Trends in HIV incidence between 2013-2019 and association of baseline factors with subsequent incident HIV among gay, bisexual, and other men who have sex with men attending sexual health clinics in England: A prospective cohort study.

BACKGROUND: Prospective cohort studies of incident HIV and associated factors among gay, bisexual, and other men who have sex with men (GBMSM) in the United Kingdom are lacking. We report time trends in and factors associated with HIV incidence between 2013 and 2019 among a cohort of GBMSM: the AURAH2 prospective study. METHODS AND
FINDINGS: Participants were recruited through 1 of 3 sexual health clinics in London and Brighton (July 2013 to April 2016) and self-completed a baseline paper questionnaire and subsequent 4-monthly and annual online questionnaires (March 2015 to March 2018), including information on sociodemographics, lifestyle, health and well-being, HIV status, sexual/HIV-related behaviours, and preexposure prophylaxis and postexposure prophylaxis (PrEP/PEP). Incident HIV was ascertained by linkage with national HIV surveillance data from Public Health England (PHE). We investigated the associations of HIV incidence with (1) baseline factors using mixed-effects Weibull proportional hazard models, unadjusted and adjusted for age, country of birth and ethnicity, sexuality, and education level; and (2) time-updated factors, using mixed-effects Poisson regression models. In total, 1,162 men (mean age 34 years, 82% white, 94% gay, 74% university-educated) were enrolled in the study. Thirty-three HIV seroconversions occurred over 4,618.9 person-years (PY) of follow-up: an overall HIV incidence rate (IR) of 0.71 (95% confidence interval (CI) 0.51 to 1.00) per 100 PY. Incidence declined from 1.47 (95% CI 0.48 to 4.57) per 100 PY in 2013/2014 to 0.25 (95% CI 0.08 to 0.78) per 100 PY in 2018/2019; average annual decline was 0.85-fold (p < 0.001). Baseline factors associated with HIV acquisition included the following: injection drug use (6/38 men who reported injection drug-acquired HIV; unadjusted conditional hazard ratio (HR) 27.96, 95% CI 6.99 to 111.85, p < 0.001), noninjection chemsex-related drug use (13/321; HR 6.45, 95% CI 1.84 to 22.64, p < 0.001), condomless anal sex (CLS) (26/741; HR 3.75, 95% CI 1.31 to 10·74, p = 0.014); higher number of CLS partners (HRs >10 partners [7/57]; 5 to 10 partners [5/60]; and 2 to 4 partners [11/293]: 14.04, 95% CI 4.11 to 47.98; 9.60, 95% CI 2.58 to 35.76; and 4.05, 95% CI 1.29 to 12.72, respectively, p < 0.001); CLS with HIV-positive partners (14/147; HR 6.45, 95% CI 3.15 to 13.22, p < 0.001), versatile CLS role (21/362; HR 6.35, 95% CI 2.18 to 18.51, p < 0.001), group sex (64/500; HR 8.81, 95% CI 3.07 to 25.24, p < 0.001), sex for drugs/money (4/55, HR 3.27, 95% CI 1.14 to 9.38, p = 0.027) (all in previous 3 months); previous 12-month report of a bacterial sexually transmitted infection (STI) diagnoses (21/440; HR 3.95, 95% CI 1.81 to 8.63, p < 0.001), and more than 10 new sexual partners (21/471, HRs 11 to 49, 50 to 99, and >100 new partners: 3.17, 95% CI 1.39 to 7.26; 4.40, 95% CI 1.35 to 14.29; and 4.84, 95% CI 1.05 to 22.4, respectively, p < 0.001). Results were broadly consistent for time-updated analysis (n = 622 men). The study's main limitation is that men may not be representative of the broader GBMSM population in England.
CONCLUSIONS: We observed a substantial decline in HIV incidence from 2013 to 2019 among GBMSM attending sexual health clinics. Injection drug use, chemsex use, and measures of high-risk sexual behaviour were strongly associated with incident HIV. Progress towards zero new infections could be achieved if combination HIV prevention including Test and Treat strategies and routine commissioning of a PrEP programme continues across the UK and reaches all at-risk populations.

Introduction

To bring the HIV epidemic under control, there has been a massive scale-up in the treatment and prevention of HIV over the past decade that has led to a gradual decline in new HIV infections globally [1]. In the United Kingdom (UK), modelling of HIV surveillance data suggests that the underlying incidence of new HIV infections has been falling steadily for more than 5 years (since 2012) [2]. The decline has been particularly marked among gay, bisexual, and other men who have sex with men (GBMSM), among whom 51% of all new HIV diagnoses occurred in the UK in 2018 [3]. In England, the modelled number of incident infections among GBMSM has declined by 65% since 2014, with the most rapid fall after 2016 [3]. The steep declines coincide with a period when increasing numbers of men accessed preexposure prophylaxis (PrEP) [4]. In addition, during this period, there were efforts to increase uptake and frequency of HIV testing, and HIV treatment guidelines changed to recommend prompt initiation of antiretroviral therapy (ART) for people newly diagnosed with HIV. Declines in new HIV diagnoses among GBMSM have also been reported in New South Wales in Australia [5] and San Francisco and New York City in the United States [6,7].

There remains, however, limited data from UK prospective studies assessing HIV acquisition risk, associated factors, and temporal trends for incident HIV [8,9]. Such data could be helpful in providing insight regarding the risk factors driving the HIV epidemic among GBMSM in England. The Attitudes to and Understanding of Risk of Acquisition of HIV 2 (AURAH2) study is among the first prospective observational cohort studies of initially HIV–negative GBMSM in England. We sought to evaluate trends in HIV incidence between 2013 and 2019 and the association of baseline and time-updated demographic, socioeconomic, health, lifestyle, and behavioural factors with HIV incidence among GBMSM participating in AURAH2.

Methods

Study design and participants

Methodological details of the study have been published previously [10]. The AURAH2 study was a prospective cohort study that recruited GBMSM who were HIV negative or of unknown HIV status from 3 large sexual health clinics in London and Brighton (56 Dean Street, London; Mortimer Market Centre, London; and Claude Nicol Clinic, Brighton) from July 2013 to April 2016. Participants were eligible if they were aged 18 years or older and had attended the study clinics for routine testing for sexually transmitted infections (STIs) or HIV. Men were classified as GBMSM for the purposes of the analysis if they met at least one of the following criteria: (i) reported being gay or bisexual; (ii) reported anal sex with a man in the past 3 months; or (iii) reported having disclosed to their family, friends, or workmates as being gay, bisexual, and/or attracted to men. Participants who consented to the study completed a confidential baseline paper questionnaire in the clinic. During the follow-up period, participants self-completed subsequent 4-monthly and annual questionnaires that were available online from March 2015 until March 2018. The baseline questionnaire gathered information on demographic, socioeconomic, lifestyle, health and well-being–related factors, knowledge and understanding of HIV, sexual behaviours, STI diagnoses, and PrEP and postexposure prophylaxis (PEP) use. The 4-monthly questionnaires assessed information on HIV status, HIV testing history, sexual behaviours, and lifestyle factors. Annual questionnaires captured the same information as the 4-monthly questionnaire and additional information on PrEP and PEP use in the past year, relationship status, and health and well-being factors as assessed on the baseline questionnaire. This study is reported as per the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guideline (

Ethics approval and participant consent

All participants provided written, informed consent before taking part. Consent to participate in the study included consent for linkage to Public Health England (PHE)’s datasets at the end of the study using limited participant identifiers. The AURAH2 study was approved by the designated research ethics committee, The National Research Ethics Service (NRES) committee London-Hampstead, ref: 14/LO/1881 in November 2014 [10]. Based on the research protocol and all versions of study documents, the AURAH2 study subsequently received permission for clinical research at the 3 participating National Health Service (NHS) sites: Chelsea and Westminster NHS Foundation Trust, Central and North West London NHS Foundation Trust, and the Brighton and Sussex University Hospitals NHS Trust. The AURAH2 study was registered on the NIHR clinical research network portfolio.

Completion of online follow-up questionnaires

Participants who completed a first online follow-up questionnaire in March 2015 had the option to complete up to 9 online questionnaires, as the follow-up finished in March 2018. When participants were due to complete a questionnaire, 2 remainder emails were sent after 2 and 4 weeks followed by a text message. If participants missed a questionnaire at any time during follow-up, they were still invited to complete subsequent questionnaires. At each online follow-up, participants were asked about the most recent date of HIV test and the result.

Baseline measures

All baseline measures were self-reported in the participant baseline questionnaire. Sociodemographic variables included age group (<25; 25 to 29; 30 to 34; 35 to 39; 40 to 44; ≥45 years), country of birth and ethnicity (white UK born; other ethnicity UK born; white non-UK born; other ethnicity non-UK born), self-reported sexual identity (gay; bisexual/other plurisexual identities), education (university degree; other qualification; no qualification), ongoing relationship (yes, living with partner; yes, not living with partner; no), employment status (employed; not employed), sufficient money for basic needs (yes; mostly; sometimes or no), and housing status (homeowner; renting including private, housing association, and council; unstable or other).

We considered the following measures of sexual/HIV-related behaviour in the preceding 3 months (classified as “yes” or “no” unless otherwise indicated): condomless anal sex (CLS), number of CLS partners (none; 1; 2 to 4; 5 to 10; >10), CLS with partners known to be HIV positive, sexual CLS role (no CLS; always insertive; always receptive; insertive and receptive [versatile]), group sex, sex for drugs or money, fisting, or sex toys use. We also considered HIV test in the previous 6 months, and bacterial STI diagnosis, number of new sexual partners (0 to 10; 11 to 49; 50 to 99; ≥100), and PrEP and PEP use in the previous 12 months. Bacterial STIs included gonorrhoea, syphilis, and chlamydia, including lymphogranuloma venereum (LGV).

Lifestyle factors included recreational drug use (injection drug use; noninjection use of 1 or more of the 3 chemsex-associated drugs [mephedrone, GHB/GBL, crystal methampethamine]; non-injection use of other drugs; no drug use), smoking status (never smoked; ex-smoker; current smoker) and alcohol consumption (higher-risk alcohol consumption: a score of ≥6 on a modified version the AUDIT-C WHO alcohol screening tool questionnaire, first 2 questions only) [11]. A total score of 6 was chosen given that AURAH2 participants were only asked the first 2 questions of the WHO AUDIT-C questionnaire rather than the full AUDIT-C. Mental health included symptoms of depression (defined as a score of ≥10 on the Patient Health Questionnaire [PHQ-9], which is the standard cutoff score used to define clinically significant depressive symptoms) [12], and anxiety symptoms (defined as a score of ≥10 on the Generalised Anxiety Disorder Scale [GAD-7], which represents the standard cutoff to define anxiety disorder) [13].

For sexual/HIV-related behaviour, mental health, and alcohol consumption measures, missing responses were considered to indicate the absence of the event or condition, because our outcome of interests was “past report of behaviours.” Where there was no report of these measures, including missing, we classified answers as “no.” For all other variables that were not classified as “yes” or “no,” missing values were excluded from the analyses.

Time-updated measures

Age, recent HIV test, CLS, CLS with 2 or more partners, sexual CLS role, group sex, chemsex (a different variable from recreational drug use variable at baseline questionnaire; “have you used drugs before or during sex (chemsex) in the last three months?”, classified as “yes” or “no”), and bacterial STI diagnosis were also used as time-varying variables derived from baseline, 4-monthly, and annual questionnaires. Relationship status, PrEP use, PEP use, recreational drug use, injection drug use, depressive symptoms, anxiety symptoms, and alcohol use were time-varying variables derived from baseline and annual questionnaires. All other variables were fixed variables that were only ascertained at baseline.

Ascertainment of incident HIV

There were 2 methods of ascertainment of incident HIV diagnosis during follow-up. First, records of all GBMSM enrolled in the AURAH2 study were linked to national HIV surveillance data by PHE [14,15]. The databases collect information on new HIV diagnoses from laboratories, genitourinary medicine (GUM) clinics, general practitioners (GPs), and other services where HIV testing takes place in England. The data linkage process was carried out using a deterministic and hierarchical algorithm, based on gender identity, date of birth, year of birth, country of birth, ethnicity, originating clinic, years in the UK, and first initial and Soundex code (a 4-character coding of an adult surname). All data collected as part of the national HIV surveillance programme in the UK is pseudo-anonymised; no names are collected. The data matching process was completed in November 2019. For each study participant that matched to the HIV surveillance dataset, PHE data were provided on date and region of HIV diagnosis, CD4 and viral load at HIV diagnosis, and if relevant, time from diagnosis to linkage to care, time from diagnosis to treatment initiation, and death.

The second method of ascertainment of new HIV diagnoses was through the online follow-up questionnaires; participants were asked about the date and results of most recent HIV test. All the participants who reported being newly diagnosed with HIV in a follow-up questionnaire were also identified as having a new HIV diagnosis in the PHE surveillance databases. Linkage with PHE databases also identified a small number of participants who were positive at entry to the study (n = 3); these men were excluded from analysis.

Statistical analysis

For the analyses of HIV incidence and baseline-associated factors, all men enrolled in AURAH2 were included. Incident HIV infection was defined as seroconversion from HIV–negative status at baseline to HIV–positive during follow-up, confirmed by PHE. Person-years (PY) of follow-up were calculated from the date of completing the baseline questionnaire until (1) the date of HIV diagnosis from PHE for men who seroconverted or (2) 3 months before the date of data linkage with PHE datasets was completed (June 30, 2019) for men who did not seroconvert. Due to the linkage with PHE data for ascertainment of the endpoint, all men could be considered as remaining under follow-up over the entire period, even if follow-up questionnaires were not completed.

HIV incidence rates (IRs) were calculated as the number of new HIV infections divided by the number of PY of follow-up, reported with 95% confidence intervals (95% CIs). IRs were calculated per 100 PY, overall and according to calendar year from 2013 until 2019. As the study started on July 30, 2013 and ended on June 30, 2019, the first 2 years (2013 to 2014) and the last 2 years (2018 to 2019) were combined. The associations of baseline factors and current calendar year as a continuous variable with HIV incidence were analysed by calculating HIV IRs and using 2-level random-intercept proportional hazard models with sexual health clinic sites defining the second level to estimate conditional hazard ratios (HRs). The conditional distribution of the response given the random effects was assumed to be a Weibull distribution. HRs with 95% CI are presented unadjusted, and adjusted for sociodemographic factors that were less likely to be influenced by HIV and sexual behaviour: age at baseline, country of birth and ethnicity, sexual identity, and education.

Changes in the annual prevalence of sexual/HIV-related risk behaviours over time were also examined. The prevalence of CLS with 2 or more partners, group sex, bacterial STI, any recreational drug use, injection drug use, noninjection chemsex-related drug use (all in the previous 3 months), and PrEP and PEP use in the previous 12 months was calculated for each year from 2013/14 to 2018/19, using all available baseline and follow-up questionnaires from all participants at each time point. Trends over calendar time during the AURAH2 study period were assessed using univariate generalised estimation equation (GEE) models with a logit link and robust standard errors, accounting for multiple questionnaires responses from individual participants.

We also performed an additional longitudinal analysis among men who completed at least 1 online follow-up questionnaire to examine time-updated factors associated with HIV incidence. We used 2-level random-intercept Poisson regression models, unadjusted and adjusted for age (time-updated), country of birth and ethnicity, sexual identity, and education, using all available baseline and follow-up questionnaires. We present these results as incidence rate ratios (IRRs) with their corresponding 95% CI. In the multivariable analyses, the whole statistical unit for a single individual with missing values was excluded from the analyses if a value for one of the covariates was missing (complete case analysis).

All analyses were planned prior to analysing final datasets from PHE in November 2019 (, and no data-driven changes took place to these analyses, except that we used mixed-effects modelling instead of Cox proportional hazard modelling (indicated in the analyses plan), in response to peer review comments. The use of hierarchical models was chosen to take into account of clustering according to clinic. All analyses were conducted using Stata statistical software (version 15.1).

Results

Characteristics of the participants

Between July 2013 and April 2016, a total of 1,162 HIV–negative men were enrolled in the study (). At baseline, the mean age of participants was 34 years (standard deviation [SD]: 10.4; interquartile range [IQR]: 26 to 39), 81.9% were of white ethnicity, 93.6% self-reported being gay, 74.4% had a university degree, 82.9% reported being employed, and 77.4% always had money to cover basic needs. In the previous 3 months, 63.9% reported having had CLS, 35.4% reported CLS with 2 or more partners, 12.7% reported CLS with HIV–positive partners, 43.1% reported group sex, 60.0% reported the use of at least 1 recreational drug, and 3.3% reported injection drug use. The type of drug injected was not ascertained in the baseline questionnaire, but all 38 people who injected drugs reported having taken at least 1 chemsex-related drug in the past 3 months. Overall, 38.0% of men reported having been diagnosed with a bacterial STI in the past year, and 5.0% and 20.7% reported ever having taken PrEP and PEP, respectively, in the past year. Three individuals did not complete the baseline questionnaire. The proportion of missing responses was low (<5% for all variables) (see footnotes in ).

Of the 1,162 men enrolled, all were included in the PHE linkage for ascertainment of new HIV diagnosis. Of the 1,162 men, 622 completed at least 1 online follow-up questionnaire (54%), of whom 483 (78% of 622) completed at least 1 annual follow-up questionnaire, and 400 men (64% of 622) were followed until the end of the study. Men who were older, had greater financial security, with more stable housing, with university level education, and were employed were more likely to continue on the study (622 men versus 540 men who completed only the baseline questionnaire) (). The number of follow-up questionnaires (4-monthly and annual) completed by the end of the study period was 3,277. Participants completed a median of 6 (IQR: 3 to 7) online questionnaires.

Trends in HIV incidence

In total, 33 of 1,162 men (2.8%) were newly diagnosed with HIV during the period from the date of completion of their baseline questionnaire until June 2019. Of all 33 diagnoses identified by the PHE linkage, 15 were self-reported by the participant on one of the AURAH2 online follow-up questionnaires. There were no additional unconfirmed self-reported HIV diagnoses. The 3 men who did not complete a baseline questionnaire were included in the incidence analysis as data on their age, HIV status, and PY of follow-up time were available from PHE. There were no deaths recorded among the 33 men diagnosed with HIV.

The overall HIV IR in this cohort with 4,618.9 PY of follow-up time was 0.71 (95% CI 0.51 to 1.00) per 100 PY (). HIV incidence fell progressively from 2013 until 2019; from 1.47 (95% CI 0.48 to 4.57) per 100 PY in 2013/2014 to 0.25 (95% CI 0.08 to 0.78) per 100 PY in 2018/2019. The incidence declined on average by 0.85-fold per year from 2013 to 2019 (p < 0·001, modelled using mixed-effects Weibull proportional hazard).

HIV incidence among GBMSM in the AURAH2 study, 2013–2019.

AURAH2, The Attitudes to and Understanding of Risk of Acquisition of HIV 2; CI, confidence interval; GBMSM, gay, bisexual, and other men who have sex with men; PY, person-years.

The most common age category at the time of new HIV diagnoses was between 35 and 44 years, with a total of 13 men (39.4%) in this age range being diagnosed with HIV, followed by men in the age category of 25 to 34 years (8 men, 24.2%), <25 years (7 men, 21.2%), and ≥45 years (5 men, 15.2%). The median (IQR) age at time of new HIV diagnosis was 35 years (26 to 40).

Association of baseline factors with incident HIV

Table 1 presents the association of baseline factors with incident HIV diagnosis. In univariable mixed-effects Weibull proportional hazard models, the factor most strongly associated with HIV acquisition was reporting injection drug use in the past 3 months, with an almost 28-fold higher rate compared to men who did not report recreational drug use (HR 27.96, 95% CI 6.99 to 111.85, global p < 0.001). The HIV IR among people who injected drugs was 4.74 (95% CI 2.13 to 10.54) per 100 PY. Having used at least 1 noninjection chemsex-related drug was also strongly associated with HIV acquisition (HR 6.45, 95% CI 1.84 to 22.64, compared to no drug use); the association with non-chemsex–related drugs was weaker (HR 3.73, 95% CI 0.99 to 14.05).

Table 1

Baseline characteristics and association with incident HIV among 1,162 GBMSM participating in the AURAH2 prospective study, 2013–2019*.

Baseline characteristics	Participants N (%)	HIV infections from baseline– 2019 n (%)	PY at risk	HIV IR per 100 PY (95% CI)	Unadjusted conditional HR (95% CI)	p-value
Demographic characteristics
Age at baseline category, years						0.4210.417[t]
<25	275 (23.9)	8 (2.9)	1087.61	0.74 (0.37–1.47)	1 (Ref)
25–29	207 (17.9)	3 (1.5)	839.50	0.36 (0.11–1.10)	0.49 (0.13–1.85)
30–34	227 (19.7)	5 (2.2)	896.65	0.56 (0.23–1.34)	0.76 (0.25–2.32)
35–39	156 (13.5)	8 (5.1)	605.63	1.32 (0.66–2.64)	1.79 (0.67–4.76)
40–44	121 (10.5)	4 (3.3)	480.92	0.83 (0.31–2.22)	1.13 (0.34–3.77)
≥45	167 (14.5)	5 (2.9)	674.09	0.74 (0.31–1.78)	1.02 (0.33–3.12)
Mean age (SD)	34 (10.4)
Median age (IQR)	31 (26–39)
Country of birth and ethnicity§						0.176
Born in the UK, white	568 (49.4)	10 (1.8)	2,296.31	0.44 (0.23–0.81)	1 (Ref)
Born in the UK, other ethnicity	60 (5.2)	1 (1.7)	242.16	0.41 (0.06–2.93)	0.94 (0.12–7.38)
Non-UK born, white	374 (32.5)	17 (4.5)	1,463.62	1.16 (0.23–1.34)	2.63 (1.21–5.76)
Non-UK born, other ethnicity	148 (12.9)	2 (1.4)	581.72	0.34 (0.66–2.64)	0.78 (0.17–3.54)
Sexual identity						0.128
Gay	1,076 (93.6)	26 (2.4)	4,291.83	0.61 (0.41–0.89)	1 (Ref)
Bisexual/other	74 (6.4)	4 (5.4)	291.26	1.37 (0.52–3.66)	2.26 (0.79–6.49)
Socioeconomic characteristics and partnership status
Education						0.0140.013[t]
University degree	853 (74.4)	17 (1.9)	3,413.05	0.49 (0.31–0.80)	1 (Ref)
Other qualification	272 (23.8)	11 (4.4)	1,108.62	1.02 (0.56–1.84)	2.01 (0.94–4.28)
No qualification	21 (1.8)	2 (9.5)	75.83	2.64 (0.66–10.55)	4.65 (1.07–20.14)
Employed†						0.074
Yes	952 (82.9)	29 (3.1)	3,767.14	0.77 (0.53–1.10)	1 (Ref)
No	197 (17.1)	1 (0.5)	812.17	0.12 (0.01–0.87)	0.16 (0.02–1.19)
Money to cover basic needs						0.6270.613[t]
All of the time	896 (77.4)	24 (2.7)	3,581.41	0.67 (0.45–1.00)	1 (Ref)
Most of the time	194 (16.8)	5 (2.6)	768.90	0.65 (0.27–1.56)	0.97 (0.37–2.54)
Sometimes/No	68 (5.9)	1 (1.5)	264.84	0.38 (0.05–2.68)	0.55 (0.07–4.09)
Housing status₴						0.3420.330[t]
Renting	680 (59.3)	13 (1.9)	2,707.24	0.48 (0.28–8.27)	1 (Ref)
Home owner	314 (27.4)	14 (4.5)	1,252.75	1.11 (0.66–1.89)	2.34 (1.10–4.97)
Unstable or other	153 (13.3)	3 (1.9)	611.33	0.49 (0.16–1.52)	1.02 (0.29–3.58)
Ongoing relationship						0.2000.191[t]
Yes, living with partner	272 (23.5)	11 (4.0)	1,080.22	1.01 (0.56–1.84)	1 (Ref)
Yes, not living with partner	193 (16.7)	3 (1.6)	783.15	0.38 (0.12–1.19)	0.38 (0.10–1.35)
No	693 (59.8)	16 (2.3)	2,755.05	0.58 (0.36–0.95)	0.57 (0.26–1.22)
Sexual/HIV-related behaviour characteristics
HIV test in the past 6 months						0.325
No	322 (27.8)	6 (1.9)	1,324.99	0.45 (0.20–1.01)	1 (Ref)
Yes	837 (72.2)	24 (2.9)	3,293.42	0.73 (0.49–1.09)	1.57 (0.64–3.85)
CLS in the past 3 months‡						0.014
No	418 (36.1)	4 (0.9)	1,704.76	0.23 (0.09–0.63)	1 (Ref)
Yes	741 (63.9)	26 (3.5)	2,913.66	0.89 (0.61–1.31)	3.75 (1.31–10.74)
Number of CLS partners in the past 3 months‡						<0.001<0.001[t]
No CLS partners	424 (36.6)	4 (0.9)	1,727.09	0.23 (0.09–0.62)	1 (Ref)
One CLS partner	325 (28.0)	3 (0.9)	1,306.35	0.23 (0.07–0.71)	0.98 (0.22–4.40)
2–4 CLS partners	293 (25.3)	11 (3.8)	1,163.99	0.95 (0.52–1.71)	4.05 (1.29–12.72)
5–10 CLS partners	60 (5.2)	5 (8.3)	212.67	2.36 (0.98–5.64)	9.60 (2.58–35.76)
More than 10 CLS partners	57 (4.9)	7 (12.3)	208.30	3.36 (1.60–7.05)	14.04 (4.11–47.98)
CLS with partners known to be HIV positive in the past 3 months‡						<0.001
No	1,012 (87.3)	16 (1.6)	4,086.01	0.39 (0.24–0.64)	1 (Ref)
Yes	147 (12.7)	14 (9.5)	532.41	2.63 (1.56–4.44)	6.45 (3.15–13.22)
Sexual role CLS in the past 3 months						<0.001
No CLS/did not state which partner	423 (36.5)	4 (0.9)	1,724.83	0.23 (0.08–0.62)	1 (Ref)
Always insertive	217 (18.7)	2 (0.9)	877.05	0.22 (0.05–0.91)	0.98 (0.18–5.35)
Always receptive	157 (13.6)	3 (1.9)	623.35	0.48 (0.15–1.49)	2.06 (0.46–9.19)
Versatile (sometimes insertive, sometimes receptive)	362 (31.2)	21 (5.8)	1,393.19	1.51 (0.9–2.31)	6.35 (2.18–18.51)
Number of new sexual partners in the past 12 months~						0.0010.001[t]
0–10 new partners	688 (59.4)	9 (1.3)	2,772.34	0.32 (0.17–0.62)	1 (Ref)
11–49 new partners	367 (31.6)	15 (4.1)	1,446.30	1.04 (0.63–1.72)	3.17 (1.39–7.26)
50–99 new partners	72 (6.2)	4 (5.6)	272.66	1.47 (0.55–3.91)	4.40 (1.35–14.29)
100 or more new partners	32 (2.8)	2 (6.3)	127.12	1.57 (0.39–6.29)	4.84 (1.05–22.41)
Group sex in the past 3 months						<0.001
No	659 (56.9)	4 (0.6) 64	2,670.75	0.15 (0.06–0.39)	1 (Ref)
Yes	500 (43.1)	64 (12.8)	1,947.67	1.33 (0.91–1.96)	8.81 (3.07–25.24)
Fisting or sex toys use in the past 3 months						0.202
No	745 (64.3)	16 (2.2)	2,982.81	0.54 (0.33–0.88)	1 (Ref)
Yes	414 (35.7)	14 (3.4)	1,635.61	0.86 (0.51–1.45)	1.59 (0.77–3.25)
Sex for drugs or money in the past 3 months						0.027
No	1,104 (95.2)	26 (2.4)	4,418.16	0.59 (0.40–0.86)	1 (Ref)
Yes	55 (4.8)	4 (7.3)	200.26	1.99 (0.75–5.32)	3.27 (1.14–9.38)
PEP use in the past 12 months						0.029
No	919 (79.3)	19 (2.1)	3,709.52	0.51 (0.33–0.80)	1 (Ref)
Yes	240 (20.7)	11 (4.6)	908.89	1.21 (0.67–2.18)	2.29 (1.09–4.81)
PrEP use in the past 12 months						0.190
No	1,101 (95)	27 (2.7)	4,408.52	0.61 (0.42–0.89)	1 (Ref)
Yes	58 (5.0)	3 (5.2)	209.49	1.43 (0.46–4.44)	2.21 (0.67–7.30)
Bacterial STI diagnoses in the past 12 months						0.001
No	719 (62.0)	9 (1.3)	2,936.07	0.31 (0.16–0.59)	1 (Ref)
Yes	440 (38.0)	21 (4.8)	1,682.35	1.25 (0.81–1.91)	3.95 (1.81–8.63)
Health and lifestyle characteristics
Smoking status						0.735
Never smoked	612 (53.1)	14 (2.3)	2,452.23	0.57 (0.34–0.96)	1 (Ref)
Ex-smoker	290 (25.2)	8 (2.8)	1,163.82	0.69 (0.34–1.37)	1.20 (0.50–2.87)
Regular smoker	250 (21.7)	8 (3.2)	977.79	0.82 (0.41–1.64)	1.41 (0.59–3.37)
Recreational drug use in the past 3 months						<0.001<0.001[t]
No	464 (40.0)	3 (0.7)	1,895.32	0.16 (0.05–0.49)	1 (Ref)
Noninjection drug and non-chemsex use	336 (29.0)	8 (2.4)	1,350.96	0.59 (0.29–1.18)	3.73 (0.99–14.05)
Chemsex-related drug use (no injection)	321 (27.7)	13 (4.1)	1,254.47	0.97 (0.61–1.79)	6.45 (1.84–22.64)
Injection drug use	38 (3.3)	6 (15.8)	126.67	4.74 (2.13–10.54)	27.96 (6.99–111.85)
Higher-risk alcohol consumption (modified WHO AUDIT-C score of ≥6)						0.714
No	935 (80.1)	25 (2.7)	3,721.68	0.67 (0.45–0.99)	1 (Ref)
Yes	224 (19.3)	5 (2.2)	896.74	0.56 (0.23–1.34)	0.83 (0.32–2.17)
Depressive symptoms (PHQ-9 score ≥10)						0.844
No	1,018 (87.8)	26 (2.6)	4,064.75	0.64 (0.43–0.93)	1 (Ref)
Yes	141 (12.2)	4 (2.8)	553.67	0.72 (0.27–1.92)	1.12 (0.39–3.20)
Anxiety symptoms (GAD-7 score ≥10)						0.462
No	1,033 (89.1)	28 (2.7)	4,118.39	0.68 (0.47–0.98)	1 (Ref)
Yes	126 (10.9)	2 (1.6)	500.03	0.39 (0.10–1.59)	0.58 (0.14–2.45)
Year of enrolment						0.430
2013	28 (2.4)	2 (7.1)	149.98	1.33 (0.33–5.33)	1 (Ref)
2014	152 (13.1)	3 (1.9)	735.62	0.4 (0.13–1.26)	0.29 (0.05–1.94)
2015	788 (67.8)	21 (2.7)	3,115.90	0.67 (0.44–1.03)	0.43 (0.09–1.93)
2016	194 (16.7)	7 (3.6)	617.36	1.13 (0.54–2.38)	0.67 (0.11–4.09)

*All measures were self-reported, missing data, or missing questionnaire for:

Age: 9 (all HIV negative); Country of birth and ethnicity, Sexuality: 12 (9 HIV negative, 3 HIV positive); University education: 16 (13 HIV negative, 3 HIV positive); Relationship status, Money status: 4 (1 HIV negative, 3 HIV positive); Employment: 13 (10 HIV negative, 3 HIV positive); Housing status: 15 (12 HIV negative, 3 HIV positive); Smoking status: 10 (7 HIV negative, 3 HIV positive); HIV test, CLS, Number of CLS partners, New sexual partners, Sexual CLS role, Group sex, Fisting or sex toys use, PEP use, PrEP use, Recreational drug use, STI diagnoses, Alcohol consumption, Depressive symptoms, and Anxiety symptoms: 3 (all HIV positive).

[t] p-value for trend.

§Other ethnicity includes black, Asian, mixed, and other ethnic group.

†Employed group includes full-time (n = 845) and part-time (n = 107) employment/self-employment; No employment group includes unemployed registered or not registered for benefits (n = 60), sick or disabled (n = 6), retired (n = 24), and other (student or training or looking after home or dependents or other) (n = 107).

₴Renting housing includes private renting and renting from council or housing association; unstable or other housing includes temporary accommodation, staying with friends or family, other accommodation, and homeless.

‡CLS with men only.

~New partners include men and women.

AURAH2, The Attitudes to and Understanding of Risk of Acquisition of HIV 2; CI, confidence interval; CLS, condomless anal sex; GAD-7, generalised anxiety disorder-7; GBMSM, gay, bisexual, and other men who have sex with men; HR, hazard ratio; IQR, interquartile range; IR, incidence rate; PEP, postexposure prophylaxis; PrEP, preexposure prophylaxis; PY, person-years; PHQ-9, patient health questionnaire-9; SD, standard deviation; STI, sexually transmitted infection; WHO-AUDIT, World Health Organization–Alcohol Use Disorders Identification Test.

Other sexual/HIV-related behaviour risk factors were strongly associated with increased risk of HIV infection: CLS (HR 3.75, 95% CI 1.31 to 10·74, p = 0.014), greater number of CLS partners, with increased risk for those having at least 2 partners (HR for 2 to 4 partners 4.05, 95% CI 1.29 to 12.72; HR for 5 to 10 partners 9.60, 95% CI 2.58 to 35.76, HR for more than 10 partners 14.05, 95% CI 4.11 to 47.98, compared with no CLS, global p < 0.001), CLS with HIV–positive partners (HR 6.45, 95% CI 3.15 to 13.22, p < 0.001), versatile CLS role (HR 6.35, 95% CI 2.18 to 18.51, p < 0.001), group sex (HR 8.81, 95% CI 3.07 to 25.24, p < 0.001), and sex for drugs or money (HR 3.27, 95% CI 1.14 to 9.38, p = 0.027) in the past 3 months; reporting a bacterial STI diagnosis in the past 12 months (HR 3.95, 95% CI 1.81 to 8.63, p = 0.001), reporting more than 10 new sexual partners in the past 12 months (HR for 11 to 49 new partners 3.17, 95% CI 1.39 to 7.26, HR for 50 to 99 new partners 4.40, 95% CI 1.35 to 14.29, HR for 100 or more new partners 4.84, 95% CI 1.05 to 22.41, compared to 0 to 10 new partners, global p = 0.001) and having used PEP in the past 12 months (HR 2.29, 95% CI 1.09 to 4.81, p = 0.029).

For socioeconomic and demographic characteristics, lower level of education was associated with increased risk of HIV infection (HR for no qualification 4.65, 95% CI 1.07 to 20.14 compared to university degree, global p = 0.014). There was some evidence that nonemployed men were at lower risk of infection than employed men (HR 0.16, 95% CI 0.02 to 1.19, p = 0.074).

Adjustment for age at baseline, country of birth and ethnicity, sexual identity, and education did not materially change the associations between incident HIV and baseline factors (). There were no significant associations of age group, housing status, financial status, relationship status, HIV test in the past 6 months, fisting or sex toys use in the past 3 months, PrEP use in the past 12 months, smoking status, alcohol consumption, country of birth and ethnicity, sexual identity, year of enrolment, depressive symptoms, and anxiety symptoms at baseline with risk of HIV infection ().

Prevalence of sexual risk behaviours over time

shows the trends in reported sexual risk behaviours, drug use, and the use of PrEP and PEP by calendar year, based on all available baseline and follow-up questionnaires from all 1,162 participants enrolled (total 4,439 questionnaires). shows that the annual prevalence of CLS with 2 or more partners in the past 3 months increased somewhat from 38.3% to 41.0% (p-value for linear trend from GEE logistic model = 0.006) between 2013/2014 and 2018, while group sex declined substantially from 46.7% to 24.2% (p < 0.001), as did bacterial STI diagnoses in the last 3 months from 20.1% to 9.2% (p < 0.001) between 2015 and 2018. For bacterial STIs, data were not included from the baseline questionnaire (since 2013) as it asked about diagnoses in the previous 12 months rather than in the last 3 months. Any recreational drug use in the past 3 months decreased from 57.2% to 45.5% (p < 0.001), while injection drug use (prevalence around 2%, p = 0.903) and the use of at least 1 chemsex-related drug (prevalence between 20% and 30%, p = 0.232) were stable (). Past 12-month PrEP use increased significantly from 2.22% to 43.4% (p < 0.001); on the other hand, PEP use peaked at 21.9% in 2016, then declined to 7.6% in 2018 (p = 0.07) ().

Annual prevalence of sexual/HIV-related behaviours among GBMSM in the AURAH2 study, 2013–2018*.

*Annual reports of (A) sexual risk behaviours in the previous 3 months, data from all available baseline, 4-monthly, and annual questionnaires (N = 4,439 questionnaires), bacterial STI in the previous 3 months, data from 4-monthly and annual questionnaires (N = 3,277 questionnaires); (B) recreational drug use in the past 3 months, data from baseline and annual questionnaires (N = 2,104 questionnaires); (C) PrEP and PEP use in the last 12 months, data from baseline and annual questionnaires (N = 2,085 questionnaires). AURAH2, The Attitudes to and Understanding of Risk of Acquisition of HIV 2; GBMSM, gay, bisexual, and other men who have sex with men; PEP, postexposure prophylaxis; PrEP, preexposure prophylaxis; STI, sexually transmitted infection.

Association of time-updated factors with incidence HIV among men who completed at least one online follow-up questionnaire

Among the 622 men who completed an online follow-up questionnaire, 19 were diagnosed with HIV during the period from the date of completion of their baseline questionnaire until June 30, 2019. With a total of 2,495 PY of follow-up time, the overall HIV IR in this subgroup of men was 0.76 (95% CI 0.49 to 1.19) per 100 PY, similar to the overall IR among all men enrolled in the AURAH2 cohort (0.71, 95% CI 0.51 to 1.00 per 100 PY). shows unadjusted and adjusted IRRs from mixed-effects Poisson models for factors associated with HIV incidence among these men (total complete observations 3,821 questionnaires). In this analysis, age, partnership status, sexual/HIV-related behaviours, PrEP and PEP use, and health and lifestyle variables were time updated, whereas ethnicity and country of birth, education, employment, sexual identity, financial status, and housing status were fixed variables that were only asked at baseline questionnaires. Longitudinal factors associated with HIV incidence among these men were quite similar to those among the 1,162 men, in particular, injection drug use (unadjusted IRR 21.67, 95% CI 3.96 to 118.30, p < 0.001), chemsex (3.89, 95% CI 1.35 to 11.22, p = 0.012), CLS with 2 or more partners, versatile CLS role, group sex (all in the previous 3 months), bacterial STI diagnosis (in the previous 12 months at the baseline questionnaire and in the past 3 months at the 4-monthly and annual questionnaires), and calendar year.

Discussion

Using a prospectively followed cohort of initially HIV–negative GBMSM in London and Brighton, we demonstrate a substantial decline in HIV incidence, from 1.47 per 100 PY to 0.25 per 100 PY between 2013 and 2019. The results of an earlier report from England’s national STI surveillance system also estimated that the annual HIV incidence among men who have sex with men attending English sexual health clinics decreased from 1.90 per 100 PY in 2012/2013 to 0.79 per 100 PY in 2016/2017 [4]. Based on the CD4 back-calculation model that is used to estimate HIV incidence among GBMSM living in England based on data on new HIV diagnoses, incidence begun to fall in 2012 [2,16].

The substantial decline in HIV incidence in our cohort was also described in some other countries [5-7,17,18]. It may be attributed to important behavioural changes within GBMSM populations. The dramatic decline in HIV infection rates in AURAH2 coincides with declines in the proportion of individuals reporting group sex and any recreational drug use since 2013, and diagnosis of bacterial STIs since 2015. The declining trends in group sex and diagnosis of bacterial STIs have been reported previously among men in AURAH2 who completed at least an online follow-up (n = 622), during the online follow-up period (2015 to 2018) [19]. This decline could be a feature of the fact that the study recruited GBMSM attending sexual health clinics for STI testing. Engagement in care for STI monitoring may have had a preventive impact on subsequent STI occurrence, or a “regression to the mean” effect may have operated because the men were recruited at a time of particularly high STI risk [19]. In contrast to these trends in STIs, group sex, and drug use overall, we observed in this study that the prevalence of CLS with 2 or more partners slightly increased, and the prevalence of injection drug use and noninjection chemsex-related drug use remained relatively stable, between 2013 and 2018 (baseline–the end of follow-up). The decline in HIV incidence is, therefore, unlikely to be solely explained by changes in sexual behaviour during this period.

Lower levels of infectious HIV in the community due to more timely HIV diagnosis and earlier treatment among those accessing HIV care are likely to have had a role in declining incidence, in line with previous prediction [20,21]. A recent study in Australia, the TAIPAN study, has demonstrated that the decrease in community-level HIV viraemia (≥200 copies/mL) from 28.6% in 2012 to 12.8% in 2017 among HIV–positive gay and bisexual men was significantly associated with decreasing HIV incidence in New South Wales and Victoria (from 0.88 per 100 PY in 2012 to 0.22 per 100 PY in 2017) [5].

PrEP use during follow-up may also have impacted on declining HIV incidence. An important finding in our study was that the fall in HIV incidence coincided with a major increase in the proportion of men reporting past 12-month PrEP use over time [22], which could indicate an association. In our study, baseline and longitudinal reported PrEP use was not associated with reduced HIV incidence. At baseline, only 5% of men reported PrEP use in the past 12 months, and possibly, these men were early PrEP takers having high-risk sexual behaviour putting them at particularly high risk of HIV infection. It is possible that no clear association was observed due to opposing factors operating—PrEP use decreasing the risk of HIV acquisition on the one hand, and PrEP use acting as an indicator of very high-risk behaviour (similar to the other markers of CLS) on the other. Moreover, in this study, past 12-month PrEP use was only asked at baseline and annual questionnaires; therefore, we do not have a complete picture of PrEP use during follow-up, or of adherence or consistency in using PrEP. Taken together, our results are consistent with the hypothesis that the benefits of ART in reducing HIV transmission in combination with increased uptake of PrEP has had a substantial impact in reducing HIV incidence in the GBMSM population.

Recreational drug use was one of the strongest factors associated with HIV incidence in this cohort. HIV incidence was especially high among men who reported the use of injection drugs, 4.8 per 100 PY, almost 28-fold higher than the incidence among men who did not report any recreational drugs. The use of noninjection chemsex-related drugs also increased the risk of HIV incidence more than 6-fold. A systematic review investigating recreational drug use in GBMSM has demonstrated that chemsex use is associated with increased risky behaviour such as CLS and group sex, as well as with an increase in STIs and poor mental health symptoms [23]. Polydrug use has also been reported to be associated with condomless sex and higher partner numbers in HIV–negative and HIV–diagnosed GBMSM in the UK [24,25]. There are limited data on injection drug use among GBMSM in the UK and Europe. Findings from the 2014 Gay Men’s Sex Survey, an online survey of 14,464 GBMSM living in the UK, suggest that injection drug use (amphetamine, crystal methamphetamine, heroin, mephedrone, GHB/GBL, and ketamine) is significantly associated with CLS with multiple partners [26]. The survey also found that injecting was most common among those who were of age 30 to 59 years, lived in London, and were HIV seropositive. Data from Australian and Canadian GBMSM cohorts have also observed strong associations between injecting drugs and sexual risk behaviours [27,28]. Further research into the barriers to accessing HIV prevention services among GBMSM who inject drugs, despite the availability of harm reduction programmes in the UK, will be useful.

We also observed that the risk of acquiring HIV was higher among GBMSM who reported high-risk sexual behaviours (CLS with multiple or HIV–positive partners, group sex, greater number of new sexual partners, versatile CLS role, and sex for drugs or money) and bacterial STI diagnoses. Risk was particularly high for men reporting group sex and those with higher numbers of CLS partners in the past 3 months. This is consistent with findings from other cohort studies in the UK and other countries [8-9,29]. Routine inquiry and documentation of these factors could enable better direction of prevention efforts at both the individual and population level.

In the AURAH2 cohort, most demographic and socioeconomic factors were not associated with incident HIV. However, we observed a higher IR among men with nonuniversity level of education that might be explained by the higher prevalence of high-risk sexual behaviours in this subgroup of men. The prevalence of past 3-month CLS at baseline was significantly higher among men with no educational qualifications, at 86% (p = 0.038), compared to men with university-level education and other qualification (). A lower educational level has been reported to be associated with risk-taking behaviours and with an increased risk of HIV seroconversion in European studies [30,31]. We did not find evidence that high alcohol use, smoking, or symptoms of depression or anxiety were associated with incident HIV in the baseline associated factors or time-updated analysis, although CIs were wide for some factors. It has previously been reported that the relationship of mental health symptoms with sexual behaviour may be complex and operate in both directions [32].

The strengths of this study include the prospective design and HIV status confirmation of all 1,162 participants enrolled in AURAH2 through linkage with national HIV surveillance data. This allows for optimum use of available information to estimate HIV incidence and trends for all men in the cohort. Prior to data linkage, we have presented our interim results restricted to men under follow-up with questionnaire [33-34], adopting the single random point method to decide HIV infection dates between self-reported first HIV positive test results and last HIV negative test results [35]. We also observed significant decline over time among these men; however, trends were only able to be calculated from 2015 until 2018 (online follow-up period), and we missed a number of diagnosis that were further identified after linking our data with PHE.

There are some limitations to this study. Men in this cohort were recruited from sexual health clinics in urban areas of London and Brighton and are predominantly highly educated, employed, in a stable economic situation, and of white ethnicity. These men may not be representative of the broader GBMSM population in England and the UK. It is possible that the incidence estimates and risk factors identified are not generalizable to GBMSM who do not attend sexual health clinics. The small number of HIV infections in each calendar year among men in this study has resulted in relatively wide CIs of IRs; therefore, IRs and associations with factors must be interpreted carefully. In addition, assessment of trends over time in sexual behaviour may be subject to “regression to the mean” as the clinic visit at which recruitment occurred may have been specifically prompted by a recent period of higher risk. For risk factors analysis, we focused on baseline factors in order to include all data from the whole cohort, which may have underestimated the associations between sexual/HIV-related behaviours and HIV incidence, including the impact of PrEP. However, we observed similar results when analysis was restricted to 622 men using time-updated variables. In terms of the time-updated analysis, the online retention of participants who initially registered in the study was not optimal; however, 64% (400 of 622) of participants who completed at least an online questionnaire were engaged in the study throughout. Our results may be sensitive to specific recall bias and social desirability bias in men’s responses in the baseline questionnaire. Data linkage to surveillance systems using pseudo-anonymised identifiers has potential for mismatches or missing seroconversions; however, this has been minimised by PHE data triangulation; all self-reported seroconversions were validated by PHE data. Lastly, this study would not include seroconversions that were not diagnosed or those that were diagnosed outside the UK.

In summary, this study provides evidence of a substantial decline in HIV incidence among a cohort of GBMSM attending sexual health clinics in England. Our data suggest that GBMSM reporting the use of recreational drugs, in particular injection drug use and chemsex drug use, high-risk sexual behaviours such as CLS with multiple partners, CLS with HIV–positive partners, group sex, and those with a bacterial STI, are at increased risk of HIV acquisition. HIV infections are also significantly higher among those with lower levels of education at baseline. Temporal trends in sexual risk behaviours and drug use in the cohort over the study period were mixed, but the marked decrease in incidence coincided with a substantial increase in PrEP use. Given similar findings from recent data among GBMSM in the UK and other countries, it is likely that the observed decline is largely related to the increase in testing and earlier ART initiation from 2013 onward and the scale-up of PrEP. Although efforts to end HIV epidemic are having a substantial effect, further improvements specially to increase HIV test coverage across all populations at risk remain very important. Sustainable and comprehensive HIV prevention and control efforts must continue in the UK to reach zero new infections by 2030.

Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) Statement The AURAH2 Study.

(DOC)

Click here for additional data file.

Longitudinal analysis of new HIV infections and their predictors among MSM in England: The AURAH2 Study–Data Analysis Plan.

(PDF)

Click here for additional data file.

Baseline sociodemographic, health and lifestyle characteristics, sexual behaviour, and PrEP and PEP use among participants who completed the baseline, 4-monthly, and annual questionnaire in the AURAH2 study.

(DOCX)

Click here for additional data file.

Adjusted associations of baseline characteristics with incident HIV among 1,162 GBMSM participating in the AURAH2 study.

(DOCX)

Click here for additional data file.

Associations between ethnicity, education, and employment characteristics with sexual behaviour measures at baseline among 1,162 GBMSM in the AURAH2 study.

(DOCX)

Click here for additional data file.

3 Mar 2021

Dear Dr Hanum,

Thank you for submitting your manuscript entitled "Trends in HIV incidence between 2013 – 2019 and baseline predictors among a prospective cohort of Gay, Bisexual, and Other Men Who Have Sex with Men attending sexual health clinics in England: the AURAH2 Study" for consideration by PLOS Medicine.

Your manuscript has now been evaluated by the PLOS Medicine editorial staff and I am writing to let you know that we would like to send your submission out for external peer review.

However, before we can send your manuscript to reviewers, we need you to complete your submission by providing the metadata that is required for full assessment. To this end, please login to Editorial Manager where you will find the paper in the 'Submissions Needing Revisions' folder on your homepage. Please click 'Revise Submission' from the Action Links and complete all additional questions in the submission questionnaire.

Please re-submit your manuscript within two working days, i.e. by March 5, 2021.

Login to Editorial Manager here: https://www.editorialmanager.com/pmedicine

Once your full submission is complete, your paper will undergo a series of checks in preparation for peer review. Once your manuscript has passed all checks it will be sent out for review.

Feel free to email us at plosmedicine@plos.org if you have any queries relating to your submission.

Kind regards,

Beryne Odeny

Associate Editor

PLOS Medicine

9 Apr 2021

Dear Dr. Hanum,

Thank you very much for submitting your manuscript "Trends in HIV incidence between 2013 – 2019 and baseline predictors among a prospective cohort of Gay, Bisexual, and Other Men Who Have Sex with Men attending sexual health clinics in England: the AURAH2 Study" (PMEDICINE-D-21-01009R1) for consideration at PLOS Medicine.

Your paper was evaluated by a senior editor and discussed among all the editors here. It was also discussed with an academic editor with relevant expertise, and sent to independent reviewers, including a statistical reviewer. The reviews are appended at the bottom of this email and any accompanying reviewer attachments can be seen via the link below:

[LINK]

In light of these reviews, I am afraid that we will not be able to accept the manuscript for publication in the journal in its current form, but we would like to consider a revised version that addresses the reviewers' and editors' comments. Obviously we cannot make any decision about publication until we have seen the revised manuscript and your response, and we plan to seek re-review by one or more of the reviewers.

In revising the manuscript for further consideration, your revisions should address the specific points made by each reviewer and the editors. Please also check the guidelines for revised papers at http://journals.plos.org/plosmedicine/s/revising-your-manuscript for any that apply to your paper. In your rebuttal letter you should indicate your response to the reviewers' and editors' comments, the changes you have made in the manuscript, and include either an excerpt of the revised text or the location (eg: page and line number) where each change can be found. Please submit a clean version of the paper as the main article file; a version with changes marked should be uploaded as a marked up manuscript.

In addition, we request that you upload any figures associated with your paper as individual TIF or EPS files with 300dpi resolution at resubmission; please read our figure guidelines for more information on our requirements: http://journals.plos.org/plosmedicine/s/figures. While revising your submission, please upload your figure files to the 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. 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 us at PLOSMedicine@plos.org.

We expect to receive your revised manuscript by Apr 30 2021 11:59PM. Please email us (plosmedicine@plos.org) if you have any questions or concerns.

***Please note while forming your response, if your article is accepted, you may have the opportunity to make the peer review history publicly available. The record will include editor decision letters (with reviews) and your responses to reviewer comments. If eligible, we will contact you to opt in or out.***

We ask every co-author listed on the manuscript to fill in a contributing author statement, making sure to declare all competing interests. If any of the co-authors have not filled in the statement, we will remind them to do so when the paper is revised. If all statements are not completed in a timely fashion this could hold up the re-review process. If new competing interests are declared later in the revision process, this may also hold up the submission. Should there be a problem getting one of your co-authors to fill in a statement we will be in contact. YOU MUST NOT ADD OR REMOVE AUTHORS UNLESS YOU HAVE ALERTED THE EDITOR HANDLING THE MANUSCRIPT TO THE CHANGE AND THEY SPECIFICALLY HAVE AGREED TO IT. You can see our competing interests policy here: http://journals.plos.org/plosmedicine/s/competing-interests.

Please use the following link to submit the revised manuscript:

https://www.editorialmanager.com/pmedicine/

Your article can be found in the "Submissions Needing Revision" folder.

To enhance the reproducibility of your results, we recommend that you deposit your laboratory protocols in protocols.io, where a protocol can be assigned its own identifier (DOI) such that it can be cited independently in the future. Additionally, PLOS ONE offers an option to publish peer-reviewed clinical study protocols. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols

Please ensure that the paper adheres to the PLOS Data Availability Policy (see http://journals.plos.org/plosmedicine/s/data-availability), which requires that all data underlying the study's findings be provided in a repository or as Supporting Information. For data residing with a third party, authors are required to provide instructions with contact information for obtaining the data. PLOS journals do not allow statements supported by "data not shown" or "unpublished results." For such statements, authors must provide supporting data or cite public sources that include it.

We look forward to receiving your revised manuscript.

Sincerely,

Beryne Odeny,

PLOS Medicine

plosmedicine.org

-----------------------------------------------------------

Requests from the editors:

- Please revise your title according to PLOS Medicine's style. Your title must be nondeclarative and not a question. It should begin with main concept if possible. Please place the study design ("A prospective cohort study,") in the subtitle (i.e., after a colon).

- The Data Availability Statement (DAS) requires revision. For each data source used in your study: If the data are not freely available, please describe briefly the ethical, legal, or contractual restriction that prevents you from sharing it. Please also include an appropriate contact (web or email address) for inquiries (again, this cannot be a study author/ co-author).

- Abstract summary - At this stage, we ask that you reformat your non-technical Author Summary. The Author Summary should immediately follow the Abstract in your revised manuscript. This text is subject to editorial change and should be distinct from the scientific abstract. The summary should be accessible to a wide audience that includes both scientists and non-scientists. Please see our author guidelines for more information: https://journals.plos.org/plosmedicine/s/revising-your-manuscript#loc-author-summary.

- Abstract:

1. Please structure your abstract using the PLOS Medicine headings (Background, Methods and Findings, Conclusions).

2. Please combine the Methods and Findings sections into one section, “Methods and findings”. Please ensure that all numbers presented in the abstract are present and identical to numbers presented in the main manuscript text.

3. Please include the actual amounts or percentages of relevant outcomes, not just hazard ratios or relative risks.

4. Please include the important dependent variables that are adjusted for in the analyses.

5. Please quantify the main results (with p values in addition to 95% CI).

6. Please include a summary of adverse events if these were assessed in the study.

7. In the last sentence of the Abstract Methods and Findings section, please describe the main limitation(s) of the study's methodology.

8. Abstract Conclusions: Please address the study implications without overreaching what can be concluded from the data; the phrase "In this study, we observed ..." may be useful. Please interpret the study based on the results presented in the abstract, emphasizing what is new.

- Please conclude the Introduction with a clear description of the study question or hypothesis.

- For this observational study, in the manuscript text, please indicate: (1) the analytical methods by which you planned to test your hypothesis, (2) the analyses you actually performed, and (3) when reported analyses differ from those that were planned, transparent explanations for differences that affect the reliability of the study's results. If a reported analysis was performed based on an interesting but unanticipated pattern in the data, please be clear that the analysis was data-driven.

- Did your study have a prospective protocol or analysis plan? Please state this (either way) early in the Methods section.

a) If a prospective analysis plan (from your funding proposal, IRB or other ethics committee submission, study protocol, or other planning document written before analyzing the data) was used in designing the study, please include the relevant prospectively written document with your revised manuscript as a Supporting Information file to be published alongside your study, and cite it in the Methods section. A legend for this file should be included at the end of your manuscript.

b) If no such document exists, please make sure that the Methods section transparently describes when analyses were planned, and when/why any data-driven changes to analyses took place.

c) In either case, changes in the analysis-- including those made in response to peer review comments-- should be identified as such in the Methods section of the paper, with rationale.

- Please ensure that the study is reported according to the STROBE guideline, and include the completed STROBE checklist as Supporting Information. Please add the following statement, or similar, to the Methods: "This study is reported as per the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guideline (S1 Checklist)." The STROBE guideline can be found here: http://www.equator-network.org/reporting-guidelines/strobe/

- Your study is observational and therefore causality cannot be inferred. Please remove language that implies causality, such as “predictive” or “due to”. Refer to associations instead.

- How was race/ethnicity defined and by whom? Why was race/ethnicity considered important in this study and what it is believed to represent [eg, are SES or genetic differences being attributed to race/ethnicity?]

- In your statistical analyses, please use hierarchical/ multilevel models given that nationwide data is likely clustered at various county/ regional levels. The potential clustering of data (e.g., among patients from the same locality or hospital) would result in spurious effect estimates and standard errors

- In statistical methods, please refer to any post-hoc corrections to correct for multiple comparisons during your statistical analyses. If these were not performed please justify the reasons. Please refer to our statistical reporting guidelines for assistance (https://journals.plos.org/plosone/s/submission-guidelines.#loc-statistical-reporting)

- Please describe how you selected your adjustment variables.

- Please specify the statistical test used to derive a p value.

- Please define the abbreviations in tables and/or Figures e.g. PY, GBMSM, CLY, PHQ-9, GAD7

- Please include p-values in table 2

- Please change p <0.0001 to P < 0.001.

- Please provide titles and legends for all figures (including those in Supporting Information files).

- Please update the access or retrieval date for all website citations to ensure that websites are still available

- Please use the "Vancouver" style for reference formatting, and see our website for other reference guidelines https://journals.plos.org/plosmedicine/s/submission-guidelines#loc-references

- Please replace “injection drug users” with “people who inject drugs.”

Comments from the reviewers:

Reviewer #1: This study reports trends in HIV incidence between 2013 and 2019 and the association of baseline and time-updated factors (demographic, socioeconomic, behavioural, lifestyle and health related) with HIV incidence, among a cohort of GBMSM in the AURAH2 prospective study.

Comments:

There are some typos in the text that need remedying.

"Supplementary material 1: Baseline socio-demographic, health and lifestyle characteristics, sexual behaviour, and PrEP and PEP use among participants who completed the baseline, four-monthly, and annual questionnaire in the AURAH2 study, 2013 - 2018"

Did the authors consider completing a comparison between groups, which may be insightful to gauge potential response bias?

It is noted that the groups in Supplementary material 1 are not independent groups, and so the authors may choose to separately amend the structure of the groups in order to draw comparisons (baseline only compared with baseline+four-monthly follow-up, for example).

Overall, the authors have applied technically appropriate statistical methods, and presented the study outcomes in a clear and concise way.

The study limitations have been suitably acknowledged in the discussion section.

Reviewer #2: This is a timely analysis of changes in HIV incidence, sexual risk behavior, and PrEP use in a cohort of initially seronegative GBMSM from 3 urban STD clinics in the UK. The results are encouraging and demonstrate declining incidence as well as a decrease in some high-risk sexual behaviors, with concomitant increase in PrEP use. While there are limitations of the work, it represents an important contribution to our knowledge of changing HIV risk among GBMSM globally. I have a few queries and suggestions for the authors to consider, in order to improve clarity of the manuscript.

Queries and suggestions:

1. Methods, study design and participants. What is the justification for combining years in two of the categories (2013/2014 and 2018/2019). One can guess, but this should be explicitly stated.

2. Methods, baseline measures. Were participants asked about sexual role taking, such as top/insertive, bottom/receptive, or versatile? If not, this should be mentioned as a limitation of the questionnaires used.

3. Methods, p. 6 lines 155-157. The cutpoints for PHQ-9 and GAD-7 need a justification. This should be easy, as both are "moderate or severe" categories, but an explanation is needed for readers not familiar with these scales and their scoring. Similarly, the selected cutpoint for AUDIT-C needs justification and a reference.

4. Methods, p. 6, lines 158-160. The handling of missing data needs more justification. Why considering missing responses as "no" responses for behavior, mental health, and alcohol consumption and other variables as missing = excluded? Were data likely to be missing at random? Was imputation considered as an option to reduce bias due to missingness?

5. Results, lines 233-235. It is said that 622 of 1162 completed at least one online follow-up questionnaire, of whom only 483 completed at least one online follow-up questionnaire. How is this possible? Please edit for clarity. It looks like 622 were included in the analysis of time-updated variables.

6. Discussion, PrEP use. How might an approach combining PrEP and CLS to develop an "unprotected sex" variable change results. Did PrEP use match risk in this study or was it underutilized by some groups?

7. Discussion, injection drug use. The degree to which risk is increased with injection drug use in this cohort is noteworthy. Do GBMSM who inject drug have access to needle exchange and opioid substitution therapy in the UK? Is there any information on the extent to which men in this cohort accessed such programs?

8. Discussion, limitations, lines 416-418. Please clarify the writing with respect to the 400 participants who are said to have competed "at least an online questionnaire" and were engaged in the study throughout. How does this relate to the earlier statements that 622 of 1162 completed at least one online follow-up questionnaire, of whom only 483 completed at least one online follow-up questionnaire.

9. Discussion, limitations. Could the authors be more specific about how the sociodemographics of the men participating in this cohort compare to those of new HIV cases among GBMSM in the UK? Which specific groups of men are underrepresented and warrant more targeted approaches? It would be nice to see some discussion on how this work relates to current known disparities in access to HIV services (for both positives and negatives) in the UK. Where might treatment as prevention and PrEP be falling short of their promise?

Minor suggested corrections or edits:

1. General. Consider whether condomless anal sex is best abbreviated "CLAS" or "CAS" rather than "CLS."

2. Methods, line 159. "missing responses were considered to indicate that the absence…" Remove "that."

3. Methods, line 189. "were include" should be "were included."

4. Results, line 227. "taken at least on chemsex-related drugs" needs editing.

5. Table 1, country of birth and ethnicity. Suggest changing "Born on the UK, other ethnicity" to "Born in the UK, other ethnicity.

6. Table 1 footnotes. Consider changing from "No group includes…" to "The no employment group includes…"

7. Supplementary Table 2. For consistency, CLS in the past 3 months should be bolded.

8. Figure 2 caption. It is said in the text that annual questionnaire data were excluded for bacterial STI due to a difference in recall periods. Please correct the Figure 2 caption to reflect this.

Reviewer #3: Linda Anne Selvey

Thanks for this manuscript, which has some useful information that confirms the findings of others. I have a number of comments/suggestions below:

1. Methods

More detail is required in the methods in relation to the analysis, particularly in terms of missing values. With missing values in the multivariable analysis, was the whole line (ie data about a single individual) excluded from the analysis, or were the missing values handled in a different way. This needs to be explicit in the methods. The total number of observations in the final model should also be included in the results section, not just in table 3.

Also in the methods there is a description of the categorisation of the CLS and new sexual partners variables. How were these classifications made and why were these categories chosen. This detail should also be included. Zero to 10 new sexual partners in the last 12 months seems like a wide category. Why not have a variable with just Zero or one new partners?

2. Editing

The paper needs a bit of an edit. For example line 189 (include vs included); line 227 (on vs one); line 236 (no full stop after 'study')

3. Discussion

There were very small numbers of HIV infections in each calendar year, therefore with wide confidence intervals. This should be included as a limitation in the discussion.

Any attachments provided with reviews can be seen via the following link:

[LINK]

1 May 2021

Submitted filename: Responses_AURAH2_HIV Incidence 2013-2019_PlosMed_R1.docx

Click here for additional data file.

14 May 2021

Dear Dr. Hanum,

Thank you very much for re-submitting your manuscript "Trends in HIV incidence between 2013 – 2019 and baseline predictors among a prospective cohort of Gay, Bisexual, and Other Men Who Have Sex with Men attending sexual health clinics in England: A prospective cohort study" (PMEDICINE-D-21-01009R2) for review by PLOS Medicine.

I have discussed the paper with my colleagues and the academic editor and it was also seen again by one reviewer. I am pleased to say that provided the remaining editorial and production issues are dealt with we are planning to accept the paper for publication in the journal.

The remaining issues that need to be addressed are listed at the end of this email. Any accompanying reviewer attachments can be seen via the link below. Please take these into account before resubmitting your manuscript:

[LINK]

***Please note while forming your response, if your article is accepted, you may have the opportunity to make the peer review history publicly available. The record will include editor decision letters (with reviews) and your responses to reviewer comments. If eligible, we will contact you to opt in or out.***

In revising the manuscript for further consideration here, please ensure you address the specific points made by each reviewer and the editors. In your rebuttal letter you should indicate your response to the reviewers' and editors' comments and the changes you have made in the manuscript. Please submit a clean version of the paper as the main article file. A version with changes marked must also be uploaded as a marked up manuscript file.

Please also check the guidelines for revised papers at http://journals.plos.org/plosmedicine/s/revising-your-manuscript for any that apply to your paper. If you haven't already, we ask that you provide a short, non-technical Author Summary of your research to make findings accessible to a wide audience that includes both scientists and non-scientists. The Author Summary should immediately follow the Abstract in your revised manuscript. This text is subject to editorial change and should be distinct from the scientific abstract.

We expect to receive your revised manuscript within 1 week. Please email us (plosmedicine@plos.org) if you have any questions or concerns.

We ask every co-author listed on the manuscript to fill in a contributing author statement. If any of the co-authors have not filled in the statement, we will remind them to do so when the paper is revised. If all statements are not completed in a timely fashion this could hold up the re-review process. Should there be a problem getting one of your co-authors to fill in a statement we will be in contact. YOU MUST NOT ADD OR REMOVE AUTHORS UNLESS YOU HAVE ALERTED THE EDITOR HANDLING THE MANUSCRIPT TO THE CHANGE AND THEY SPECIFICALLY HAVE AGREED TO IT.

Please ensure that the paper adheres to the PLOS Data Availability Policy (see http://journals.plos.org/plosmedicine/s/data-availability), which requires that all data underlying the study's findings be provided in a repository or as Supporting Information. For data residing with a third party, authors are required to provide instructions with contact information for obtaining the data. PLOS journals do not allow statements supported by "data not shown" or "unpublished results." For such statements, authors must provide supporting data or cite public sources that include it.

To enhance the reproducibility of your results, we recommend that you deposit your laboratory protocols in protocols.io, where a protocol can be assigned its own identifier (DOI) such that it can be cited independently in the future. Additionally, PLOS ONE offers an option to publish peer-reviewed clinical study protocols. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols

Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript.

Please note, when your manuscript is accepted, an uncorrected proof of your manuscript will be published online ahead of the final version, unless you've already opted out via the online submission form. If, for any reason, you do not want an earlier version of your manuscript published online or are unsure if you have already indicated as such, please let the journal staff know immediately at plosmedicine@plos.org.

If you have any questions in the meantime, please contact me or the journal staff on plosmedicine@plos.org.

We look forward to receiving the revised manuscript by May 21 2021 11:59PM.

Sincerely,

Beryne Odeny,

Associate Editor

PLOS Medicine

plosmedicine.org

------------------------------------------------------------

Requests from Editors:

1. In the author summary, under the sub-heading, “what do these findings mean?”, please remove language that implies attribution or cause. Use phrases such as “may potentially be attributed to…” In the second bullet point replace the word “should” with “may potentially” or “could” or similar.

2. Please replace “injection drug users” with “people who inject drugs.” For example, line 272.

3. Please remove the “&” in reference # 11.

Comments from Reviewers:

Reviewer #2: The revision has addressed prior comments, and I believe the article is acceptable in its present form.

However, I would also suggest that the authors consider reducing the numeric results in the abstract, dropping either the numerators and denominators, the p values, or both, to make the abstract findings more readable and potentially include some of the other interesting findings, such as the increase in PrEP use, decrease in PEP and some risk behaviors, but lack of association of PrEP with the outcome.

I also note two very minor edits that are needed, below.

Minor edits:

1. Abstract: In the very long sentence on baseline associations, an extra "and" appears before "previous 12-month report of a bacterial STI diagnosis" and there is no HR with 95% CI provided for the finding on new sexual partners.

2. on p.14 under table 2, the sentence starting "90% men" needs an edit. Perhaps "The vast majority (27/30 or 90%) of men newly diagnosed with HIV were of White ethnicity."?

Any attachments provided with reviews can be seen via the following link:

[LINK]

21 May 2021

Submitted filename: Responses_AURAH2_HIV Incidence 2013-2019_PlosMed_R2.docx

Click here for additional data file.

25 May 2021

Dear Dr. Hanum,

Thank you very much for re-submitting your manuscript "Trends in HIV incidence between 2013 – 2019 and baseline predictors among a prospective cohort of Gay, Bisexual, and Other Men Who Have Sex with Men attending sexual health clinics in England: A prospective cohort study" (PMEDICINE-D-21-01009R3) for review by PLOS Medicine.

I have discussed the paper with my colleagues and the academic editor and it was also seen again by three reviewers. I am pleased to say that provided the remaining editorial and production issues are dealt with we are planning to accept the paper for publication in the journal.

The remaining issues that need to be addressed are listed at the end of this email. Any accompanying reviewer attachments can be seen via the link below. Please take these into account before resubmitting your manuscript:

[LINK]

***Please note while forming your response, if your article is accepted, you may have the opportunity to make the peer review history publicly available. The record will include editor decision letters (with reviews) and your responses to reviewer comments. If eligible, we will contact you to opt in or out.***

In revising the manuscript for further consideration here, please ensure you address the specific points made by each reviewer and the editors. In your rebuttal letter you should indicate your response to the reviewers' and editors' comments and the changes you have made in the manuscript. Please submit a clean version of the paper as the main article file. A version with changes marked must also be uploaded as a marked up manuscript file.

Please also check the guidelines for revised papers at http://journals.plos.org/plosmedicine/s/revising-your-manuscript for any that apply to your paper. If you haven't already, we ask that you provide a short, non-technical Author Summary of your research to make findings accessible to a wide audience that includes both scientists and non-scientists. The Author Summary should immediately follow the Abstract in your revised manuscript. This text is subject to editorial change and should be distinct from the scientific abstract.

We expect to receive your revised manuscript within 1 week. Please email us (plosmedicine@plos.org) if you have any questions or concerns.

We ask every co-author listed on the manuscript to fill in a contributing author statement. If any of the co-authors have not filled in the statement, we will remind them to do so when the paper is revised. If all statements are not completed in a timely fashion this could hold up the re-review process. Should there be a problem getting one of your co-authors to fill in a statement we will be in contact. YOU MUST NOT ADD OR REMOVE AUTHORS UNLESS YOU HAVE ALERTED THE EDITOR HANDLING THE MANUSCRIPT TO THE CHANGE AND THEY SPECIFICALLY HAVE AGREED TO IT.

Please ensure that the paper adheres to the PLOS Data Availability Policy (see http://journals.plos.org/plosmedicine/s/data-availability), which requires that all data underlying the study's findings be provided in a repository or as Supporting Information. For data residing with a third party, authors are required to provide instructions with contact information for obtaining the data. PLOS journals do not allow statements supported by "data not shown" or "unpublished results." For such statements, authors must provide supporting data or cite public sources that include it.

To enhance the reproducibility of your results, we recommend that you deposit your laboratory protocols in protocols.io, where a protocol can be assigned its own identifier (DOI) such that it can be cited independently in the future. Additionally, PLOS ONE offers an option to publish peer-reviewed clinical study protocols. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols

Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript.

Please note, when your manuscript is accepted, an uncorrected proof of your manuscript will be published online ahead of the final version, unless you've already opted out via the online submission form. If, for any reason, you do not want an earlier version of your manuscript published online or are unsure if you have already indicated as such, please let the journal staff know immediately at plosmedicine@plos.org.

If you have any questions in the meantime, please contact me or the journal staff on plosmedicine@plos.org.

We look forward to receiving the revised manuscript by Jun 01 2021 11:59PM.

Sincerely,

Beryne Odeny,

Association Editor

PLOS Medicine

plosmedicine.org

------------------------------------------------------------

Final requests from Editors:

Thank you for responding to previous comments. Before we proceed, please make the following changes:

1. Please remove the first mention of "prospective cohort" from the title. Kindly consider revising the title to, "Trends in HIV incidence between 2013 – 2019 and baseline predictors among Gay, Bisexual, and Other Men Who Have Sex with Men attending sexual health clinics in England: A prospective cohort study"

2. For consistency, please replace the term "predictors" with "factors" in the title and throughout the manuscript and tables.

Comments from Reviewers:

Any attachments provided with reviews can be seen via the following link:

[LINK]

28 May 2021

Submitted filename: Response_AURAH2Incidence_PlosMed_R3.docx

Click here for additional data file.

1 Jun 2021

Dear Dr Hanum,

On behalf of my colleagues and the Academic Editor, Dr. Susan Marie Graham, I am pleased to inform you that we have agreed to publish your manuscript "Trends in HIV incidence between 2013 – 2019 and association of baseline factors with subsequent incident HIV among Gay, Bisexual, and Other Men Who Have Sex with Men attending sexual health clinics in England: A prospective cohort study" (PMEDICINE-D-21-01009R4) in PLOS Medicine.

Before your manuscript can be formally accepted you will need to complete some formatting changes, which you will receive in a follow up email. Please be aware that it may take several days for you to receive this email; during this time no action is required by you. Once you have received these formatting requests, please note that your manuscript will not be scheduled for publication until you have made the required changes.

In the meantime, please log into Editorial Manager at http://www.editorialmanager.com/pmedicine/, click the "Update My Information" link at the top of the page, and update your user information to ensure an efficient production process.

PRESS

We frequently collaborate with press offices. If your institution or institutions have a press office, please notify them about your upcoming paper at this point, to enable them to help maximise its impact. If the press office is planning to promote your findings, we would be grateful if they could coordinate with medicinepress@plos.org. If you have not yet opted out of the early version process, we ask that you notify us immediately of any press plans so that we may do so on your behalf.

We also ask that you take this opportunity to read our Embargo Policy regarding the discussion, promotion and media coverage of work that is yet to be published by PLOS. As your manuscript is not yet published, it is bound by the conditions of our Embargo Policy. Please be aware that this policy is in place both to ensure that any press coverage of your article is fully substantiated and to provide a direct link between such coverage and the published work. For full details of our Embargo Policy, please visit http://www.plos.org/about/media-inquiries/embargo-policy/.

To enhance the reproducibility of your results, we recommend that you deposit your laboratory protocols in protocols.io, where a protocol can be assigned its own identifier (DOI) such that it can be cited independently in the future. Additionally, PLOS ONE offers an option to publish peer-reviewed clinical study protocols. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols

Thank you again for submitting to PLOS Medicine. We look forward to publishing your paper.

Sincerely,

Beryne Odeny

Associate Editor

PLOS Medicine

Table 2

HIV incidence among GBMSM participating in the AURAH2 prospective study, 2013–2019.

Calendar year	PY	No. of HIV infections	IR (per 100 PY)	95% CI
2013/2014	203.55	3	1.47	0.48–4.57
2015	953.53	10	1.05	0.56–1.95
2016	1,139.29	11	0.97	0.53–1.74
2017	1,134.80	6	0.53	0.24–1.18
2018/2019	1,187.69	3	0.25	0.08–0.78
Overall	4,618.86	33	0.71	0.51–1.00

AURAH2, The Attitudes to and Understanding of Risk of Acquisition of HIV 2; CI, confidence interval; GBMSM, gay, bisexual, and other men who have sex with men; IR, incidence rate; PY, person-years.

Table 3

Association of time-updated factors with incident HIV among 622 GBMSM who completed at least 1 online follow-up questionnaire, 2013–2018*.

	Unadjusted IRR (95% CI)	p-value	Adjusted€ IRR (95% CI)	p-value
Demographic characteristics
Age (time-updated) per year	3,785 obs	0.843	3,770 obs	0.4
	1.00 (0.96–1.05)		1.02 (0.97–1.06)
Age (time-updated) category	3,785 obs	0.676	3,770 obs	0.325
<25	Ref		Ref
25–29	0.22 (0.02–1.93)		0.65 (0.21–1.92)
30–34	0.41 (0.07–2.23)		0.61 (0.22–1.97)
35–39	0.72 (0.16–3.23)		0.99 (0.19–5.17)
40–44	0.35 (0.04–3.14)		0.49 (0.05–4.92)
≥45	0.86 (0.23–3.21)		1.21 (0.28–5.21)
Country of birth and ethnicity	3,782 obs	0.953	3,770 obs	0.905
Born in the UK, white	Ref		Ref
Born in the UK, other ethnicity	1.63 (0.20–13.29)		1.77 (0.21–15.04)
Non-UK born, white	0.97 (0.28–3.31)		1.00 (0.29–3.46)
Non-UK born, other ethnicity	0.74 (0.09–6.03)		0.79 (0.09–6.54)
Sexual identity	3,793 obs	0.639	3,770 obs	0.569
Gay	Ref		Ref
Bisexual/other	1.63 (0.21–12.54)		1.82 (0.23–14.34)
Socioeconomic characteristics and partnership status
University education	3,805 obs	0.923	3,770 obs	0.932
Yes	Ref		Ref
No	0.94 (0.29–3.06)		0.95 (0.29–3.09)
Employed	3,772 obs	0.305	3,760 obs	0.243
Yes	Ref		Ref
No	0.34 (0.04–2.64)		0.29 (0.03–2.32)
Money to cover basic needs	3,805 obs	0.744	3,770 obs	0.829
All of the time	Ref		Ref
Most of the time	1.29 (0.29–5.83)		1.43 (0.30–7.06)
Sometimes/No	0.10 (0.05–0.18)		0.12 (0.05–0.25)
Housing status	3,750 obs	0.611	3,738 obs	0.701
Home owner	Ref		Ref
Renting	0.56 (0.17–1.85)		0.66 (0.16–2.71)
Unstable/other	0.97 (0.19–4.82)		1.12 (0.18–6.81)
Ongoing relationship**	1,536 obs	0.094	1,522 obs	0.148
Yes	Ref		Ref
No	0.63 (0.36–1.08)		0.65 (0.36–1.17)
Sexual/HIV-related behaviour characteristics
Recent HIV test†	3,699 obs	0.34	3,651 obs	0.329
No	Ref		Ref
Yes	1.87 (0.51–6.80)		1.90 (0.52–6.92)
CLS in the past 3 months	3,821 obs	0.871	3,770 obs	0.196
No	Ref		Ref
Yes	1.09 (0.38–3.14)		2.71 (0.60–12.23)
CLS with 2 or more partners	3,819 obs	0.005	3,770 obs	0.004
One/none	Ref		Ref
2 or more	6.19 (1.72–22.17)		9.39 (2.07–42.66)
Sexual role CLS in the past 3 months	3,803 obs	0.705	3,752 obs	0.016
No CLS/did not state which partner	Ref		Ref
Always insertive	-		-
Always receptive	0.95 (0.18–4.88)		2.47 (0.35–17.67)
Versatile (sometimes insertive, sometimes receptive)	1.79 (0.60–5.32)		4.55 (1.01–21.11)
Group sex in the past 3 months	3,819 obs		3,770 obs
No	Ref	0.043	Ref	0.029
Yes	2.98 (1.03–8.61)		3.51 (1.14–10.77)
PEP use in the past 12 months**	1,530 obs	0.971	1,512 obs	0.888
No	Ref		Ref
Yes	1.04 (0.12–8.90)		1.16 (0.13–10.11)
PrEP use in the past 12 months**	1,532 obs	0.97	1,512 obs	0.999
No	Ref		Ref
Yes	0.96 (0.12–7.81)		0.99 (0.13–7.51)
Bacterial STI diagnoses‡	3,819 obs	0.005	3,770 obs	0.002
No	Ref		Ref
Yes	4.46 (1.57–12.68)		5.93 (1.95–18.03)
Health and lifestyle characteristics
Recreational drug use in the past 3 months**	1,536 obs	0.152	1,518 obs	0.111
No	Ref		Ref
Yes	4.81 (0.56–41.26)		5.83 (0.66–50.97)
Chemsex in the past 3 months	3,819 obs	0.012	3,770 obs	0.006
No	Ref		Ref
Yes	3.89 (1.35–11.22)		4.81 (1.57–14.74)
Injection drug use in the past 3 months**	1,536 obs	<0.001	1,518 obs	0.001
No	Ref		Ref
Yes	21.67 (3.96–118.30)		18.99 (3.39–106.14)
Higher-risk alcohol consumption** (modified WHO AUDIT-C equals ≥6)	1,536 obs	0.26	1,521 obs	0.335
No	Ref		Ref
Yes	2.10 (0.58–7.63)		1.91 (0.51–7.08)
Depressive symptoms** (PHQ-9 score ≥10)	1,536 obs	0.818	1,521 obs	0.701
No	Ref		Ref
Yes	1.28 (0.15–10.64)		1.53 (0.17–13.31)
Anxiety symptoms** (GAD-7 score ≥10)	1,537 obs	0.559	1,526 obs	0.681
No	Ref		Ref
Yes	1.88 (0.23–15.60)		2.06 (0.23–18.30)
Calendar year as a continuous variable	3,821 obs	<0.001	3,769 obs	0.004
	0.52 (0.45–0.59)		0.47 (0.28–0.78)
Calendar year category	3,821 obs	0.053	3,769 obs	0.01
2013–2014	Ref		Ref
2015	0.26 (0.07–1.05)		0.17 (0.04–0.82)
2016	0.35 (0.10–1.19)		0.20 (0.05–0.83)
2017–2018	0.06 (0.01–0.54)		0.05 (0.01–0.44)

*Total complete observations: 3,821 questionnaires; sexual/HIV-related behaviour data were based on the last time man asked; number of new sexual partners, fisting or sex toys, sex for drugs or money, and smoking status were not included in the analysis because they were only asked at the baseline questionnaire.

€Adjusted for age (time-updated), country of birth and ethnicity, sexual identity, and university education.

**Data were not collected at the 4-monthly questionnaire (only baseline and annual questionnaires).

†In the past 6 months at the baseline questionnaire and in the past 3 months at the 4-monthly and annual questionnaires.

‡In the past 12 months at the baseline questionnaire and in the past 3 months at the 4-monthly and annual questionnaires.

CI, confidence interval; CLS, condomless anal sex; GAD-7, generalised anxiety disorder-7; GBMSM, gay, bisexual, and other men who have sex with men; IRR, incidence rate ratio; PEP, postexposure prophylaxis; PHQ-9, patient health questionnaire-9; PrEP, preexposure prophylaxis; STI, sexually transmitted infection; WHO-AUDIT, World Health Organization–Alcohol Use Disorders Identification Test.