Medication Non-adherence and Condomless Anal Intercourse Increased Substantially During the COVID-19 Pandemic Among MSM PrEP Users: A Retrospective Cohort Study in Four Chinese Metropolises

ORIGINAL RESEARCH

published: 29 April 2022

doi: 10.3389/fmed.2022.738541

Frontiers in Medicine | www.frontiersin.org 1 April 2022 | Volume 9 | Article 738541

Edited by:

Reza Lashgari,

Shahid Beheshti University, Iran

Reviewed by:

Kuldeep Singh,

National Institute of Malaria Research

(ICMR), India

Gengfeng Fu,

Jiangsu Provincial Center for Disease

Control and Prevention, China

Junjie Wang,

Chinese Center for Disease Control

and Prevention, China

*Correspondence:

Hong Shang

[email protected]

Junjie Xu

[email protected]

†

These authors have contributed

equally to this work

Specialty section:

This article was submitted to

Infectious Diseases–Surveillance,

Prevention and Treatment,

a section of the journal

Frontiers in Medicine

Received: 09 July 2021

Accepted: 28 March 2022

Published: 29 April 2022

Citation:

Gao Y, Hu Q, Leuba SI, Jia L, Wang H,

Huang X, Chen Y, Wang H, Zhang J,

Chu Z, Zhang L, Wang Z, Shang H,

Xu J and CROPrEP Study Team

(2022) Medication Non-adherence

and Condomless Anal Intercourse

Increased Substantially During the

COVID-19 Pandemic Among MSM

PrEP Users: A Retrospective Cohort

Study in Four Chinese Metropolises.

Front. Med. 9:738541.

doi: 10.3389/fmed.2022.738541

Medication Non-adherence and

Condomless Anal Intercourse

Increased Substantially During the

COVID-19 Pandemic Among MSM

PrEP Users: A Retrospective Cohort

Study in Four Chinese Metropolises

Yangyang Gao

1,2,3,4†

, Qinghai Hu

1,2,3,4†

, Sequoia I. Leuba

, Le Jia

1,2,3,4

, Hongyi Wang

1,2,3,4

Xiaojie Huang

, Yaokai Chen

, Hui Wang

, Jing Zhang

1,2,3,4

, Zhenxing Chu

1,2,3,4

Lukun Zhang

, Zixin Wang

, Hong Shang

1,2,3,4

, Junjie Xu

1,2,3,4

and CROPrEP Study Team

National Health Commission Key Laboratory of Acquired Immunodeﬁciency Syndrome (AIDS) Immunology (China Medical

University), National Clinical Research Center for Laboratory Medicine, The First Afﬁliated Hospital of China Medical

University, Shenyang, China,

Key Laboratory of AIDS Immunology, Chinese Academy of Medical Sciences,

Shenyang, China,

Key Laboratory of AIDS Immunology of Liaoning Province, Shenyang, China,

Collaborative Innovation

Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, China,

Department of Epidemiology, U niversity of

North Carolina at Chapel Hill, Chapel Hill, NC, United States,

Center for Infectious Diseases, Beijing Youan Hospital, Capital

Medical University, Beijing, China,

Chongqing Public Health Medical Center, Chongqing, China,

Department of Infectious

Diseases, National Clinical Center for Infectious Diseases, Third People’s Hospital of Shenzhen, Second Afﬁliated Hospital of

Southern University of Science and Technology, Shenzhen, China,

Faculty of Medicine, The Jockey Club School of Public

Health and Primary Care, The Chinese University of Hong Kong, Hong Kong, Hong Kong SAR, China

Background: The coronavirus disease (COVID-19) pandemic has impacted HIV

prevention strategies globally. However, changes in pre-exposure prophylaxis (PrEP)

adherence and HIV-related behaviors, and their associations with medication adherence

among men who have sex with men (MSM) PrEP users remain unclear since the onset

of the COVID-19 pandemic.

Methods: A Retrospective Cohort Study of HIV-negative MSM PrEP users was

conducted in four Chinese metropolises from December 2018 to March 2020, assessing

the changes in PrEP adherence and HIV-related behaviors before and during the COVID-

19. The primary outcome was poor PrEP adherence dete rmined from self-reported

missing at least one PrEP dose in the previous month. We used multivariable logistic

regression to determine factors correlated with poor adherence during COVID-19.

Results: We enrolled 791 eligible participants (418 [52.8%] in daily PrEP and 373

[47.2%] in event-driven PrEP). Compared with the data conducted before the COVID-19,

the proportion of PrEP users decreased from 97.9 to 64.3%, and the proportion of poor

PrEP adherence increased from 23.6 to 50.1% during the COVID-19 [odds ratio (OR)

3.24, 95% conﬁdence interval (CI) 2.62–4.02]. While the percentage of condomless anal

intercourse (CAI) with regular partners (11.8 vs. 25.7%) and with casual partners (4.4

Gao et al. PrEP Adherence During the COVID-19 Pandemic

vs. 9.0%) both signiﬁcantly increased. The proportion of those who were tested for HIV

decreased from 50.1 to 25.9%. Factors correlated with poor PrEP adherence during the

COVID-19 included not being tested for HIV (adjusted odds ratio [aOR] = 1.38 [95% CI:

1.00, 1.91]), using condoms consistently with regular partners (vs. never, aOR = 2.19

[95% CI: 1.16, 4.13]), and being married or cohabitating with a woman (vs. not married,

aOR = 3.08 [95% CI: 1.60, 5.95]).

Conclusions: Increased poor PrEP adherence and CAI along with the decrease in HIV

testing can lead to an increase in HIV acquisition and drug resistance to PrEP. Targeted

interventions are needed to improve PrEP adherence and HIV prevention strategies.

Keywords: COVID-19, pre-exposure prophylaxis (PrEP), adherence–compliance–persistence, men who have sex

with men (MSM), condomless anal intercourse (CAI)

INTRODUCTION

Since the declaration of the coronavirus disease 2019 (COVID-

19) pandemic by the World Health Organization (WHO) on

11 March 2020, social distancing has interrupted hospital-

based HIV prevention met hods, HIV care, and testing services,

particularly among men who have sex with men (MSM) (

1, 2).

Almost one quarter (23%) of new HIV infections globally in

2019 were among MSM, and the percentage of incident HIV

infections among MSM was even higher in the Asia-Paciﬁc region

(3). The HIV incidence among Chinese MSM has increased from

3.24/100 PY (95% CI: 2.81–3.74) in 2005–2008 to 5.95/100 PY

(95% CI: 5.37–6.56) in 2012–2018 (4). New strategies to prevent

HIV transmission, especially those that are eﬀective despite social

distancing, are needed to address t he increasing HIV epidemic

among Chinese MSM.

Pre-exposure prophylaxis (PrEP) is an innovative and eﬀective

biomedical HIV prevention s trate gy for people at high risk

of HIV infection (

5). PrEP is a medication that is usually

taken daily or event-driven to prevent HIV transmission and

is frequently tenofovir/emtricitabine (TDF/FTC). If used with

optimal adherence, PrEP is highly eﬀective at preventing HIV

transmission (6, 7). However, if adherence is <40%, PrEP is no

longer protective against HIV transmission (8). Since the onset

of the COVID-19 pandemic, few studies have assessed PrEP

adherence but several have reported that the number of PrEP

users has decreased signiﬁcantly (9, 10). In the United K ingdom,

Belgium, and Australia, there have been 80.0, 47.0, and 4 1.8%

reductions in HIV PrEP users after the outbreak of COVID-

19, respectively (

11–13). In addition to decreasing the use of

PrEP, changes in HIV-related sexual behaviors and increased

barriers to accessing HIV prevention and testing services during

the COVID-19 pandemic could lead to an increase in HIV

acquisition (9, 11, 14). Little is known about possible changes

Abbreviations: COVID-19, coronavirus disease 2019; PrEP, pre-exposure

prophylaxis; MSM, men who have sex with men; OR, odds ratio; CI, conﬁdence

interval; CAI, condomless anal intercourse; WHO, World Health Organization;

PY, person-years; TDF/FTC, tenofovir/emtricitabine; CROPrEP, the China Real-

world Oral Intake of PrEP; IQR, interquartile range; HIVST, HIV self-testing; aOR,

adjusted odds ratio.

in PrEP adherence and HIV-related sexual and testing behaviors

from before to during the COVID-19 pandemic.

This study was based on the China Real-world Oral Intake

of PrEP (CROPrEP) project, which is an ongoing multi-center,

real-world trial of HIV PrEP among Chinese MSM to assess the

eﬀectiveness and adherence of daily or event-driven PrEP (

15).

Participants would complete ﬁve follow-up visits that included

an online questionnaire and a clinic visit at 4, 12, 24, 36, and

48 weeks after enrollment. After clinical evaluations and HIV

laboratory testing, participants received TDF/FTC tablets to use

as PrEP. We, thus, investigated PrEP adherence and HIV-related

sexual and testing behaviors among Chinese MSM PrEP users

and determining factors c orrelated with poor adherence before

and during the COVID-19 outbreak. Our ﬁndings will help

researchers develop interventions to maintain and support PrEP

use during the pandemic.

METHODS

Study Design

The study recruited 791 MSM aged 16–65 years from four major

Chinese cities (Shenyang, Beijing, Shenzhen, and Chongqing)

from December 2018 to March 2020. In this study, we invited

participants to complete two online self-administered surveys.

The aim of this study was to determine changes in PrEP

adherence and HIV-related and testing behaviors among PrEP-

using Chinese MSM from before to during the COVID-19

outbreak. The median interval between the 4-week visit and

this additional online sur vey was 28 weeks, and the interquartile

range (IQR) was 24–36 weeks.

Participants

The inclusion criteria for this additional online survey were t h e

following: (1) participants of the CROPrEP project, (2) screened

to be HIV-negative at the most recent follow-up visit, and (3)

had not yet completed t he ﬁnal follow-up visit at Week 48. We

excluded those who did not complete a Week 4 follow-up visit as

data from this visit were used to provide information from before

the COVID-19 outbreak.

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Gao et al. PrEP Adherence During the COVID-19 Pandemic

Data Collection

This additional online survey assessing changes in PrEP

adherence and HIV-related sexual and testing behaviors due to

the COVID-19 pandemic was developed by a panel consisting of

HIV epidemiologists, clinicians, and MSM-serving community-

based organization members. This questionnaire was then pilot-

tested among 15 MSM volunteers who were not CROPrEP

participants and was revised based on their comments. A link

to this additional online questionnaire was shared among all

participants in CROPrEP by using the WeC hat (i.e., a popular

social media platform) group. If participants did not complete

the survey within 24 h, project staﬀ reminded them of the

invitation v ia a phone call or a text message. Participation in

this additional online survey was voluntary, refusal to participate

had no eﬀect on their participation in the CROPrEP project,

and data were conﬁdential and used only for research purposes.

Each individual account was allowed to access the online

questionnaire only once to avoid duplicate responses (refer to

Supplementary Appendix 1).

Measures

Before the COVID-19, measures were determined from the 4-

week follow-up visit for CROPrEP, conducted between October

2018 and November 2019, and during the COVID-19, measures

were determined from the additional online survey conducted

between February and March 2020. Baseline background

characteristics assessed included type of PrEP regimen, age,

education, monthly income, marital status, sexual identity, and

lockdown restrictions experience (during the COVID-19 survey

only). We asked about HIV-related sexual behaviors, such as

primary locations to seek male sexual partners, the number

and types of male sexual partners, frequency of sexual acts,

frequency of condomless anal intercourse (CAI) with s peciﬁc

types of male sexual partners, and sexualized drug use. For

HIV testing behavior, we asked about the self-perceived risk of

HIV infection, H IV test behavior in the past month, location

of the HIV test [i.e., facility-based HIV testing or HIV self-

testing (HIVST)], and self-assessment of the frequency of HIV

testing compared with pre-COVID-19 (during the COVID-19

survey only). To assess changes, we also asked whether they

had experienced lockdown restrictions due to COVID-19, how

frequently were they concerned about the COVID-19 pa ndemic

(i.e., never, sometimes, often, and always), or whether they had

delayed a scheduled follow-up visit for the CROPrEP project

(refer to Supplementary Appendix 2).

Male sexual partners were deﬁned as regular (i.e., those who

were in a stable relationship and did not involve transactional

sex) or casual (i.e., those who were not in a stable relationship

and did not involve transactional sex). Sexualized drug use

was deﬁned as using any of the following drugs during sexual

relations in the previous month: rush poppers (alkyl nitrites),

cocaine, methamphetamine, ketamine, and bath salts. Having

delayed a scheduled follow-up visit for the CROPrEP project

was deﬁned as attending a follow-up visit after the previously

scheduled appointment date by 7 days or more.

Outcome

Self-reported PrEP adherence was deﬁned based on a

comprehensive evaluation of the self-reported missed PrEP

doses and sexual behaviors. Poor adherence was deﬁned as the

following: (1) missing doses among daily PrEP users in the past

month and (2) missing doses among event-driven PrEP users if

they had sexual behaviors in the past month. If not deﬁned as

having poor adherence, participants were deﬁned as having good

adherence during the COVID-19 (

16).

Statistical Analysis

We analyzed the demographics and HIV-related behaviors of

Chinese MSM PrEP users using frequencies and percentages.

We then used the generalized estimating equation (GEE model-

Binary logistic regression) to analyze the changes in adherence

and HIV-related behaviors sexual and testing behaviors, and

PrEP use in the past month from before (using data from the

4-week follow-up visit from CROPrEP) and during the COVID-

19 outbreak (using data collected from the additional online

survey during COVID-19). We then assessed factors correlated

with poor adherence using univariable and multivariable logistic

regression models adjusted for age, education, and monthly

income. A two-tailed value of p below 0.05 and between 0.05

and 0.10 was considered statistically signiﬁcant and marginally

signiﬁcant, respectively. All statistical analyses were performed

using SPSS

software version 25.0 (IBM Corp, Armonk,

NY, US).

Ethical Review

This study was reviewed and approved by the Medical Science

Research Ethics Committee of the First Aﬃliated Hospital of

China Medical University ([2018]2015-139-5) and was registered

with the Chinese Clinical Trial Registry (C hiCTR-IIN-17013762).

After providing online informed consent, eligible participants

were asked to complete the additional questionnaire and had

the opportunity to review and modify their responses. All data

and informed consent were password-protected a nd stored in

a secure server, and only the principal investigator had access

to the database. E ach participant was compensated $4.20 (30

Yuan) after completing the additional online survey (refer to

Supplementary Appendix 3).

RESULTS

Baseline Characteristics

Before the COVID-19 outbreak, 1,023 MSM were enrolled in

the CROPrEP trial, and 931 (91.0%) were invited to participate

in this survey. During the COVID-19 pandemic, 841 (90.3%)

invited participants completed the online survey, and of these

participants, 791 (9 4.1%) were included in the data analysis

(300 in Shenyang, 362 in Beijing, 61 in Shenzhen, and 68 in

Chongqing) (refer to Figure 1). The median age of participants

was 30 years (IQR: 26–36 years), 79.6% (630/791) had an

education level of college and above, 38.1% (301/791) had a

monthly income of 2,001–6,000 Yuan (∼$310–92 9), and 81.0%

(641/791) self-described their sexual identity as a homosexual. In

response to COVID-19, 93.6% (740/791) of participants reported

Frontiers in Medicine | www.frontiersin.org 3 April 2022 | Volume 9 | Article 738541

Gao et al. PrEP Adherence During the COVID-19 Pandemic

FIGURE 1 | Study proﬁle.

experiencing COVID-19 lockdown restrictions, such as physical

distancing, community restrictions, and the banning of indoor

gatherings (refer to Table 1).

Changes in HIV-Related Sexual Behavior,

HIV Testing, and PrEP Adherence From

Before to During the COVID-19 Pandemic

Sexual acts, sexualized drug use, HIV testing, and PrEP use

and adherence sharply decreased as more participants had no

partner during the pandemic. The percentage of participants

who had regular or no male sexual partners in the past month

greatly increased from 33.4% (264/791) before to 74.0% (585/791)

during COVID-19, and the percentage of those who used the

internet as their primary location to seek male sexual partners

dropped from 60.4% (478/7 91) before to 25.3% (200/791) during

COVID-19. In addition, sexual activity, such as frequency of

sexual acts, having 2 or more male sexual partners and having

either a regular or casual male s exual partner greatly decreased

from before to during COVID-19. However, the proportion

of CAI with regular (11.8–25.7%) and casual (4.4–9.0%) male

sexual partners incre ased during COVID-19. Sexualized drug

use sharply decreased from 39.8% (315/791) before to 24.1%

(191/791) during COVID-19. HIV testing behaviors sharply

decreased from 50.1% (396/791) of participants having been

tested for HI V in the past month before COVID-19 to

25.9% (205/791) during COVID-19, including HIVST (34.5%

(273/791) before to 20.7% (164/791) during COVID-19) or

through a facility [26.9% (213/791) before to 6.4% (51/791)

during COVID-19]. Prevention of HIV also decreased as PrEP

use dropped from 97.9% (774/791) before to 64.5% (510/791)

and poor PrEP adherence increased from 23.6% (187/791)

before to 50.1% (396/791) during COVID-19. Participants also

delayed a scheduled follow-up visit for the CROPrEP trial more

during COVID-19 (14.5%, 115/791) than before (10.0%, 79 /791)

(refer to Table 2).

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Gao et al. PrEP Adherence During the COVID-19 Pandemic

TABLE 1 | Characteristics of Chinese MSM PrEP users during the COVID-19

pandemic (N = 791).

Characteristic Participants (n, %)

PrEP regimen

Daily 418 (52.8)

Event-driven 373 (47.2)

Age (years)

18-24 130 (16.4)

25-39 534 (67.5)

40-65 127 (16.1)

Education

High school and below 161 (20.4)

College and above 630 (79.6)

Average monthly income (RMB, Yuan)

<2,000 129 (16.3)

2,001-6,000 301 (38.1)

6,001-10,000 153 (19.3)

More than 10,000 208 (26.3)

Marital status

Not married 499 (63.1)

Married or cohabitating with a woman 61 (7.7)

Cohabitating with a male 203 (25.7)

Divorced, separated, or widowed 28 (3.5)

Sexual identity

Homosexual 641 (81.0)

Bisexual 126 (15.9)

Heterosexual 3 (0.4)

Not sure 21 (2.7)

Experienced lockdown restrictions in response to COVID-19*

Yes 740 (93.6)

No 51 (6.4)

Data are from the additional online survey administered during the COVID-19 pandemic.

MSM, men who have sex with men; PrEP, pre-exposure prophylaxis; COVID-19,

Coronavirus disease 2019.

Lockdown restrictions include physical distancing of two meters when individuals have

to leave their homes, community restrictions, and the banning of indoor gatherings.

In the generalized estimating equations model, there was a

signiﬁcant decrease in the odds of using PrEP (odds ratio (OR)

= 0.04 [95% CI: 0.02, 0.07], p < 0.001) and a signiﬁcant increase

in the odds of self-reporting missing at le ast one PrEP dose (O R =

3.24 [95% CI: 2.62, 4.02], p < 0.0 01) and in the odds of delaying a

scheduled CROPrEP follow-up visit (OR = 1.54 [95% CI: 1.13,

2.08], p = 0.006) compared during to before the COVID-19

pandemic. Additionally, there were signiﬁcant reductions in the

odds of having been tested for HIV in the past month (OR = 0.3 5

[95% CI: 0.28, 0.43], p < 0 .001) . In concordance with the decrease

in HIV-related sexual behavior, there was a signiﬁcant increase

in the odds of self-perceiving risk of HIV infection as compared

with no risk (OR = 3.41 [95% CI: 2.72, 4.28], p < 0. 001). By

contrast, among those still having sexual behavior during the

COVID-19, there were signiﬁc ant increases in the odds of having

CAI wit h regular male sexual partners (OR = 2.61 [95% CI: 1.76,

2.87], p < 0.001) and marginal increases in the odds of having

CAI with casual male sexual partners (OR = 2.09, 95% CI: 0.92,

4.72, p = 0.077) compared to before COVID-19 (refer to Table 2).

Factors Correlated With Poor PrEP

Adherence During the COVID-19 Pandemic

About half of the participants (396/791, 50.1%) were deﬁned

as having poor PrEP adherence during the COVID-19. After

adjusting for age, education, and income, the following factors

over the past month were associated with increased odds of poor

PrEP adherence during the COVID-19 pandemic: being married

or cohabitating with a woman (compared with not married:

aOR = 3.08 [95% CI: 1.60, 5.95], p < 0.001), using condoms

consistently with regular male sexual partners (compared with

never using condoms: aOR = 2.1 9 [95% CI: 1.16, 4.13], p =

0.016), and often concerned about the COVID-19 pandemic

(compared with always concerned: aOR = 1.45 [95% CI: 1.07,

1.97], p = 0.017). Knowing the HIV status of regular male sexual

partners (aOR = 1.44 [95% CI: 0.98, 2.11], p = 0.065) and not

having been tested for HIV in the previous month (compared

with have been tested for HIV: aOR = 1.38 [95% CI: 1.00–1.91],

p = 0.050) were associated with marginally higher odds of poor

PrEP adherence. There was no diﬀerence in the odds of poor or

good PrEP adherence based on the PrEP dosing regimen (event-

driven vs. daily: aOR = 1.09 [95% CI: 0.82, 1.45], p = 0.560) (refer

to Table 3).

DISCUSSION

In this retrospective cohort study in China, we found a dramatic

increase in poor PrEP adherence along with decreases in HIV

testing, the number of male sexual partners, and sexual acts

during the COVID-19 pandemic. Factors correlated with the

increased odds of poor PrEP adherence during COVID-19

included not having an HIV test conducted in the last month,

using condoms consistently with regular male sexual partners,

and being married or cohabitating with a woman. Among those

who had regular or casual male sexual partners, the percentage

of those who had CAI subst antia lly increased during COVID-

19 compared with the percentage before the pandemic. This

may result in an increased risk of HIV infection and drug

resistance in this sexually active group during the pandemic.

Thus, public health oﬃcials should promote safer sex behaviors

among those who are sexually active during COVID-19. In

addition, poor PrEP adherence during the pandemic was found

among participants wit h likely less access to MSM-speciﬁc HIV

care, such as MSM married or cohabitating with a woman and

MSM who had not been tested for HIV in the last month. To

improve PrEP adherence, public health oﬃcials must improve

outreach to these subpopulations, such as sending at-home HIV

tests, re-inforcing risks for HIV acquisition if poor adherence

to PrEP, and if poor adherence is likely to continue, suggesting

stopping PrEP use to prevent drug resistance. Knowledge about

challenges to PrEP use due to COVID-19 provides ﬁrst-hand

real-world evidence of issues that must be addressed prior to

wide-spread PrEP implementation globally.

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Gao et al. PrEP Adherence During the COVID-19 Pandemic

TABLE 2 | Changes in sexual behaviors, HIV testing, and PrEP adherence among during compared to before the COVID-19 (N = 791).

Before COVID−19

During COVID−19 Odds ratio P-value

n (%) n (%) (95% CI)

HIV–related sexual behaviors in the past month

Primary location to seek male sexual partners

Internet 478 (60.4) 200 (25.3) 0.22 (0.18, 0.27) <0.001

Park/Bathroom/Club 49 (6.2) 6 (0.8) 0.12 (0.05, 0.27) <0.001

Had regular or no male sexual partners 264 (33.4) 585 (74.0) 5.68 (4.60, 701) <0.001

Frequency of sexual acts

More than once a week 413 (52.2) 125 (15.8) 0.17 (0.14, 0.21) <0.001

Once a week or less than once a week 321 (40.6) 224 (28.3) 0.58 (0.47, 0.72) <0.001

No sex 57 (7.2) 442 (55.9) 16.31 (12.04, 22.10) <0.001

Sexual partners in the past month

Had two or more male sexual partners 536 (67.8) 136 (17.2) 0.10 (0.08, 0.12) <0.001

Had regular male sexual partners 467 (59.0) 249 (31.5) 0.32 (0.26, 0.39) <0.001

Had casual male sexual partners 317 (40.1) 134 (16.9) 0.30 (0.24, 0.38) <0.001

Condom use with regular male sexual partners

Consistently 220 (47.1) 121 (48.6) 1.05 (0.79, 1.44) 0.745

Most or sometimes 192 (41.1) 64 (25.7) 0.05 (0.36, 0.70) <0.001

Never 55 (11.8) 64 (25.7) 2.61 (1.76, 2.87) <0.001

Condom use with casual male sexual partners

Consistently 167 (52.7) 74 (55.2) 1.13 (0.75, 1.71) 0.566

Most or sometimes 136 (42.9) 48 (35.8) 0.73 (0.348, 1.11) 0.143

Never 14 (4.4) 12 (9.0) 2.09 (0.92, 4.72) 0.077

Sexualized drug use

315 (39.8) 191 (24.1) 0.21(0.17, 0.26) <0.001

HIV testing behaviors in the past month

Had HIV test 396 (50.1) 205 (25.9) 0.35 (0.28, 0.43) <0.001

Had HIV test through HIVST 273 (34.5) 164 (20.7) 0.50 (0.40, 0.61) <0.001

Had facility–based HIV testing 213 (26.9) 51 (6.4) 0.19 (0.13, 0.26) <0.001

PrEP status in the past month

PrEP regimen

Daily 410 (51.8) 418 (52.8) 1.04 (0.86, 1.26) 0.682

Event-driven 381 (48.2) 373 (47.2) 0.96 (0.79, 1.17) 0.682

Used PrEP 774 (97.9) 510 (64.5) 0.04 (0.02, 0.07) <0.001

Poor PrEP adherence 187 (23.6) 396 (50.1) 3.24 (2.62, 4.02) <0.001

Delayed scheduled CROPrEP follow–up visit 79 (10.0) 115 (14.5) 1.54 (1.13, 2.08) 0.006

Self–perceived risk of HIV infection

No risk 160 (20.2) 367 (46.4) 3.41 (2.72, 4.28) <0.001

Low risk (<25%) 419 (53.0) 315 (39.8) 0.59 (0.48, 0.72) <0.001

Moderate risk (25–49%) 142 (18.0) 68 (8.6) 0.43 (0.32, 0.58) <0.001

High risk (50–75%) 52 (6.6) 24 (3.0) 0.45 (0.27, 0.72) 0.001

Very high risk (>75%) 18 (2.3) 17 (2.1) 0.94 (0.49, 1.82) 0.862

ALL data are among Chinese MSM PrEP users.

COVID-19, coronavirus disease 2019; MSM, men who have sex with men; PrEP, pre-exposure prophylaxis; HIVST, HIV self-testing.

CROPrEP, China Real-world Oral Intake of PrEP.

Before COVID-19 estimates were determined from the 4th week follow-up visit of the China Real-world Oral Intake of PrEP (CROPrEP) project conducted between October 2018 to

November 2019.

Sexual acts included receptive anal intercourse, insertive anal intercourse, and oral intercourse.

Only people with regular or casual partners answered the question.

Sexualized drug use in the past month included use of rush poppers (alkyl nitrites), cocaine, methamphetamine, ketamine, and bath salts before or during sexual activity.

In this study, similar to peer studies ﬁnding decreases in the

number of sexual partners and sexual practices since the onset

of COVID-19 (

10, 14, 17), we observed that 93.5% of Chinese

MSM PrEP users were impacted by lockdown restrictions and

had fewer sexual partners and fewer sexual acts. These decreases

may suggest t hat our participants overall may have temporarily

lower risks of HIV infection. Nevertheless, no excess risks among

MSM PrEP users were found in developing countries before.

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Gao et al. PrEP Adherence During the COVID-19 Pandemic

TABLE 3 | Factors correlated with poor adherence to PrEP among Chinese MSM PrEP users during the COVID-19 (N = 791).

Poor adherence Good adherence Odds ratio Adjusted odds ratio P-value

n = 396, n (%) n = 395, n (%) (95% CI) (95% CI)

PrEP regimen

Event-driven 192 (48.5) 181 (45.8) 1.11 (0.84, 1.47) 1.09 (0.82, 1.45) 0.560

Daily 204 (51.5) 214 (54.2) Reference Reference

Marital status

Married or cohabitating with a woman 45 (11.4) 16 (4.1) 3.10 (1.70, 5.63) 3.08 (1.60, 5.95) 0.001

Cohabitating with male 98 (24.7) 105 (26.6) 1.03 (0.74, 1.43) 1.00 (0.72, 1.40) 0.973

Divorced, separated, or widowed 15 (3.8) 13 (3.3) 1.36 (0.64, 2.88) 1.43 (0.64, 3.18) 0.382

Not married 238 (60.1) 261 (66.1) Reference Reference

Primary location to seek male sexual partners

No male sexual partner 197 (49.7) 173 (43.8) 1.48 (1.05, 2.09) 1.47 (1.04, 2.09) 0.030

Park/Bathroom/Club 3 (0.8) 3 (0.8) 1.30 (0.26, 6.59) 1.02 (0.20, 5.26) 0.985

Had regular male sexual partners 109 (27.5) 106 (26.8) 1.34 (0.91, 1.97) 1.27 (0.86, 1.88) 0.224

Internet

87 (22.0) 113 (28.6) Reference Reference

HIV–related sexual behaviors in the past month

Had two or more male sexual partners

Yes 65 (16.4) 71 (18.0) 0.90 (0.62, 1.30) 0.83 (0 .57, 1.20) 0.333

No 331 (83.6) 324 (82.0) Reference Reference

Had regular male sexual partners

Yes 130 (32.8) 119 (30.1) 1.13 (0.84, 1.53) 1.07 (0.79, 1.45) 0.665

No 266 (67.2) 276 (69.9) Reference Reference

Had casual male sexual partners

Yes 61 (15.4) 73 (18.5) 0.80 (0.55, 1.17) 0.79 (0 .55, 1.15) 0.224

No 335 (84.6) 322 (81.5) Reference Reference

Condom use with regular male sexual partners

Consistently 71 (54.6) 50 (42.0) 2.22 (1.19, 4.11) 2.19 (1.16, 4.13) 0.016

Most or sometimes 34 (26.2) 30 (25.2) 1.77 (0.88, 3.57) 1.74 (0.84, 3.61) 0.135

Never 25 (19.2) 39 (32.8) Reference Reference

Condom use with casual male sexual partners

Consistently 34 (55.7) 40 (54.8) 0.85 (0.25, 2.88) 0.96 (0.28, 3.35) 0.951

Most or sometimes 21 (34.4) 27 (37.0) 0.78 (0.22, 2.76) 0.82 (0.23, 3.00) 0.769

Never 6 (9.8) 6 (8.2) Reference Reference

Know the HIV status of regular male sexual partners

Yes 95 (39.4) 72 (30.9) 1.46 (1.00, 2.13) 1.44 (0 .98, 2.11) 0.065

No 146 (60.6) 161 (69.1) Reference Reference

HIV testing behaviors in the past month

Had HIV test

No 304 (76.8) 282 (71.4) 1.32 (0.96, 1.82) 1.38 (1.00, 1.91) 0.050

Yes 92 (23.2) 113 (28.6) Reference Reference

Self–assessment of the frequency of HIV testing

compare to pre-COVID-19

Increase 6 (1.5) 7 (1.8) 0.93 (0.31, 2.79) 0.87 (0.29, 2.66) 0.809

Decrease 111 (28.0) 86 (21.8) 1.40 (1.00, 1.93) 1.46 ( 1.05, 2.03) 0.026

No change 279 (70.5) 302 (76.5) Reference Reference

Concerned about the COVID−19 pandemic

Never 2 (0.5) 1 (0.3) 2.52 (0.23, 28.09) 2.90 (0.25, 33.44) 0.393

Sometimes 59 (14.9) 44 (11.1) 1.69 (1.08, 2.65) 1.74 (1.11, 2.75) 0.017

Often 193 (48.7) 171 (43.3) 1.42 (1.05, 1.92) 1.45 (1.07, 1.97) 0.017

Always 142 (35.9) 179 (45.3) Reference Reference

COVID-19, coronavirus disease 2019; MSM, men who have sex with men; PrEP, pre-exposure prophylaxis.

Adjusted odds ratios were obtained through multivariable analysis and were adjusted for age, education, and monthly income.

Internet include geosocial networking applications including WeChat, QQ, Blued or Jacked.

Concerned about the COVID-19 pandemic was deﬁned as how often obtaining information about COVID-19 through social media and other material proactively.

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Gao et al. PrEP Adherence During the COVID-19 Pandemic

However, compared with those sexually active individuals before

the pandemic, among those who were sexually active during

the pandemic, a much higher percentage had CAI with sexual

partners. PrEP cannot be used to replace condoms completely

and is a part of a comprehensive prevention strategy that

includes counseling and behavioral interventions promoting

condom use, abstinence, and monogamy (18, 19). An online

survey among MSM from the United States found conﬂicting

results and did not ﬁnd an eﬀect on condom use during

COVID-19 (20). A possible explanation is that China was the

ﬁrst country impacted by COVID-19 and quickly introduced

physical distancing restrictions and lockdowns, leading to sudden

signiﬁcant changes in lifestyle and sexual practices, while other

countries c ould have anticipated potential restrictions based on

news from China. In the future, public health oﬃcials must target

individuals who are likely to maintain sexual activity during

times where general sexual activity drops and promote safer

sex, such as high PrEP adherence and condom use. In addition,

we strongly recommend that medical staﬀ and community

volunteers popularize safety knowledge regularly and emphasize

the signiﬁcance of PrEP good adherence.

As suboptimal PrEP adherence will decrease the eﬀectiveness

of PrEP (

21), hence, all global public health sections highlight the

importance of maintaining high medication adherence among

subjects who take oral PrEP pills before or after the COVID-19

era. We found worse adherence during COVID-19 as more t han

one-third (35.7%) of participants did not obtain PrEP reﬁlls, and

a half (50.1%) self-reported missing at least one PrEP dose in the

previous month. Our ﬁndings are similar to the incre ase in the

proportion who discontinued PrEP use and the increase in the

mean number of missed PrEP doses found among MSM in the

Southern United States (

22). I ndividuals may have discontinued

PrEP use because they were no longer engaging in sexual activity

since COVID-19. Among those still engaging in sexual activity,

they could have been unable to access PrEP and thus had

worse adherence because they could not access PrEP or PrEP

support when facilities were closed due to lockdowns. If users

discontinued using PrEP, public he alth oﬃcials should reach out

frequently to see if t he y would like to begin using PrEP again,

and if users had worse adherence to PrEP, practitioners should

ensure access to medication through a no-contact method, such

as the mail and counsel users on the importance of adherence to

prevent HIV transmission.

Frequent HIV testing can also help prevent HIV transmission,

but during the COVID-19 pandemic, the rate of HIV testing was

substantially reduced and correlated with poor PrEP adherence

among C hinese MSM PrEP users. Our ﬁnding of less HIV

testing, both HIVST and facility-based HIV-testing, was similar

to results from other studies (

23, 24). An online survey from

the Southern United States also found that one-quarter of MSM

PrEP users encountered obstacles to HIV testing (22). These

diﬃculties in accessing HIV testing could have been caused by

the physical distancing restrictions in response to COVID-19 and

thus restricting access to facility-based HIV testing. However,

continuous use of PrEP pills when infected with HIV can lead

to HIV drug resistance events (

25, 26), and PrEP users must

be tested for HIV at frequent intervals. More web-based health

promotion (e.g., text messaging) and home-based HIV-testing

(e.g., oral self-tests) were practical tools for raising awareness

of sexual health and HIV-testing in the United Kingdom and

Africa (

27, 28). Thus, to ﬂatten the curve of the COVID-19

pandemic, we suggest providing counseling and HIVST through

a no-contact method to PrEP users to ensure timely knowledge

of HIV serostatus and prevent HIV drug resistance.

Along with decreased HIV testing, using condoms

consistently with regular male sexual partners was signiﬁcantly

correlated with increased odds of poor PrEP adherence during

COVID-19. Consistent with our results, low PrEP ad h erence in

East Africa was associated with using condoms with all types of

partners (

29). We additionally found a decrease in self-perceived

risk of HIV acquisition among PrEP users during COVID-19,

which may be from decreased sexual activity or using condoms

consistently with regular male sexual partners.

In addition to consistent condom use with regular male

sexual partners, being married or cohabitating with a woman

was also correlated with poor PrEP adherence during COVID-

19. Due to traditional Chinese culture and attitudes toward

homosexuality, up to 25–35% of Chinese MSM have already been

in a heterosexual marriage and more than 70% of MSM may

eventually form a family with a woman to have children and help

conceal their homosexuality (

30). Similarly, MSM partnering

with a woman for cultural reasons also occurs in Nigeria and

India (31, 32). However, despite this common practice, little

is known about MSM who are married or cohabiting with a

woman and their adherence to PrEP. It is possible that these

partnered MSM feared disclosure of their PrEP use and, thus,

sexual orient ati on, leading to poor PrEP adherence. Discrete yet

eﬀective strategies are needed to improve PrEP adherence among

MSM married or cohabitating with a woman.

Strengths and Limitations

By surveying changes in PrEP adherence and HIV-related

behaviors from before to during the COVID-19 pandemic from a

large population of Chinese MSM who used PrEP in four Chinese

cities, our results were more representative. We were additionally

able to stratify diﬀerences in adherence during the COVID-

19 by PrEP re gimen and found no diﬀerence in ad h erence

between them. By being the ﬁrst study to identify changes in

PrEP adherence and HI V-related behaviors among Chinese MSM

from before to during the COVID-19 pandemic, we were able

to determine obstacles to PrEP adherence due to lockdown that

must be addressed in possible future societal restrictions. A

limitation of this study was that it used self-reported me asures

to deﬁne PrEP adherence. Another limitation was that we asked

sensitive questions about sexual activities and our data may

have been inﬂuenced by social desirability bias. To address this

issue, the survey was conducted online, was self-reported, and

was anonymous.

CONCLUSION

We demonstrated a substantial increase in poor adherence and

CAI among those sexually active, and a decrease in HIV testing

among Chinese MSM who used PrEP from before to during

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Gao et al. PrEP Adherence During the COVID-19 Pandemic

the COVID-19 pandemic. Our results suggest that some MSM

PrEP users have a likely increased risk of HIV acquisition during

COVID-19, and health workers should develop online targeted

interventions, such as adding online follow-up, promoting safer

sex, PrEP adherence, and condom use, providing no-contact

counseling and HIVST to increase knowledge of HIV serostatus,

and prevent drug resistance event to PrEP, and dis cret e strategies

to reach out to MSM married or living with a woman to promote

PrEP adherence.

DATA AVAILABILITY STATEMENT

The datasets presented in this study can be found in online

repositories. The names of the repository/repositories

and accession number(s) can be found in the

article/Supplementary Material.

ETHICS STATEMENT

This study was reviewed and approved by the Medical Science

Research Ethics Committee of the First Aﬃliated Hospital

of China Medic a l University ([2018]2015-139-5) and was

registered with the Chinese Clinical Trial Registry (ChiCTR-

IIN-17013762). The patients/participants provided their written

informed consent to participate in this study.

CROPrEP STUDY TEAM

Members of the CROPrEP study team not included in the

authors’ list include, Xiaoqing He, Yao Li, Fang Zhao, Yijun Duan,

Rui Li, Shangcao Li, Hang Li, Zhili Hu, Rantong Bao, Sitong Cui,

Zhaozhen Liu, Zehao Ye, and Xiaoyun Shi.

AUTHOR CONTRIBUTIONS

YG conceived and designed the study and analyzed the data. LJ,

QH, HoW, XH, YC, HuW, LZ and ZC performed the study.

YG, QH, and SL draw the ﬁgures and tables. YG, QH, ZW, and

SL wrote and revised the manuscript. All authors reviewed and

approved t he ﬁnal manuscript.

FUNDING

This study was supported by the Mega-Projects of National

Science Research for the 13th Five-Year Plan [2017ZX10201101],

the National Natural Science Foundation of China

[81872674], and the National Science and Technology Major

Project [2018ZX10101001-001-003].

ACKNOWLEDGMENTS

We thank the MSM who participated in this study and the staﬀ of

community-based organizations who contributed to its success.

SUPPLEMENTARY MATERIAL

The Supplementary Material for this article can be found

online at: https://www.frontiersin.org/articles/10.3389/fmed.

2022.738541/full#supplementary-material

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Conﬂict of Interest: Gilead sciences inc. donated all the PrEP drugs for the

CROPrEP.

The authors declare that the research was conducted in the absence of any

commercial or ﬁnancial relationships that could be construed as a potential

conﬂict of interest.

Publisher’s Note: All claims expressed in this article are solely those of the authors

and do not necessarily represent those of their aﬃliated organizations, or those of

the publisher, the editors and the reviewers. Any product that may be evaluated in

this article, or claim that may be made by its manufacturer, is not guaranteed or

endorsed by the publisher.

Zhang, Wang, Shang, Xu and CROPrEP Study Team. This is an open-access article

distributed under the terms of the Creative Commons Attribution License (CC BY).

The use, distribution or reproduction in other forums is permitted, provided the

original author(s) and the copyright owner(s) are credited and that the original

publication in this journal is cited, in accordance with accepted academic practice.

No use, distribution or reproduction is permitted which does not comply with these

terms.

Frontiers in Medicine | www.frontiersin.org 10 April 2022 | Volume 9 | Article 738541