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. 2021 Feb 4;16(2):e0245925. doi: 10.1371/journal.pone.0245925

Low use of condom and high STI incidence among men who have sex with men in PrEP programs

Oskar Ayerdi Aguirrebengoa 1,2,*, Mar Vera García 1, Daniel Arias Ramírez 3, Natalia Gil García 3, Teresa Puerta López 1, Petunia Clavo Escribano 1, Juan Ballesteros Martín 1, Clara Lejarraga Cañas 1, Nuria Fernandez Piñeiro 1, Manuel Enrique Fuentes Ferrer 4, Mónica García Lotero 1, Estefanía Hurtado Gallegos 1, Montserrat Raposo Utrilla 1, Vicente Estrada Pérez 2,5, Jorge Del Romero Guerrero 1, Carmen Rodríguez Martín 1,2
Editor: J Gerardo García-Lerma6
PMCID: PMC7861516  PMID: 33539363

Abstract

Objective

Since the recent introduction of preexposure prophylaxis (PrEP), several studies have reported a decrease in the use of condoms and a rise in STIs among users. This rise in risk behavior associated with the advent of PrEP is known as “risk compensation.” The aim of this study is to measure clinical and behavioral changes associated with the introduction of PrEP by analyzing condom use for anal intercourse, number of sexual partners, sexualized drug use and STI incidence.

Methods

We performed a retrospective descriptive study of PrEP users followed every 3months over a 2-year period spanning 2017–2019 in a referral clinic specializing in STI/HIV in Madrid, Spain. One hundred ten men who have sex with men and transgender women underwent regular screening for STIs and hepatitis C virus (HCV) infection. Sociodemographic, clinical, and behavioral data were gathered for all subjects studied.

Results

The risk compensation observed in this study consisted primarily of a lower rate of condom use, while the number of sexual partners and recreational drug consumption remained stable. We observed a very high incidence of STIs in this sample, particularly rectal gonorrhea and chlamydia. The factors shown to be independently associated with the presence of an STI on multivariate analysis were age below 30 years and over 10 sexual partners/month.

Conclusion

The incidence of STI acquisition was higher than expected, indicating a need for strategies to minimize this impact, particularly among younger individuals with a higher number of sexual partners.

Introduction

HIV preexposure prophylaxis (PrEP) is a preventive measure that consists of administering antiretroviral drugs to uninfected individuals who engage in high-risk sexual behavior in order to avoid infection [1]. Several randomized clinical trials comparing tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC) to a placebo have confirmed that daily oral PrEP is safe and effective [2–4]. The efficacy of PrEP in preventing infection is strongly correlated with levels of adherence [1].

The FDA approved the use of TDF/FTC as PrEP in 2012, and the Centers for Disease Control and Prevention (CDC) have recommended the treatment since 2014 [5]. The IPERGAY trial [6], in which on-demand PrEP was prescribed, before and after sexual activity, showed the same efficacy as the PROUD Study [7], in which PrEP was taken daily. In October 2019, the FDA approved a second drug combination, tenofovir alafenamide (TAF)/FTC, for PrEP in men who have sex with men (MSM) and in transgender women (TGW) [8]. The WHO recommends offering PrEP to people at “substantial” risk of infection who belong to population groups in which the incidence of HIV is over 3 infections per 100 person-years (PY) as well as other preventive measures such as condom use, screening for other STIs, and universal access to early diagnosis and antiretroviral treatment (ART) [9]. The most relevant indications for PrEP use in MSM and TGW are condomless sex with multiple partners, presence of a bacterial STI infection in the rectum, and use of drugs to engage in sexual intercourse [10, 11]. It is believed that PrEP is a cost-effective approach in such cases [12].

Since the introduction of this preventive measure, several studies have reported a decrease in the use of condoms and a rise in STIs among users of PrEP [13]. The concept of exhibiting higher sexual risk after adoption of a safety mesure like PrEP is known as “risk compensation” [14].

In November 2019, the Spanish Ministry of Health announced that it would include PrEP as a publicly funded additional measure of protection against HIV infection within the country’s national health system [15]. An increase in PrEP is to be expected in light of this decision, particularly in large cities. Therefore, knowledge of risk compensation among these individuals is essential in order to design specific strategies to limit such compensatory behavior.

The aim of this study is to measure clinical and behavioral changes and risk compensation associated with the advent of PrEP by analyzing condom use for anal intercourse, number of sexual partners, sex-related recreational drug use, and STI incidence.

Methods

Study design and study population

We performed a retrospective descriptive study of PrEP users followed over the 2-year period spanning from 2017 to 2019 in a specialized referral clinic for STI/HIV located in Madrid, Spain. A total of 110 MSM and TGW were selected, all of them complete the duration of the study period, which consisted of outpatient visits every three months. On-demand care, was also provided in cases of clinical or epidemiologic suspicion of STI transmission; all infections diagnosed during these unscheduled visits were addressed in the subsequent screening. The eligibility criteria was taking PrEP, so all participants had sexual risk indications for this preventative measure as proposed by the guidelines [9, 10] and started taking PrEP at the first visit of the study.

Variables

In the first day visit and at the end of 2-year study period, a structured epidemiological questionnaire was completed systematically to gather sociodemographic, clinical, and behavioral data, which included gender (MSM or TGW), age (20–30; 31–40; >40), region of origin (Spain, Latin America, other), adherence to PrEP (calculated the number of days taking PrEP: high: >90%, low: <90%), condom use before and after PrEP (>50%; <50%, or never), number of sexual partners before and after PrEP (1–5, 6–10, 11–50, >50), substance use (alcohol, cannabis, poppers, cocaine, ecstasy, MDMA, GHB, mephedrone, and methamphetamine), sexualized drug use (condomless sex occurring under the effects of drugs and type), “slamming” (injection of recreational drugs), “chemsex” (sexual activity typically with multiple partners under the effects of drugs), use of substances for erectile enhancement, and dating-app use.

During the 2-year study period, all participants had the following tests performed every 3 months: HIV serology (chemiluminescent micro-particle immunoassay (CMIA) with Western blot confirmation) and syphilis testing (RPR, EIA, and TPPA). Swab-based throat and rectal samples were performed systematically by a health-care professional to detect the following: Neisseria gonorrhoeae (NG) by means of Gram staining, Thayer-Martin agar, API NH, and PCR; Chlamydia trachomatis (CT) by PCR; lymphogranuloma venereum (LGV) via genotyping; and NG and CT screening of urine samples by PCR. Serology testing for HCV infection (CMIA) was conducted every 6 months. All users of PrEP included were vaccinated against hepatitis A and B infection at the beginning of the study. No patients with acute or chronic hepatitis participated in the study. Follow-up of STIs detected in on-demand visits was included as part of the following scheduled visit.

Statistical analysis

Qualitative variables are expressed as absolute and relative frequencies. Continuous variables are summarized as mean values and standard deviation (SD) or median and interquartile range (IQR) in case of nonnormal distribution. McNemar’s test for paired data was used to compare qualitative variables (frequency of condom use and number of sexual partners) before and after PrEP.

Every 6 months, we calculated the total number of CT and NG diagnoses in the pharynx, rectum, and urethra as well as all cases diagnosed with acute syphilis and HCV infection. We further calculated the incidence rate per 100 person-years (PY) for CT, NG, syphilis, and HCV. Additionally, we determined the overall infection rates (all infection sites combined/any site) by dividing the number of infections by the total time at risk.

A bivariate analysis was performed using the Poisson regression model to identify baseline characteristics related to the rate of incidence of any STI at 2 years. Factors found to be significant on bivariate analysis (p<0.05) were entered into a multivariate Poisson regression model. For the multivariate analysis, related to drug use, the variable sexualized drug was used and not chemsex, as all drugs were accounted for in the former category. Incidence rate ratios are presented alongside their corresponding 95% confidence interval. For all comparisons, the null hypothesis was rejected for a bilateral test of alpha risk of <0.05. Statistical analysis was performed using the STATA statistical software package, release 15.0.

Ethics statement

Data were obtained from a structured epidemiological questionnaire completed systematically in the course of ordinary clinical practice. All data derived from medical histories were fully anonymized prior to access. The study protocol was approved by the IRB of Hospital Clínico San Carlos, approval Number: 20/214-E. The ethics committee waived the need for informed consent, since the information obtained for the study is collected in routine clinical practice. The study did not include minors.

Results

All participants in this study were MSM with the exception of two TGW. Mean patient age was 34.7 years (SD: 6.72) with a range of 20 to 60 years. Table 1 contains descriptive variables such as age and region of origin as well as the STIs diagnosed during the enrollment visit, that is, before beginning PrEP.

Table 1. Descriptive variables for the population studied and STIs detected on enrollment.

Variables % (N)
Age
20–30 21.8 (24)
31–40 58.2 (64)
>40 20.0 (22)
Region of origin
Spain 76.4 (84)
Latin America 12.7 (14)
Other 10.9 (12)
STIs detected on screening visit
NG
Pharynx 16.4 (18)
Rectum 22.7 (25)
Urethra 0 (0)
CT
Pharynx 2.7 (3)
Rectum 12.7 (14)
Urethra 1.8 (2)
Syphilis 5.4 (6)
Positive hepatitis C virus serology 0.9 (1)
No. of STIs detected on screening visit
0 55.5 (61)
1 28.2 (31)
2 15.5 (17)
3 0.9 (1)
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During the 2-year study period, 98.2% (n = 108) of patients reported high adherence to the drug.

Behavioral changes concerning condom use and number of sexual partners before and after PrEP were analyzed (Table 2). As of the initiation of PrEP, 78.2% (n = 86) of users reported a reduction in condom use for anal intercourse; this decrease was statistically significant (p<0.001). Before PrEP, 85.4% (n = 94) of participants used condoms usually (>50%) in anal intercourse; 10.0% (n = 11) occasionally (<50%) and 4.5% (n = 5) never. After PrEP, the 30.0% (n = 34) of participants used condoms usually, 50.0% (n = 55) occasionally and 20.0% (n = 22) never. Of the individuals studied, 80.9% reported no increase in the number of sexual partners since beginning PrEP, which reflected no statistically significant change. Before PrEP, 32.7% (n = 36) had 1–5 sexual partners per month, 47.3% (n = 52) 6–10, 15.5% (n = 17) 11–50 and 4.5% (n = 5) more than 50 per month. After PrEP, the 31.8% (n = 35) had 1–5 sexual partners per month, 40.0% (n = 44) 6–10, 24.5% (n = 27) 11–50 and 3.6% (n = 4) more than 50 sexual partners per month.

Table 2. Behavioral changes concerning condom use and number of sexual partners before and after PrEP.

Enrollment without PrEP % (N) After two years on PrEP % (N)
Use of condom in anal intercourse
    • Usually (>50%) 85.4 (94) 30.0 (34)
    • Occasionally (<50%) 10.0 (11) 50.0 (55)
    • Never (0%) 4.5 (5) 20.0 (22)
Number of sexual partners per month
    • 1–5 32.7 (36) 31.8 (35)
    • 6–10 47.3 (52) 40.0 (44)
    • 11–50 15.65 (17) 24.5 (27)
    • >50 4.5 (5) 3.6 (4)
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Alcohol and other recreational drugs were consumed by 94.5% (n = 104) of PrEP users, and 89.1% (n = 98) reported no increased consumption of these substances. Excessive alcohol consumption and use of poppers, GHB, and cocaine were the most common drugs used (Fig 1). While under the effects of these substances, 85.4% (n = 89) engaged in condomless sexual intercourse. The drugs most closely associated with condomless sex were methamphetamine, mephedrone, GHB and poppers. Over half, 53.6% (n = 59), took part in chemsex, with a median number of sessions per year of 4 (IQR: 2–12). Two individuals practiced slamming. Erection-enhancing substances were consumed by 67.3% (n = 74).

Fig 1. Frequency of recreational-drug consumption and unprotected sexual intercourse under the influence of these drugs.

Fig 1

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Prior to beginning PrEP, 84.5% (n = 93) used dating apps to search for sexual partners, and 55.5% (n = 61) made reference to this on their profile.

No cases of HIV Infection were diagnosed during the study period. The detection rate for STIs of any type was 197.369 cases per 100 PY (Table 3). This table presents the STIs detected during the 2-year study period as well as the rates of infection by pathogen and by location. The most frequently detected diseases were NG and CT of the rectum. An analysis of the incidence rate at 12, 18, and 24 months revealed no statistically significant changes when compared to the first semester (IRR12m: 1.214; p = 0.148; IRR18m: 1.015; p = 0.917; IRR24m:0.891; p = 0.891).

Table 3. Frequency of STIs among PrEP users during the study period (n = 110).

No. Frequency per 100 PY
NG
Pharynx 61 29.365 (22.46–37.72)
Rectum 174 83.761 (71.77–97.17)
Urethra 23 11.072 (7.19–16.13)
Any location 219 105.423 (91.92–120.35)
CT
Pharynx 13 6.258 (3.33–10.70)
Rectum 129 62.099 (51.85–73.79)
LGV of the rectum 39 18.774 (13.35–25.66)
Urethra 24 11.553 (7.40–17.19)
Any location 155 74.615 (63.33–87.33)
Syphilis
Early latent 19 9.15 (5.51–14.28)
Primary 4 1.93 (0.52–4.93)
Secondary 9 4.33 (1.98–8.22)
Total 32 15.404 (10.54–21.74)
Acute hepatitis C 4 1.93 (0.52–4.93)
Total STIs, any site 410 197.369 (178.72–217.43)
6-month visit 106 191.751 (156.91–231.91)
12-month visit 118 232.788 (192.68–278.78)
18-month visit 100 194.553 (158.30–236.63)
24-month visit 86 170.770 (136.59–210.90)
Number of STIs in any site over 2 years: % (N)
0 5.5 (6)
1 16.4 (18)
2 14.5 (16)
3 12.7 (14)
4 11.8 (13)
5 17.3 (19)
≥6 21.8 (24)
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Table 4 shows the relationship between sociodemographic, clinical and behavioral characteristics and the incidence rate for any STI among the PrEP users studied. On bivariate analysis, the variables associated with a higher rate of incidence were age, number of sexual partners per month of over 10, condomless sex under the influence of drugs (sexualized drug use), participation in chemsex, dating-app use and lower use of condoms for anal sex. A multivariate analysis was performed by including those variables found to be statistically significant in the bivariate analysis (p<0.05). For variables related to drug use, we decided to include the variable sexualized drug use and not chemsex, as all drugs were accounted for in the former category. The factors shown to be independently associated with the presence of an STI on multivariate analysis were age below 30 years and over 10 sexual partners per month.

Table 4. Demographic, clinical, and behavioral factors associated with STI presence among PrEP users (N = 110).

Characteristics Univariate IRR p Multivariate p
Age
Age Continuous 0.970 (0.95–0.99) <0.001 0.978 (0.96–0.99) 0.007
20–30 1
31–40 0.956 (0.76–1.21) 0.700
>40 0.690 (0.50–0.95) 0.022
Region of origin
Spain 1
Other 1.078 (0.86–1.35) 0.506
No. of STIs at enrollment visit, that is, before start of PrEP
0 1
1 0.929 (0.75–1.15) 0.505
2 1.204 (0.89–1.64) 0.233
No. of sexual partners/month before start of PrEP
<10 1
>10 1.311 (1.05–1.64) 0.018 1.257 (1.00–1.58) 0.047
Condom use for anal intercourse before start of PrEP
>50% 1
<50% 1.284 (1.00–1.64) 0.046 1.247 (0.97–1.61) 0.086
Condomless sex under the effects of recreational drugs
No 1
Yes 1.53 (1.15–2.04) 0.003 1.315 (0.98–1.76) 0.072
Condomless sex under the effects of recreational drugs, by drug type*
Alcohol 0.977 (0.78–1.23) 0.847
Cannabis 1.537 (1.14–2.07) 0.005
Poppers 1.184 (0.97–1.44) 0.089
Cocaine 1.321 (1.06–1.64) 0.012
Ecstasy 1.097 (0.78–1.54) 0.782
MDMA 1.095 (0.86–1.40) 0.469
GHB 1.592 (1.30–1.94) <0.001
Mephedrone 1.543 (1.27–1.87) <0.001
Methamphetamine 1.453 (1.17–1.80) 0.001
Chemsex
No 1
Yes 1.363 (1.12–1.66) 0.002
Dating apps
No 1
Yes 1.442 (1.06–1.96) 0.019 1.278 (0.93–1.75) 0.126
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* Each of the drugs are evaluated as yes/no and the reference category is "no".

Discussion

This study evaluated risk compensation among users of PrEP by measuring condom use, number of sexual partners, drug consumption and STI presence. Some existing studies have found no decrease in condom use associated with PrEP [1]. However, among the PrEP users included in the Kaiser cohort, 41% decreased the use of condoms after beginning PrEP [16] as compared with 78% reported here, although we found no independent relationship between condomless sex and an increase in STI incidence.

Although some studies [17] have found an increase in the number of sexual partners, this change did not reach statistical significance for our cohort: 81% had the same number of sexual partners, and a similar rate (74%) was found in a cohort studied in San Francisco [16].

Though chemsex is a common practice among PrEP users, our data reveal no increase in drug use associated with this preventive measure. Although, we found that 15.6% of patients reported missing a dose while under the effects of alcohol or other recreational drugs, this was no significant difference, a finding also reported in the study by O’Halloran et al. [18].

McCormack et al. [6] compared the incidence of STI transmission between users and non-users of PrEP, finding no difference. Nguyen et al. [19] analyzed the rate of STI transmission before and after initiation of PrEP (48 vs. 84 cases per 100 PY) and found a significant increase, partially owing to a greater number of patient visits and STI screening procedures. We observed 197 STI cases per 100 PY, which is substantially above the rate described in most research published to date [13]. The most common infection found in the study by Nguyen et al. [19] was chlamydia (29 cases per 100 PY) followed by rectal gonorrhea and syphilis, both of which had a rate of 15 infections per 100 PY. In our study, the most common infections were rectal gonorrhea (84 cases per 100 PY), rectal chlamydia (62 cases per 100 PY), pharyngeal gonorrhea (29 cases per 100 PY), and rectal LGV (19 cases per 100 PY). These rates are significantly higher than those reported previously, with the exception of syphilis, which was consistent with other reports (15 infections per 100 PY). However, Beymer et al. [20] found that syphilis infection showed the greatest increase after the start of PrEP.

Presence of an STI was most closely related to sexualized drug use followed by a higher number of sexual partners and less frequent condom use. Nonetheless, age under 30 years and over 10 sexual partners per month were the only factors independently associated with the presence of an STI, reaching statistical significance. Young-adult and adolescent MSM and TSW are particularly susceptible to STI/HIV infection [21]. Guidelines could recommend PrEP for adolescents belonging to these population groups, thus making analyses of risk compensation in these individuals particularly beneficial.

Despite the high rate of STI transmission observed, the reduction in condom use was not the only factor involved in the increased rate of infection, as found in other studies [20]. Frequent STI screening in asymptomatic individuals, searching for signs of infection in extragenital sites, many of which show no symptoms, and sample-taking performed by health-care professionals instead of self-testing all facilitate STI detection in cases that would otherwise go unnoticed.

The present study has certain limitations that should be considered. First, it is a retrospective descriptive study conducted in a single specialist center for STI/HIV and includes a small sample size. However, it is the first study of risk compensation in PrEP users carried out in Spain, the number of patients lost to follow-up was very low, and prospective data were recorded meticulously. Other than the results from MSM, the TGW results were not found representative as there were only two participants in the study. In addition to regularly scheduled appointments, several visits were held on demand due to clinical or epidemiologic suspicion of STI transmission. To facilitate data recording and analysis, infections detected during these on-demand visits were addressed in the subsequent scheduled examination, thereby increasing the number of infections per visit. Another limitation of this study is the absence of a control group made up of MSM/TSW who do not use PrEP, in order to compare STI incidence. Future research should include comparisons of cohorts of users and nonusers of PrEP to compare STI incidence and behavioral changes between both groups. This method of preventing HIV infection was included as a publicly funded measure covered under the Spanish national health system, which suggests the potential for additional research in the future.

The risk compensation observed in this study consisted primarily of a lower rate of condom use, while the number of sexual partners and recreational drug consumption remained stable. The incidence of STI acquisition was higher than expected, indicating a need for strategies to minimize this impact, particularly among younger individuals with a higher number of sexual partners.

Data were obtained through a structured epidemiological questionnaire completed systematically filled during the ordinary clinical practice. For this research no specific grant was received from any funding agency in the public, commercial or not-for-profit sectors. All data derived from medical histories were fully anonymized prior to access.

Supporting information

S1 Database

(XLS)

Click here for additional data file. (129.5KB, xls)
S1 File. Variables label.

(PDF)

Click here for additional data file. (181.6KB, pdf)

Acknowledgments

Charles Baker, Luisa María Cabello Ballesteros.

Data Availability

All relevant data are within the manuscript and its Supporting Information files.

Funding Statement

The authors received no specific funding for this work.

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Decision Letter 0

J Gerardo García-Lerma

27 Oct 2020

PONE-D-20-27294

Low use of condom and high STI incidence among men who have sex with men and in transgender women in PrEP programs

PLOS ONE

Dear Dr. Ayerdi Aguirrebengoa,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

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Please note that both reviewers raised important questions that should be addressed in a revised version of the manuscript including concerns about overinterpreting results with n=2 TGW (and inclusion of TGW in the title), patterns of PrEP use (daily/on demand), and some of the statistical interpretations. 

==============================

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Academic Editor

PLOS ONE

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Reviewers' comments:

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Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: No

Reviewer #2: Partly

**********

2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

Reviewer #2: Yes

**********

3. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: Yes

**********

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Reviewer #1: Yes

Reviewer #2: No

**********

5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: This manuscript describes clinical and behavioral characteristics of a cohort of PrEP users in Madrid, Spain. The study provides valuable data on STI incidence, sexual risk and substance use behaviors in this group, and this report is especially timely given the recent expansion of public medical coverage in Spain to include PrEP. The regular collection of STI screening data that is clinically verified is an especially valuable contribution. However, there are many methodological details not presented that make interpreting this paper challenging.

Major issues:

1) The title and abstract describe the cohort as “men who have sex with men and transgender women” but the cohort in fact only includes 2 TGW. While there is a clear need for data on STI incidence and behavioral risk factors among TGS PrEP users, I don’t believe it’s appropriate to group them with the rest of this this cohort with the ability to do more detailed sub-group analyses to determine whether the findings are consistent for this population. I believe it would be more appropriate exclude these two participants from this analysis and define the cohort as exclusively cisgender men who have sex with men.

2) The Methods section is currently lacking in sufficient detail to interpret the results and discussion presented. Most critically, I question whether this can be accurately described as a study of risk compensation among PrEP users because there is no control group of non-PrEP users (as mentioned in the limitations), it is not clear whether all participants were already on PrEP at the commencement of the study, and what time frame was being recalled when asked about condom use and substance use before the study. Because high sexual risk and STI infection are indications for PrEP prescription in the first place, this could simply be reporting STI incidence in a cohort of high-risk MSM. Still could be valuable to report, but not in the risk compensation framing.

3) Some details that should be added to the Methods to help interpret this study are as follows:

a. What was the eligibility criteria for participants?

b. Where all participants on PrEP at baseline?

c. What was assessed at baseline and at follow-up surveys? How many follow-up surveys were conducted? Unclear whether it was one at the end of the study or at each of the 3 month screening visits.

d. Adherence to PrEP was assessed as >90% of what? Doses? Over how many days?

e. Condom use before/after PrEP: Time frame for each? What does % refer to? Partners, encounters?

f. Number of partners before/after PrEP: Time frame for each?

g. Time frame/frequency for substance use behaviors? Also, since substance use as defined was near-universal (94.5%), perhaps the authors could consider a different definition of this variable that would have more variability. I assume alcohol use is highly prevalent in this population (as it is in the general population) and not all use is necessarily problematic. The same can be said for drugs like cannabis.

Minor issues:

1) The third paragraph of the Results section could use some copy-editing. Sentence construction like “…the 85.4% (94) use condom usually” is not grammatically correct. Furthermore, the number in parenthesis can be easily confused as a reference number. Would recommend revising to “…85.4% (n=94) of participants used condoms usually” throughout this paragraph.

2) Some improper hyphenation of terms: “recreational-drug use”,

3) Would recommend revision of a few terms:

a. “Qualitative variables” should be “Dichotomous variables”

b. “Quantitative variables” should be “Continuous variables”

c. “Toxic habits” should be “substance use”

d. “univariate analysis” should be “bivariate analysis” (because the model was testing associations between two variables)

4) Some typos identified:

a. “analized” should be “analyzed”

b. “inercourse" should be “intercourse”

c. A couple of instances of “more tan”, which should be “more than”

5) Reference 15 appears to be missing a title.

Reviewer #2: This paper presents an analysis of clinic patients using PrEP from 2017 thru 2019 that looked at the association of STI incidence and condom use, number of sex partners, chemsex. A significant decrease in condom use for anal intercourse was observed after PrEP initiation, but no significant change in number of partners was observed. There were also no changes in recreational drug use observed. This research is important and current as the research on PrEP use and behavioral disinhibition, or risk compensation, is still new and findings have future implications for PrEP implementation.

The manuscript needs to be reviewed for grammar and syntax, preferably by a native English speaker to improve clarity of your prose. Below are my comments and questions.

Minor comments and questions:

-You establish that alcohol and other recreational drugs use are common and 90% reported no increase in the study period. With that said, a lot of data are presented regarding drug use and condomless sex, however it does not seem related to the research question regarding PrEP use. For conciseness, is it possible to omit these findings since they do not relate to, or contribute to answering, the research question?

-The previous comment applies to findings on erection-enhancing substances and using dating apps.

-It would be nice to have a table or figure representing the data on behavioral changes regarding condom use and number of sexual partners before and after PreP was initiated

-Variables are not operationalized the same way. For example, "unprotected sex…" and "condomless sex…" are referring to the same thing. Variable names should be consistent throughout the text and with tables and figures.

Abstract:

-Was statistical significance for the analysis conducted set to 0.10? Methods section indicates only 0.05 threshold. Unless the 0.10 threshold was used for model building (regression analysis), this value should be consistent for significance testing.

Introduction:

-Was the any previous efforts to alleviate risk compensation behaviors in the specialized referral clinic this study took place?

Methods:

-Statistical analysis - count data is quantitative data, not qualitative, is it not?

Results:

- "We found that 15.6% of patients reported missing a dose while under the effects of alcohol or other recreational drugs."

I suggest moving this to the discussion section; this finding seems extraneous and does not contribute to the research question, although it is interesting.

-"Alcohol and other recreational drugs were consumed by 94.5% PrEP users, of whom 89.9% reported no increased consumption of these substances"

Was alcohol and recreational drug use assessed at the follow-up points to examine change in drug use during PrEP use or was change in drug use assessed only at the end?

-"Condomless sex under the influence of recreational drugs" and "Sexualized drug" are referring to the same thing, however the former is only used in the table. I suggest adding this explanation in the text or making it consistent.

-"…changes were compared to the first semester." Because STI incidence/IRR's are being calculated, were the assessment of STI's at each follow-up point ensured to be new infections if STI was reported at baseline or previous follow-up points.

-"Condom use for anal intercourse before start of PrEP" was not significant in the univariate analysis; the confidence interval includes 1 indicating the null hypothesis of no association is not rejected. Please change results and relevant text accordingly.

-Infrequent condom use does not need to be reported as significant at <0.10 if significance threshold is <0.05 for all other analyses.

Discussion:

- "In spite of evidence indicating that engaging in chemsex increases the risk of STI transmission, in our study we observed no significant difference in adherence, a finding also reported in the study by O’Halloran et al. (18)." What is the no difference in adherence referring to? PrEP? And how is the first part (chemsex) of this statement related to this study finding?

-Are there any current or planned future strategize for the specialized referral clinic this study took place?

Tables and figures:

-Was Age and Condomless sex under the influence by drug type analyzed differently than the other variables? A reference category in the univariate analysis is not specified.

-How was the Age variable coded in the multivariate analysis? Based on the results and 0.978 point estimate patients over 30 years old were the reference group?

-Why was Condomless sex under the influence by drug type and Chemsex not included in the multivariate analysis? Chemsex indicates a significant association (as well as some few drugs in the first variable) in the univariate analysis. The rationale for this is found in the results, but I suggest moving to methods section so that readers are aware of this decisions before reading the results/table. Or possibly, you could not present the data not being used in the final report.

**********

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Reviewer #1: No

Reviewer #2: Yes: Jeffrey S Becasen

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PLoS One. 2021 Feb 4;16(2):e0245925. doi: 10.1371/journal.pone.0245925.r002

Author response to Decision Letter 0

20 Nov 2020

Dear Editor and Reviewers,

We are very grateful for considering this manuscript for publication and for the suggestions you have made. The review is answered below and we remain available for any additional suggestions.

Journal Requirements:

When submitting your revision, we need you to address these additional requirements.

1. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found at

https://journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf and https://journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf

2. Please include additional information regarding the survey or questionnaire used in the study and ensure that you have provided sufficient details that others could replicate the analyses. For instance, if you developed a questionnaire as part of this study and it is not under a copyright more restrictive than CC-BY, please include a copy, in both the original language and English, as Supporting Information.

The information has been obtained through the questions that are systematically asked in the usual clinical practice in the STI/PrEP consultation. The variables collected are detailed in the methodology section. Therefore, a validated questionnaire is not used. In the same way, we have also made other publications previously, for example: Ayerdi Aguirrebengoa O, Vera Garcia M, Rueda Sanchez M, D Elia G, Chavero Méndez B, Alvargonzalez Arrancudiaga M, Bello León S, Puerta López T, Clavo Escribano P, Ballesteros Martín J, Menendez Prieto B, Fuentes ME, García Lotero M, Raposo Utrilla M, Rodríguez Martín C, Del Romero Guerrero J. Risk factors associated with sexually transmitted infections and HIV among adolescents in a reference clinic in Madrid. PLoS One. 2020 Mar 16;15(3):e0228998. doi: 10.1371/journal.pone.0228998. PMID: 32176884; PMCID: PMC7075699.

3. In the Methods, please discuss whether and how the questionnaire was validated and/or pre-tested. If this did not occur, please provide the rationale for not doing so.

Answered in the previous question.

4. Your ethics statement should only appear in the Methods section of your manuscript. If your ethics statement is written in any section besides the Methods, please delete it from any other section.

Updated.

Reviewers' comments:

Reviewer's Responses to Questions

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: This manuscript describes clinical and behavioral characteristics of a cohort of PrEP users in Madrid, Spain. The study provides valuable data on STI incidence, sexual risk and substance use behaviors in this group, and this report is especially timely given the recent expansion of public medical coverage in Spain to include PrEP. The regular collection of STI screening data that is clinically verified is an especially valuable contribution. However, there are many methodological details not presented that make interpreting this paper challenging.

Major issues:

1) The title and abstract describe the cohort as “men who have sex with men and transgender women” but the cohort in fact only includes 2 TGW. While there is a clear need for data on STI incidence and behavioral risk factors among TGS PrEP users, I don’t believe it’s appropriate to group them with the rest of this this cohort with the ability to do more detailed sub-group analyses to determine whether the findings are consistent for this population. I believe it would be more appropriate exclude these two participants from this analysis and define the cohort as exclusively cisgender men who have sex with men.

We agree that the results found in two transgender women can not be representative. However, it is common to find a small percentage of transgender people in PrEP cohorts in developed countries (example reference), so we would prefer not to exclude them from the study. This two participants have presented a very similar behavior so the results of the analysis would be very similar. We fully agree with the reviewer, so we have modified the title, leaving only MSM, and also we have included a section in the discussion commenting on this limitation.

Example Reference: Hoornenborg E, Coyer L, Achterbergh RCA, Matser A, Schim van der Loeff MF, Boyd A, van Duijnhoven YTHP, Bruisten S, Oostvogel P, Davidovich U, Hogewoning A, Prins M, de Vries HJC; Amsterdam PrEP Project team in the HIV Transmission Elimination AMsterdam (H-TEAM) Initiative. Sexual behaviour and incidence of HIV and sexually transmitted infections among men who have sex with men using daily and event-driven pre-exposure prophylaxis in AMPrEP: 2 year results from a demonstration study. Lancet HIV. 2019 Jul;6(7):e447-e455. doi: 10.1016/S2352-3018(19)30136-5. Epub 2019 Jun 6. PMID: 31178284.

Title: Low use of condom and high STI incidence among men who have sex with men in PrEP programs.

However, if the reviewers consider it necessary to exclude the two participants,

we are ready to modify it.

2) The Methods section is currently lacking in sufficient detail to interpret the results and discussion presented. Most critically, I question whether this can be accurately described as a study of risk compensation among PrEP users because there is no control group of non-PrEP users (as mentioned in the limitations), it is not clear whether all participants were already on PrEP at the commencement of the study, and what time frame was being recalled when asked about condom use and substance use before the study. Because high sexual risk and STI infection are indications for PrEP prescription in the first place, this could simply be reporting STI incidence in a cohort of high-risk MSM. Still could be valuable to report, but not in the risk compensation framing.

The participants were not taking PrEP on baseline (recruitment visit) and al lof them started with the medication that day. Since then, the presence of STIs has been evaluated during the two-year follow-up. In addition, the variables: condom use, number of sexual partners and drug use, have been compared between the recruitment visit (without PrEP), and second year follow up visit (after two years on PrEP) to assess risk compensation.

We remain available for any further clarification.

3) Some details that should be added to the Methods to help interpret this study are as follows:

a. What was the eligibility criteria for participants? Updated.

b. Where all participants on PrEP at baseline? Updated.

c. What was assessed at baseline and at follow-up surveys? How many follow-up surveys were conducted? Unclear whether it was one at the end of the study or at each of the 3 month screening visits. Updated, in the firts visit and at the end.

d. Adherence to PrEP was assessed as >90% of what? Doses? Over how many days? The adherence of the PrEP was calculated by dose and days. Adherence above 90% was considered when they took more than 81 tablets every 3 months (90 days). Updated.

e. Condom use before/after PrEP: Time frame for each? What does % refer to? Partners, encounters? Updated. Table 2.

f. Number of partners before/after PrEP: Time frame for each? Updated. Table 2.

g. Time frame/frequency for substance use behaviors? Also, since substance use as defined was near-universal (94.5%), perhaps the authors could consider a different definition of this variable that would have more variability. I assume alcohol use is highly prevalent in this population (as it is in the general population) and not all use is necessarily problematic. The same can be said for drugs like cannabis.

The substance use was analyzed the first day and two years follow up visit. This is the reason, we used “sexualized drugs” variable for the statistical analized.

Minor issues:

1) The third paragraph of the Results section could use some copy-editing. Sentence construction like “…the 85.4% (94) use condom usually” is not grammatically correct. Furthermore, the number in parenthesis can be easily confused as a reference number. Would recommend revising to “…85.4% (n=94) of participants used condoms usually” throughout this paragraph. Updated.

2) Some improper hyphenation of terms: “recreational-drug use”, Updated.

3) Would recommend revision of a few terms:

a. “Qualitative variables” should be “Dichotomous variables”. We prefer to keep the term “qualitative variables” since it includes both: dichotomous (yes/no) and polytomous (condom use…) variables.

b. “Quantitative variables” should be “Continuous variables”. Updated.

c. “Toxic habits” should be “substance use”: Updated

d. “univariate analysis” should be “bivariate analysis” (because the model was testing associations between two variables) Updated.

4) Some typos identified:

a. “analized” should be “analyzed”: Updated

b. “inercourse" should be “intercourse”: Updated

c. A couple of instances of “more tan”, which should be “more than”: Updated

5) Reference 15 appears to be missing a title.Updated, Press reléase.

Reviewer #2: This paper presents an analysis of clinic patients using PrEP from 2017 thru 2019 that looked at the association of STI incidence and condom use, number of sex partners, chemsex. A significant decrease in condom use for anal intercourse was observed after PrEP initiation, but no significant change in number of partners was observed. There were also no changes in recreational drug use observed. This research is important and current as the research on PrEP use and behavioral disinhibition, or risk compensation, is still new and findings have future implications for PrEP implementation.

The manuscript needs to be reviewed for grammar and syntax, preferably by a native English speaker to improve clarity of your prose. Below are my comments and questions.

Minor comments and questions:

-You establish that alcohol and other recreational drugs use are common and 90% reported no increase in the study period. With that said, a lot of data are presented regarding drug use and condomless sex, however it does not seem related to the research question regarding PrEP use. For conciseness, is it possible to omit these findings since they do not relate to, or contribute to answering, the research question?

We agree that the information provided on drugs is not entirely necessary to answer the research question. However, there are not so many studies that analyze drug use among PrEP users (none in Spanish population), so we consider is a relevant information, which if it seems right to you, we would prefer to keep.

-The previous comment applies to findings on erection-enhancing substances and using dating apps. Same answer as the previous question.

-It would be nice to have a table or figure representing the data on behavioral changes regarding condom use and number of sexual partners before and after PreP was initiated

Table 2 included.

-Variables are not operationalized the same way. For example, "unprotected sex…" and "condomless sex…" are referring to the same thing. Variable names should be consistent throughout the text and with tables and figures. Updated.

Abstract:

-Was statistical significance for the analysis conducted set to 0.10? Methods section indicates only 0.05 threshold. Unless the 0.10 threshold was used for model building (regression analysis), this value should be consistent for significance testing.

No, statistical significance value was 0.05. Updated.

Introduction:

-Was the any previous efforts to alleviate risk compensation behaviors in the specialized referral clinic this study took place.

The preventive advice for safe sex is offered to all PrEP users, as indicated in PrEP guidelines.

Methods:

-Statistical analysis - count data is quantitative data, not qualitative, is it not? Statistical analysis updated.

Results:

- "We found that 15.6% of patients reported missing a dose while under the effects of alcohol or other recreational drugs." I suggest moving this to the discussion section; this finding seems extraneous and does not contribute to the research question, although it is interesting.

Updated.

-"Alcohol and other recreational drugs were consumed by 94.5% PrEP users, of whom 89.9% reported no increased consumption of these substances". Was alcohol and recreational drug use assessed at the follow-up points to examine change in drug use during PrEP use or was change in drug use assessed only at the end?

Just at the end.

-"Condomless sex under the influence of recreational drugs" and "Sexualized drug" are referring to the same thing, however the former is only used in the table. I suggest adding this explanation in the text or making it consistent.

Updated. Added in the text.

-"…changes were compared to the first semester." Because STI incidence/IRR's are being calculated, were the assessment of STI's at each follow-up point ensured to be new infections if STI was reported at baseline or previous follow-up points.

On baseline we just have the new STI detected in enrollment visit and we do not have previous STI data. So to comparing STI incidence, we calculate it from first 6 months period. Table 3. All of them were new STI detected during the study.

-"Condom use for anal intercourse before start of PrEP" was not significant in the univariate analysis; the confidence interval includes 1 indicating the null hypothesis of no association is not rejected. Please change results and relevant text accordingly.

To avoid an excessive number of data in table 4, the confidence interval has been rounded to two decimal places. The real confidence interval is (1.004129-1.644366) and therefore does not include 1.

-Infrequent condom use does not need to be reported as significant at <0.10 if significance threshold is <0.05 for all other analyses. Updated.

Discussion:

- "In spite of evidence indicating that engaging in chemsex increases the risk of STI transmission, in our study we observed no significant difference in adherence, a finding also reported in the study by O’Halloran et al. (18)." What is the no difference in adherence referring to? PrEP? And how is the first part (chemsex) of this statement related to this study finding? Error, updated.

-Are there any current or planned future strategize for the specialized referral clinic this study took place? Intensify preventive advice especially among younger PrEP users.

Tables and figures:

-Was Age and Condomless sex under the influence by drug type analyzed differently than the other variables? A reference category in the univariate analysis is not specified.

Updated. Included for age and explained with a note in table 4 for “Condomless sex under the effects of recreational drugs, by drug type”.

-How was the Age variable coded in the multivariate analysis? Based on the results and 0.978 point estimate patients over 30 years old were the reference group?

Updated.

-Why was Condomless sex under the influence by drug type and Chemsex not included in the multivariate analysis? Chemsex indicates a significant association (as well as some few drugs in the first variable) in the univariate analysis. The rationale for this is found in the results, but I suggest moving to methods section so that readers are aware of this decisions before reading the results/table. Or possibly, you could not present the data not being used in the final report.

Updated.

Kind regards,

Oskar Ayerdi

Attachment

Submitted filename: Response to rewiewers.docx

Click here for additional data file. (31.4KB, docx)

Decision Letter 1

J Gerardo García-Lerma

18 Dec 2020

PONE-D-20-27294R1

Low use of condom and high STI incidence among men who have sex with men in PrEP programs

PLOS ONE

Dear Dr. Ayerdi Aguirrebengoa,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

==============================

Although much improved, one of the reviewers still has some minor comments that need to be addressed before we can consider it for publication. 

==============================

Please submit your revised manuscript by Feb 01 2021 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:

  • A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.

  • A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.

  • An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: http://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols

We look forward to receiving your revised manuscript.

Kind regards,

J. Gerardo García-Lerma, Ph.D.

Academic Editor

PLOS ONE

[Note: HTML markup is below. Please do not edit.]

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #1: (No Response)

**********

2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Yes

**********

3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: Yes

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: No

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: No

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: Overall, I find this manuscript to be much improved following revisions. Aside from a few more minor comments, enumerated below, I find this manuscript to be publishable.

Minor comments:

1. Did any participants discontinue PrEP over the course of the follow-up? Or was the sample selected to include only those who stayed on PrEP for the duration of the study period? Either way, please include this information in the Methods section.

2. Table 3 mentions "any distant metastases" under "CT" but this was not included in the Methods section.

3. This manuscript would benefit for one more round of copy-editing for English grammar/style, especially in the Methods and Results sections. Some suggested revisions:

Methods:

- The sentence about eligibility criteria should read: "The eligibility criteria was taking PrEP, so all participants had sexual risk indications for this preventative measure as proposed by the guidelines [reference? More clarity on which guidelines needed here] and started taking PrEP at the first visit of the study."

- "sexualized drug use" instead of just "sexualized drugs"

Results:

- "the 85.4% (n=94) of participants" should just read "85.4% (n=94) of participants". There are a few other instances of this sentence structure in the same paragraph, which should be revised similarly.

- "...consumed by 94.5% of PrEP users" (missing the word of)

- some inconsistency with how % are reported, i.e. sometimes with (n=) and sometimes without. Please revise such that all are consistent and according to journal standards.

- "It is also determined the number of diagnosed STIs per individual." - I don't understand this sentence and it is not clear what result this is reporting.

**********

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Reviewer #1: Yes: Maria Zlotorzynska

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PLoS One. 2021 Feb 4;16(2):e0245925. doi: 10.1371/journal.pone.0245925.r004

Author response to Decision Letter 1

4 Jan 2021

PONE-D-20-27294R1

Low use of condom and high STI incidence among men who have sex with men in PrEP programs

Dear Editor,

We are very grateful for the feedback we have received. All the comments have been taken into consideration and we revised the manuscript accordingly. Responses to such comments point-by-point are sent below. We attached revised manuscript in two versions: one clean revised version and a version with track changes.

We remain at your disposal for any additional clarification.

Kind regards

Minor comments:

1. Did any participants discontinue PrEP over the course of the follow-up? Or was the sample selected to include only those who stayed on PrEP for the duration of the study period? Either way, please include this information in the Methods section. All participants selected stayed on PrEP during study period. Updated in methods section.

2. Table 3 mentions "any distant metastases" under "CT" but this was not included in the Methods section. Mistake updated, we would mean “Any location”.

3. This manuscript would benefit for one more round of copy-editing for English grammar/style, especially in the Methods and Results sections. Some suggested revisions:

Methods:

- The sentence about eligibility criteria should read: "The eligibility criteria was taking PrEP, so all participants had sexual risk indications for this preventative measure as proposed by the guidelines [reference? More clarity on which guidelines needed here] and started taking PrEP at the first visit of the study." Updated.

- "sexualized drug use" instead of just "sexualized drugs" Updated.

Results:

- "the 85.4% (n=94) of participants" should just read "85.4% (n=94) of participants". There are a few other instances of this sentence structure in the same paragraph, which should be revised similarly. Updated.

- "...consumed by 94.5% of PrEP users" (missing the word of) Updated.

- some inconsistency with how % are reported, i.e. sometimes with (n=) and sometimes without. Please revise such that all are consistent and according to journal standards. Updated.

- "It is also determined the number of diagnosed STIs per individual." - I don't understand this sentence and it is not clear what result this is reporting.

We wanted to make references to the number of STIs diagnosed, but this information is clear enough in Table 3, so this sentence has been removed from the results.

Attachment

Submitted filename: Response to Reviewers.docx

Click here for additional data file. (14.9KB, docx)

Decision Letter 2

J Gerardo García-Lerma

11 Jan 2021

Low use of condom and high STI incidence among men who have sex with men in PrEP programs

PONE-D-20-27294R2

Dear Dr. Ayerdi Aguirrebengoa,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

An invoice for payment will follow shortly after the formal acceptance. To ensure an efficient process, please log into Editorial Manager at http://www.editorialmanager.com/pone/, click the 'Update My Information' link at the top of the page, and double check that your user information is up-to-date. If you have any billing related questions, please contact our Author Billing department directly at authorbilling@plos.org.

If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org.

Kind regards,

J. Gerardo García-Lerma, Ph.D.

Academic Editor

PLOS ONE

Additional Editor Comments (optional):

Reviewers' comments:

Acceptance letter

J Gerardo García-Lerma

25 Jan 2021

PONE-D-20-27294R2

Low Use of Condom and High STI Incidence among men who have sex with men In PrEP Programs

Dear Dr. Ayerdi Aguirrebengoa:

I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department.

If your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information please contact onepress@plos.org.

If we can help with anything else, please email us at plosone@plos.org.

Thank you for submitting your work to PLOS ONE and supporting open access.

Kind regards,

PLOS ONE Editorial Office Staff

on behalf of

Dr. J. Gerardo García-Lerma

Academic Editor

PLOS ONE

Associated Data

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