AMADAS ANÓNIMAS Y CASI OLVIDADAS

The quantitative survey results are presented in three sections, with key findings summarized after each section:

 In the first section, descriptive statistics from the sample of 400 survey respondents are presented. Because primary data from potential HIV cure-related studies are rare, the descriptive statistics obtained from this survey provide a rare glimpse at their attitudes and perceptions, and can be very informative to clinician-researchers and policy-makers in designing and recruiting for HIV cure studies in the future. Below, I summarized the key results from the descriptive statistics, drawing attention to particular results that revealed important findings.

 In the second section, bivariate associations of various factors with respondents’ willingness to participate – the dependent variable – are presented. The statistical significance and magnitude of the bivariate associations between respondents’ willingness to participate in all types of HIV cure-related studies and their perceptions of the importance of potential benefits in motivating their participation, their perceptions of the likelihood that certain potential risks could deter their participation, and their socio-demographic characteristics and global attitudes towards HIV cure research are examined.

 In the third section, I presented the results of the multivariate regression analyses. The

statistical significance and magnitude of the associations between willingness to participate and the respondents’ perceptions of the importance of each potential benefit and potential risk are examined, controlling for the socio-demographic characteristics.

Descriptive Statistics Table 3. Survey Sample Size

Survey responses Number

Respondents who completed the survey 343

Respondents who partially completed the survey (at least through the question of willingness to participate in HIV cure studies)

57

Respondents identifying they are ineligible to participate in the survey 9

Total survey responses 409

Total survey responses included in the analysis 400

After excluding five survey responses because of incompleteness of the responses, we recruited 409 study participants, of which 400 were eligible for the study and thus included in the analysis (Table 3). Of those, 343 respondents completed the survey by answering all questions and 57 partially completed the survey, but answered at least one question of interest regarding HIV cure research. Most questions were answered by more than 350 respondents. We did not make all the survey questions mandatory as this might have affected the survey completion and caused significant attrition issues. This was a convenience sample derived from willing respondents who had access to HIV treatment/cure listservs from which they were recruited. This sample was not representative of the entire community of people living with HIV in the United States. We discuss the limitations of the survey further in the Discussion section.

Figure 6. Gender of Respondents (n=400)

The gender of the respondents is represented in Figure 7. We recruited 77% males, 22% females and <1% transgendered individuals. One individual selected “other” but did not specify his/her gender identification. While this sample is not representative of the population of people living with HIV in the United States, it may reflect those who are interested in HIV cure-related issues. The sample has proportionally more females than a previous U.S. survey conducted in 2010 – 2011[49].

Figure 7. Age Group of Respondents (n=400)

Respondents ranged in ages between 19 and 74 years of age (Figure 8). The average age was 50 years old and the median was 51 years. The highest proportion of survey respondents were between the ages of 46 and 60 years old. This may again reflect those with an interest in HIV cure- related research in the United States. Younger ages may have been under-represented. The sample

derived may reflect the aging population of people living with HIV in the United States and this should be kept in mind for future HIV cure study design.

Figure 8. Ethnicity of Respondents (n=400)

Ethnicity of survey respondents is reflected in Figure 9. We obtained a sample that was ethnically diverse: 65% Caucasians/Whites, 17% African-Americans/Blacks, 12% Hispanic/Hispanic descent, and 4% mixed. This sample was also proportionally more diverse than the one derived from the previously completed U.S. survey on willingness to participate in HIV cure-related studies [49].

Figure 9. Highest Level of Education Completed (n=399)

Nearly all survey respondents had at least a high school or GED degree, 6% had some college, 20% had an associate degree, 26% had completed an undergraduate degree, 17% had completed a master’s degree or its equivalent and 6% had completed a doctorate degree (Figure

10). Compared to the previous U.S. survey [49], we were able to recruit respondents who were of proportionally lower educational backgrounds. This sample may be slightly more representative of the HIV epidemic in the United States, although it may remain biased towards those with greater income, who have access to the internet and HIV cure research information.

Figure 10. Yearly Household Income (U.S. Dollars) of Respondents (n=399)

Yearly household incomes of survey respondents are depicted in Figure 11. More than one- third (37%) earned less than $25,000 annually and another third (35%) earned more than $50,000 annually.

Figure 11. Residence of Survey Respondents (n=394) 6 respondents did not specify their place of residence

The map in Figure 12 shows the geographic distribution of the survey respondents. There were 38 states represented in the survey. The highest recruiter sites were California (n = 104), Florida (n = 26) and New York (n = 22). Outside of the continental United States, two respondents were from Puerto Rico. There were 6 respondents did not specify their place of residence.

Figure 12. Self-Reported Health Status of Respondents (n=400)

Figure 13. Respondents’ Feeling of Control over Health Care (n=400)

Most survey respondents (94%) described themselves as either very healthy, healthy or somewhat healthy (Figure 13). This may be because most (98%) of them were also taking HIV medication (2% were not taking HIV medication) (data not shown). Most (81%) also indicated that they had control over their own health, compared to 14% who did not have control (5% don’t know/not sure) (Figure 14).

Figure 14. Percentage of Respondents’ Lifetime Living with HIV Diagnosis (n=394)

Our survey included respondents who have been diagnosed with HIV for less than a year (3%) and up to 36 years. Half of the respondents have lived with an HIV diagnosis for 18 years or more. The distribution of years since first diagnosis is mostly uniform between <1 year and 30 years. We calculated the percentage of respondents’ lifetime living with an HIV diagnosis by dividing the difference between the number of years lived with HIV and the age of the respondents (Figure 15). If a respondent was first diagnosed with HIV in 2015, we used 0.5 in the numerator (instead of zero). The largest group (47%) had lived with HIV for 26 – 50% of their lifetime, followed with those who lived with HIV for up to 25% of their lifetime (37%). A significant minority of respondents (16%) have lived with HIV for more than half of their lifetime.

Volunteering for and participation in previous HIV treatment research was relatively high, at 44%, compared with 55% who never volunteered to take part in an HIV treatment study (figure not shown). Volunteering for a study does not necessarily mean than the respondent actually

Figure 15. Respondents have Ever Been in or Volunteered for an HIV Cure Study (n=400) In comparison, a smaller proportion of survey respondents had ever volunteered for or participated in HIV cure-related studies (7%), compared with 91% who had never volunteered nor participated (Figure 16). A total of 6.2% indicated that they actually participated in at least one HIV cure study. We did not define “HIV cure research participation” so this figure reflected the

participants’ own interpretation of HIV cure-related research. Only 7 out of 400 survey respondents were currently enrolled in an HIV cure-related study.

With regards to general interest in HIV cure research, 97% of respondents said that they were interested (versus 1% that answered no) and 95% answered that they were generally interested in medical issues (versus 3% that were specifically not interested) (data not shown).

Figure 16. Willingness to Consider Participating in HIV Cure-Related Studies

We asked survey respondents to indicate whether they would consider participating in 14 different types of HIV cure-related studies (Figure 17). We provided the definitions of these different cure strategies in lay terms and used the survey as an educational opportunity. Respondents were able to answer “Yes”, “No”, or “Don’t know/not sure” for any and all 14 types of studies, or skip any of the questions. The response rate for each of the 14 types was approximately n = 350 – 360 out of a possible 400. In addition, we asked a separate question asking if respondents would be willing to enroll their infant living with HIV in a pediatric HIV cure-related study, which resulted in a much smaller response rate (n=169). For each of the main 14 types of HIV cure-related studies, more than 50% of those who responded indicated they would be willing to participate in that study type. The highest rejection rate was 21% for studies that involve latency reversing agents. For many study types, the response rate for “Don’t know/not sure” exceeded the response rate for “No.”

Willingness to participate may not reflect actual participation in the future, the

would quality for or enter. However, the graph shows the hierarchy of the different kinds of studies that potential participants would be explicitly willing to join. Respondents were more willing to participate in simple studies (e.g. surveys, basic blood draws, interviews and focus groups) than in studies that are seemingly riskiest modalities (e.g. transplanting stem cells, use of latency-reversing agents and intensification of HIV treatment). The higher the level of intervention, the lower the willingness to participate rate and the greater the rejection rate and the unsure rate are. These data may underscore the need to better educate potential volunteers about the different types of HIV cure studies and their potential risks. While most studies currently enrolling participants are pilot studies with small number of participants, these data should be kept in mind as studies get scaled up.

Figure 17. Total Number of Types of HIV Cure-Related Studies respondents are Willing to Consider Participating in (n=361)

A total of 361 respondents answered “Yes” or “No” to being willing to participate in at least one of the 14 types of studies (Figure 18). Of the 361 respondents, 26% indicated that they would be willing to participate in all 14 types of studies, while the other 74% were willing to participate in some (or none) of the studies but not all 14. This makes up the dependent variable in the bivariate and multivariate quantitative analysis. Respondents who were willing to participate in all 14 types of

studies are defined as “very willing to participate” in HIV cure-related studies, while the other 74% are defined as “relatively less willing to participate.” It is important to remember that the relatively less willing to participate respondents may be willing to participate in several types of HIV cure- related studies, but they are simply not yet willing to participate in all types of studies that we asked about. In general, nearly half (48%) were willing to participate in at least 12 of the 14 types of studies, and only 1% were expressly unwilling to participate in any type of HIV cure-related studies, including the lowest risk modalities.

We compared two sets of questions: considering participation in the different types of HIV cure-related studies, given that one had previously participated in a similar (HIV or non-HIV) health study in the past (Figure 19). The sample size was too small to make any significant observations or comparisons for many types of studies and we should be cautious when interpreting claims based on a sample of 2, 3, 4 or 5 people for some of the types of studies (e.g. gene therapy, unique antibodies or molecules, latency-reversing agents, therapeutic vaccines or first-in-human studies). Nonetheless, based on their prior experience, data show that most participants would be willing to participate in HIV cure studies that are similar to studies they had participated in the past.

Participants are most reluctant, however, to consider participating in future HIV cure-related studies that would involve: 1) intensification of treatment, 2) phase II or III studies or 3) focus group

discussions (red bars in Figure 19 below).

Using Likert scales, we asked participants to indicate which potential benefits would either be very important, somewhat important, barely important or not at all important in their motivation to consider participating in HIV cure-related studies. Figure 19 below shows each factor in relation to the others, but also shows the relative importance of the “personal benefits,” “clinical benefits” and “social benefits” categories compared to each other. The perceived clinical benefits or social

benefits appear to be more important motivators, on average, than personal benefits when considered as a category.

Figure 18. Willingness to Consider Participating in HIV Cure-Related Studies after Having Previously Participated in Similar (HIV or non-HIV) Health Study in the Past

Figure 19. Importance of Factors to Motivate Considering Participating in HIV Cure-Related Studies Highlighting specific motivational factors (Figure 20 above), we note that:

 Although HIV cure studies confer little to no benefit, it is possible that potential study participants still perceive the likelihood of benefits when deciding to join studies.

 The data show that we should not underestimate the importance of emotional and mental benefits in HIV cure research participation, since feeling good about contributing to HIV cure research is the most popular perceived personal benefit (80% very likely to

motivate), and social benefits of helping find a cure for HIV, helping other people with HIV in the future and contributing to scientific knowledge were three of the four highest ranked benefits overall (95%, 90% and 88% very likely to motivate, respectively).

 Potential participants value gaining knowledge about their health (78% very likely to motivate). This is interesting as most of the research data are not given to the study participants individually. This raises questions about the need to communicate study data (in the aggregate) and advancements in science to study participants and may highlight the importance of clinical contact factors for study participants.

 Hope that health will improve was also a strong motivating factor. Again, research may not confer direct clinical benefits and in fact, there is the possibility of harm when advancing medical knowledge. The high rating of this factor underscores the need to protect against the risk of therapeutic and curative misconception.

 There are also perceived potential personal clinical benefits, such as the desire to improve one’s immune system.

 Reducing the HIV reservoir was perceived as a clinical benefit although we know from research that a reservoir decrease may not confer any direct clinical benefit. Study participants would need a substantial (logs worth) reduction in the size of their proviral DNA replication-competent HIV reservoir in order to reduce time to viral rebound. Scientists need to be careful how reservoir reductions are discussed in the informed consent forms.

 Compensation in the form of meals, reimbursements and transportation costs were the three lowest ranked motivating factors overall.

Figure 20. Likelihood of Factors to Discourage Considering Participation in HIV Cure-Related Studies

In terms of the perceived risks likely to discourage considering participating in HIV cure research, personal clinical risks appeared to be more likely to demotivate than personal risks or burdens or potential social risks (Figure 21). Activation of genes that would cause cancer (49% very likely to discourage) and the possibility of developing resistance to HIV treatment (37% very likely to discourage) were the most prevalent deterrents. The need for intense commitment did not appear to be strong deterrents of participation. Spinal tap (26% very likely to discourage) and bone marrow biopsies (22% very likely to discourage) were the least favorite study procedures. Hair loss (32% very likely to discourage) was a stronger possible deterrent than more immediate symptoms/side effects, such as vomiting (23%), pain (14%), headache (13%) or nausea (13%). The burden categories reveal that we should not underestimate the importance of addressing possible obstacles like

transportation or parking to encourage participation. Finally, the risk of transmitting HIV to others (in the case of an unsuspected viral rebound) was a real possible deterrent (28% very likely to discourage), and may speak to the desire of study participants to “do no harm” during their study participation.

Figure 21. Willingness to Stop HIV Treatment as Part of an HIV Cure-Related Study (n=359)

An important feature of some HIV cure research design is the need to interrupt treatment to assess time to viral rebound or predictors of rebound. Among the survey respondents, 68% of

potential HIV cure research participants were very willing or somewhat willing to stop treatment as part of HIV cure research (Figure 22). These numbers are somewhat higher than those obtained in the previous U.S. survey, whereas one third (34%) of respondents stated that they would be very willing or willing to participate in a study that involved treatment interruption, compared to 34% who said that they would be somewhat willing and 32% said that they would not be at all willing [49]. These results may reflect the different study sample used or the need to better educate potential study participants about the possible risks of treatment interruption.

Figure 22. Importance of Factors in Making a Decision about Considering Participation in an HIV Cure-Related Study

Survey participants rated the importance of various practical factors in making a decision to participate in an HIV cure study (Figure 23). The HIV cure research modality being investigated (58%) was slightly more important than the research site (56%), the way information was given (55%), the Principal Investigator (44%) or the study nurse of the study (32%).

Figure 23. How would Participants Most Likely Describe Themselves in they were to Participate in an HIV Cure-Related Study (n=348)

Potential HIV cure research volunteers would also prefer to be described as “study participants” (44%), “partners in research” (25%) or “volunteers” (10%), as opposed to “research subjects” (8%), “patients” (7%) or “guinea pig” (Figure 24). These appellations show the importance of treating study participants with respect and to be careful with terms used to describe them and are consistent with the qualitative study results.

Figure 24. Personal Beliefs about an HIV Cure

Furthermore, we asked survey respondents to answer whether they thought they could be cured versus whether they hoped they could be cured. The hope of being cured (90% of survey respondents) was higher than the expected possibility that one could actually be cured (47% of

study respondents). Hope to be cured – now or in the future – may possibly be a strong motivating factor in whether to join a study.

Figure 25. How Many Years Do Participants Think it will take to Find a Cure for HIV (n=350) We were surprised to find that 8% of participants thought a cure for HIV infection was presently in existence (Figure 26). This finding seems incompatible with the fact that our

convenience sample has regular access to HIV-related information about treatment or cure. The majority of survey respondents thought a cure would be available within 5 years (27%) or in 6 – 10 years (33%). Close to a third (27%) thought a cure would take between 11 – 50 years to be

discovered. A tiny fraction (3%) thought a cure would never materialize.

A cure for HIV infection should meet the expectations of the people living with HIV. We thus asked the survey respondents to report what a cure meant to them (categories were provided). Not transmitting HIV to others (68%), completely eliminating HIV from the body (68%) and no more HIV treatment needed (65%) emerged as the three strongest categories, above the practical factors of no longer testing positive on the antibody HIV test (31%).

In summary, key descriptive findings from the survey include: