HIV cure: an acceptability scientific agenda : Current Opinion in HIV and AIDS

Secondary Logo

Journal Logo

IMPLEMENTATION: PREP, ART AND VACCINES: Edited by Elvin Geng

HIV cure: an acceptability scientific agenda

Bonney, Evelyn Y.a; Lamptey, Helenab; Kyei, George B.a,b,c

Author Information
Current Opinion in HIV and AIDS 18(1):p 12-17, January 2023. | DOI: 10.1097/COH.0000000000000771
  • Open

Abstract

INTRODUCTION

Although antiretroviral therapy (ART) has been revolutionary in transforming HIV from a death sentence 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]. 

FB1
Box 1:
no caption available

The main obstacle to an HIV cure is the persistence of transcriptionally silent and immunologically inert latent proviruses in quiescent memory CD4+ 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 investigated for an HIV cure. First, is the shock and kill approach (latency reactivation), whereby small molecules are used to force proviral reactivation from latency under the cover of ART. Induction of de-novo virion synthesis is then 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 molecules will be used to modify the surroundings of the integrated virus to send it into ‘deep latency’ such that upon discontinuation of ART, the virus will not reactivate [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, immunotherapies such as the use of broadly neutralizing antibodies 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 pursued [10,23▪▪]. Each approach may lead to treatments 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 dimensions 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 developed 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 qualify as cure. Researchers anticipate the two forms of cure. The first, termed ‘eradication cure’ or ‘sterilizing cure’ involves complete eradication of all replication-competent provirus from the infected person, including removal of viruses in cellular and anatomical reservoirs [2,3▪,10,25,26]. The second 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 eradication cure as the ideal. However, given the enormous difficulty that eradication of HIV presents to researchers, a more likely scenario will 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, instead of 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 participants were not aware of functional cure, when it was explained to them, 90% were willing to participate in long-term remission trials. In qualitative interviews done 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 studies 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 (50 copies/ml) after participants stop ART and the time taken for the viral load to reach the threshold for restarting ART (which can range from 1000 to 10 000 copies/ml) depending on the study [34▪▪]. Set-point studies evaluate the participants’ immune systems’ control of HIV during treatment interruptions. These are much longer studies 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]; therefore, frequent viral load measurements, often once week, must be done to inform when ART should be resumed [45]. This may inconvenience trial participants 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 differences in 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 including 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 most patients 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 establishment.

It is important to emphasize that many stakeholders in the fight against HIV do not fully understand 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 preexposure 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 different side effects, time commitment for trial participation, length of trial and frequency of monitoring, factors that may determine whether patients want to participate. Few studies have examined stakeholder 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. Participants were made to choose and make tradeoffs between cure types (immunotherapy, latency reversal, gene therapy and combination therapies) and trial characteristics, namely trial duration, consultation frequency, trial outcomes and moderate and severe side effects. Overall, patients preferred immunotherapy, 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 determine 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 participation in cure related clinical trials were done outside Africa where the greatest burden of HIV exists. Therefore, it is not clear what people living in Africa want from an HIV cure. Some of the strategies such as gene therapy, for example modification of T cell ex vivo and reinfusion into 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 determining 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 accomplish this goal will require deliberate collaborations among basic scientists, economists, implementation scientists, clinical trialists and social and behavioural scientists. Collaboration is critical because true identification 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 different 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 termination 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 backgrounds could come together to perform these important 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 work to 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 participate in trials. Most studies show that patients and caregivers know little about the HIV cure strategies that are being developed [48,52]. Education and advocacy 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, ethicists, 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

REFERENCES

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.
4. Cohn LB, Chomont N, Deeks SG. The biology of the HIV-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.
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 naïve and experienced men who have sex with men living with HIV. BMC Infect Dis 2022; 22:383.
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/research-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 CD4+ T 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 CD4+ T.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▪▪. Dubé K, Kanazawa J, Dee L, et al. Considerations for designing and implementing combination HIV cure trials: findings from a qualitative in-depth, interview study in the United States. AIDS Res Ther 2021; 18:75.
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.
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. Dubé 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.
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.
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 treatment 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. Lelièvre 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. Dubé 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 antiretroviral 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:e03444-20https://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 Retroviruses 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, interruption. 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 reluctant to propose HIV cure-related clinical trials with, 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 conversations 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 analytical treatment interruptions: a qualitative inquiry. AIDS Res Hum Retroviruses 2022; 38:50–63.
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 choice experiment. J Int AIDS Soc 2020; 23:e25443.
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.
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.
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.
Keywords:

analytical treatment interruption; HIV cure; HIV cure acceptability; HIV cure research

Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc.