Willingness to participate in future HIV vaccine trials among men who have sex with men and female sex workers living in Nairobi, Kenya.

OBJECTIVE: To evaluate factors associated with willingness to participate in future HIV vaccine trials among men who have sex with men and female sex workers living in Nairobi, Kenya.
BACKGROUND: Working with 'key populations', those at elevated risk of HIV acquisition, is important to conduct efficient HIV prevention trials. In Nairobi Kenya, HIV infection is higher in men who have sex with men (MSM) and female sex workers (FSW) than in the general adult population, hence the need to establish if they would be willing to participate in future HIV vaccine trials.
METHODS: We administered a structured questionnaire to MSM and FSW enrolled in a simulated vaccine efficacy trial (SiVET). The SiVET was an observational study designed to mimic the rigors of a clinical trial to assess HIV risk characteristics at baseline. After 12-15 months of follow-up, a structured questionnaire was administered to evaluate hypothetical willingness to participate in future HIV vaccine trials.
RESULTS: Of 250 persons (80% MSM by design) enrolled in SiVET, 214 attended the final study visit and 174 (81%) of them expressed hypothetical willingness to participate in future HIV vaccine trials. These were 82% of MSM and 80% of FSW of those who attended the final study visit. Having a very good experience in the SiVET trial predicted willingness to participate in future HIV vaccine trials. Motivating factors for participation included a desire to receive education about HIV (59%) and to receive healthcare (57%).
CONCLUSIONS: Our data demonstrate high willingness among key populations in Kenya, to participate in future HIV vaccine trials after completing participation in a SiVET. The findings suggest that these groups might be a reliable target population for consideration in future HIV vaccine trials. Assessment of willingness to participate in these populations provides important information that may help to inform future education and recruitment efforts for vaccine trials. Improving the research experience for members of key populations could impact their willingness to participate in HIV vaccine trials.

Introduction

The world continues to experience the challenge of the HIV/AIDS pandemic; based on 2018 estimates, 37.9 million people are living with HIV around the world with 67% of these people living in sub-Saharan Africa and 1.6 million people in Kenya [1-5]. Interventions for prevention and treatment of HIV, including behavioural, structural and biomedical options, have become increasingly available and helped to combat the pandemic [1, 2, 5].

Over the past three decades there has been a drop in the annual number of new HIV infections, from a peak of 2.9 million globally in 1997 to 1.7 million in 2018 and a decline in the global incidence–prevalence ratio, from 11.2% in 2000 to 4.6% in 2018. Despite the overall decline in new HIV infections, sub-Saharan Africa continues to contribute the majority of incident cases with 800,000 new infections in 2018 [3, 5, 6]. Progress is slower than what is required to reach the world 2020 milestone of less than 500,000 new infections [1, 2, 5].More than half of the new infections are among members of key populations, and their sexual partners, who are at a higher risk of HIV infection compared to the general population. Men who have sex with men (MSM) and sex workers are 21times more likely to acquire HIV infection compared to adults in the general population and account for 17% and 6% of the new global infections [5]. In Kenya, among MSM, the incidence has been reported at 10.9 per 100 person-years of observation [7] and among female sex workers (FSW), at 5.6 per 100 person-years of observation [8]. This is estimated to account for 14–15% of all new infections in the country [9, 10]. The high incidence results in a relatively high national HIV prevalence, among FSW at 29.3% and MSM at 18.2% [10].

The high HIV incidence among key populations is indicative of an unmet medical need for HIV prevention services including the need for a safe and effective HIV vaccine to end the pandemic [4, 11]. Prioritizing key populations for prevention and treatment is likely to have a significant effect on reducing HIV transmission and the national burden of disease in Kenya [6, 12]. Key populations are suitable for inclusion in efficacy trials as the primary beneficiaries of an effective HIV vaccine [11, 13].

To achieve the objectives of any HIV prevention clinical trial, understanding logistic and statistical power considerations and ensuring participants are motivated to complete the study are all key issues [14]. Preparedness studies can be important precursors but ‘willingness to participate’ studies do not always predict actual participation, perhaps in part because it is hard to convey the commitment necessary to the potential participants [15, 16]. Simulated Vaccine Efficacy Trials (SiVETs) are observational studies that have been designed to mirror the procedures of actual HIV vaccine trials. SiVETs enable researchers to gauge important elements in clinical trials including; recruitment, enrolment, retention of the suitable population, participant compliance with protocol procedures, willingness to participate in the trials and evaluate potential barriers to participation [17, 18]. SiVETs have been performed among high risk populations in several countries including Uganda [13, 19], Zambia [20] and South Africa [18]. Such trials have not previously been conducted among MSM and FSW in Kenya.

Between Oct 2017 and Sep 2018, we interviewed MSM and FSW who had completed participation in a SiVET in Nairobi, Kenya, to determine their willingness to participate in future HIV vaccine trials.

Methods

Setting

Potential participants were recruited from the Sex Workers Outreach Program (SWOP-Kenya) clinics serving FSW and MSM in Nairobi after community engagement and demand creation activities. The program offers services including HIV risk reduction counselling, anti-retroviral treatment (ART), HIV pre-exposure prophylaxis (PrEP), condoms and family planning services and diagnosis and treatment of sexually transmitted infections (STI) in an FSW and MSM friendly setting. Participants were referred and escorted from SWOP-Kenya clinics to the KAVI-Institute of Clinical research (KAVI-ICR) of the University of Nairobi.

Sample size

A sample size of 250 for the SiVET was calculated based on being able to estimate a one-year retention rate of 80% with a precision of ±5%. The target was to enrol 200 MSM and 50 FSW. The choice to enrol 20% FSW was deliberate because HIV incidence is higher among Kenyan MSM than Kenyan FSW; we also wished to avoid stigma and any hard feelings among our partners at SWOP-Kenya and agreed that enrolling some women would be appropriate.

Recruitment and screening

SWOP-Kenya clinic staff and affiliated peer outreach workers recruited potential participants from the clinics and hot spots, providing background information about the SiVET study. Hot spots are areas such as streets, bars, hotels or massage parlours in Nairobi where sex workers operate. HIV-uninfected persons were asked to participate in a study that entailed the delivery of hepatitis B vaccination to mirror the requirements of a HIV vaccine efficacy trial requiring follow up for 12 to 15 months (follow up was initially set to 15 months, but later amended to 12 months due to logistical and funding reasons). Those interested were pre-screened and then referred to KAVI-ICR for more information about the trial, an assessment of understanding of the study requirements, after which participants signed informed consent forms.

KAVI-ICR staff screened participants on the following eligibility criteria: age 18 years and above, residing in Nairobi, sexually active in the preceding 3months, willing to undergo HIV risk assessment and HIV testing, able to provide contact information, willing to be contacted by study staff and willing to return for study visits. FSW had to be actively involved in sex work for at least 3 months before screening and agree to use long-acting reversible non-barrier contraceptives such as injectable and implantable hormonal contraceptives, intrauterine devices or had a documented tubal ligation. We excluded participants who were HIV infected, had active hepatitis B infection, were known to be pregnant or were nursing mothers, had prior severe reactions to vaccines or had any significant clinical condition as assessed by the investigator.

Study data

At enrolment, participants completed an interviewer-administered questionnaire on sociodemographics, HIV risk behaviour and knowledge of HIV prevention methods. Information on their past medical history, including vaccinations and adverse reactions to vaccines, was also obtained.

Sociodemographic data included age and the highest level of education achieved. For the assessment of HIV risk behaviour we asked about: Frequency of alcohol consumption, the number of sex partners and new sex partners, use of any illicit drugs, practice of insertive or receptive anal sex and frequency of condom use in the preceding month. We administered an alcohol use disorder screening test, the CAGE [21] instrument, to classify participants.

We evaluated HIV prevention knowledge by asking participants: ‘How do you think HIV/AIDS can be prevented from an infected person to an uninfected person?’ Participants’ responses were then scored using a predetermined list of correct ways to prevent HIV infection categorized into behavioural and biomedical prevention methods. Biomedical prevention methods included pre-exposure prophylaxis, post-exposure prophylaxis, prevention of mother to child transmission, treatment as prevention, and voluntary medical male circumcision. Behavioural prevention methods included abstinence, condom use, monogamy, limiting the number of sexual partners, use of clean needles by injecting drug users, and avoiding sharing razors/blades/injection needles.

At the participants’ last visit, those who were HIV negative completed an interview questionnaire on willingness to participate in HIV vaccine trials. While those who were HIV infected were excluded from the interview. We asked the following question: ‘Would you be willing to participate in a future HIV vaccine trial if it had exactly the same procedures as the SiVET study?’ Possible responses were ‘yes very likely’, ‘maybe yes’, ‘maybe not’, ‘no not at all’, and ‘don’t know’. Participants gave reasons for their responses.

Statistical methods

Data were captured and managed in OpenClinica version 3.0, transferred and analysed in STATA version 14.0. Overall and stratified (MSM and FSW) data on sociodemographics, HIV risk behaviour, HIV prevention knowledge and their SiVET experience were summarised using frequency and percentages. Participants were classified as willing to participate in future HIV vaccine trials if their response was ‘yes very likely’ or ‘maybe yes’ to participate in an HIV vaccine efficacy trial designed in the same way as the SiVET. We used chi-square tests to assess the relationship between participants’ willingness to participate and their sociodemographic characteristics, HIV risk behaviour, HIV prevention knowledge and their SiVET experience for both the overall data and the data stratified by population (MSM and FSW).

Univariate logistic regression was used to evaluate the association of all variables with willingness to participate; factors associated with willingness to participate at p<0.20 on log likelihood test were included in the initial multivariable model (except for age and trial population that were included a priori). Factors were retained in the multivariable model if the log likelihood test p-value of inclusion of a factor was less than 0.05.

Ethical statement

The study protocol was approved by the research ethics committee of Kenyatta National Hospital and University of Nairobi (KNH-UoN ERC; Ethical approval number P137/03/2015). Written informed consent to participate in the SiVETstudy was provided by all the participants before screening. All participants with confirmed HIV infection were referred to their primary SWOP-Kenya clinic or other local HIV care and treatment facilities if preferred. Participants were reimbursed 800 Kenya shillings (approximately US $8) for their time and effort at each scheduled study visit.

Results

Recruitment, screening and enrolment

A total of 739 potential participants were referred from SWOP-Kenya clinics to KAVI-ICR (Fig 1). Of these, 368 (49.8%) were eligible for screening for the SiVET and 250 (68%) met the eligibility criteria and were enrolled. The main reasons for exclusion at screening were: active hepatitis B infection [HBsAg+ (n = 14)], pre-existing medical conditions (n = 41) and potential participants declining enrolment (n = 47). After 12–15 months of study follow-up 87% remained on study; 217 (87%) completed the SiVET while 33(13%) had discontinued. The primary reasons for not completing study follow-up included: HIV infection, loss to follow-up and relocation outside of Nairobi (the study area).

Fig 1

Flow diagram of participant recruitment, screening, enrollment into SiVET study and assessment of willingness to participate in future HIV vaccine trials.

M = MSM, F = FSW.

Therefore, 219 (217 completed SiVET and 2 who had their final study visit before end of trial) were eligible for the willingness to participate in a future HIV vaccine trial interview. Overall, 214(86%) participants completed the interview and were included in the analysis, while 5 were excluded from the analysis because of HIV infection.

Participant characteristics and willingness to participate in future HIV vaccine trials

At their final study visit, 174 (81%) (Table 1) participants expressed willingness to participate in preventive HIV vaccine trials in the future. The proportion was similar among MSM 137(82%) and FSW 37(80%). Fourty (19%) participants were not willing to participate and the main reason given was time commitment, fear that their HIV status would be disclosed to others without their permission and the strict contraception requirements.

Table 1

Characteristics of 214 participants enrolled in a simulated HIV vaccine trial in Nairobi and the proportion willing to enroll in a future HIV vaccine trial, Nairobi, Kenya; Sep 2015-Sep 2018.

Characteristic	All		Men who have sex with men (MSM)				Female sex workers (FSW)
			N = 168				N = 46
	(N = 214)		(N = 168)		Willing to Participate		(N = 46)		Willing to participate
	N	(%)	N	(%)	N	(%)	N	(%)	N	(%)
Total	214	(100)	168	(79)	137	(82)	46	(21)	37	(80)
Age, years
18–24	89	(42)	81	(48)	64	(79)	08	(17)	08	(100)
25–34	72	(34)	54	(32)	44	(81)	18	(39)	16	(89)
≥35	53	(24)	33	(20)	29	(88)	20	(44)	13	(65)
Highest level of education Completed
Primary	40	(19)	19	(11)	15	(79)	21	(46)	16	(76)
Secondary	116	(54)	95	(57)	78	(82)	21	(46)	19	(90)
Tertiary/Higher	58	(27)	54	(32)	44	(81)	04	(08)	02	(50)
Alcohol use in the last month
Never	77	(36)	63	(37)	53	(84)	14	(30)	14	(100)
Sometimes	137	(64)	105	(63)	84	(80)	32	(70)	23	(72)
Alcohol before sex in the last month
Never	133	(62)	110	(65)	92	(84)	23	(50)	22	(96)
Sometimes	81	(38)	58	(35)	45	(78)	23	(50)	15	(65)
Alcohol CAGE score†
≤1	189	(88)	149	(89)	123	(83)	40	(87)	33	(83)
≥2	25	(12)	19	(11)	14	(74)	06	(13)	04	(67)
Illicit drug use in the last month
Yes	160	(75)	118	(70)	94	(80)	42	(91)	35	(83)
No	54	(25)	50	(30)	43	(86)	04	(09)	02	(50)
Number of sex partners in the last month
≤1	59	(28)	52	(31)	45	(87)	07	(15)	05	(71)
2	47	(22)	41	(24)	32	(78)	06	(13)	05	(83)
≥3	108	(50)	75	(45)	60	(80)	33	(72)	27	(82)
New sex partners in the last month
0	106	(50)	97	(58)	80	(82)	09	(20)	08	(89)
1	34	(16)	27	(16)	21	(78)	07	(15)	07	(100)
≥2	74	(34)	44	(26)	36	(82)	30	(65)	22	(73)
Insertive Anal sex in the last month
No	39	(23)	39	(23)	35	(90)	n/a	n/a	n/a	n/a
Yes	129	(77)	129	(77)	102	(79)	n/a	n/a	n/a	n/a
Receptive anal sex in the last month
No	137	(64)	91	(54)	70	(77)	46	(100)	37	(80)
Yes	77	(36)	77	(46)	67	(87)	00	(00)	00	(00)
Condom use in the last month
Sometimes	43	(20)	40	(24)	31	(78)	03	(07)	01	(33)
Always	171	(80)	128	(76)	80	(80)	43	(93)	27	(87)
Number of known HIV behavioral Preventive methods
0	00	(00)	00	(00)	00	(00)	00	(00)	00	(00)
1	35	(16)	30	(18)	25	(83)	05	(11)	05	(100)
2–3	116	(54)	87	(52)	45	(85)	29	(63)	11	(79)
4–6	63	(30)	51	(30)	41	(80)	12	(26)	08	(67)
Number of known HIV biomedical preventive methods
0	81	(38)	71	(42)	62	(87)	10	(22)	09	(90)
1–2	92	(43)	72	(43)	28	(78)	20	(43)	12	(92)
3–4	41	(19)	25	(15)	13	(77)	16	(35)	10	(77)
Experience in SiVET Study
Good	93	(43)	74	(44)	51	(69)	19	(41)	14	(74)
Very good	121	(57)	94	(56)	86	(91)	27	(59)	23	(85)

CAGE score of ≤1 was an indication of no alcohol problem and a score of ≥2 indicated of alcohol problem.

n /a = not applicable.

Predictors of willingness to participate in future HIV vaccine trials

Table 2 shows correlates of willingness to participate in an HIV vaccine trial, individually in bivariate analyses and in a final multivariable model. In the adjusted analysis, reporting a very good experience (compared to a good experience, as none of the participants reported a poor experience) in the SiVET study (aOR 5.54, 95% CI 2.39, 12.89, P-value <0.001) and reporting always using protection with condoms during sexual intercourse (aOR 2.53, 95% CI 0.99, 6.45 p-value 0.050) were associated with increased willingness to participate in a future HIV vaccine trial. Whereas knowledge of one to two or three to four HIV/AIDS biomedical prevention methods were less likely to be willing to participate compared with those with no knowledge (aOR 0.38, 95% CI 0.15, 0.93 P-value 0.035 and aOR 0.30, 95% CI 0.09, 0.93 P-value 0.036, respectively).

Table 2

Predictors of willingness to participate in future HIV vaccine trial among the 214 participants in a simulated vaccine trial.

Predictor	Unadjusted			Adjusted
	OR	95% CI	P-Value	aOR	95% CI	P-Value
Participant
MSM	Ref			Ref
FSW	0.93	(0.41,2.13)	0.86	1.00	(0.38,2.67)	0.996
Age, years
18–24	Ref			Ref
25–34	1.18	(0.52, 2.67)	0.69	1.45	(0.59, 3.57)	0.415
≥35	0.90	(0.39, 2.11)	0.81	1.16	(0.42, 3.24)	0.767
Highest level of education completed
Primary	Ref
Secondary	1.48	(0.61, 3.61)	0.39
Tertiary/Higher	1.11	(0.42 3.00)	0.83
Alcohol use in the last month
None	Ref
Sometimes	0.53	(0.24, 1.16)	0.11
Alcohol use before sex in the last month
Never	Ref			Ref
Sometimes	0.46	(0.23,0.92)	0.03	0.55	(0.25,1.24)	0.148
Illicit drug use in the last month
No	Ref
Yes	1.20	(0.53, 2.71)	0.66
Alcohol CAGE score
≤1	Ref
≥2	0.54	(0.21, 1.41)	0.21
Number of sex partners last month
≤1	Ref
2	0.67	(0.25, 1.80)	0.42
≥3	0.75	(0.32, 1.75)	0.50
Number of new sex partners in the last month
0	Ref
1	0.95	(0.35, 2.63)	0.93
≥2	0.74	(0.35, 1.57)	0.44
Receptive anal Sex in the last month
No	Ref
Yes	1.88	(0.86, 4.09)	0.11
Insertive anal Sex in the last month
No	Ref
Yes	0.43	(0.14, 1.32)	0.14
Condom use in the last month
Sometimes	Ref			Ref
Always	1.68	(0.76, 3.76)	0.198	2.53	(0.99, 6.45)	0.050
Number of known HIV Behavioral Prevention methods
1	Ref
2–3	0.75	(0.26,2.17)	0.601
4–6	0.58	(0.19,1.78)	0.345
Number of known HIV Biomedical Prevention methods
0	Ref
1–2	0.51	(0.22,1.17)	0.107	0.38	(0.15,0.93)	0.035
3–4	0.44	(0.17,1.15)	0.095	0.30	(0.09,0.93)	0.036
Experience in SiVET study
Good	Ref			Ref
Very good	3.91	(1.86, 8.22)	<0.001	5.54	(2.39, 12.89	<0.001

Factors that would motivate potential participation in future HIV vaccine trial

More than half of the participants reporting willingness to participate in future HIV vaccine trials reported getting education about HIV (59%) or getting access to healthcare services (57%) as factors that motivated their participation (Table 3); other motivating factors reported included altruism, access to HIV counselling and testing services, hope of being protected against HIV, relationships with the clinic staff, and the need to stay busy.

Table 3

Motivating factors for future participation in HIV Vaccine trials among 174 SiVET participants reporting willingness to participate.

Motivator	No. Responses	%
Education about HIV	103	59
Healthcare	99	57
Altruism	69	40
Regular HIV VCT	69	40
Hope of being protected against getting HIV	64	37
Other responses including Reimbursement, liking the staff, an activity to keep them busy	34	20

Discussion

Among MSM and FSW from Nairobi who had completed a SiVET trial, about four of five said they would be willing to participate in a future HIV vaccine trial. These findings suggest that these groups might be a reliable target population to consider in future HIV vaccine efficacy trials.

Our study found three factors significantly associated with willingness to participate in future HIV vaccine trials. Overall, most of the participants reported that they had a ‘very good’ experience in the SIVET, and no one reported a bad experience. Those whose experience was better (i.e., ‘very good’ vs. ‘good’) were more likely to express willingness to participate in future vaccine trials. Exploring factors that could improve participant experiences, and the potential barriers and motivators to participation could guide best practice and address concerns expressed by members of key populations engaged for participation in HIV vaccine trials. Participants only reported very good and good experiences; because feedback was collected by the same staff that had interacted with the participants over the period of the study, this is a possible source of response bias.

Those who reported more consistent condom use were more willing to participate in future HIV vaccine trials. It is possible that these participants were more aware of their HIV risk, and interested in reducing it through participation in a trial. However, we did not find any association between alcohol use, drug use or number of sex partners and willingness to participate.

We found that participants with knowledge of biomedical HIV prevention methods were less likely to be willing to participate in future HIV vaccine trials compared to those with no knowledge of available methods. Surprisingly, a significant proportion of participants had no knowledge of biomedical prevention methods against HIV even with the presence of campaigns promoting these methods in Kenya and at the SWOP clinics where participants were recruited from. This observation may be due to disconnect between the open-ended approach used in this study (i.e., our interviewers asked open ended questions to participants, without specific prompts) and the specific prevention methods provided. It would be useful to further explore and understand reasons for this observation and institute mitigating measures if required.

Several factors were reported as motivators for participation in future HIV vaccine trials. Access to health care services and information, also previously cited in similar studies in East Africa [19, 22], were reported as important motivating factors. Access to healthcare is a challenge in these communities [23]; clinical researchers have a responsibility to provide the highest available standard of HIV prevention services to populations at risk of HIV participating in HIV vaccine trials. It is important to continually highlight this unmet medical need in order to influence policy and increase access to essential services to underserved communities. Altruism was reported as a motivating factor by several participants in the SiVET, this lines up with a systemic literature review [16] and a study among MSM and high risk women in America [24] that found altruism as the major motivator to participate in HIV vaccine trials.

Among those who were not willing to participate, fear that their HIV status would be disclosed to others, or unwillingness to comply with the requirements for use of contraception during the trial were the main reasons given against future participation. In Uganda and among young gay men in America fear of vaccine side effects was the main reason for not willing to participate [25, 26] while in America, ethnic minority communities reported fear that the trial vaccine would cause HIV infection [27]. Although HIV/AIDS awareness in the general population is high in Kenya, key population groups still face HIV stigma, discrimination and violence, all of which may deter people from participation because it is related to HIV/AIDS [4, 9, 12].

Our findings are comparable to those from a study in China among MSM where 77% reported willingness [28]. Although these participants had not just undertaken a simulated trial, this study used computer assisted self-interview method to assess willingness to participate, which may have reduced response bias (i.e., the participants may have been less inclined to say what they thought the investigators “wanted to hear”). However, our level of willingness was lower than findings in other studies, i.e.91% of willingness among a cohort of young gay men in America [26], 94% willingness among healthy low risk adults in an observational cohort in Kenya [15], 95% in a rural community-based cohort study in Uganda [14] and 99% among high risk men and women from fishing communities cohort study in Uganda [19]. This difference in willingness rates could be due to differences in study population, and/or study procedures. Unlike the five other studies [14, 15, 19, 26, 28], our study population had just participated in a simulated clinical trial, thus our study’s participants’ expression of willingness was less hypothetical hence may have been a more accurate reflection of actual willingness to participate.

Although participants’ willingness to participate is essential for the enrolment in trials, high levels of reported willingness to participate may not necessarily translate into actual trial participation. A Kenyan study that compared hypothetical and actual willingness to participate in the same clinic as our study found that only 30% of the participants who had previously expressed hypothetical willingness to participate in HIV vaccine trials actually presented for screening in the subsequent vaccine trial [15]. These were volunteers that had participated in a cohort study, but not one designed to mimic the rigors of clinical trial participation (they had fewer follow up visits and no vaccines were administered).

Our study had some limitations. The sample size of 46 FSW was small and does not allow for statistical comparison with MSM, and also does not allow many findings or conclusions to be made about FSW participation and willingness. In this study we were not required to collect data regarding MSM sex work hence not able to assess the willingness to participate of those engaged in sex worker. The Hepatitis B vaccine used in the SiVET is already licenced hence it might not fully represent the experience involving a trial with an experimental HIV vaccine; the experience however, realistically unpackages and demystifies actual clinical trial participation, hence may serve as a more valuable gauge of willingness compared to hypothetical scenarios where participants are simply told about clinical trials.

Conclusions

The study demonstrated a high level of willingness to participate in future HIV vaccine trials among MSM and FSW in Nairobi, Kenya, after participating in a study designed to mimic the rigors of a clinical trial. This suggests that these groups might be a reliable target population for inclusion in future HIV vaccine trials. Assessment of willingness to participate in these populations provides important information that may help inform future education and recruitment efforts for vaccine trials. Improving the research experience for members of key populations could help impact their willingness to participate in HIV vaccine trials.

PDF Risk assessment questionnare.

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PDF Vaccine Trial Willingness questionnare.

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6 Jan 2020

PONE-D-19-31011

Willingness to participate in future HIV vaccine trials among men who have sex with men and female sex workers living in Nairobi, Kenya.

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Reviewer #1: Partly

Reviewer #2: Yes

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Reviewer #1: I Don't Know

Reviewer #2: Yes

**********

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Reviewer #1: Yes

Reviewer #2: Yes

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Reviewer #2: Yes

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5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: Reviewer’s comments

The presented data is timely in the efforts to recruit key populations in HIV vaccine trials. Targeting men who have sex with men and female sex workers for future trials is essential because these are the most affected groups in SSA. Nevertheless, some parts of the manuscript need some revisions to increase clarity. These are:

Abstract

The conclusion lines 44-47 needs revision. This statement does not match the key results. The authors should modify this statement to increase clarity.

Introduction

The first paragraph, from line 54… should start with the current global, regional, and national HIV prevalence, followed by specific key populations' HIV prevalence. Part of this description appears between lines 60 and 66.

Discussion

The authors should discuss their results before relating to others' work. See, for example, lines 215 – 216; what does the willingness of four of five respondents mean in the context of this study?

Line 257-261, access to health services as a motivator to take part in HIV vaccine trials have been reported from other low-income countries besides Uganda and Kenya. It would be nice to expand this particular discussion by using additional related citations.

Additionally, the authors must discuss the limitations and mitigations of this study. For example, the questionnaire was administered 12-15 months after the trial. Would this gap in terms of timing influence the obtained results?

Conclusion

Lines 275 – 281, should be rephrased to match the current key study results. For example, the issue of improving recruitment and retention was not part of the key results. Although it is an important recommendation, I think other issues about the current results should be emphasized first.

Reviewer #2: The manuscript focuses on assessing the willingness to participate in future vaccine trials among MSM and female sex workers in Kenya. As the study assessed the willingness among the participants of a SiVET, it is claimed that the reported willingness maybe closer to the willingness to participate in actual trials.

Major comments:

1. The first sentence in the Introduction (line numbers 54, 55) seems to make a sweeping statement about achievement of success in care, treatment and prevention. This statement needs to be qualified and specified – i.e., which achievements are being referred to – biomedical or public health achievements?

2. It is not clear whether and what percentage of MSM participants engaged in sex work. That information may be important for future trials.

3. Given the findings that those with (good) knowledge about HIV biomedical prevention methods had lower odds to participate in future trials, it is important to know what were these prevention methods that were asked in the questionnaire (e.g., PrEP, microbicides?) Whether this information (on prevention methods) was provided as part of SiVET?

4. Sample size calculation: How the decision to enroll 200 MSM and 50 FSW was arrived at from the calculated sample size of 250?

5. It is not clear what is meant by “…included in a backward elimination algorithm of multivariable logistic regression to arrive at a final model, retaining those variables with a p <0.05”. Whether it means only those variables with p <0.05 were included in the final multivariable model? But it does not seem to be the case (Table 2).

6. Whether the five new infections occurred among MSM or FSWs?

7. In the discussion section, the authors could comment on the reported reasons for not willing to participate: “time commitment, fear that their HIV status would be disclosed to others without their permission and the strict contraception requirements”. For example, the prevalence of HIV-related stigma/discrimination in Kenya seems to be associated with the second concern.

Minor comment:

There are minor language errors (e.g., line 146: “participants’ were classified”, which can be corrected by careful proofreading.

**********

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Reviewer #1: No

Reviewer #2: No

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26 May 2020

19-Feb-2020

Re: PONE-D-19-31011

Willingness to participate in future HIV vaccine trials among men who have sex with men and female sex workers living in Nairobi, Kenya.

Dear Dr. Newman,

Thank you for your comments on our manuscript. Below, we list each comment, with our responses shown. We look forward to hearing from you soon.

Sincerely,

Elizabeth Mutisya

1. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found at

http://www.journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf and http://www.journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf

Authors’ response: We have reviewed the above and confirm we meet these requirements

2. Please include additional information regarding the survey or questionnaire used in the study and ensure that you have provided sufficient details that others could replicate the analyses. For instance, if you developed a questionnaire as part of this study and it is not under a copyright more restrictive than CC-BY, please include a copy, in both the original language and English, as Supporting Information.

Authors’ response: Thank you for this comment; we have now included a copy of our questionnaire uploaded as supporting information. (S1 File PDF Risk assessment questionnaire)

3. We note that you have stated that you will provide repository information for your data at acceptance. Should your manuscript be accepted for publication, we will hold it until you provide the relevant accession numbers or DOIs necessary to access your data. If you wish to make changes to your Data Availability statement, please describe these changes in your cover letter and we will update your Data Availability statement to reflect the information you provide.

Authors’ response: The KAVI-ICR agrees to open data access. The data collected by KAVI-ICR can be made available to other bona fide researchers, upon application to access the necessary data from which this manuscript was generated. The corresponding and other co-author emails have been provided and they could be contacted anytime for further clarifications and/or support to access the data.

Reviewer #1: Reviewer’s comments

The presented data is timely in the efforts to recruit key populations in HIV vaccine trials. Targeting men who have sex with men and female sex workers for future trials is essential because these are the most affected groups in SSA. Nevertheless, some parts of the manuscript need some revisions to increase clarity. These are:

Abstract

The conclusion lines 44-47 needs revision. This statement does not match the key results. The authors should modify this statement to increase clarity.

Authors’ response: We have changed the language some to better reflect our findings in the results.

Introduction

The first paragraph, from line 54… should start with the current global, regional, and national HIV prevalence, followed by specific key populations' HIV prevalence. Part of this description appears between lines 60 and 66.

Authors’ response: Thank you for your comment. While we appreciate that it often seems like most HIV clinical research papers start this way, the important take home message here is that we are not on target to achieve upcoming milestones to reduce incidence, and that an HIV vaccine remains an important goal. To do this, we need volunteers for upcoming efficacy trials. We feel our research supports the inclusion of these key populations in future trials.

Discussion

The authors should discuss their results before relating to others' work. See, for example, lines 215 – 216; what does the willingness of four of five respondents mean in the context of this study?

Authors’ response: We have added another sentence to the beginning of the discussion text prior to discussing others’ work.

Line 257-261, access to health services as a motivator to take part in HIV vaccine trials have been reported from other low-income countries besides Uganda and Kenya. It would be nice to expand this particular discussion by using additional related citations.

additionally, the authors must discuss the limitations and mitigations of this study. For example, the questionnaire was administered 12-15 months after the trial. Would this gap in terms of timing influence the obtained results?

Authors’ response: Thank you for these comments. We have included references outside of Uganda and Kenya. We also kindly refer the reviewer to the last paragraph of the discussion, where we summarize limitations and mitigations. We also respectfully remind the reviewer that the questionnaire was administered 12-15 months after enrollment, on the last study visit.

Conclusion

Lines 275 – 281, should be rephrased to match the current key study results. For example, the issue of improving recruitment and retention was not part of the key results. Although it is an important recommendation, I think other issues about the current results should be emphasized first.

Authors’ response: Thank you for these comments. In this paragraph, we aren’t talking about improving recruitment and retention, instead we are noting that those who reported a better experience in the SiVET were more likely to report being willing to participate, suggesting that participants who felt their needs met were probably more likely to enroll into a future trial. Perhaps I am not understanding your question?

Reviewer #2: The manuscript focuses on assessing the willingness to participate in future vaccine trials among MSM and female sex workers in Kenya. As the study assessed the willingness among the participants of a SiVET, it is claimed that the reported willingness maybe closer to the willingness to participate in actual trials.

Major comments:

1. The first sentence in the Introduction (line numbers 54, 55) seems to make a sweeping statement about achievement of success in care, treatment and prevention. This statement needs to be qualified and specified – i.e., which achievements are being referred to – biomedical or public health achievements?

Authors’ response:

We have stated in the introduction section that “there are various approaches available to public health including behavioural, structural and biomedical intervention”

2. It is not clear whether and what percentage of MSM participants engaged in sex work. That information may be important for future trials.

Authors’ response: It would have been valuable information, however in this particular study we were not required to collect data regarding sex work.

3. Given the findings that those with (good) knowledge about HIV biomedical prevention methods had lower odds to participate in future trials, it is important to know what were these prevention methods that were asked in the questionnaire (e.g., PrEP, microbicides?) Whether this information (on prevention methods) was provided as part of SiVET?

Authors’ response: Both biomedical and behavioural HIV prevention methods were included in the questionnaire. We have also included the specific HIV preventive methods have also been in the text.

We have included the risk assessment questionnaire as an attachment. The information on prevention methods provided is found on page 3numbers 10 and 11. (S1 File PDF Risk assessment questionnaire)

4. Sample size calculation: How the decision to enroll 200 MSM and 50 FSW was arrived at from the calculated sample size of 250?

Authors’ response: Our decision to enroll 250 volunteers, 20% of whom would be FSW by design, was also based on feasibility considerations. We were most interested in reaching out to the MSM communities in Nairobi where HIV risk remains high, however our partner SWOP works with both male and female sex workers. To avoid stigma and bad feelings with our partners, we agreed to enroll a certain percentage of women into the study and settled on 20%.

5. It is not clear what is meant by “…included in a backward elimination algorithm of multivariable logistic regression to arrive at a final model, retaining those variables with a p <0.05”. Whether it means only those variables with p <0.05 were included in the final multivariable model? But it does not seem to be the case (Table 2).

Authors’ response: The decision to keep a variable in the multivariable model was dependent on the model log likelihood ratio test p-value for the inclusion of a given variable and not Wald p-value, except for age and trial population as these were considered a priori confounders.

We have corrected the text in our methods to make it clearer “Univariate logistic regression was used to evaluate the association of all variables with willingness to participate; factors associated with willingness to participate at p<0.20 on log likelihood test were included in the initial multivariable model (except for age and trial population that were included a priori). Factors were retained in the multivariable model if the log likelihood test p-value of inclusion of a factor was less than 0.05”.

6. Whether the five new infections occurred among MSM or FSWs?

Authors’ response: The five new HIV infections occurred among MSM.

We have added the information text in the results section and Fig 1 HIV infected. “5M: 0F”

7. In the discussion section, the authors could comment on the reported reasons for not willing to participate: “time commitment, fear that their HIV status would be disclosed to others without their permission and the strict contraception requirements”. For example, the prevalence of HIV-related stigma/discrimination in Kenya seems to be associated with the second concern.

Authors’ response: Information on the reported reasons for not willing to participate has been added in the discussion section. Additional related citations have been included in the reference.

We have expanded the discussion citing Newman PA, Duan N, Roberts KJ, Seiden D, Rudy ET, Swendeman D, et al. HIV vaccine trial participation among ethnic minority communities: barriers, motivators, and implications for recruitment. J Acquir Immune D

To comment on the “fear that their HIV status would be disclosed to others without their permission“ indicates stigma/discrimination and we have expanded in the discussion section that “although HIV/AIDS awareness is high in Kenya, key population groups still face HIV stigma, discrimination and violence hence, this may deter people from participation because it is related to HIV/AIDS“

Minor comment:

There are minor language errors (e.g., line 146: “participants’ were classified”, which can be corrected by careful proofreading.

Authors’ response: We have reviewed the paper again, and there are minor corrections and clarifications throughout that we hope make it clearer.

Submitted filename: Response to reviewers.docx

Click here for additional data file.

22 Jun 2020

PONE-D-19-31011R1

Willingness to participate in future HIV vaccine trials among men who have sex with men and female sex workers living in Nairobi, Kenya.

PLOS ONE

Dear Dr. Mutisya,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

The authors have made a few of the revisions suggested by the two reviewers, and these are helpful. However, several of the reviewers' comments are not adequately responded to; and some are only responded to in the Reviewer's comments, with no corresponding changes in the manuscript. This is not sufficient. Also, please indicate the exact Line number in the manuscript where each revision has been made to ensure the reviewer/editor can locate them. This is more important since a few of the comments seem not to be responded to.

For example, Reviewer 1: "The first paragraph...should start with current global, regional and national prevalence." The response to the reviewer is inadequate.

In the conclusion: Your response, "Perhaps I am not understanding your question" is unfortunately not helpful. Both reviewers have suggested that you stay closer to your findings when you make recommendations based on your study.

Reviewer 2:

1. The added sentence is too general and thus does not adequately address the reviewer's comment.

2. The response is ok, but you must now add this as a specific study limitation.

3. "We have also included the specific HIV preventive methods in the text."  Please specifically indicate where these are these in the text.

4. Please indicate that you have incorporated this explanation into the manuscript text (not only in response to the reviewer) and indicate the line number where it appears in the revised manuscript.

7. The reference mentioned as "expanded the discussion citing" is in fact nowhere in the reference list. Also, simply adding 1 reference does not adequately address the reviewer's comment.

Finally, you have included several comments that you added to your track changed version, however you have not in fact made these changes; it appears that a number of newly added references are missing. Please carefully revise and proofread before resubmission, and make sure to actually add the new references as citations in the text, and to the reference list!

Line 277 "insert to include refs 11& 12" ??

Line 320 - 321  You left in (REF) and (REF). You must actually include the reference number here; and the newly added references must be indicated in the Reference list at the end. There are no apparent changes however to the reference list, despite the claim that a few new references have been added.

Line 328:"insert ref number 3" ??

Please submit your revised manuscript by Aug 06 2020 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:

A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.

A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.

An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: http://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols

We look forward to receiving your revised manuscript.

Kind regards,

Peter A Newman, Ph.D

Academic Editor

PLOS ONE

[Note: HTML markup is below. Please do not edit.]

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step.

31 Jul 2020

30th Jul 2020

RE: PONE-D-19-31011R1

Willingness to participate in future HIV vaccine trials among men who have sex with men and female sex workers living in Nairobi, Kenya.

Dear Dr. Newman,

Thank you for your comments on our manuscript. Below, we list each comment with our responses shown. We look forward to hearing from you soon.

Sincerely,

Elizabeth Mutisya

The authors have made a few of the revisions suggested by the two reviewers, and these are helpful. However, several of the reviewers' comments are not adequately responded to; and some are only responded to in the Reviewer's comments, with no corresponding changes in the manuscript. This is not sufficient. Also, please indicate the exact Line number in the manuscript where each revision has been made to ensure the reviewer/editor can locate them. This is more important since a few of the comments seem not to be responded to.

Authors’ response: Thank you for the helpful suggestions. We have reviewed the manuscript and confirm corresponding changes to the document. We have indicated the exact line number where revision has been made.

For example, Reviewer 1: "The first paragraph...should start with current global, regional and national prevalence." The response to the reviewer is inadequate.

Authors’ response: Thank you for the clarification. We have included the current global, regional and national HIV prevalence and specific key population HIV prevalence in the first paragraph of the introduction and expanded the citation. Lines 51-70

Abstract

The conclusion lines 44-47 needs revision. This statement does not match the key results. The authors should modify this statement to increase clarity 43-46

Authors’ response: Thank you for the comment. We have changed the language to better emphasize our study findings lines 44-47

In the conclusion: Your response, "Perhaps I am not understanding your question" is unfortunately not helpful. Both reviewers have suggested that you stay closer to your findings when you make recommendations based on your study.

Authors’ response: Thank you for the clarification. We have changed the language to better emphasize our study findings. Lines 316-319

Discussion

The authors should discuss their results before relating to others' work. See, for example, lines 215 – 216; what does the willingness of four of five respondents mean in the context of this study?

Authors’ response: We have rearranged the paragraphs in the discussion section to first discuss the results of this study before relating to others’ work, from lines 235-275

Reviewer 2:

1. The added sentence is too general and thus does not adequately address the reviewer's comment.

Authors’ response: Thank you for the clarification. We have added the global, regional and national HIV prevalence and specific key population HIV prevalence in the first paragraph of the introduction to qualify the HIV successes and challenges. Lines 51-70

2. The response is ok, but you must now add this as a specific study limitation.

Authors’ response: Thank you for the reminder. We have included information not collected regarding MSM sex work as a study limitation. Lines 304-306

3. "We have also included the specific HIV preventive methods in the text." Please specifically indicate where these are these in the text.

Authors’ response: This information did not appear in the initial manuscript. However, in the revised manuscript we had included the specific biomedical and behavioral HIV preventive methods in lines 142-147

4. Please indicate that you have incorporated this explanation into the manuscript text (not only in response to the reviewer) and indicate the line number where it appears in the revised manuscript.

Authors’ response: Please find the following sample size calculation information under METHODS -SAMPLE SIZE lines 103-107

A sample size of 250 for the SiVET was calculated based on being able to estimate a one-year retention rate of 80% with a precision of ±5%. The target was to enrol 200 MSM and 50 FSW. The choice to enrol 20% FSW was deliberate because HIV incidence is higher among Kenyan MSM than Kenyan FSW; we also wished to avoid stigma and any hard feelings among our partners at SWOP-Kenya and agreed that enrolling some women would be appropriate.

7. The reference mentioned as "expanded the discussion citing" is in fact nowhere in the reference list. Also, simply adding 1 reference does not adequately address the reviewer's comment.

Authors’ response: Thank you for the comment. Reported reasons for not willing to participate have been added in the discussion section of the revised manuscript and the related citations have been included in the reference list. For ease of access please find this information in lines (273-280) and reference list numbers (25, 26, 27, 4, 9 & 12)

Finally, you have included several comments that you added to your track changed version, however you have not in fact made these changes; it appears that a number of newly added references are missing. Please carefully revise and proofread before resubmission, and make sure to actually add the new references as citations in the text, and to the reference list!

Authors’ response: Thank you for the comments regarding track changed version. We have reviewed the paper again, and there are corrections and clarifications throughout that we hope make it clearer. The reference list has been reviewed and can confirm the additional citations have been included.

Line 277 "insert to include refs 11& 12" ??

Authors’ response: These added citations appear in lines (288& 291) of the revised manuscript and are included in the reference list numbers 14 &15.

Line 320 - 321 You left in (REF) and (REF). You must actually include the reference number here; and the newly added references must be indicated in the Reference list at the end. There are no apparent changes however to the reference list, despite the claim that a few new references have been added.

Authors’ response: The lines mentioned 320-321 appear in a paragraph with information related to reported motivators for participation now lines 263-272 in the revised manuscript. The citations reflecting this information is references numbers 19,22,23,16 &, 24.

Line 328:"insert ref number 3" ??

Authors’ response: The line 328 appears in a paragraph with information related to reasons for not willing to participate in future trial. This information now appears in lines 273-280 and the references to the information are numbers 4,9,12, 25, 26 & 27

Please submit your revised manuscript by Aug 06 2020 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:

• A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.

• A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.

• An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

Authors’ response: We have reviewed the above and included the above items in our submission.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

Authors’ response: We have reviewed and made changes in the financial disclosure. The updated statement is included in the cover letter.

We have reviewed the guidelines of the figure file and confirm we meet these requirements.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: http://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols

Authors’ response: We did review the above and confirm we meet these requirements. Our URL https://doi.org/10.3886/E119622V1

We have also reviewed and expanded the acknowledgment section to include persons/teams who offered their assistance lines 321-325

We have also reviewed and included Supporting information S1 Fig.tif Fig 1 in lines 414

Submitted filename: Response to reviewers.docx

Click here for additional data file.

10 Aug 2020

Willingness to participate in future HIV vaccine trials among men who have sex with men and female sex workers living in Nairobi, Kenya.

PONE-D-19-31011R2

Dear Dr. Mutisya,

We’re pleased to inform you that your manuscript has now been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

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Kind regards,

Peter A Newman, Ph.D

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments:

13 Aug 2020

PONE-D-19-31011R2

Willingness to participate in future HIV vaccine trials among men who have sex with men and female sex workers living in Nairobi, Kenya.

Dear Dr. Mutisya:

I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department.

If your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information please contact onepress@plos.org.

If we can help with anything else, please email us at plosone@plos.org.

Thank you for submitting your work to PLOS ONE and supporting open access.

Kind regards,

PLOS ONE Editorial Office Staff

on behalf of

Dr. Peter A Newman

Academic Editor

PLOS ONE