Risk factors associated with sexually transmitted infections and HIV among adolescents in a reference clinic in Madrid.

INTRODUCTION: Adolescents have a higher incidence of sexually transmitted infections (STIs) than persons of older age groups. The WHO emphasises the need to adopt specific and comprehensive prevention programmes aimed at this age group. The objective of this work was to analyse the prevalence of HIV/STIs among adolescents and to identify the sociodemographic, clinical and behavioural markers associated with these infections, in order to promote specific preventive strategies.
METHODOLOGY: Retrospective descriptive study of adolescents, aged 10-19 years, who were attended to for the first consultation between 2016 and 2018 in a reference STI clinic in Madrid. All adolescents were given a structured epidemiological questionnaire where information on sociodemographic, clinical and behavioural characteristics was collected. They were screened for human inmmunodeficiency virus (HIV) and other sexually transmitted infections (STIs). The processing and analysis of the data was done using the STATA 15.0 statistical package.
RESULTS: The frequency of HIV/STIs detected among all adolescents was: gonorrhoea 21.7%, chlamydia 17.1%, syphilis 4.8% and HIV 2.4%. After conducting a multivariate analysis, the independent and statistically significant variables related to the presence of an STI were having first sexual relations at a young age and having a history of STIs. Latin American origin was just below the level of statistical significance (p = 0.066). DISCUSSION/
CONCLUSIONS: Adolescents who begin sexual relations at an early age or those who have a history of HIV/STIs are at higher risk of acquiring STIs. Comprehensive prevention programmes aimed specifically at adolescents should be implemented, especially before the age of 13 years.

Introduction

Adolescence is considered to be the transitional age between childhood and adulthood, from 10 to 19 years [1]. Adolescents are at higher risk of acquiring sexually transmitted infections (STIs) compared to adults and they should be considered a special population in terms of STIs [2]. Many are having sexual relations at increasingly young ages and using alcohol and drugs during sex [3]. They may also face barriers of access to the healthcare system due to lack of awareness and knowledge, incompatibility of their schedule or concerns for their anonymity and confidentiality [4]. This carries an elevated risk of contracting an STI, including the human immunodeficiency virus (HIV). In addition, there are no guidelines relating to the frequency of STI screenings in adolescents.

Worldwide, it is estimated that 357.4 million cases of the four most common curable STIs occur annually: chlamydia (130.9 million cases), gonorrhoea (78.3 million), syphilis (5.6 million) and trichomoniasis (142.6 million) [5,6]. The annual epidemiological report by the European Center for Disease Control (ECDC) reports that, in the year 2016, 403,807 cases of chlamydia infection were reported in Europe, primarily among women aged 15–25 years, 2,043 cases of lymphogranuloma venereum (LGV), especially in men who have sex with men (MSM) older than 25 years, 75,349 episodes of gonorrhoea, which mainly affected MSM aged 20–34 years and women aged 15–19 years, and 29,365 cases of syphilis mostly in MSM older than 25 years[7]. In Spain, the reported STI incidence during 2017 for chlamydia was 24,55 cases per 100.000 people/year, gonorrhoea 18,74 cases per 100.000 people/year and syphilis 10,61 cases per 100.000 people/year, comparable to those described in Europe [8].

In 2017, there were 1.8 million adolescents living with HIV worldwide, which represents 5% of the total prevalence. Of those adolescents, 85% resided in sub-Saharan Africa [9]. In the same year, 250,000 new infections were diagnosed among persons aged 15–19 years, 16% of the total of new cases, the majority being in women of sub-Saharan Africa. In developed countries, new cases among adolescents are mostly diagnosed in men [10]. There were 25,353 new cases in the European Union, the majority in men, 38.2% were in MSM and 11.1% were between 15–24 years old [11]. In Spain, 3,381 new diagnoses of HIV were reported in 2017, 84.6% in men and the majority aged 25–34 years [12].

The World Health Organisation (WHO) highlights the need to adopt a comprehensive package of essential preventive interventions against HIV and other STIs [13]. Therefore, it is necessary to know updated epidemiological data in order to develop specific preventive strategies regarding sexual health[14].

The aim of this study was to analyse the prevalence of STIs/HIV among adolescents and to identify the sociodemographic, clinical and behavioural markers associated with these pathologies, in order to establish specific preventive measures.

Methodology

Study design and analysed population

Retrospective descriptive study in adolescents, aged 10–19 years, who were attended to for the first time between 1st of January of 2016 and 31th of December 2018 in a free and easily accessible STI clinic located in Madrid. During this period, a total of 12,474 persons, with issues related to HIV / STIs, were seen to for the first consultation, aged 1–84 years, of which 3% (374) were adolescents.

Variables

The data were obtained through a structured epidemiological questionnaire where information on sociodemographic, clinical and behavioural characteristics was collected: sex (men or women), age, sexual behavior (heterosexual men, men who have sex with men, women), origin (Spain, Latino America, Europe, Africa, Asia, North America), number of sexual partners year (0–5, 6–50, >50), number of sexual partners lifetime (1–10, 11–25, 26–100, >100), age of first sexual relations (≤13, 14–16, 17–19), type of sexual practices (oral sex, vaginal sex, insertive anal intercourse, receptive anal intercourse), frequency in the systematic use of condom (0%, <50%, ≥50%, 100%) or other preventive measures (post-exposure prophylaxis, pre-exposure prophylaxis), history of STIs, diagnoses of STIs at the time of first consultation (gonorrhea, chlamydia, syphilis, HIV), toxic habits (use of each drug, unprotected sexual practice that occurred under each effect: alcohol, tabacco, cannabis, cocaine, poppers, MDMA/ecstasy, ketamine, metanfetamine/crystal/tina, GHB, mephedrone), use of mobile applications in the search for sexual contacts and others (sex workers, victims of sexual abuse).

The following diagnostic tests were carried out based on the risk of acquiring HIV/STIs. HIV serologies (CMIA and Western Blot confirmation), syphilis (dark field microscopy, RPR, EIA and TPPA) and hepatotropic viruses: hepatitis A virus (HAV), hepatitis B virus (HBV) and hepatitis C virus (HCV) through chemiluminescent microparticle immunoassay (CMIA), Architect (Abbott). Past HBV infection is characterized by the presence of HBcAc and HBsAc with absence of HBsAg. Acute HBV infection is characterized by the presence of HBsAg and immunoglobulin M (IgM). During the initial phase of infection, patients are also seropositive for hepatitis B e antigen (HBeAg). Chronic infection is characterized by the persistence of HBsAg for at least 6 months (with or without concurrent HBeAg). Genital and extra-genital exudates were taken for the detection of: Neisseria gonorrhoeae (NG) by Gram staining, culture in Thayer Martin medium, NH API and PCR, and Chlamydia trachomatis (CT), PCR, and genotyped for lymphogranuloma venereum (LGV).

Statistical analysis

The qualitative variables are shown with their frequency distribution. The quantitative variables are summarised with the average and standard deviation or with the median and interquartile range (IQR) if they do not fit within a normal distribution. The association between qualitative variables and the presence of an STI was carried out using the chi-squared test or Fisher’s exact test, if necessary. A logistic regression model was adjusted with the objective of identifying the factors that are independently associated with the presence of an STI. The factors that were introduced in the logistic regression model were those that presented a p <0.10 in the bivariate analyze and/or clinically relevant. A significance level of 5% was accepted for all variables. The processing and analysis of the data was done using the STATA 15.0 statistical package.

Ethic statement

The data were obtained through a structured epidemiological questionnaire systematically filled during the usual clinical practice. For the study, all data of the medical history were obtain fully anonymized before accessed them and the ethics committee waived the requirement for informed consent. The protocol was approved by the CEIC Hospital Clínico San Carlos, approval Number: 19/469 (S2).

Results

Between January of 2016 and December of 2018, a total of 374 adolescents came to a reference STI clinic in Madrid for the first consultation. In 2016, 119 (31.8%) were attended to; in 2017, 111 (29.7%) and in 2018, 144 (38.5%).

Of the total number, 62.6% (234) were men. According to sexual behavior, 39.8% (149) were MSM, 22.7% (85) heterosexual men (HTX) and 37.4% (140) women (W) who had sex with men. Of these women, 5% (7) also had sex with women. The average age, of the three categories of transmission, was 17.9 years (± 1.1) with a minimum age of 13 years (Table 1).

Table 1

Description of the sociodemographic, clinical and behavioural characteristics of adolescents at attended in the first consultation 2016–2018, according category of exposure (n = 374).

%(n)	MSM 39.8 (149)	HTX 22.7 (85)	Women 37.4 (140)	Global 100 (374)
Origin
Spain	72.5 (108)	50,6 (43)	53.6 (75)	60.4 (226)
Latino America	18.1 (27)	36.5 (31)	31.4 (44)	27.3 (102)
Europe	7.3 (11)	4.8 (4)	10 (14)	7.8 (29)
Africa	2.0 (3)	7.1 (6)	2.9 (4)	3.5 (13)
Asia	0 (0)	1,2 (1)	1,4 (2)	0.8 (3)
North America	0 (0)	0 (0)	0.7 (1)	0.3 (3)
Average age	18.1 (±0.9)	18.0 (±1.1)	17.7 (±1.2)	17.9 (+/-1.1)
Age of first sexual relations
≤13	12.75 (19)	21.18 (18)	8.57 (12)	13.10 (49)
14–16	53.02 (79)	61.18 (52)	68.57 (96)	60.70 (227)
17–19	30.87 (46)	14.12 (12)	17.86 (25)	22.19 (83)
Unknown	3.36 (5)	3.53 (3)	5.00 (7)	4.01 (15)
Number of sexual partners previous year
0–5	49.66 (74)	74.12(63)	85.00 (119)	68.45 (256)
6–50	32.89 (49)	1.18 (1)	0.00 (0)	2.41 (9)
>50	5.37 (8)	14.12 (12)	17.86 (25)	2.41 (9)
Unknown	12.08 (18)	7.06 (6)	3.57 (5)	7.75 (29)
Number of sexual partners/lifetime
1–10	49.4 (74)	56.4 (48)	77.9 (109)	61.7 (231)
11–25	16.1 (24)	20.0 (17)	11.4 (16)	15.2 (57)
26–100	16.1 (24)	10.6 (9)	2.1 (3)	9.6 (36)
>100	6.0 (9)	2.4 (2)	0 (0)	2.9 (11)
Unknown	12,1 (18)	10,6 (9)	8,6 (12)	10,4 (39)
Sex workers
Yes	6.04 (9)	1.18 (1)	3.57 (5)	4.01 (15)
No	85.23 (127)	82.35 (70)	82.86(116)	83.69 (313)
Unknown	8.72 (13)	16.47 (14)	13.57 (19)	12.30 (46)
Victims of sexual abuse
Yes	0.7 (1)	0 (0)	7.9 (11)	3.2 (12)
No	66.4 (99)	70,6 (60)	62.9 (88)	66.0 (247)
Unknown	32.9 (49)	29.4 (25)	29.3 (41)	30.8(115)
History of STIs
Yes	17.5 (29)	11.8 (10)	5.0 (7)	12.3 (46)
No	80.54 (120)	88.24 (75)	95.00(133)	87.70 (328)
Use of apps to find sexual relations
Yes	53.69 (80)	2.35 (2)	2.14 (3)	22.73 (85)
No	14.77(22)	38.82 (33)	39.29 (55)	29.41 (110)
Unknown	31.54 (47)	58.82 (50)	58.57 (82)	47.86 (179)
Diagnosed STIs	47.7 (71)	45.9 (39)	35.7 (50)	42.8 (160)
Gonorrhoea	30.2 (45)	22.4(19)	12.2(17)	21.7 (81)
Chlamydia	10.1 (15)	25.9 (22)	19.3 (27)	17.1 (64)
Syphillis	10.1(15)	1.2 (1)	1.4 (2)	4.8 (18)
HIV	7.4(9)	0	0	2.4 (9)

Fig 1 (Fig 1) illustrates the type of sexual practice and the systematic use of condom according to sexual behavior. As can be seen, there is little use of condom in all sexual practices, particularly notable in anal intercourse among heterosexuals and even lower in oral sex.

Fig 1

Type of sexual practices and use of condom according to sexual behavior (N = 374).

Abbreviations: OS: oral sex; VS: vaginal sex; IAI: insertive anal intercourse and RAI: receptive anal intercourse.

Among the adolescents analysed, 42.8% (IQ95%:37.7–48.0) were diagnosed with an STI at the time of the first consultation, a total of 160. There were 110 adolescents with one STI, 41 with two and nine with three concomitant infections. Table 1 illustrates the frequencies of STIs according to sexual behavior. In adolescents diagnosed with STIs, 50.6% (81) had a gonorrhoea infection. There were 52 cases in MSM, of which 40.4% (21) were rectal, 38.5% (30) pharyngeal and 21.1% (11) urethral. In HTX, 100% were urethral. Among women, there were 21 cases, of which 66.7% (14) were cervical, 23.8% (5) pharyngeal and 9.5% (2) rectal. Of the 160, 40.0% (64) had chlamydia. Among MSM, there were 18 cases, 61.1% (11) were rectal, 27.8% (5) pharyngeal and 11.1% (2) urethral. All chlamydia in the HTX were urethral. In women, there were 28 cases, 85.7% (24) in the cervix and 14.3% (4) in the pharynx. There were no cases of LGV. In addition, 11.3% (18) presented syphilis: 21.1% (15) among MSM with STIs, 2.6% (1) of HTX and 4% (2) of women. Of those diagnosed with syphilis, 27.8% were detected in the primary phase, 38.9% secondary, 27.8% early latent and 5.6% late latent.

Regarding other STIs, 11.3% (18) had condyloma acuminatum, 7.5% (12) Ureaplasma urealyticum urethritis and 7.5% (12) anogenital herpes: 75% (9) genital and 25% (3) perianal. There were two cases of vaginal trichomoniasis (1.3%).

The prevalence of HIV among adolescents was 2.4% [9/372(IQR95%:1.1–4.15)], all MSM aged 18–19 years, with the exception of one who was 15. The prevalence of HIV among MSM was 7.4% (9/149). Two MSM who came to the first consultation with a previous diagnosis of HIV were not included, both in antiretroviral therapy (ART). The temporal development of the prevalence of HIV, among MSM, was: 8% (4/50) in 2016, 8.7% (4/46) in 2017 and 1.9% (1/53) in 2018. In 77.8%, information on the CD4 lymphocyte count was available upon diagnosis. The median CD4 count was 659 cells/ml (IQR: 626.5–669). There were no late diagnoses (<350 cells/ml CD4). Three of the nine diagnosed had no previous serologies. Of all MSM, two received postexposure prophylaxis (PEP) and one pre-exposure prophylaxis (PrEP) throughout their lives.

Regarding hepatitis B, 1.3% (4) had serological markers of a past hepatitis infection, 0.3% (1) acute and 0.3% (1) chronic; 16.7% (44) past hepatitis A and one hepatitis C cured. According to vaccination, 90.4% (281) vaccinated for HBV and 3.0% (8) for HAV.

Of all adolescents with STIs, 28.1% (45) were asymptomatic. Of genital gonorrhoea and chlamydia infections, 23.1% were asymptomatic as well as 55.7% of the extra-genital cases.

Table 2 analyses the frequency of drug use and unprotected sexual practices (USPs) that occurred under its effect. The 41.7% of MSM use psychotropic drugs, the 46.7% of HTX and 21.4% of women. Alcohol was the most frequent substance under which most USPs occurred. However, other substances such as methamphetamine, mephedrone or poppers, were associated with less condom use.

Table 2

Analysis of the frequency of drug use and unprotected sexual practices (USPs) that occurred under its effect.

% (n)	Use %(n/315)	USPs under its effect %(n/Use)
Alcohol, tabacco and other drugs	62.2 (196)	27.55 (54)
• Alcohol	42.5 (134)	35.07 (47)
• Tabacco	34.0 (107)
• Psychotropic drugs	34.9 (110)	22.8 (23)
Cannabis	25.71 (81)	17.28 (14)
Cocaine	3.81 (12)	58.33 (7)
Poppers	3.17 (10)	90.00 (9)
MDMA/Ecstasy	3.17 (10)	50.00 (5)
Ketamine	0.95 (3)	66.67 (2)
Metanfetamine/Crystal/Tina	0.63 (2)	100.00 (2)
GHB	0.63 (2)	50.00 (1)
Mephedrone	0.32 (1)	100.0 (1)

Table 3 shows the factors studied with the presence of STIs during the first consultation in the clinic among all adolescents. A multivariate analysis was conducted with the variables that presented a p<0.10 in the bivariate analysis (sexual behavior, origin, age of first sexual, number of sexual partners in the previous year, history of STIs and USPs under the effect of drugs). The variable, use of apps to find sexual relations, had not been included taking into account given the high number of unknown data. The independent and statistically significant variables related to the presence of an STI were: having first sexual relations at a young age and a history of STIs. Latin American origin was just below the level of statistical significance (p = 0.066).

Table 3

Analysis of the factors associated with the presence of STIs among adolescents during the first consultation (n = 374).

	STI YES (n = 160) %(n)	STI NO (n = 214) %(n)	p Bivariate	OR (IC95%) Bivariate	OR (IC95%) Multivariate	p Multivariate
Sexual behavior			0.099
MSM	47.7 (71)	52.3 (78)		1.64 (1.02–2.63)	1.39 (0.77–2.50)	0.269
HTX	45.9 (39)	54.1 (46)		1.53 (0.88–2.64)	1.17 (0.63–2.16)	0.605
W	35.7 (50)	64.3 (90)		1	1
Origin			0.067
Spain	38.5 (87)	61.5 (139)		1	1
Latin America	53.9 (55)	46.1 (47)		1.87 (1.16–3.00)	1.68 (0.97–2.93)	0.066
Europe	37.9 (11)	62.1 (18)		0.98 (0.44–2.17)	1.18 (0.47–2.98)	0.723
Others	41.2 (7)	58.8 (10)		1.12 (0.41–3.05)	1.13 (0.35–3.65)	0.832
Age of first sexual relations			<0.001
≤13	69.4 (34)	30.6 (15)		6.28 (2.88–13.69)	5.39 (2.23–13.02)	0.000
14–16	44.1 (100)	55.9 (127)		2.18 (1.26–3.86)	2.76 (1.47–5.18)	0.002
17–19	26.5 (22)	73.5 (22)		1	1
Number of sexual partners in the previous year			0.011
0–5	40.2 (103)	59.8 (153)		1	1
6–50	40 (32)	60 (48)		0.99 (0.59–1.65)	0.76 (0.42–1.37)	0.361
>50	88.9 (8)	11.1 (1)		11.88 (1.47–96.44)	5.85 (0.62–55.60)	0.124
History of STIs			0.001
Yes	65.2 (30)	34.8 (16)		2.86 (1.50–5.45)	1.39 (1.09–1.79)	0.008
No	39.6 (130)	60.4 (198)		1	1
USPs under the effect of drugs			0.305
Yes	52.2 (12)	47.8 (11)		1.56 (0.66–3.66)
No	41.2 (112)	58.8 (160)		1
Use of apps to find sexual relations			0.031
Yes	40.0 (34)	60.0 (51)		1.95 (1.06–3.59)
No	25.5 (28)	74.5 (82)		1

Discussion

In this study a high frequency of STIs has been observed in all sexual categories of transmission, mainly gonorrhoea and chlamydia. In the US, more than half of STIs occur among persons aged 15–24, despite the fact that they only represent 25% of the sexually active population [13]. The Centers for Disease Control and Prevention (CDC) reports chlamydia as the most prevalent bacterial STI in the US, its highest rate being in young women, also reflected in the female adolescents in our study. In our study, gonorrhoea and syphilis were more frequent among MSM just as in other studies [8]. The incidence of LGV in adolescents is low in other European regions, however in this study there was no cases [2].

The prevalence of HIV among the adolescents studied is lower than that found in some regions of the world. In sub-Saharan Africa it is 16%, with two out of three of cases being in women [15]. However, the figures resemble those found in developed countries and match with those of the most frequent sexual behavior [11]. All HIV-positive cases were MSM. The decline in new diagnoses between 2017 and 2018 is notable. These preliminary data suggest the decreasing trend in the incidence of HIV, as is the case in developed countries where combination HIV prevention programmes have been implemented [16]. In Spain, younger MSM could gain a greater preventive benefit by implementing new additional strategies such as pre-exposure prophylaxis (PrEP) [17].

In this study the use of condom is low in all sexual practices, especially in oral sex. Some individuals, particularly youth, may engage in oral sex instead of vaginal sex because they believe it to be less risky for STIs transmission. The risk for oral sex is lower compared with vaginal or anal sex, however unprotected oral sex is also associated with the acquisition and transmission of STDs infection [18].

Despite adolescents being a target population, there are no specific recommendations regarding the frequency of STI/HIV screening [19]. The high frequency of asymptomatic STIs makes screening for STIs solely based on clinical symptoms relatively ineffective [20]. As well as this, adolescents may be reluctant to report their sexual practices or may not consider their symptoms important through lack of awareness [21,22]. For these reasons, an STI/HIV screening should be considered, not only on clinical suspicion, but also through the identification of sociodemographic and behavioural markers.

The use of alcohol and drugs with sex reduces the perception of risk and tends toward unprotected sexual practices [23]. Yet, in our study, the use of these substances and the number of sexual partners in the previous year have not shown independent or statistically significant association with the presence of STIs. All cases of HIV were detected among MSM. However, the sexual behavior has not been associated as a risk indicator for the presence of other STIs, as is the case among adults [16]. By contrast, Latin American origin was close to statistical significance as an independent factor associated with the presence of STIs, possibly relating to poor healthcare resources and insufficient sex education [24].

Approximately 11% of the world’s adolescents start having sexual relations before the age of 15 [25]. In our study, 9%-22% had their first sexual relations before the age of 14, according to sexual behavior. Beginning sexual relations at a young age, especially at 13 or younger, and the presence of a history of STIs are factors which have been independently associated with the presence of HIV/STIs, as has also been reported in other publications [26]. These indicators, found in our study, can help establish specific prevention programs in this age group. To optimise this preventive effort, it should be aimed at persons in the early phase of adolescence, between 10 to 13 years, which is considered a critical period for primary intervention, as from this age onwards the preventive messages offered have shown less impact [27,28].

In our study, the use of mobile applications in the search for sexual contacts has not been a factor associated with the presence of STIs [29]. However, the use of social networks for the screening and control of STIs has proven to be a cost-effective measure among adults in regions with a high prevalence of STIs. In addition to school or family education, technological advances may be ideal additional resources that incorporate preventive measures such as contact tracing or post-treatment control with a truly beneficial impact. [30,31]

The limitations of this work are that it is a descriptive and retrospective study carried out in a single STI/HIV center in Spain and that, despite the heterogeneity of the adolescents analysed, it may not be possible to extrapolate its results to the general population. On the other hand, there are very few cohorts of adolescents in which studies of this type have been conducted.

Adolescents who have a history of STIs or who begin sexual relations at an early age are at higher risk of acquiring STI/HIV. Comprehensive prevention programmes aimed specifically at adolescents should be implemented, especially before the age of 13 years.

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7 Jan 2020

PONE-D-19-33032

ADOLESCENTS, STIs AND HIV IN MADRID

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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

Reviewer #2: Yes

**********

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: No

Reviewer #2: Yes

**********

4. 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

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: General comments

The study presented by Ayerdi Oskar et al., is an interesting study whose objective has been to analyze the prevalence of STI / HIV among adolescents and identify the sociodemographic, clinical and behavioral markers associated with these pathologies, in order to establish specific preventive measures . It is a novel study that provides information on this highly vulnerable population group and also assesses the importance of early detection of these STIs not only based on symptomatic parameters but also on sociodemographic and behavioral variables, as they are many of these asymptomatic infections. . In general, the format of the tables is very improved, being necessary to correct arithmetic errors, and to unify criteria when presenting the results of the same, the limitation of the study regarding being a descriptive study with the participation of a single center and the difficulty of extrapolating the results to the entire population is perfectly indicated in the text.

Specific comments

1. Title: The title is very short and not very informative, not reflecting the objective of the article properly, on the other hand, precisely because it is very short it makes no sense to put acronyms on it and not put the words with its full name, it is not correct to put acronyms on the titles of scientific works, unless strictly necessary, this being not the case.

2. Authors: Powerfully draws attention to the high number of authors for an article whose methodology is simple, it would be convenient to justify the reason for this decision.

3. Summary: In the methodology section the acronym "HIV / STIs: HIV, HAV, HBV, HCV", being the first time they are cited in the text must go with the full word and in brackets its corresponding acronym.

4. Introduction: As in the previous case, for the acronym “ECDC” the first time the complete word with its acronyms should be named in parentheses.

5. Methodology:

- The ethical aspects are not described, was the study reviewed and approved by an Ethics Committee?

- In the regression they propose, they do not explain what procedures they followed to analyze the regression adjustment criteria performed.

- When “structured epidemiological questionnaire” is mentioned in the variables, it is not mentioned if said questionnaire was prepared exclusively for the sample of adolescent population or if it is the questionnaire that is systematically filled out for the entire population that attends the STI center of Madrid .

- When talking about “transmission category” it would be more correct to talk about “sexual behavior”. Apply this throughout the entire text.

6. Results:

- Table 1. “Description of the sociodemographic, clinical and behavioral characteristics of adolescents at atended in the first consultation 2016-2018, according to category of exposure”:

• Review the numerical results of the “Global” column as errors are detected.

• Regarding the variables “Post-exposure prophylaxis” (PEP) and “Pre-exposure prophylaxis” (PrEP) the numerical figures that appear in the MSM exposure category are reversed, instead of% (n) they are n (% ).

• “Oral contraceptives”, I do not think it is necessary to include this in the table since the use of oral contraceptives protects from an unwanted pregnancy but not from the acquisition and / or transmission of its which is what the article is about.

Figure 1. “Type of sexual practices and use of condom according to transmission category”:

• "As can be seen, there is little use of condom in all sexual practices, particularly notable in anal intercourse among heterosexuals", it should also be added that it is even lower under condom use in the case of oral sex (5.5 %, 2.9% and 4.4%).

• It is striking that there is VS in MSM (vaginal sex in men who have sex with men), it would be interesting to clarify whether in the category MSM men are also considered, although sometimes they have sex with men other times they have it with women.

- Table 2. “Analysis of the frequency of drug use and unprotected sexual practices (USPs) that occurred under its effect”:

• It is necessary to improve the format of the table, it is not understood why you put "psycotropics drugs" and then again when you talk about type of drugs you put "psycotropics drugs" again, in both cases the assigned numerical values do not match.

• You have to unify criteria in the tables: in table 1 the legend is at the foot of the table and in table 2 the legend is in the headboard and in table 3 the legend is again at the foot of the table.

- Table 3. “Analysis of the factors associated with the presence of STIs among adolescents during the first consultation (n = 374)”:

• “A multivariate analysis was conducted with the variables that presented a p <0.10 in the univariate analysis ……, it is a mistake and it is not univariate but bivariate, it is the bivariate analysis that leads to a multivariate analysis to confirm the statistical significance of the variables eliminating confusion factors.

• Where are the results of that bivariate analysis?

• Again, criteria must be unified: the p values of the multivariate analysis when they do not give significance or are all put in a middle dash or left blank.

7. Discussion:

- Acronym “CDC”: idem as explained above: “Centers for Disease Control and Prevention” (CDC).

-”Likewise, the low incidence of LGV in adolescents matches with other European regions”, does not coincide with the results section when it says: “there were no cases of LGV”, so there was no low incidence directly there was not.

- Regarding the scarce use of condoms in oral sex, it is necessary to comment in this section that oral sex is also a form of its transmission, and this statement must be referenced.

8. Bibliography: The regulations of the journal regarding how to write bibliographic references in Vancouver style must be thoroughly reviewed and criteria must be unified, in general: in the online documents there are many links to the internet and the date of access, as with the "doi", capital letters when they are not necessary, links that are wrong or that give you an error "page not found".

Reviewer #2: This is a very interesting study that provides data on STIs in adolescents and their potential risk behaviours, a topic on which there is little literature to date. However, there are some specific areas for improvement which I suggest to review.

Abstract - Methods: As noted in the manuscript, other diagnostic tests are carried out in addition to those mentioned. Since this is the abstract, I suggest not to specify any of them.

Introduction:

- Line number 4: add a reference.

- Second paragraph, first line: adding “curable” after “four most common” would be more accurate.

- It would be interesting to provide the data on the incidence of STIs in Spain (as in the previous lines total data are reported, not incidences).

Methods:

- Study design...: Specify exact dates. Describe the potential users of the clinic (age range).

- I suggest explaining the diagnostic tests in a separate section. I think that diagnostic tests require a broader explanation, (techniques and protocol followed to request them). The authors should mention all the diagnostic tests included. The technique used for CD4 should also be recorded. Definition of past/acute/chronic hepatitis B should be included.

Results:

- If data are available, it would be interesting to know the reason for consultation.

- Last line of second paragraph: The maximum age can be ignored since it is an inclusion criterion.

- Table 1: Some figures do not seem to be correct (the sum of the parts in some columns is greater than the total, for example). On the other hand, I think it would be useful to add a row with the number of patients for whom the data is unknown.

- I deduce that some of the patients have more than one STI, I suggest specifying it in the text.

- Table 2: “Psychotropic drugs” appears twice.

Discussion:

- Last sentence of first paragraph: The authors should not comment on the “low” incidence of LGV as it is zero.

- I suggest placing third paragraph at the end.

Figure1: MSM instead of HSH.

Finally, I recommend language and writing editing. The authors should review the use of abbreviations and the writing of the species names according to the journal guidelines. In the text, reference numbers should be cited in square brackets. Moreover, the authors should review the format of the references.

**********

6. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

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Reviewer #1: No

Reviewer #2: No

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24 Jan 2020

Dear Editor and Reviewers,

Thank you for considering our manuscript to PLOS ONE. After careful review, we have submited the 'Manuscript', 'Revised Manuscript with Track Changes', 'Response to Reviewers' and additional supporting information.

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

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Updated.

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. If you developed and/or translated 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.

A special questionnaire was not used to the study. The data were obtained through a structured epidemiological questionnaire systematically filled during the usual clinical practice (structured medical history). Tha variables have been included in the manuscript. Information on sociodemographic, clinical and behavioural characteristics was collected: sex (men or women), age, sexual behavior (heterosexual men, men who have sex with men, women), origin (Spain, Latino America, Europe, Africa, Asia, North America), number of sexual partners year (0-5, 6-50, >50), number of sexual partners lifetime (1-10, 11-25, 26-100, >100), age of first sexual relations (≤13, 14-16, 17-19), type of sexual practices (oral sex, vaginal sex, insertive anal intercourse, receptive anal intercourse), frequency in the systematic use of condom (0%, <50%, ≥50%, 100%) or other preventive measures (post-exposure prophylaxis, pre-exposure prophylaxis), history of STIs, diagnoses of STIs at the time of first consultation (gonorrhea, chlamydia, syphilis, HIV), toxic habits (use of each drug, unprotected sexual practice that occurred under each effect: alcohol, tabacco, cannabis, cocaine, poppers, MDMA/ecstasy, ketamine, metanfetamine/crystal/tina, GHB, mephedrone), use of mobile applications in the search for sexual contacts and others (sex workers, victims of sexual abuse).

3. In the ethics statement in the manuscript and in the online submission form, please provide additional information about the patient records/samples used in your retrospective study.

Specifically, please ensure that you have discussed whether all data/samples were fully anonymized before you accessed them and/or whether the IRB or ethics committee waived the requirement for informed consent.

If patients' parents/guardians provided informed written consent to have data/samples from their medical records used in research, please include this information

The data were obtained through a structured epidemiological questionnaire systematically filled during the usual clinical practice. For the study, all data of the medical history were obtain fully anonymized before accessed them and the ethics committee waived the requirement for informed consent. The protocol was approved by the CEIC Hospital Clínico San Carlos, approval Number: 19/469 (S2).

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"Ethic Committee approval number: 19/469-E"

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Reviewers' comments:

Reviewer's Responses to Questions

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: Yes

Reviewer #2: Yes

________________________________________

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: No

Reviewer #2: Yes

We will include the database in the supporting information section so that it is fully available.________________________________________

4. 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

Reviewer #2: No

The manuscript has been reviewed by a native translator from the United Kingdom.________________________________________

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: General comments

The study presented by Ayerdi Oskar et al., is an interesting study whose objective has been to analyze the prevalence of STI / HIV among adolescents and identify the sociodemographic, clinical and behavioral markers associated with these pathologies, in order to establish specific preventive measures . It is a novel study that provides information on this highly vulnerable population group and also assesses the importance of early detection of these STIs not only based on symptomatic parameters but also on sociodemographic and behavioral variables, as they are many of these asymptomatic infections. . In general, the format of the tables is very improved, being necessary to correct arithmetic errors, and to unify criteria when presenting the results of the same, the limitation of the study regarding being a descriptive study with the participation of a single center and the difficulty of extrapolating the results to the entire population is perfectly indicated in the text.

Specific comments

1. Title: The title is very short and not very informative, not reflecting the objective of the article properly, on the other hand, precisely because it is very short it makes no sense to put acronyms on it and not put the words with its full name, it is not correct to put acronyms on the titles of scientific works, unless strictly necessary, this being not the case.

The new title proposed: Frequency of sexually transmitted infections/HIV and the associated risk factors among adolescents in a refence STI Clinic of Madrid

2. Authors: Powerfully draws attention to the high number of authors for an article whose methodology is simple, it would be convenient to justify the reason for this decision.

The main reason could be that the study participants have been attended by several doctors of the center. The contribution of each co-author is described and also included as supporting information.

Contributorship statemet:

Oskar Ayerdi Aguirrebengoa: Substantial contributions to the conception or design of the work; or the acquisition, analysis, or interpretation of data for the work. Drafting the work or revising it critically for important intellectual content; AND Final approval of the version to be published; AND Agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Mar Vera García: Substantial contributions to the acquisition of data for the work. Revising it critically for important intellectual content. Final approval of the version to be published. Agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Montserrat Rueda Sanchez: Substantial contributions to the acquisition of data for the work. Drafting the work and revising it critically for important intellectual content. Final approval of the version to be published. Agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Giovanna D´Elia: Substantial contributions to the acquisition of data for the work. Drafting the work and revising it critically for important intellectual content. Final approval of the version to be published. Agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Belén Chavero Méndez: Substantial contributions to the acquisition of data for the work. Drafting the work and revising it critically for important intellectual content. Final approval of the version to be published. Agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

María Alvargonzalez Arrancudiaga: Substantial contributions to the acquisition of data for the work. Drafting the work and revising it critically for important intellectual content. Final approval of the version to be published. Agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Sandra Bello León: Substantial Substantial contributions to the acquisition of data for the work. Drafting the work and revising it critically for important intellectual content. Final approval of the version to be published. Agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Teresa Puerta López: Substantial contributions to the acquisition of data for the work. Revising it critically for important intellectual content. Final approval of the version to be published. Agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Petunia Clavo Escribano: Substantial contributions to the acquisition of data for the work. Revising it critically for important intellectual content. Final approval of the version to be published. Agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Juan Ballesteros Martín: Substantial contributions to the acquisition of data for the work. Revising it critically for important intellectual content. Final approval of the version to be published. Agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Blanca Menendez Prieto: Substantial contributions to the acquisition of data for the work. Revising it critically for important intellectual content. Final approval of the version to be published. Agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Manuel Enrique Fuentes Ferrer: Substantial contributions to design of the work; analysis and interpretation of data for the work; revising it critically for important intellectual content. Final approval of the version to be published. Agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Mónica García Lotero: Substantial contributions to the acquisition of data for the work. Revising it critically for important intellectual content. Final approval of the version to be published. Agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Montserrat Raposo Utrilla: Substantial contributions to the conception or design of the work; and the analysis and interpretation of data for the work. Revising it critically for important intellectual content. Final approval of the version to be published. Agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Carmen Rodríguez Martín: Substantial contributions to the conception or design of the work. Drafting the work or revising it critically for important intellectual content. Final approval of the version to be published. Agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Jorge Del Romero Guerrero: Substantial contributions to the conception or design of the work and the acquisition of data for the work. Drafting the work or revising it critically for important intellectual content. Final approval of the version to be published. Agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

3. Summary: In the methodology section the acronym "HIV / STIs: HIV, HAV, HBV, HCV", being the first time they are cited in the text must go with the full word and in brackets its corresponding acronym. Updated.

4. Introduction: As in the previous case, for the acronym “ECDC” the first time the complete word with its acronyms should be named in parentheses. Updated.

5. Methodology:

- The ethical aspects are not described, was the study reviewed and approved by an Ethics Committee? All data were obtain fully anonymized before accessed them and the ethics committee waived the requirement for informed consent. The protocol was approved by the CEIC Hospital Clínico San Carlos, approval Number: 19/469 (S2).

- In the regression they propose, they do not explain what procedures they followed to analyze the regression adjustment criteria performed.

The factors that were introduced in the logistic regression model were those that presented a p <0.10 (which was explained in results) in the bivariate analyze and/or clinically relevant.

This sentence is added in the paragraph of statistical analysis.

- When “structured epidemiological questionnaire” is mentioned in the variables, it is not mentioned if said questionnaire was prepared exclusively for the sample of adolescent population or if it is the questionnaire that is systematically filled out for the entire population that attends the STI center of Madrid.The information obtained through the questionnaire or complete sexual history is the one is used in the center to create the medical history methodically. A specific questionnaire has not been created for this study. In the methodology all the variables that have been taken into account have been included

- When talking about “transmission category” it would be more correct to talk about “sexual behavior”. Apply this throughout the entire text.Updated.

6. Results:

- Table 1. “Description of the sociodemographic, clinical and behavioral characteristics of adolescents at atended in the first consultation 2016-2018, according to category of exposure”:

• Review the numerical results of the “Global” column as errors are detected. The unknown value has been described and all the table 1. data has been updated.

• Regarding the variables “Post-exposure prophylaxis” (PEP) and “Pre-exposure prophylaxis” (PrEP) the numerical figures that appear in the MSM exposure category are reversed, instead of% (n) they are n (% ). Regarding PEP and PrEP, it is decided to give these information in the text.

• “Oral contraceptives”, I do not think it is necessary to include this in the table since the use of oral contraceptives protects from an unwanted pregnancy but not from the acquisition and / or transmission of its which is what the article is about. Removed.

Figure 1. “Type of sexual practices and use of condom according to transmission category”:

• "As can be seen, there is little use of condom in all sexual practices, particularly notable in anal intercourse among heterosexuals", it should also be added that it is even lower under condom use in the case of oral sex (5.5 %, 2.9% and 4.4%). Updated.

• It is striking that there is VS in MSM (vaginal sex in men who have sex with men), it would be interesting to clarify whether in the category MSM men are also considered, although sometimes they have sex with men other times they have it with women. Updated.

- Table 2. “Analysis of the frequency of drug use and unprotected sexual practices (USPs) that occurred under its effect”:

• It is necessary to improve the format of the table, it is not understood why you put "psycotropics drugs" and then again when you talk about type of drugs you put "psycotropics drugs" again, in both cases the assigned numerical values do not match. Updated.

To facilitate compression, part of the information has been passes to the text.

• You have to unify criteria in the tables: in table 1 the legend is at the foot of the table and in table 2 the legend is in the headboard and in table 3 the legend is again at the foot of the table. Unified.

- Table 3. “Analysis of the factors associated with the presence of STIs among adolescents during the first consultation (n = 374)”:

• “A multivariate analysis was conducted with the variables that presented a p <0.10 in the univariate analysis ……, it is a mistake and it is not univariate but bivariate, it is the bivariate analysis that leads to a multivariate analysis to confirm the statistical significance of the variables eliminating confusion factors. The multivariate analysis was conducted with the variables that presented a p<0.10 in the biivariate analysis. This variables have been included in the text: sexual behavior, origin, age of first sexual, number of sexual partners in the previous year, history of STIs and USPs under the effect of drugs.The variable, use of apps to find sexual relations, had not been included taking into account given the high number of unknown data.

• Where are the results of that bivariate analysis? In the 4th and 5th columns have been included “bivariate”.

• Again, criteria must be unified: the p values of the multivariate analysis when they do not give significance or are all put in a middle dash or left blank. Unified.

7. Discussion:

- Acronym “CDC”: idem as explained above: “Centers for Disease Control and Prevention” (CDC). Updated.

-”Likewise, the low incidence of LGV in adolescents matches with other European regions”, does not coincide with the results section when it says: “there were no cases of LGV”, so there was no low incidence directly there was not. Updated.

- Regarding the scarce use of condoms in oral sex, it is necessary to comment in this section that oral sex is also a form of its transmission, and this statement must be referenced. Updated.

8. Bibliography: The regulations of the journal regarding how to write bibliographic references in Vancouver style must be thoroughly reviewed and criteria must be unified, in general: in the online documents there are many links to the internet and the date of access, as with the "doi", capital letters when they are not necessary, links that are wrong or that give you an error "page not found". All the bibliography has been revised and updated.

Reviewer #2: This is a very interesting study that provides data on STIs in adolescents and their potential risk behaviours, a topic on which there is little literature to date. However, there are some specific areas for improvement which I suggest to review.

Abstract - Methods: As noted in the manuscript, other diagnostic tests are carried out in addition to those mentioned. Since this is the abstract, I suggest not to specify any of them. Updated.

Introduction:

- Line number 4: add a reference. Updated.

- Second paragraph, first line: adding “curable” after “four most common” would be more accurate. Updated.

- It would be interesting to provide the data on the incidence of STIs in Spain (as in the previous lines total data are reported, not incidences). Updated.

Methods:

- Study design...: Specify exact dates. Describe the potential users of the clinic (age range). Updated.

- I suggest explaining the diagnostic tests in a separate section. I think that diagnostic tests require a broader explanation, (techniques and protocol followed to request them). The authors should mention all the diagnostic tests included. The technique used for CD4 should also be recorded. Definition of past/acute/chronic hepatitis B should be included.The determination of lymphocyte subpopulations T CD4 + / T CD8 + was performed by flow cytometry in Aquios CL (Beckman Coulter). We have not included this information in the methodology since this study has not analyzed the immunological situation of the patients HIV diagnosed. Rest of the suggestions have been updated.

Results:

- If data are available, it would be interesting to know the reason for consultation. All of them went to the center for issues related to HIV / STIs, included in the manuscript.

- Last line of second paragraph: The maximum age can be ignored since it is an inclusion criterion. Updated.

- Table 1: Some figures do not seem to be correct (the sum of the parts in some columns is greater than the total, for example). On the other hand, I think it would be useful to add a row with the number of patients for whom the data is unknown. The unknown value has been described and all the table 1. data has been updated.

- I deduce that some of the patients have more than one STI, I suggest specifying it in the text. Included in the text.

- Table 2: “Psychotropic drugs” appears twice. Updated.

Discussion:

- Last sentence of first paragraph: The authors should not comment on the “low” incidence of LGV as it is zero. Updated.

- I suggest placing third paragraph at the end. It is a very interesting suggestion and we have commented for a long time among the drafting team. If you agree, we would prefer to leave it in that order for the moment. However, we believe that it is a possibility so we are available to make the change.

Figure1: MSM instead of HSH. Updated.

Finally, I recommend language and writing editing. The authors should review the use of abbreviations and the writing of the species names according to the journal guidelines. In the text, reference numbers should be cited in square brackets. Moreover, the authors should review the format of the references. square brackets. Reviewed.

________________________________________

6. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.

Reviewer #1: No

Reviewer #2: No

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29 Jan 2020

RISK FACTORS ASSOCIATED WITH SEXUALLY TRANSMITTED INFECTIONS AND HIV AMONG ADOLESCENTS IN A REFERENCE CLINIC IN MADRID

PONE-D-19-33032R1

Dear Dr. AYERDI,

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

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Additional Editor Comments (optional):

Reviewers' comments:

24 Feb 2020

PONE-D-19-33032R1

Risk factors associated with sexually transmitted infections and HIV among adolescents in a reference clinic in Madrid

Dear Dr. Ayerdi Aguirrebengoa:

I am 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.

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on behalf of

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Academic Editor

PLOS ONE