Changes in mental and sexual health among MSM using HIV pre-exposure prophylaxis during the SARS-CoV-2 pandemic: longitudinal analysis of the SwissPrEPared cohort study

DOI: https://doi.org/10.4414/SMW.2022.w30192

Babette L. Winterab, Frédérique Hovaguimianac, Roger D. Kouyoscd, Axel Jeremias Schmidtef, Enos Bernasconig, Dominique L. Brauncd, Alexandra Calmyh, Julia Nottere, Marcel Stoecklei, Bernard Surialj, Vanessa Christinetk, Matthias Cavassinil, Carsten Depmeierm, Severin Läuchlin, Emmanuelle Boffi El Amario, Matthias Reinachera, Manuela Rasia, Philip Bruggmannp, David Haerryq, Raphaël Bizer, Nicola Lows, Andreas Lehnert, Boris B. Quednowb, Jan S. Fehra, Benjamin Hampelau

aDepartment of Public and Global Health, Epidemiology, Biostatistics and Prevention Institute, University of Zurich, Zurich, Switzerland

bExperimental and Clinical Pharmacopsychology, Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zurich, Zurich, Switzerland

cDivision of Infectious Diseases and Hospital Epidemiology, University Hospital of Zurich, Zurich, Switzerland

dInstitute of Medical Virology, University of Zurich, Zurich, Switzerland

eDivision of Infectious Diseases and Hospital Epidemiology, Cantonal Hospital St. Gallen, St. Gallen, Switzerland

fSigma Research, London School of Hygiene and Tropical Medicine, London, United Kingdom

gDivision of Infectious Diseases, Regional Hospital Lugano, University of Geneva and University of Southern Switzerland, Lugano, Switzerland

hHIV/AIDS Unit, Division of Infectious Diseases, Geneva University Hospital, Geneva, Switzerland

iDivision of Infectious Diseases and Hospital Epidemiology, University Hospital Basel, University of Basel, Basel, Switzerland

jDepartment of Infectious Diseases, Bern University Hospital, University of Bern, Bern, Switzerland

kCheckpoint Vaud, Lausanne, Switzerland

lDivision of Infectious Diseases, University Hospital of Lausanne, Lausanne, Switzerland

mPrivate Practice Kalkbreite, Zurich, Switzerland

nDermatological Centre Zurich, Zurich, Switzerland

oInfectious Diseases and Internal Medicine Private Practice, Geneva, Switzerland

pArud Centre for Addiction Medicine, Zurich, Switzerland

qPositive Council, Zurich, Switzerland

rDepartment of Epidemiology and Health Systems, Centre for Primary Care and Public Health (Unisanté), University of Lausanne, Lausanne, Switzerland

sInstitue of Social and Preventive Medicine, University of Bern, Bern, Switzerland

tSwiss AIDS Federation, Zurich, Switzerland

uCheckpoint Zurich, Zurich, Switzerland

*These authors contributed equally.

Summary

BACKGROUND: Changes in mental and sexual health among men having sex with men (MSM) due to the SARS-CoV-2 pandemic remain unclear.

METHODS: Design: Longitudinal analysis of an ongoing, multicentre, pre-exposure prophylaxis (PrEP) cohort (NCT03893188) in Switzerland. Participants: HIV-negative MSM aged ≥18 who completed at least one questionnaire before and one after the start of the SARS-CoV-2 pandemic. Outcomes: Primary: mental health, defined as anxiety and depression scores assessed by the Patient Health Questionnaire-4. Secondary: sexual behaviour, well-being, PrEP use and disruption of care. Outcomes were assessed over seven periods corresponding to different SARS-CoV-2 prevention measures in Switzerland. We performed pairwise comparisons between periods (Wilcoxon signed rank test).

RESULTS: Data from 1,043 participants were included. Whilst anxiety scores remained stable over time, depression scores worsened in the second wave and the second lockdown period compared to pre-pandemic scores. This was confirmed by pairwise comparisons (pre-SARS-CoV-2/second wave and pre-SARS-CoV-2/second lockdown: p <0.001). Downward trends in sexual activity,sexualized substance use, and a switch from daily to "event-driven" PrEP were found. Disruption of care affected 42.6% (790/1856) of daily PrEP users’ follow-up visits.

CONCLUSION: In this longitudinal analysis of a PrEP cohort enrolling MSM, depression scores worsened in the second wave and the second lockdown compared to the pre-pandemic period.

Introduction

To mitigate the viral transmission of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), many governments introduced prevention measures based on social and behavioural restrictions (e.g. physical distancing, stay-at-home policies or quarantining) [1]. Although beneficial on many levels, these prevention measures have also been suggested to result in a widening of social, health and economic disparities between population groups [2], and to contribute to the development of mental health issues such as anxiety or depression [3–8].

The negative impact of SARS-CoV-2 prevention measures on mental health outcomes has been particularly pronounced in some minorities and evidence suggests that members of the lesbian, bisexual, gay and transgender (LGBT) community have been disproportionally affected by social and behavioural restrictions leading to isolation [3, 9–11]. These minorities were also found to be at higher risk of developing new mental health diseases [10, 12] or of experiencing a worsening of pre-existing mental health conditions [5, 7]. These aspects, along with higher prevalences of mental health problems (e.g. depression, anxiety and problematic substance use) [13, 14], greater economic insecurity, poorer job stability and less support from their families [15, 16], make members of the LGBT community more likely to experience negative consequences of the SARS-CoV-2 public health crisis [3, 10, 12].

The introduction of stringent prevention measures probably affected other health-related dimensions that are particularly relevant to the LGBT community. There is, for instance, conflicting evidence as to whether the SARS-CoV-2 pandemic resulted in a change in sexual behaviour: although some studies suggested a reduction in sexual activity among men having sex with men (MSM) during the first wave of the pandemic, other studies reported an increase in the number of sexual encounters [2, 8, 17, 18]. There is also uncertainty regarding the effect of the SARS-CoV-2 prevention measures on the quality of HIV prevention care, but evidence seems to indicate that access to and taking of pre-exposure prophylaxis (PrEP) were negatively affected [2, 12, 17, 19].

Longitudinal data are decisive in obtaining a reliable assessment of the impact of the SARS-CoV-2 pandemic on mental and sexual health outcomes. Therefore, we performed a longitudinal data analysis within a selected subgroup of the SwissPrEPared study, with the aim of investigating the effects of the SARS-CoV-2 prevention measures on mental and sexual health over a one-year period. More specifically, we were interested in describing how anxiety and depression, sexual behaviour, substance use, PrEP use and disruption of care varied over the different phases of the pandemic in MSM in Switzerland.

Materials and methods

We followed the "Strengthening the Reporting of Observational Studies in Epidemiology" (STROBE) statement for the reporting of observational studies [20]. The SwissPrEPared study was approved by all cantonal ethical committees (lead canton: Zurich, Switzerland – registration number: 2018-02015) and was registered with ClinicalTrials.gov (NCT03893188). Written informed consent was obtained from all participants included in this study.

Study design and setting

Data were obtained from the ongoing SwissPrEPared study, which is a large, multicentre, nationwide cohort study that aims to follow individuals interested in PrEP longitudinally over a three-year period. Recruiting centres are located in seven Swiss cities and consist of large tertiary referral hospitals, sexual health clinics and private clinical practices (e.g. general practitioners, infectious diseases specialists or dermatologists).

All study centres are part of the SwissPrEPared programme, which ensures standardization of PrEP counselling and STI (sexually transmitted infection) screening across the country. Programme participants have access to a secure, web-based, online platform where they complete standardized questionnaires on their personal electronic devices before their scheduled counselling. Counselling and STI screening occur at regular intervals, following the latest international recommendations: every three months for participants on daily PrEP and at least every six months (or less) for those taking PrEP intermittently (i.e. either daily for limited periods of time ["holiday PrEP"] or before and after sex ["event-driven" PrEP]) [21].

Study participants

The design and cohort profile of the SwissPrEPared study have been described elsewhere [22]. This ongoing cohort enrols HIV-negative individuals aged ≥18 years and presenting for PrEP counselling at participating centres. Potential study participants are informed of study enrolment in print and online magazines. No restrictions are applied to those with no indication for PrEP or those declining further PrEP use.

In this analysis, only MSM were included, i.e. either cis-MSM (assigned male at birth, self-identifying as male, having sex with men) or trans-MSM (assigned female at birth, self-identifying as male, having sex with men). Participants included in the analysis completed at least one questionnaire assessing mental health outcomes before the start of the SARS-CoV-2 pandemic in Switzerland (defined as February 28, 2020) and at least one thereafter.

Study outcomes

The primary outcome was defined as mental health outcomes, assessed using the Patient Health Questionnaire-4 (PHQ-4) [23]. This screening instrument consists of four questions based on a four-point Likert-type scale and evaluates the likelihood of depression (two questions) and anxiety (two questions) (see Appendix, table S1 for a comprehensive description of this instrument). Each question is rated from 0–3 (with higher values indicating a poorer outcome), thereby yielding a maximum score of 6 for each of the subscales. A score of 3 or greater on each subscale identifies potential cases of depression or anxiety and should prompt further evaluation and, in some cases, referral to specialized care.

The following endpoints were considered as secondary outcomes:

Finally, we were also interested in assessing whether the quality of HIV prevention care was affected by the SARS-CoV-2 prevention measures. Thus, we evaluated disruption of care, defined as the proportion of participants unable to attend their follow-up visits as scheduled (i.e. three months + two weeks between each recorded visit). Disruption of care was assessed in participants who started daily PrEP before January 1, 2020 and was not evaluated in those on intermittent PrEP (i.e. "holiday" or "event-driven" PrEP), since visit schedules for such individuals may differ between centres.

The outcomes were assessed over seven different periods corresponding to the varying prevention measures introduced (or lifted) by the Swiss Ministry of Health (Appendix, figure S1) [26]. These periods were defined as:

Statistical methods

The aim of this study was primarily descriptive: the primary outcome, defined as mental health outcomes (i.e. PHQ-4 anxiety and depression subscales, ordinal variables), was assessed over time by comparing the participants’ scores on each subscale (ranging from 0 to 6) between the different periods. We performed pairwise comparisons between periods using the Wilcoxon signed rank test with Bonferroni adjustment for multiple testing in the case of statistically significant results (p <0.05). For the primary outcome (i.e. PHQ-4 depression or anxiety subscales), 21 comparisons were performed; thus, a level of £0.002 was considered significant. Alternative approaches (e.g. Friedman’s ANOVA) were not applicable because the group sizes varied over time.

In the phase preceding March 1, 2020, for participants with multiple previous questionnaires, only the latest (i.e. the closest in time to March 1, 2020) was considered. The same approach was used for participants with more than one questionnaire during the other periods – only the last questionnaire completed during that period was considered – so as to maximize the potential effect of time on the outcome.

Secondary outcomes were assessed over all periods using the same approach as described above: for ordinal and continuous variables we performed pairwise comparison using the Wilcoxon signed rank test with adjustment for multiple comparisons; for binary/nominal variables we used the McNemar test. To quantify disruption of care, a descriptive analysis of the time lag between visits in daily PrEP users was performed.

Additional exploratory analyses included dichotomization of the primary outcome (i.e. depression/anxiety screening: positive for scores ≥3 and negative for scores ≤2) and assessing the association of pre-existing anxiety or depression with poor mental health over time (using generalized estimating equation models that accounted for repeated measurements over time). For the latter, pre-existing anxiety or depression were defined as a score ≥3 on the relevant subscale at baseline, i.e. during the pre-SARS-CoV-2 period.

Categorical variables were expressed as proportions, continuous variables as median and interquartile range. A level of significance of 0.05 was used, unless multiple comparisons were performed. All statistical analyses were conducted in R, version 4.1.0. A detailed list of the libraries used in this work is provided in the Appendix.

Results

Data were collected from 14 participating centres between April 10, 2019 and March 22, 2021. Overall, 1,326 participants were assessed for eligibility (figure 1). Of these, 26 participants were found to be ineligible (two tested positive for HIV, one was unable to follow the study requirements and 23 declined study participation), whilst five withdrew their consent before the first visit (one concerned by data protection, one with infrequent PrEP use, three for unknown reasons). Thus, 1,295 participants were enrolled in the SwissPrEPared study by February 28, 2020. Of these, 252 were further excluded, either due to a lack of mental health data (129 with missing questionnaire before February 28, 2020 and 75 with missing questionnaire after this date), or because they did not identify as MSM (n = 48). Thus, data from 1,043 participants were eventually included in the analysis.

Figure 1 Flow diagram.

MSM: men having sex with men; PHQ-4: Patient Health Questionnaire-4

Baseline characteristics

Table 1 outlines participants’ baseline characteristics (i.e. pre-SARS-CoV-2 period). Median age was 40 years (IQR: 33–47). All participants were MSM, predominantly identifying as cis-male (1040/1043, 99.7%). The majority were born in Switzerland (641/1043, 61.5%), while 497/1043 (47.7%) had a university degree.

Table 1Participants with mental health data – baseline characteristics.

Overall (n = 1043)
Age Median [IQR] 40 [33–47]
Gender Male 1043 (100%)
– Cis-male 1040 (99.7%)
– Trans-male 3 (0.3%)
Country of origin Switzerland 641 (61.5%)
Germany 105 (10.1%)
France 35 (3.4%)
Brazil 27 (2.6%)
Italy 18 (1.7%)
Others (each <18 participants) 217 (20.8%)
– European countries 92 (42.4%)
– Non-European countries 125 (57.6%)
Education University 497 (47.7%)
Higher education (excluding university) 242 (23.2%)
Apprenticeship 193 (18.5%)
High school/Baccalaureate 67 (6.4%)
No or compulsory school 20 (1.9%)
Other 24 (2.3%)

“Cis” refers to individuals for whom sex assigned at birth matches gender identity. “Trans” refers to a discrepancy between sex assigned at birth and the reported gender identity.

On the PHQ-4 anxiety and depression subscales, most participants scored 0, 1 or 2 (figure 2, pre-SARS-CoV-2 period). When considered as a binary endpoint (score ≥ 3 on each subscale), 8% (83/1043) and 5.3% (55/1043) of the participants screened positive at baseline for anxiety and depression respectively.

Figure 2 Anxiety and depression scores over the different SARS-CoV-2 periods in a sample of the SwissPrEPared cohort. Scores of 3 or greater identify potential cases of anxiety or depression.

PHQ-4: Patient Health Questionnaire-4.

Baseline data on sexual behaviour, well-being and PrEP use are outlined in table 2 (pre-SARS-CoV-2 period). The median sexual partner count was 6 (IQR: 3–12), 91.7% (956/1043) of the participants reported having sex with casual partners and 9.6% (100/1043) reported consistent condom use. Concern about substance use was reported by 5.3% of participants, whilst 17.2% reported using chemsex substances, 16.8% reported using Ecstasy, 17.4% cocaine and 22.8% cannabis over the past three months. The median sexual happiness score was 7 (IQR: 6–8) and around half the participants reported a comfortable financial situation (546/1043, 52.3%). Most participants were on PrEP at baseline (880/1043, 84.4%), with 64.3% (671/1043) using a daily regimen. Overall self-reported adherence (never missed a dose: 59.5%, 84.3% and 66.7% in daily, "event-driven" and "holiday" PrEP users respectively) was acceptable.

Primary outcome: anxiety and depression screening over time

Examination of the different periods indicated that most participants reported PHQ-4 anxiety scores of 0, 1 or 2 (figure 2 and Appendix, table S2) and that the proportion of participants with a positive anxiety screening was stable over time (figure 3 and Appendix, table S2). Pairwise comparisons of anxiety scores between the different periods revealed no significant differences (Appendix, table S4). Similar results were found for the comparisons of positive anxiety screenings (Appendix, table S4).

Figure 3 Proportion of participants (with 95% CIs) who screened positive for anxiety or depression over the different SARS-CoV-2 prevention periods. A positive screening was defined as a score of 3 or greater on the relevant Patient Health Questionnaire-4 (PHQ-4) subscale. The McNemar test was used to compare outcome proportions between periods (two-sided test). 

Compared to the pre-SARS-CoV-2 period, depression scores reported in the second wave and second lockdown period shifted towards both higher ratings on the ordinal scale and to more positive screenings (figures 2 and 3 and Appendix, table S2). Pairwise comparisons confirmed significant differences for these specific periods (ordinal scale, pre-SARS-CoV-2/second wave and pre-SARS-CoV-2/second lockdown: p <0.001; positive screening, pre-SARS-CoV-2/second wave: n = 684, p = 0.048; positive screening, pre-SARS-CoV-2/second lockdown: n = 545, p = 0.017, Appendix, table S4).

Secondary outcomes

For a comprehensive overview of all secondary outcomes, see Appendix, table S2.

Sexual behaviour over time

Both the median number of sexual partners and the occurrence of sex with casual partners followed a biphasic pattern over time, with an initial decrease during the first lockdown and first easing periods and a second decline during the second wave and second lockdown. Pairwise comparisons confirmed these changes in sexual behaviour over time (p <0.002; Appendix, table S4). Compared to the pre-SARS-CoV-2 period, systematic condom use decreased over time, whilst the proportion of participants reporting no condom use increased. These differences between baseline and the following periods were confirmed by pairwise comparisons (Appendix, table S4). Data on the adaptation of sexual and dating behaviour were only available from the first easing period. From this time point, the proportion of participants reporting having no sexual contact steadily decreased. Similar results were found for those reporting having fewer online dates. Pairwise comparisons confirmed these differences between periods (Appendix, table S4). Finally, none of the endpoints related to substance use varied markedly over time, except for the use of chemsex substances (which declined during the first lockdown and easing) and the use of ecstasy (which declined over time compared to baseline). These findings were confirmed when performing pairwise comparisons (Appendix, table S4).

Well-being over time

Sexual happiness remained stable over time, with pairwise comparisons showing differences between only a few periods (Appendix, tables S3 and S4). Robust follow-up data on financial coping were only available from the second wave period. There were no marked differences between periods (Appendix, table S4).

PrEP use over time

The proportion of participants reporting taking PrEP on the day of the study visit showed a universal upward trend over time, except during the first lockdown period. This trend was confirmed by the pairwise analysis (Appendix, table S4). There were only minor fluctuations in PrEP regimens over time, except during the first easing period, when a reduction in daily PrEP and an increase in "holiday" and "event-driven" PrEP was reported. Pairwise comparisons of the pre-SARS-CoV-2 period and the first easing period confirmed these findings (Appendix, table S4). Self-reported adherence remained stable over time, with overall good adherence across all PrEP regimens, and showed no significant differences between periods (Appendix, tables S3 and S4).

Disruption of care

Figure 4 illustrates the lengths of time between follow-up visits occurring during the SARS-CoV-2 pandemic in daily PrEP users who started PrEP before Jan 1, 2020 (n = 534 PrEP users). The median time between visits was 13.3 weeks (IQR 11.3–17.8). Disruption of care, namely visits with a time interval >14 weeks, affected 42.6% of the visits (790/1856 visits).

Figure 4 Histogram showing the lengths of time (in weeks) between follow-up visits occurring during the SARS-CoV-2 pandemic in daily PrEP users who started PrEP before Jan 1, 2020 (n = 534 PrEP users).

The median time between visits was 13.3 weeks (IQR 11.3–17.8). Disruption of care, namely visits with a time interval >14 weeks, affected 42.6% of the visits occurring during the SARS-CoV-2 pandemic (790/1856 visits).

Association of pre-existing anxiety or depression with poor mental health over time

The effects of pre-existing (i.e. baseline) anxiety or depression on the likelihood of screening positive for anxiety or depression was assessed over six different periods (i.e. from the pre-lockdown period to the end of the second lockdown). Participants with pre-existing anxiety or depression were more likely to screen positive for anxiety over time (pre-existing anxiety: OR 5.6, 95%CI 3.6–8.9, p <0.001; pre-existing depression: OR 2.8, 95%CI 1.6–4.8, p <0.001). Similar results were found when screening positive for depression was considered as the outcome (pre-existing anxiety: OR 2.7, 95%CI 1.6–4.6, p <0.001; pre-existing depression: OR 5.9, 95%CI 3.3 to 10.6, p <0.001).

Discussion

In this longitudinal analysis including 1,043 MSM from a large, ongoing, prospective, nationwide HIV PrEP study, we examined the effect of SARS-CoV-2 prevention measures on mental and sexual health over a one-year period. Whilst anxiety scores remained stable over time, we found that depression screenings, assessed both on the PHQ-4 ordinal scale and as a binary outcome (positive/negative screening), worsened in the second wave and second lockdown period when compared to the pre-pandemic phase. Further analyses revealed changes in sexual behaviour and substance use over the different periods (e.g. downward trends in the number of sexual partners and the occurrence of sex with casual partners and a decline in chemsex and Ecstasy use), as well as changes in the way participants used PrEP (i.e. switching from daily PrEP to "holiday" or "event-driven" PrEP). Finally, we were able to show that the SARS-CoV-2 pandemic resulted in the disruption of important care, with more than 40% of scheduled visits occurring later than initially planned.

Using a longitudinal design, our analysis suggests negative effects of the SARS-CoV-2 pandemic on mental health. This is consistent with results from previously published, smaller, cross-sectional studies [2, 3, 8, 10, 16] and from a few cohort studies including other populations [27, 28]. In contrast to other reports, however, only a small fraction of our cohort (i.e. less than 10%) screened positive for anxiety or depression. A possible explanation for these findings may be that our cohort included mostly middle-aged, well-educated MSM originating from Switzerland, who reported a comfortable initial financial situation that was maintained over the course of the pandemic. These characteristics are in marked contrast with factors suggested to result in poorer mental health outcomes (such as younger age, an immigration background, belonging to an ethnic minority and financial insecurity) [2, 10, 16] and should prompt the development of recruitment strategies targeted at younger, less educated individuals [22]. Another reason for these results might be the use of coping mechanisms, such as the use of dating apps or social media to maintain social contacts or obtain emotional support [7]. Finally, the fact that the individuals included in our analysis were part of a prevention programme with regular follow-up visits may also have played a beneficial role, as evidence suggests that retention in care yields better mental and sexual health outcomes [29].

The data analysis on sexual behaviour suggested a downward, biphasic trend in the number of sexual partners and in the occurrence of sex with casual partners, which reflected, to some extent, the introduction and lifting of the SARS-CoV-2 prevention measures over time. Similarly, the decline observed in Ecstasy and chemsex substances use might also be attributed to the different phases of the SARS-CoV-2 pandemic, when social life in Switzerland was restricted (Appendix, figure S1). These findings are in line with other studies reporting an adaptation of sexual behaviour over the course of the time periods with different pandemic-related prevention measures [8, 10, 12, 17, 18, 30, 31]. In our study, however, ratings on sexual happiness remained stable over time. Because one would expect that a restricted social and sexual life would lead to lower sexual happiness ratings, the stability in happiness ratings might reflect a certain degree of social desirability bias in the answers related to the number of partners and/or sex with casual partners. This suggests that the individuals included in our study may not have fully adhered to physical distancing recommendations. These findings are consistent with studies reporting a lack of adaptation in sexual behaviour over the course of the pandemic (“quarantine-fatigue”) [18, 32], as well as with other reports where individuals at considerable risk of HIV were found to maintain a certain degree of exposure to risky situations [8, 31, 33].

Our study revealed that SARS-CoV-2 restrictions resulted in disruption of care, which is consistent with other studies reporting interruptions in access to PrEP/ HIV care during the pandemic [2, 17, 31, 34, 35]. The potential magnitude of these issues is of concern, as only modest SARS-CoV-2-related disruptions to HIV testing may result in substantial short-term increases in new HIV infections [36]. Interestingly, disruption of care occurred in our study despite the fact that, similar to other PrEP programmes [33, 37], two large SwissPrEPared centres offered telehealth services and home self-testing during lockdown phases. Thus, although telehealth seems to represent a good alternative in times of limited access to PrEP services [35, 37, 38], it may not fully substitute in-person visits, especially when STI or HIV screenings are needed [35]. These findings emphasize the need to maintain access to in-person health care in order to minimize collateral damage due to the SARS-CoV-2 pandemic or any other public health emergency.

This study provides longitudinal data on mental and sexual health outcomes over the different phases of the SARS-CoV-2 pandemic, including pre-pandemic data. In contrast to previously published studies [2, 3, 8, 10, 16], we used validated instruments with good psychometric properties for outcome assessment [39] and applied them to a large sample from an ongoing, prospective PrEP cohort, which enabled us to make robust inferences on mental and sexual health trajectories over time.

Our analysis has some limitations, however. Firstly, our cohort was a mostly middle-aged, well-educated and financially comfortable MSM population, and we cannot exclude that a certain degree of selection bias occurred. However, our findings remain applicable to several PrEP cohorts from other high-income countries which share a similar profile to ours [40–43]. Secondly, because the framing of some questions (e.g. number of sexual partners) referred to a rather wide time span (i.e. previous three months), the effect of shorter time periods, such as the pre-lockdown or first lockdown periods, on the study outcomes may have been underestimated: because of recall bias and the rather long time elapsed between visits, we cannot exclude that when participants completed their questionnaire at the beginning of a new prevention measures phase, their outcome assessment referred to the previous period rather than the period under consideration. Thus, in the case of multiple questionnaires completed in the same period, we selected the assessment nearest to the end of the period to maximize the effect of the period being considered on the participant’s responses. Thirdly, when assessing the effects of the different periods on mental and sexual health outcomes, we did not use more complex methodological approaches, such as interrupted time series [44] or unsupervised machine learning [45], since the main aim of this study was primarily descriptive and performing additional analyses was unlikely to change the main findings of this paper.

In this longitudinal analysis focusing on a subset of participants from a large, ongoing, prospective PrEP cohort study, there was a worsening of depression screening scores assessed with the PHQ-4 questionnaire over the different phases of the SARS-CoV-2 pandemic. Additional analyses identified changes in sexual behaviour, in substance use, in the way participants used PrEP and in their access to HIV prevention care over time. Follow-up data from the ongoing SwissPrEPared study (NCT03893188) will help evaluate the long-term effects of the SARS-CoV-2 prevention measures on mental and sexual health outcomes in MSM and other sexual minorities.

Availability of data and material

The small, highly representative and individual-level datasets analyzed during the current study and used to generate table S1 and figures S1 to S4 and the Appendix are not publicly available due to the sensitive nature of the data they contain. Source data are thus not provided with this paper. Investigators with a request for selected data should send a proposal to the SwissPrEPared e-mail address (info[at]swissprepared.ch). The provision of data will be considered by the Scientific Board of the SwissPrEPared cohort study and the relevant study team. Data provision is subject to Swiss legal and ethical regulations and will be detailed in a material and data transfer agreement.

Authors' contributions

BLW, FH, RDK and BH participated in study conception and design, data interpretation and critical revision of the manuscript. BLW and FH drafted the first manuscript. FH and RDK performed the statistical analyses. AJS, MRe, MRa, EB, EBEA, DLB, AC, MC, VC, CD, SL, JN, MS, BS, PB and JN participated in data acquisition and critical revision of the manuscript. DH, RB, NL, AL, BBQ and JSF participated in study conception and design and critical revision of the manuscript. All authors listed on the title page have read the manuscript, attest to the validity and legitimacy of the data and its interpretation, and agree to its submission.

Notes

Financial disclosure

This work was supported by the Federal Office of Public Health [approval number: 19.022422], Merck Sharp & Dohme (MSD), and the Swiss HIV Cohort Study [grant number: SHCS_281]. BLW, FH and BH were supported by the Federal Office of Public Health [approval number: 19.022422]. BLW, FH, RDK and EB were supported by the Swiss National Science Foundation [grant 10001C_192814; #BSSGI0_155851; #177499]. RDK was supported by Gilead Sciences and the National Institutes of Health. The funding organizations had no role in the design and conduct of the study; in the collection, management, analysis or interpretation of the data; or in the preparation, review or approval of the manuscript.

Potential competing interests

DLB received advisory fees from Gilead Sciences, Merck & Co., AbbVie and ViiV Healthcare. EB’s institution received advisory fees and travel grants from Gilead Sciences, MSD, ViiV Healthcare, Pfizer AG and Abbvie. JN received travel grants from Gilead sciences. MS’s institution received advisory fees and travel grants from Gilead Sciences, MSD and ViiV Healthcare. BS’s institution received travel grants and advisory fees from Gilead Sciences. MC’s institution received payments from Gilead Sciences, MSD and ViiV Healthcare for research and meeting fees, outside of this work. PG received research and travel grants unrelated to this publication from Gilead Sciences and Abbvie. DH’s institution received funding unrelated to this publication from Abbvie, Gilead Sciences, GSK, Janssen, MSD, Pfizer, Sandoz and ViiV Healthcare and consulting fees from Gilead and ViiV Healthcare. RB’s institution received funding from Geneva and Lausanne University, Geneva High School for Social Work (HETS) and General Direction for Health canton Vaud. RB’s institution received advisory fees from the Federal Commission for Tobacco Prevention. JF received research grants unrelated to the submitted work from Merck & Co., Gilead Sciences and ViiV Healthcare. JF and BH received advisory fees from the Federal Commission for Issues Relating to Sexually Transmitted Infections (FCSTI). BH’s institution received research and travel grants from ViiV Healthcare, MSD and Gilead Sciences. BH received advisory fees from Gilead Sciences and ViiV Healthcare. The other authors declare no competing interests.

Babette L. Winter

Department of Public and Global Health, Epidemiology, Biostatistics and Prevention Institute

Hirschengraben 84

CH-8001 Zurich

babette.winter2[at]uzh.ch

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Appendix: supplementary data

The appendix is available in the pdf version of the article.