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A global survey of HIV-positive people's attitudes towards cure research
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Download the PDF here
from Jules: sounds like generally HIV prospective cure study participants do not really understand much about cure or participating in a cure research study and the risks.
HIV Medicine Feb 2017 - R Simmons,1 M Kall,2 S Collins,3 G Cairns,4 S Taylor,5 M Nelson,6 S Fidler,7 K Porter1 and J Fox8 on behalf of the
Collaborative HIV Eradication of viral Reservoirs (CHERUB) Survey collaboration
1MRC, Clinical Trials Unit University College, London, UK, 2Public Health England, London, UK, 3i-Base, London, UK,
4NAM, London, UK, 5Birmingham Heartlands Hospital, Birmingham, UK, 6Chelsea and Westminster Hospital, London,
UK, 7Imperial College, London, UK and 8Guy's and St Thomas' Hospital, London, UK
Abstract
Objectives
Involvement of people living with HIV (PLHIV) in the design of HIV cure studies is important, given the potential risks to participants. We present results of an international survey of PLHIV to define these issues and inform cure research.
Methods
PLHIV were recruited in June−November 2014 through HIV websites, advocacy forums, social media and 12 UK HIV clinics. The survey included questions concerning demographics, HIV disease history, the desirability of types of cure and the patient's willingness to accept potential toxicity and treatment interruption (TI). We examined factors associated with TI and willingness to accept substantial risks.
Results
A total of 982 PLHIV completed the survey; 87% were male, 79% white and 81% men who have sex with men (MSM). Fifty-one per cent were aged 25-44 years and 69% were UK residents. The median time since diagnosis was 7 years [interquartile range (IQR) 2-17 years]. Eighty-eight per cent were receiving antiretrovirals (91% reported undetectable viral load). Health/wellbeing improvements (96%) and an inability to transmit HIV (90%) were more desirable cure characteristics than testing HIV-negative (69%).
Ninety-five per cent were interested in participating in cure studies, and 59% were willing to accept substantial risks. PLHIV with a low CD4 count [201-350 cells/μL vs. ≥ 350 cells/μL; odds ratio (OR) 2.11; 95% confidence interval (CI) 1.11-4.00] were more likely to accept risks, whereas those with limited knowledge of HIV treatments vs. excellent/good knowledge and those aged ≥ 65 years vs. 45-64 years were less likely to accept risks [OR 0.58 (95% CI 0.37-0.90) and OR 0.18 (95% CI 0.07-0.45), respectively].
TI was acceptable for 62% of participants, with the main concerns being becoming unwell (82%), becoming infectious (76%) and HIV spreading through the body (76%).
Conclusions
Cure research was highly acceptable to the PLHIV surveyed. Most individuals would accept risks, including TI, even in the absence of personal benefit. An optimal cure would improve health and minimize onward transmission risk.
Introduction
Combination antiretroviral therapy (cART) for HIV infection has been immensely successful at reducing mortality and morbidity and prolonging life expectancy [1-4] but requires lifelong adherence to medication which might have unknown long-term side effects. The prospect of taking treatment for decades drives the strong community interest in an HIV cure, to remove the necessity for continuous drug adherence and to limit side effects while also reducing the risk of onward transmission.
To date, a sterilizing cure, that is, elimination of HIV, has been achieved only once, by a Berlin patient who has remained virus free since 2007 [5]. However, remission of HIV infection has been observed in a number of small groups of individuals in the Viro-Immunological Sustained CONtrol after Treatment Interruption (VISCONTI) study who initiated cART in primary HIV infection (PHI), where 15.6% of individuals maintained viral suppression for a number of years after interrupting therapy [6], and most recently in a child receiving ART from birth [6].
A number of phase I/II clinical trials are currently underway to investigate novel interventions, in addition to cART, that may act to limit the viral reservoir and hence confer either remission or sterilizing cure modalities [7]. These are "proof-of-concept" studies which aim to assess the safety and efficacy of a novel intervention, and are not intended or expected to cure HIV infection in the research participants [8]. Moreover, trials may require treatment interruption to allow assessment of the intervention.
The prospect of asking healthy people living with HIV (PLHIV) to enter a research study without any expectation of a medical benefit and often with highly uncertain risks raises ethical questions [9-11]. Finding an acceptable risk−benefit balance is important in order for a clinical trial to proceed. Consultation with HIV community groups and PLHIV is vital to inform the design of cure studies, so that participant needs are met, the ability to enrol is assessed and an understanding is gained of the knowledge base of targeted groups and what risks they would deem acceptable.
We conducted a broad-ranging web-based survey asking PLHIV to address key issues in HIV cure research in order to gain an understanding of the beliefs about cure, motivations and concerns about taking part in cure studies. We aimed to identify factors associated with willingness to participate in cure research and willingness to interrupt cART within a cure study.
Ninety-five per cent (929) of respondents (with no sex difference) were willing to participate in a cure study, with no significant difference in willingness between sterilizing and remission cure studies (92% and 87%, respectively). Seventy-one per cent (697 of 979) of respondents would participate in a cure study even if there were no personal benefits. Over half (55%) of respondents believed a cure was likely within 10 years. Participation in a study was more likely if a cure was believed to be likely within 5 years compared with 10 years (92% vs. 86%, respectively; P < 0.001).
Perceptions of a cure
The most desired cure outcomes were: 'no risk of HIV-related health problems' (96%), 'never need to take HIV medications' (91%), 'no longer having HIV in your body' (91%) and 'no risk of passing HIV to sexual partners (even off treatment)' (91%). The least desired cure outcomes were: 'stopping HIV medications for a number of years but possibility of restarting' (62%), 'ability to inform people that they did not have HIV '(67%), and 'testing HIV negative' (69%) (Fig. 1). Individuals diagnosed within the past 2 years were more likely to find the following categories extremely desirable compared with those diagnosed earlier: 'testing HIV negative '(P-trend <0.001), 'telling people that you do not have HIV' (P-trend < 0.001), 'no longer having HIV in your body' (P-trend = 0.007), 'no longer having to see a doctor for regular monitoring' (P-trend = 0.04), and 'no longer feel bad or worry because you have HIV' (P-trend = 0.03).
Factors associated with accepting substantial risks
Overall, 59% (576 of 982) of participants were willing to accept substantial risks. Twenty-three per cent (227 of 978) would agree to allowing their CD4 cell count to drop to 200 cells/μL, 39% (379 of 978) would allow their viral load to be detectable for 6 months or more (15% would allow both), and 34% (332 of 981) would accept severe or extremely severe side effects without personal benefit.
The only factors associated with accepting substantial risks were a current CD4 count of 201-350 cells/μL (P = 0.001) and a detectable viral load (P = 0.04), whereas older respondents (P = 0.001), those diagnosed in the past 2 years (P = 0.03), those with limited knowledge about HIV or HIV treatments (P = 0.008) and those who had never had a CD4 count <350 cells/μL (P = 0.006) were less likely to accept substantial risks.
After adjustment for all factors in multivariable logistic regression models (Table 3), factors associated with being willing to participate in, and accepting extreme outcomes as part of, cure research were having a current CD4 count of 201-350 cells/μL compared with a current CD4 count of ≥350 cells/μL [odds ratio (OR) 2.11; 95% confidence interval (CI) 1.11, 4.00] and being USA-born compared with UK-born (OR 1.68; 95% CI 1.00-2.83). Those with little or no knowledge about HIV or HIV treatments compared with excellent/good knowledge were less likely to agree to accept substantial risks (OR 0.58; 95% CI 0.37-0.90), as were those aged ≥ 65 years compared with those aged 45-64 years (OR 0.18; 95% CI 0.07-0.45).
Factors associated with accepting treatment interruption
A treatment interruption of some months as part of a clinical trial was reported as acceptable ("yes, definitely" or "probably") for 62% (606 of 979) of respondents. No single factor was identified as being associated with willingness to have a treatment interruption. The major concerns with a treatment interruption were: becoming unwell (82% reporting being "very or moderately concerned"), CD4 T-cell count decreases (72%) and viral load becoming detectable (72%). Irrespective of sex, becoming unwell was the leading concern; however, a higher proportion of women were more concerned than men about CD4 count decrease (76% vs. 71%, respectively), a detectable viral load (78% vs. 71%) and HIV spreading through their body (81% vs. 76%) (Fig. 2).
Discussion
Our results indicate a high level of interest in HIV cure research among self-selected survey respondents, regardless of demographic or immunological status, personal benefit or risk and the type of cure offered (sterilizing or remission). An optimal cure was linked with personal health and reduced infectiousness. Notably, eliminating the risk of HIV-related health problems was more desirable than testing HIV negative or informing persons of their status. Treatment interruption was considered acceptable by the majority, with over half of respondents willing to accept risks much greater than would be expected as part of a structured treatment interruption.
Little difference was found in the willingness of persons to participate in a sterilizing or remission cure study, which is reassuring given current progress skewed towards a functional cure [12]. This contrasts with a small Australian survey (n = 20) of persons participating in a cure clinical trial who indicated a strong preference for a sterilizing cure [13].
Our results suggest that participation in cure research irrespective of personal benefits can be anticipated to be high, despite risks, which may include a treatment interruption. These findings were similar to responses among PLHIV at a Food and Drug Administration (FDA) meeting on drug development and HIV cure research [14]. Two in five respondents were willing to allow a detectable viral load, one in three were willing to endure side effects, and one in five were willing to have a low CD4 count. Those less likely to participate in cure trials were older individuals, consistent with other areas of research such as cancer research [15], and those more likely to participate were those with a good knowledge of HIV science and HIV treatments.
The most clinically relevant cure trial requires a treatment interruption. A much larger US survey identified that participation in treatment interruption studies was linked to altruistic and health resource considerations [16]. With uniform health care in our primarily UK-based survey, high levels of acceptability of treatment interruption as part of cure research were found regardless of age group, immune status and treatment history, with no independent predictors for participating in a treatment interruption identified. The main concern with treatment interruption was becoming unwell rather than CD4 cell count decline or viral load becoming detectable. In reality, treatment interruption in cure studies involves intensive viral load monitoring with immediate intensification upon viral rebound, which should be explained to participants at enrolment.
Peay et al. suggested that the term 'cure' could result in unrealistic expectations, particularly in regard to personal benefit, and careful consideration should be given to the language when recruiting persons for research purposes [10]. However, our findings contradict this view, with participants reporting a realistic expectation of the time to a cure and a willingness to take part in cure trials with no personal benefit.
Interestingly, participants were less interested in testing negative than they were in personal health benefit and being noninfectious, consistent with findings among the Australian respondents [13]. However, the responses in this study are a reflection of time since HIV diagnosis, with those recently diagnosed being more likely to focus on emotional/social aspects rather than personal health.
Our study tried to reflect the views of PLHIV towards cure research to improve study design and recruitment processes, and to focus on patient-led outcomes. The high proportion of respondents taking the time to complete the free-text field suggests enthusiasm for research in this field, which represents an opportunity to engage the community in cure research development.
The main limitation of the study was the lack of diversity in terms of gender, ethnicity and sexual orientation, which is common in such research and may reflect the predominately online recruitment method. Respondents were, however, geographically representative among PLHIV resident within the UK [17]. In contrast to previous surveys, however, respondents were not heavily treatment experienced, had relatively high CD4 counts and were relatively recently diagnosed, which makes this survey more aligned to potential cure trial participants than previous studies. Further work is needed to reach women and nonwhite populations to determine whether the factors associated with their participation differ.
Overall, there are high levels of enthusiasm for HIV cure research among PLHIV. Cure programmes aimed at a functional cure (which includes a health benefit and reduced infectiousness) are desired as much as a sterilizing cure. Clinically relevant cure outcomes that PLHIV can relate to must be incorporated into HIV cure research strategies and surrogate markers of these factors included as outcomes.
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