interruptions, in
HIV cure-related research. HIV Res Clin Pract 2021; 22:14 –30.
54.
&&
Dube K, Kanazawa J, Campbell C, et al. Considerations for increasing racial,
ethnic, gender, and sexual diversity in HIV cure-related research with analy-
tical treatment interruptions: a qualitative inquiry. AIDS Res Hum Retroviruse s
2022; 38:50– 63.
A study among Bioethicist, people living with HIV and their advocates, biomedical
cure researchers, sociobehavioural scientists and HIV care providers that was
dedicated to the question of ATI appropriateness.
55. Protiere C, Arnold M, Fiorentino M, et al. Differences in, HIV cure clinical trial
preferences of French people living with HIV and physicians in the, ANRS-
APSEC study: a discrete choiceexperiment. J Int AIDS Soc 2020; 23:e25443.
Implementation: PrEP, ART and vaccines
16 www.co-hivandaids.com Volume 18 Number 1 January 2023

56. Dube K, Simoni J, Louella M, et al. Acceptability of cell and gene therapy for
curing HIV infection among people living with HIV in the Northwestern, United
States: a qualitative study. AIDS Res Hum Retroviruses 2019; 35:649 –659.
57. Ndung’u T, McCune JM, Deeks SG. Why and where an HIV cure is needed
and how it might be achieved. Nature 2019; 576:397– 405.
58. Wulandari LPL, He SH, Fairley CK, et al. Preferences for preexposure
prophylaxis for HIV: a systematic review of discrete choice, experiments.
eClinicalMedicine 2022; 51:101507.
59.
&
Dommaraju S, Odeny TA, Okaka S, et al. Preferences of, people living with
HIV for differentiated care models in Kenya: a discrete choice experiment.
PLoS One 2021; 16:e0255650.
The article illustrates how DCE could be used for patient preferences in HIV care.
60. Bruns C. Using human-centered design to develop a program to engage
South African men, living with HIV in care and treatment. Glob Health Sci
Pract 2021; 9(Suppl 2):S234–S243; https://doi.org/10.9745/GHSP-D-21-
00239.
61.
&&
Mukherjee TI, Zerbe A, Falcao J, et al. Human-centered design for public
health innovation: codesigning a multicomponent intervention to support,
youth across the HIV care continuum in Mozambique. Glob Health Sci Pract
2022; 10:e2100664.
This article does an excellent job of showing how the five steps of design thinking
could be used to fashion an intervention for youth living with HIV in resource-limited
setting.
62. Beres LK, Simbeza S, Holmes CB, et al. Human-centered design lessons for
implementation science: improving the implementation of a, patient-centered
care intervention. J Acquir Immune Defic Syndr 2019; 82:S230 –S243.
63. Wittenberg E, Bharel M, Bridges JFP, et al. Using best-worst scaling to,
understand patient priorities: a case example of Papanicolaou tests for
homeless, women. Ann Fam Med 2016; 14:359 –364.
64. Hendriks A, Wijnen B, van Engelen R, et al. A best-worst, scaling in
Colombian patients to rank the characteristics of HIV/AIDS treatment. J
Med Econ 2018; 21:468– 473.
HIV cure: an acceptability scientific agenda Bonney et al.
1746-630X Copyright ©2022 The Author(s). Published by Wolters Kluwer Health, Inc. www.co-hivandaids.com 17