Version 1.0 9th Jan 2013
AURAH Protocol
A cross sectional questionnaire study of sexual risk behaviour, attitudes to HIV transmission, antiretroviral treatment for prevention and wellbeingin HIV-negative individuals at risk of HIV-infection recruited from sexual health clinics
Attitudes to and Understanding of Risk of Acquisition of HIV:
AURAH Study
Version1.0
9thJan2013 REC Ref: 13/LO/0246
AURAH Study Group
Core group:Dr Alison Rodger
Dr Fiona Lampe
Prof Andrew Phillips
Dr Andrew Speakman
(Department of Infection and Population Health, UCL, Royal Free Campus)
HIV clinic leads / teams:Dr Richard Gilson (Mortimer Market Clinic, London)
Dr Martin Fisher/Nicky Perry (Brighton and Sussex University Hospital)
Dr David Asboe/Dr Nneka Nwokolo/Dr Rachael Jones/Christopher Scott(Chelsea and Westminster/Dean St Clinic/West London Sexual Health Centre)
Dr Rebecca O’Connell (Newham Sexual Health Centre)
Dr Michael Brady (Kings)
Dr Dan Ivens (Royal Free Hospital)
Prof Jane Anderson (Homerton)
Dr Sris Allen (Coventry)
Advisory Group (additional collaboraters):
Prof Lorraine Sherr (Department of Infection and Population Health, UCL, Royal Free Campus)
Prof Graham Hart (Department of Infection and Population Health, UCL)
Simon Collins (HIV i-Base)
Prof Anne Johnson (Department of Infection and Population Health, UCL)
Dr Alec Miners (Health Services Research Unit, London School of Hygience and Tropical Medicine)
Prof Jonathan Elford (Department of Public Health, City University, London)
Coordinating centre:
HIV Epidemiology and Biostatistics Group, Research Department of Infection and Population Health, UCL, Royal Free Campus
Sponsor: UCL
CONTENTS
- Background
2. Aim
2.1 Objectives
3. Methods
3.1 Study design
3.2 Setting
3.3 Study population
3.4 Sample size
3.5 Recruitment
3.6 Consent
3.7 Data collection
3.8 Role of study nurse/research assistant
3.8.1 Documents held by study nurse
3.8.2 Study nurse tasks
3.9 Measurements
3.9.1 Study log
3.9.2 Questionnaire
3.9.3 Clinic data
3.10 Data analysis
3.10.1 Transfer of data to coordinating centre
3.10.2 Data entry
3.10.3 Statistical methods
3.11 Pilot study
4 Ethical considerations
4.1 Ethical review
4.2 Patient information
4.3 Confidentiality
4.4 Data security
5. Study management
5.1 Setting up study procedures
5.2 Funding for the study in each centre
5.3 Incentives for participants
5.4 Monitoring of recruitment
5.5 Data monitoring
5.6 Data analysis and publications
6. Timetable
7. References
Appendix 1: Patient Information Sheet and Consent Form
1. BACKGROUND AND RATIONALE
During 2010, 6660 people were newly diagnosed with HIV in the UK, and the estimated number of people living with HIV in the UK was 91,500 by the end of that year [1] Although the annual number of new diagnoses has not risen since 2005 in the UK population overall, this figure is increasing among men who have sex with men (MSM), and among heterosexuals believed to be infected within the UK, suggesting that the number of new infections occurring within the UK is rising. [2]
Evidence of on-going or increasing HIV transmission among MSM [1-4] is consistent with evidence of increases in sexual risk behaviour in this group. Studies of MSM in the UK [3, 5-10] and elsewhere [11-14] have found increases in the prevalence of unprotected anal intercourse among MSM since the mid-1990s – coincident with the widespread use and success of combination antiretroviral treatment for HIV in developed countries. There have also been increases in diagnoses of other sexually transmitted infections over this period. [15-17].
Sexual transmission risk arises as a result of the negotiation of sex practices, or lack thereof, between HIV positive and HIV negative individuals – involving the perceptions and behaviours of both and which often differ according to serostatus. Hence strategies aimed at reduction of HIV transmission need to address differences in both HIV positive and negativeindividual’sperceptions, choices and behaviours [18]. This is particularly relevant when considering how the Swiss statement [19](which stated that that HIV-positive individuals on effective ART with undetectable VL for at least six months and without sexually STIs are sexually non-infectious) and also the HPTN 052 study [20] (which demonstrated areduction of heterosexualtransmission in the immediate ART treatment arm of 96%), might have reached and influenced HIV negative persons in different ways to their HIV positive counterparts. Reports from outside Europe suggest (even before the Swiss Statement was released) that HIV negative MSM perceive a number of sexual practices with HIV positive MSM on ARVs as less risky than with HIV positive MSM not on ARVs (18). More recently an increased likelihood in HIV negative MSM to engage in risky sexual practices (e.g. unprotected anal sex) in serodiscordant relationships where their partner reports an undetectable viral load has been described [21]. Current data from the UK which inform on these themes from the perspective of HIV negative MSM –in particular attitudes to unprotected sex with individuals of unknown HIV status - and describes them in the context of mental/general health features, STI history, alcohol and drug use (and similarities/differences with counterpart data from HIV positive MSM), are limited.
The ASTRA study (undertaken by the AURAH investigators in 2011/12) investigated current levels of sexual risk behaviour, beliefs about viral suppression and transmission risk, the role of ART use and other factors in transmission risk behaviours and beliefs in a large (n=3100) unselected sample of HIV-infected patients under care in the UK, and among key demographic subgroups (MSM; Black African men and women; recently diagnosed people).
The AURAH study will examine similar themes in a cohort of UK HIV negative individuals (using identical or similar questions to ASTRA, as relevant given the different serostatus) to assess knowledge of, and attitudes to HIV transmission risks and the role of ART, and to assess the prevalence of medical and psychological symptoms (e.g. hepatitis C, depression and anxiety), quality of life, lifestyle factors (e.g. drug and alcohol use) and their possible links to sexual risk behaviours.
Data from this study will additionally contribute to an understanding of how knowledge of ART and detectable/undetectable viral loads in HIV negative individuals may affect their attitudes and perceptions which lead to sexual risk behaviours with partners of unknown and/or known HIV status in the UK. A subgroup comparison between the MSM HIV negative and MSM HIV positive groupings will also allow identification of similarities and differences in lifestyle features between the two groups e.g. alcohol/drug use, psychiatric and medical comorbidities etc. Previous studies have illustrated high prevalence rates of depression, anxiety, drug and alcohol use in MSM [22]. Comparison of the two groups will facilitate estimation of the specific effect of HIV and HIV treatments on health, wellbeing and lifestyle among MSM.
While it is important to understand patterns of sexual risk behaviour and attitudes to HIV transmission in HIV negative at risk groups through the AURAH study, it is also important to study longitudinally the incidence and predictors of new infections among groups atparticular at risk of HIV, and to assess changes over time risk behaviour within individuals. The rising incidence of HIV in MSM in the UK clearly points to a need for research in this group. In particular, little is known regarding changes in sexual behaviour during crucial periods such as primary HIV-infection and immediately following an HIV-diagnosis nor on variability in sexual risk behaviour over time at an individual level (including on the duration of periods of very high risk). Although there are cohort studies of MSM that provide some limited information on these issues [23-26] there have been no studies among individuals at risk of HIV infection in the UK.In order to address these latter questions we propose to apply for additional funding to set up a prospective cohort study of HIV-negative MSM at risk of HIV infection, recruited from UK sexual health clinics. Information from such a study would contribute to understanding of patterns of HIV transmission in the UK, provide information for modelling studies of the UK epidemic, and help to inform prevention efforts. The AURAH cross sectional study will provide preliminary feasibility data for this planned prospective study in particular recruitment data and the acceptability to MSM for planned prospective follow up
2.STUDY AIMS AND OBJECTIVES
2.1 Aims
- To assess patterns of sexual behaviour, and attitudes to sexual risk, among HIV negative adults at risk of HIV-infection, and any associations with socio-demographic factors such as sexuality, ethnicity, age and social class.
- To compare HIV-negative individuals at risk of HIV infection to HIV-positive outpatients, with respect to sexual risk and attitudes, beliefs about HIV transmission risk, physical and psychological symptoms, quality of life, lifestyle and health and wellbeing
- To assess the feasibility of recruiting a HIV negative cohort for longitudinal follow up to study the incidence and predictors of new infections among MSM in particular at risk of HIV, and to assess changes over time of risk behaviour within individuals
2.2 Objectives
- To estimate levels of high-risk sexual behaviour (recent condomless (unprotected) vaginal or anal sex) in HIV negative individuals attending GUM sexual health clinic according to demographic groups (sexuality; ethnicity).
- Among those who have had high-risk sex, to describe the distribution of: number of sexual partners; number of times had sex; type of sex; reasons for not using condom
- To assess, in HIV negative subjects, the prevalence of psychological and physical symptoms (i.e. depression, anxiety) and lifestyle factors (i.e. drug and alcohol use) and whether demographic/social factors, psychological and physical symptoms, quality of life and lifestyle factors are associated with high-risk sexual behaviours
- To investigate the association between HIV status and health and lifestyle factors by comparing these factors between the HIV-positive and HIV-negative study groups
- To investigate HIV negative individuals beliefs regarding the effect of ART in HIV positive individuals, and undetectable viral load, on HIV transmission risk (transmission risk beliefs)
- To assess whether transmission risk beliefs in HIV negative subjects are linked to sexual behaviour
- To investigate attitudes to starting immediate ART including attitudes to starting ART to reduce transmission risks to other, if they became HIV infected
3. METHODS
3.1 Study design
A cross-sectional self-administered questionnaire study. AURAH will use a modified version the ASTRA self-administered questionnaire andwill be conducted among HIV negative individualsattending for routine sexually transmitted infection (STI) and/or HIV testing in 10UK GUM clinics
3.2 Setting
Adults attending selected sexual health clinics in the UK (Mortimer Market Clinic, Dean St Clinic, West London Clinic, The Kobbler Centre, Brighton Sexual Health Centre, Kings Sexual Health Centre, Newham Sexual Health Centre, Royal Free-Marlborough clinic, Coventry Sexual Health Centre, Homerton Sexual Health Centre).
3.3 Study population
Each centrewill attemptto include a representative sample of patients attending for STI screening.However, particular attention will be paid to recruiting target numbers of HIV-negative MSM and Black African participants, in order to recruit from the demographic groups at greatest risk of HIV in the UK, and among whom HIV incidence may be increasing.
Inclusion criteria:
HIV negative (or undiagnosed)subjectsaged >= 18 years, attending for routine sexually transmitted infection (STI) or HIV testing in GUM clinics
Exclusion criteria: Unable to complete questionnaire in English due to language difficulties; already diagnosed as HIV positive.
3.4 Sample size
The study will ascertain a large amount of information to enable us to address objectives set out in section 2. Three of the main objectives are to
(i) Ascertain the proportion of individuals who report that they have had condomless sex in the past 3 months with a partner of unknown or positive status and that one of the reasons for this was “I knew there was a risk of acquiringHIV but I am not so concernedabout having the disease that it made me want to have sex using a condom.” This will be calculated as a proportion of all study participants and as a proportion of all participants reporting condomless sex.
(ii) Ascertain the proportion of individuals who report that they have had condomless sex in the past 3 months with a positive partner who give a reason as”I thought the risks of catching HIV were low because my partner was taking anti-retroviral therapy.”
(iii) Compare the prevalence of PHQ-9 depression between HIV-+ve and HIV-ve individuals, separately for HIV negative MSM, heterosexual men and women, black African men and women
With 2000 total sample size, 1000 MSM, 1000 heterosexuals (500 men and 500 women), of whom 600 are Black African, the study will be able to estimate the proportions relating to objective (i) above, with the precision shown in table A below, for estimated response proportions of , 5%, 10%, 15% and 20%, within the major demographic subgroups. For objective (ii) the denominator will be the number of subjects who report condomless sex in the past 3 months (estimated to be 50% of the total number), and the estimated proportion is expected to be lower, so precision is shown in Table B for proportions of 5% and 10%. For objective iii the study will have 80% power to detect the differences in prevalence of depression shown in Table C for the major demographic subgroups, with 5% 2-sided significance level
TABLE A. Precision for 95% confidence intervals for a single proportion according to major demographic subgroups
Target number in AURAH / 95% Confidence interval for prevalence of 5% / 95% Confidence interval for prevalence of 10% / 95% Confidence interval for prevalence of 15% / 95% Confidence interval for prevalence of 20%MSM / 1000 / +/- 1.35 / +/- 1.86 / +/- 2.22 / +/- 2.48
All Heterosexual men
Black African heterosexual men / 500
300 / +/- 1.90
+/-2.45 / +/- 2.63
+/- 3.40 / +/- 3.15
+/- 4.05 / +/- 3.51
+/- 4.53
All women
Black African women / 500
300 / +/- 1.90
+/-2.45 / +/- 2.63
+/- 3.40 / +/- 3.15
+/- 4.05 / +/- 3.51
+/- 4.53
TABLE B. Precision for 95% confidence intervals for a single proportion according to major demographic subgroups
Target number in AURAH / 95% Confidence interval for prevalence of 5% / 95% Confidence interval for prevalence of 10%MSM / 500 / +/- 1.90 / +/- 2.63
All Heterosexual men
Black African heterosexual men / 250
150 / +/-2.70
+/- 3.50 / +/- 3.7
+/- 4.8
All women
Black African women / 250
150 / +/-2.70
+/- 3.50 / +/- 3.7
+/- 4.8
TABLE C. Differences between two proportions detectable with 80% power at 2-sided 5% significance level, according to major demographic subgroups
Estimated final numbers in ASTRA / Target number in AURAH / (ii) Difference in prevalence of depression that could be detected , comparing HIV+ve with HIV-ve individuals, assuming 25% prevalence in HIV+ve people (in all groups)MSM / 2250 / 1000 / 4.5%
All Heterosexual men
Black African heterosexual men / 400
200 / 500
300 / 7.5%
10.0%
All women
Black African women / 700
450 / 500
300 / 6.8%
8.5%
3.5 Recruitment
The AURAH study will recruit in 10 UK specialist GUM clinics until the target number of patients has been enrolled or until the study endpoint of December 2013. It is anticipated that recruitment will start in November 2012. Consecutive subjects attending the GUM clinic will be identified, approached and invited to take part. Each centre will identify specific clinics each week at which subjects will be recruited, aiming to ensure a representative study population (with target recruitment for MSM and black African subjects). During the consenting process, it will be reiterated that the study is for HIV undiagnosed individuals only.
3.6 Consent
All subjects who are invited to participate will be given an information sheet about the study. Those who agree to complete the questionnaire will be asked to sign a consent form. The form will include anoptional section for consent to be contacted about reminders prize draw results and, in the future if further funding is obtained, for prospective follow up as part of a new study.Participantswho agree to be contactable will be asked for their preferred contact details (email addressand mobile number for SMS contact). The consent form will note that their contact details will only be used for these purposes and will be held securely outside the clinic as part of the central study records but will be deleted after a period of twoyears
3.7 Data collection
The study questionnaire will be self-administered. Participants will be invited to complete the paper based questionnaire while waiting for their GUM appointments, or directly following their appointment, whichever is most convenient for the patient and/or appropriate for each particular clinical centre. Participants will be asked to complete the questionnaire on the same day, in the clinic. If this cannot be done, it will be possible for participants to take away the questionnaire, which can be completed at a later time and posted back in the pre-paid envelope to the research team. However, in order to maximise the study response rate, completion of the questionnaire in the clinic is the greatly preferred option, and will be encouraged as far as possible.
3.7.1 Study questionnaire
There will be separate versions of the questionnaire (A5 booklet size) for men and women. Each questionnaire will have a study number pre-completed on the first page. Participants will be given a questionnaire, pen and envelope. A private area within the clinic will be available for completion of questionnaires, if desired. Once completed, the questionnaires can be placed in a sealed envelope and put in a box in the clinic. For participants who take the questionnaire away to complete at a later time and have consented to be contacted, the study nurse will reiterate to thepatient that a maximum of 2 reminders will be sent to the supplied contact details if the questionnaire has not been received within a month. The questionnaire will not be available in any languages other than English.
3.8 Role of clinic based study staff
The study nurseor research assistant in each clinic will have a major role, being responsible for the day-to-day running and co-ordination of the study within each clinical centre.
3.8.1 Documents held by study nurse/research assistant
- Information sheets
- Consent forms
- Study log (including email addresses/mobile numbers for consenting participants)
- Numbered paper questionnaires (and pens)
- Pre-paid envelopes addressed to research team
3.8.2 study nurse/research assistant tasks