3ASTRA PROTOCOL

Version 1.0 01/07/2010

Antiretrovirals, Sexual Transmission Risk and Attitudes (ASTRA)

A questionnaire study of sexual risk behaviour, attitudes to HIV transmission and attitudes to antiretroviral treatment, among HIV-infected patients under care in UK centres

ASTRA Study Group

Core group:

Dr Fiona Lampe

Dr Alison Rodger

Prof Andrew Phillips

Dr Andrew Speakman

(Department of Infection and Population Health, UCL, Royal Free Campus)

HIV clinic leads / teams:

Dr Alison Rodger, Prof Margaret Johnson, Anne Carroll (Royal Free Hospital, London)

Dr Richard Gilson, Dr Simon Edwards, (Mortimer Market Clinic, London)

Dr Martin Fisher, Nicky Perry (Brighton and Sussex University Hospital)

Prof Jane Anderson, Sifiso Mguni (Homerton Hospital, London)

Dr Ed Wilkins, Cynthia Murphy (North Manchester General Hospital)

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 Anna-Maria Geretti (Department of Virology, Royal Free Hampstead NHS Trust)

Dr Bill Burman (Department of Public Health, University of Colorado)

Dr Alec Miners (Health Services Research Unit, London School of Hygience and Tropical Medicine)

Prof Jonathan Elford (Department of Public Health, City University, London)

Research centre: HIV Epidemiology and Biostatistics Group, Research Department of Infection and Population Health, UCL, Royal Free Campus

CONTENTS

1. 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

3.7.1 Paper questionnaire

3.7.2 CASI questionnaire

3.7.3 French questionnaire

3.8 Role of study nurse

3.8.1 Documents held by study nurse

3.8.2 Study nurse tasks

3.9 Measurements

3.9.1 Study nurse log

3.9.2 Questionnaire

3.9.3 Clinic data

3.10 Data analysis

3.10.1 Transfer of data to research 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 Monitoring of recruitment

5.3 Data monitoring

5.4 Data analysis and publications

6. Timetable

7. References

Abbreviations:

ART Antiretroviral therapy

MSMMen who have sex with men

CASIComputer assisted self-interviewing
1. Background

About 80,000 people live with HIV in the UK, of which 75% are diagnosed and under NHS care (HPA 2008). About 70% of those under care are taking antiretroviral treatment (ART). Effective ART has resulted in a dramatic improvement in life expectancy (Mocroft 2003), and a steady increase in HIV prevalence in the UK. Despite continued prevention efforts, the numbers of new HIV infections taking place in the UK is rising, both among men who have sex with men (MSM), and among heterosexual individuals (HPA 2008).

HIV incidence is driven by patterns of sexual risk behaviour among people with and without HIV infection. Community-based studies have reported that, from the mid-1990s until recently, rates of unprotected anal intercourse have increased among MSM (Mercer 2004; Elford 2004; Dodds 2004; Hart 2005; Elford 2006; Dodds 2007; Fisher 2007). These trends occurred co-incident with the advent of effective ART, raising debate as to whether a new optimism surrounding HIV treatment and prognosis was one of the driving factors in changes in risk behaviour (Elford 2002; Elford 2005).

Among HIV-infected individuals, a significant proportion of MSM (10-30%), and a lower proportion of heterosexual individuals, report recent unprotected sex with partners of HIV-negative status or unknown HIV status (Fenton 2002; Kozal 2004; Dave 2006; Dodds 2007; Sadler 2007; Elford 2007; Sherr 2007; Williamson 2008), thereby posing a risk of HIV transmission to an uninfected person. An important question is whether use of ART tends to lead to increases in sexual risk behaviour at an individual level. Evidence from existing studies gives little suggestion of this phenomenon to date. A meta-analysis based on studies from 1996 to 2003 showed that there was considerable heterogeneity in study results concerning the association of ART use with sexual risk behaviour (with several statistically significant results in both directions), but overall found no evidence of association when combining these differing estimates (Crepaz 2004). Subsequent HIV-clinic-based studies (carried out up to 2005) have found either no association between ART use (and/or viral suppression) and sexual risk behaviour (Kozal 2004, Elford 2007), or have found that patients on ART in fact tended to have somewhat lower levels of sexual risk behaviour than patients not taking ART (Stephenson 2003; Glass 2004). Similarly, in a trial of treatment interruption, the ART continuation strategy was associated with lower rates of sexual risk behaviour than the ART interruption strategy (Burman 2008).

However, over recent years, there has been a fundamental change in the messages and information received by HIV-infected individuals regarding transmission risk. There has been increasing awareness, among the scientific community, that successful virological suppression with ART may lead to a profound reduction in an individual’s infectiousness. In 2008, an internationally well respected group of Swiss HIV clinicians and researchers issued a statement indicating that the risk of transmitting HIV through unprotected sex is extremely low if the infected partner has a suppressed plasma viral load and no other sexually transmitted disease (Vernazza 2008). This statement received widespread attention in the UK and world-wide, and caused huge controversy and debate (Bernard 2008). There is concern that patterns of risk behaviour among HIV-infected people may now be changing, and that existing results cannot be extrapolated to the current time.

Since the “Swiss statement”, there have been no studies of HIV transmission risk perceptions and behaviours among HIV-infected individuals the UK, and therefore the effect of changing messages about ‘safe sex’ is not known. In addition, the interplay between ART use and sexual behaviour may be complex: few existing studies have assessed the role of potentially important co-factors (Crepaz 2004), such as time since diagnosis, time since starting ART, ART side-effects, health and well-being, psychological distress, HIV disclosure, and specific beliefs regarding viral suppression and infectiousness.

The ASTRA study aims to investigate current levels of sexual risk behaviour, to assess beliefs about viral suppression and transmission risk, to assess the role of ART use and other factors in transmission risk behaviours and beliefs, and to investigate changes over time in these factors, in a large 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 results will have implications for understanding HIV transmission and targeting prevention efforts. In particular, the results will be of great relevance to a new HIV treatment strategy that is currently under consideration - whether ART should be offered to all people infected with HIV in the UK (rather than delayed until an individuals CD4 count falls below 350/mm3) (Phillips 2007; Neaton 2008). The individual benefit of early versus delayed ART is being evaluated in an international randomised trial (START). Results from ASTRA regarding the current link between ART use and sexual risk behaviour will be important in assessing the potential public health impact of this strategy. ASTRA will also investigate attitudes to starting ART among HIV patients not currently treated, providing information on the acceptability of a strategy of widespread treatment.

2. Aim

To assess sexual risk behaviours, beliefs about HIV transmission risk, and attitudes to use of early antiretroviral treatment, in patients with HIV under care within the UK, and to investigate trends over time in these factors.

2.1 Objectives

(i) to estimate levels of high-risk sexual behaviour (recent unprotected vaginal or anal sex with a partner of unknown or negative HIV status) in HIV-infected patients under care in the UK, according to demographic groups (HIV transmission group; sexuality; ethnicity)

(ii) 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

(iii) to assess whether ART use, current undetectable viral load, and other factors (demographic/social factors, psychological and physical symptoms, quality of life, lifestyle factors, HIV-related factors, time since starting ART and ART adherence) are associated with high-risk sexual behaviour

(iv) to investigate patients’ beliefs regarding the effect of ART, and undetectable viral load, on HIV transmission risk (transmission risk beliefs)

(v) to assess whether transmission risk beliefs are linked to sexual behaviour among ART-treated patients

(vi) to investigate attitudes to starting immediate ART, among ART naïve patients

(vii) to assess whether transmission risk beliefs and other factors (demographic/social factors, psychological and physical symptoms, quality of life, lifestyle factors and HIV-related factors), are associated with attitudes to starting immediate ART, among ART-naïve patients

(viii) to assess trends over a three year period in high-risk sexual behaviour and transmission risk beliefs according to demographic group, and to assess trends in attitudes towards starting ART among untreated patients

(ix) in a subset of patients, to assess the extent to which sexual behaviour and transmission risk beliefs change over time within individuals, and to investigate whether factors such as starting ART are associated with these changes

(x) in a subset of patients, to investigate the association of questionnaire-assessed factors (demographic/social factors. psychological and physical symptoms, quality of life, lifestyle factors, sexual behaviour, ART adherence) with laboratory and clinical outcomes (virological failure, major morbidity, mortality, hospital admissions).

3. Methods

3.1 Study design

Two cross-sectional self-administered questionnaire studies will be conducted among UK HIV outpatients, in 2010/11 (ASTRA 1) and 2013/14 (ASTRA 2). A prospective sub-study will be conducted in a subgroup of participants, linking the questionnaire data with routine clinic data. A small pilot study will be carried out prior to the first cross-sectional study (see section 3.11).

3.2 Setting

The questionnaire studies will be conducted among HIV outpatients attending clinics in five centres in the UK: Royal Free Hospital (London), Mortimer Market Clinic (London), Homerton Hospital (London), Brighton and Sussex University Hospital and North Manchester General Hospital.

3.3 Study population

Each study aims to include a representative sample of outpatients attending for care at each centre, irrespective of antiretroviral treatment status.

Inclusion criteria: HIV-infected individuals aged >=18 years, attending for outpatient

care.

Exclusion criteria: Unable to complete questionnaire in English or French due to language or cognitive difficulties. Too ill or distressed to complete questionnaire.

3.4 Sample size

The sample size calculation is based on the endpoint of high-risk sex in the past three months, and on two major objectives: the ability to detect a difference between patients on and off ART in the proportion who report high-risk sex (objective iii), and the ability to detect a difference over time in the prevalence of high-risk sex (objective viii). The calculations are based on 80% power and 5% two-sided significance level, and assume that the overall proportion of patients reporting high-risk sex (in the past three months) in the first study is 15% (Kozal 2004; Sadler 2007; Elford 2007; Williamson 2008; Sherr 2007).

Sample size for objective iii: Assuming 75% of patients are on ART, and the proportion of patients off ART who report high-risk sex is 12%, 3349 patients would be required to detect a difference of 4% (16% of patients on ART reporting high-risk sex).

Sample size for objective viii: In order to detect a difference of 3% between ASTRA 1 and ASTRA 2 in the prevalence of recent high-risk sex (from 15% to 18%), 2468 patients would be required in each study. 3593 subjects would be required to detect a difference of 3.5% in major demographic subgroups (from 19% to 22.5% in MSM, assuming MSM comprise 65% of the total study population; from 7% to 10.5% in Black Africans, assuming Black Africans comprise 30% of the total study population).

The estimated minimum numbers of patients recruited over a four to six month period is approximately 1400 each for the Royal Free and Mortimer Market clinics, 900 in Brighton, 700 in Homerton and 700 in Manchester (total 5100). With a 75% response rate, a total of 3825 patients might be expected to complete the questionnaire on each occasion, providing adequate power for each of the above comparisons.

3.5 Recruitment

Recruitment to each cross-sectional study will take place in each centre over a six month period, as the majority of patients under care would be expected to attend over this period. The first cross-sectional study (ASTRA 1) will recruit from October 2010 to March 2011/April 2011. Each centre will identify specific clinics each week at which patients will be recruited, aiming to ensure a representative study population, and that the majority of outpatients under care have been invited to participate. Consecutive patients attending these clinics will be approached by the study nurse or HIV doctor and invited to participate (see section 3.8). Centres can offer a small incentive for participation of up to £2.50 per person (e.g. drink voucher; prize draw). Recruitment will continue at least until the target number of patients has been attained, or until the end of the six-month period. The second cross-sectional study (ASTRA 2) will be conducted three years later, and will recruit in the same way.

3.6 Consent

Patients 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. Patients will be asked to sign a second, additional consent, if they agree to linkage of their questionnaire responses with routine clinic data (see section 3.9.3). Experience from previous questionnaire studies (Sherr 2008) suggests that approximately 60-70% of patients may consent to this linkage.

3.7 Data collection

The study questionnaire will be self-administered. Participants will be invited to complete the questionnaire while waiting for their outpatient appointments, or directly following their appointment, whichever is most convenient for the patient and/or appropriate for each particular clinical centre. Each clinical centre will have the option of using paper questionnaires alone for the study, or a combination of paper and computerised questionnaires (CASI - computer-assisted self-interviewing [Schackman 2008]). 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 a paper 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 Paper questionnaire

There will be separate versions of the paper questionnaire (A5 booklet) 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, the study nurse will ask if the patient agrees to give an email address, in case it is necessary to send a reminder, if a completed questionnaire has not been received. One reminder only will be sent.

3.7.2 CASI questionnaire

A computerised version of the questionnaire has the advantage of automatically presenting the appropriate gender-specific questions to participants and automating any necessary skips, and may be preferred by some participants. The computerised questionnaire will be available on two or three fixed PC’s or laptops in a private area within the clinic. Participants using the CASI questionnaire will be allocated a code sheet, which will contain a unique study number to be entered into the computer by the study nurse, prior to the participant completing the questionnaire. The study nurse will explain how to use the CASI system, and then the questionnaire will be self-completed by the participant. Using CASI is straightforward and should not present difficulty for participants familiar with using a keyboard.

3.7.3 French questionnaire

The patient information sheet will clearly state that a French version of the paper questionnaire is available, if preferred.

3.8 Role of study nurse

The study nurses 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

  • Information sheets
  • Consent forms
  • Study log
  • Numbered paper questionnaires (and pens)
  • Pre-paid envelopes addressed to research team
  • Numbered code sheets for CASI completion
  • Numbered French translated paper quesitonnaires
  • List of study numbers linked to email addresses, for participants who took the quesitonnaire away and agreed to an email reminder if necessary,

3.8.2 Study nurse tasks

In each centre, the study nurse(s) will undertake the following tasks:

  • Together with the clinical and research team, deciding on clinics/days to recruit to the study
  • Together with the clinical and research team, deciding on how best to organise study recruitment and completion of questionnaires
  • Ensuring, as far as possible, systematic selection of patients invited to participate
  • Inviting patients to participate and distributing the study information sheet
  • Obtaining patients’ written informed consent to participate, with or without additional written consent for linkage with clinc data
  • Completing the study log (see section 3.9.1)
  • Distributing paper questionnaires to participants
  • Identifying a suitable private space for participants to complete the paper questionnaire, if desired
  • Entering the study number and date on paper questionnaires
  • Ensuring completed questionnaires in sealed envelopes are placed in the box provided
  • Allocating CASI code sheets, if required
  • Organising CASI completion, and entering the study number and date into the computer
  • Ensuring completed CASI quesitonnaire responses are securely saved on the computer
  • Encouraging questionnaire completion in the clinic
  • If agreed with the patient, recording the email addresses of patients who opt to complete a paper questionnaire out of the clinic, in order for to a reminder to be sent if necessary.
  • Liasing with the core group at the research department regarding any necessary reminders for participants who provided email addresses, and sending out reminder emails
  • Faxing (or emailing) the study log to the research centre each week, after the clinic numbers have been removed
  • Downloading CASI data and sending back to the reseach centre electronically each week
  • Having paper questionnaires available for colleciton by courrier (after first week, then monthly)
  • Communicating with the core group regarding study progress and any problems identified
  • Storing the study log and consent forms securely in the clinic

3.9 Measurements