3 Dec 2019: Werner RN, Gaskins M, Nast A, Dressler C (2019) Correction: Incidence of sexually transmitted infections in men who have sex with men and who are at substantial risk of HIV infection – A meta-analysis of data from trials and observational studies of HIV pre-exposure prophylaxis. PLOS ONE 14(12): e0226209. https://doi.org/10.1371/journal.pone.0226209 View correction
Men who have sex with men (MSM) and who engage in condomless anal intercourse with casual partners are at high risk of acquiring sexually transmitted infections (STIs), but reliable epidemiological data are scarce. Studies on HIV pre-exposure prophylaxis (PrEP) enrol MSM who indicate that they engage in behaviour that puts them at high risk of acquiring HIV. Because they also screen for STIs at regular intervals, these studies may serve as a valuable source to estimate incidence rates of STIs in this subpopulation of MSM.
We systematically searched for trials and observational studies of PrEP in MSM that reported data on the incidence of STIs during the study period. Incidence rates were calculated as events per 100 person-years (py) with 95% confidence intervals (CI). Data from individual studies were pooled building subgroups along study types and geography. We performed sensitivity analyses, including data only from studies that met pre-defined quality criteria.
Twenty-four publications on 20 studies were included. The majority of studies reported that sexual behaviour and/or STI incidence remained stable or decreased during the study period. For syphilis, incidence rates ranged from 1.8/100py to 14.9/100py, the pooled estimate was 9.1/100py (95%-CI: 7.7–10.9). Incidence rates for gonorrhoea and chlamydia of any site ranged from 13.3/100py to 43.0/100py and 15.1/100py to 48.5/100py, respectively. Considering only studies that met the criteria for sensitivity analysis yielded pooled estimates of 39.6/100py (95%-CI: 32.9–47.6) and 41.8/100py (95%-CI: 33.9–51.5), respectively. The overall estimate for hepatitis C incidence was 1.3/100py (95%-CI: 1.0–1.8).
Despite partly heterogeneous results, the data depict high incidence rates of STIs among MSM who engage in higher-risk sexual behaviours such as condomless sex with casual partners. This subpopulation of MSM requires access to STI screening at close intervals. By offering access to structures that provide regular STI monitoring and prompt treatment, PrEP may not only decrease HIV incidence but also have beneficial effects in decreasing the burden of STIs.
Citation: Werner RN, Gaskins M, Nast A, Dressler C (2018) Incidence of sexually transmitted infections in men who have sex with men and who are at substantial risk of HIV infection – A meta-analysis of data from trials and observational studies of HIV pre-exposure prophylaxis. PLoS ONE 13(12): e0208107. https://doi.org/10.1371/journal.pone.0208107
Editor: Peter M. Mugo, KEMRI Wellcome Trust Research Programme, KENYA
Received: September 17, 2018; Accepted: November 12, 2018; Published: December 3, 2018
Copyright: © 2018 Werner et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Data Availability: All relevant data are within the manuscript and its Supporting information files.
Funding: The author(s) received no specific funding for this work.
Competing interests: The authors have declared that no competing interests exist.
Data on the epidemiology of sexually transmitted infections (STIs) suggest a high burden of disease worldwide . Increases in the incidence of chlamydia, gonorrhoea and syphilis infections have been observed in numerous countries, particularly among men who have sex with men (MSM) [2–6]. At the same time, the decreasing susceptibility of bacterial pathogens such as Neisseria gonorrhoeae [7–11] and Mycoplasma genitalium [12,13] to antimicrobials is becoming a major public health problem, especially given evidence that the risk of HIV transmission is higher in the presence of other STIs [14–17].
Reliable data on the incidence of STIs among sexual minorities are difficult to obtain [18–20]. In some countries, reporting systems for STIs may include information on the probable route of transmission. However, calculating incidence rates for STIs among MSM from these population-based data can rely only on reported cases for the numerator and estimates of the denominator, which is unknown (i.e., the total number of MSM at risk of acquiring an STI) [21,22]. Therefore, from an epidemiological viewpoint, a more reliable method to generate estimates of STI incidence rates in sexual minorities is to use incidence data from longitudinal cohort studies.
In the present systematic review and meta-analysis, we aimed to generate effect estimates for incidence rates of STIs in MSM who engage in sexual behaviours that put them at high risk of acquiring STIs. To do so, we used data on the incidence of STIs diagnosed during the study period in participants from studies on HIV pre-exposure prophylaxis (PrEP). PrEP is a biomedical form of primary HIV prevention that has been shown to be highly effective in clinical trials [23–26] and cohort studies [27–35]. Most PrEP trials and cohort studies only enrol MSM who indicate that they engage in behaviour that puts them at high risk of acquiring HIV, which is usually defined in these studies as reporting having had condomless anal intercourse within a specified amount of time with a specified minimum number of partners. Because they also screen for STIs at regular intervals, these studies may serve as a valuable source of STI incidence data in this subpopulation of MSM.
Materials and methods
We conducted a systematic review and meta-analysis of data on the incidence of STIs in published trials and cohort studies of PrEP in MSM at risk of HIV infection. A review protocol was developed and followed but not published (S1 File).
Publications were eligible if they reported results from clinical studies of PrEP in MSM at risk for HIV infection and had a follow-up period of at least three months. To be included, studies had to report the incidence of STIs other than HIV and provide sufficient data on the person-years of follow-up to calculate incidence rates. Any form of testing for STIs had to be performed at regular intervals; studies that relied exclusively on self-reported incidence data were not included. We considered full-text publications and conference abstracts. Language was restricted to English, French and German.
Information sources and search strategy
We searched Ovid MEDLINE, Embase and Cochrane CENTRAL on 28 September 2017 and conducted an update search on 25 July 2018 covering the period from the inception of the data base through the date of the search. Autoalerts for all searches were included through 1 August 2018. The full search strategies can be viewed in the online supplement (S1 File). Resource limitations meant that authors were contacted for missing data only for studies that had been included in the original search.
Study selection and data collection
We checked all identified records for eligibility using a two-step process, screening titles and abstracts first, and assessing full texts of records included thereafter. Data were extracted by two evaluators (RNW and CD). Disagreement was resolved by discussion or by involving a third investigator (AN, MG). Apart from incident STI diagnoses and corresponding person-years of follow up, data were extracted on study type and characteristics, baseline characteristics of the sample, and any reported changes in sexual behaviour or STI incidence. We did not extract data that were only presented graphically. As data from a randomised controlled trial suggests that PrEP could have an effect on the incidence of genital herpes , we considered data on genital herpes only if these were reported separately for placebo or non-intervention arms. For data on hepatitis B, we chose the same approach since tenofovir is an established medication for chronic hepatitis B.
Assumptions, simplifications and calculations
If incidence rates with 95% confidence intervals (95%-CIs) and the total person-years of follow-up were not reported, we calculated person-years as follows: If possible, we multiplied the number of participants per visit by the length of time since the previous visit, or by multiplying the number of participants by the mean follow-up time. Where only the overall number of participants at baseline and at the end of follow-up were reported and the number of participants for each time point was missing, we calculated person-years by multiplying the number of participants who completed the study plus half the number of participants who had not completed the closing visit by the length of the follow-up period. For all of these approaches, we used the number of incident diagnoses whenever possible; however, in some cases only the number of participants infected was available.
Incidence rates were calculated as events per 100 person-years of follow-up. Assuming a Poisson distribution, we used log incidence rates and corresponding standard errors to determine incidence rates with 95%-CIs. If no incident cases occurred during follow-up, we added a correction of 0.5 to the number of cases and person-years of follow-up as described in similar studies [37,38].
Synthesis of the results
STI incidence data were grouped according to study type and geography. We calculated pooled estimates of the incidence rates and 95% CIs using a random effects model to account for methodological and clinical differences between the studies. Heterogeneity was quantified by means of the Higgins’s I-squared test statistic . All calculations were performed using Stata SE 14 (metan command package).
Assessment of the quality of the data
In order to evaluate the quality of the data, three criteria were established: First, we evaluated whether the data on incidence rates or numbers of incident STI diagnoses and person-years of follow-up were explicitly reported or easy to calculate or interpret. Second, we assessed whether studies reported having performed screening procedures for the detection of STIs during the follow-up. To satisfy this quality criterion, studies had to explicitly state having performed screening procedures at a minimum of six monthly intervals and in accordance with the Centers for Disease Control and Prevention (CDC) recommendations for STI screening in sexually active MSM . Third, we evaluated the size of each study, considering more than 500 person-years of follow-up to be an indicator of higher quality incidence data.
To examine sources of heterogeneity, we separately evaluated subgroups along study design and geography. We performed a sensitivity analysis for each outcome, only considering data extracted from studies that explicitly reported incidence rates (or provided easy-to-interpret data for numbers of incident diagnoses and person-years of follow-up) and that reported having applied STI screening methods that met our quality criterion #2. We did not undertake any formal tests of publication bias in our meta-analysis because our outcome of interest (i.e., STI incidence rates) was not an efficacy outcome that might have led to the selective publication of study results.
Our literature search yielded 2416 records, of which 1581 remained after duplicates had been removed. Of these, 1456 were excluded during the title and abstract screening, leaving 125 publications to be evaluated as full texts. Finally, 24 publications reporting the results of 20 studies were included. Fig 1 depicts the numbers of records identified, included and excluded .
Depicts the number of records identified, included and excluded, and the reasons for exclusions.
The 20 studies were: three double-blind, placebo-controlled RCTs [23,24,26,42,43], one double-blind, active-controlled RCT , one open-label RCT  with STI incidence data derived from the PrEP group only, and 15 cohort studies [27–34,45–53]. A total of 11,918 participants were enrolled in these studies, yielding a cumulative 11,686.0 person-years of follow-up. Table 1 gives an overview of study types, inclusion criteria, sample sizes and baseline characteristics.
Quality of data
Data on incidence rates for some or all of the reported STIs were directly reported or easy to interpret in 14 studies [25,27–31,34,42,43,45–48,51–53]. Eighteen studies explicitly reported the application of screening methods as recommended by the CDC for some or all of the STIs assessed [24–31,33,34,42–47,50,51]. Six studies had at least 500 person-years of follow-up, fulfilling our criterion for large study size [23,29–31,42,43,46,48,49]. Table 2 gives an overview of our assessment of data quality for each study.
Changes in sexual behaviour and STI incidence during the study period
Two RCTs [24,26] and four cohort studies [28,32,33,50] reported that sexual behaviour had not changed with respect to condom use and/or the number of sexual partners. Two of these studies [28,50] and one further cohort study  additionally reported no change in the incidence of STIs. One retrospective cohort study  reported an increase in STI incidence compared to the time before PrEP initiation. However, this increase was not significant after adjusting for the number of screening visits. A decrease in the number of sexual partners and instances of condomless anal intercourse was observed in an RCT  and its open-label extension . A smaller overall STI incidence in the second compared to the first half of the study was reported in one cohort . In contrast, decreasing rates of condom use were reported in three cohort studies [30,47,52], and increasing incidence rates for STIs observed in two cohort studies [27,29]. Four studies did not report on changes in sexual behaviour or STI incidence during the follow-up [25,44–46].
One active-controlled RCT  and seven cohort studies [27–29,33,34,49,51] reported data on the incidence of any STI diagnosis, comprising a total of 2105.7 person-years (py) of follow-up. One of these studies specifically reported the incidence of any bacterial STI diagnosis (gonorrhoea, chlamydia or syphilis) . Incidence rates ranged from 33.0/100py (95%-CI: 27.5–39.6) in the active-controlled RCT  to 99.8/100py (95%-CI: 82.6–120.6) in an Australian cohort study , yielding a pooled estimate of 72.4/100py (95%-CI: 58.8–89.1, I2 = 94.9%). The heterogeneity of the incidence rates remained high when only cohort studies conducted in North America [28,29,33,34,50,51] were considered [pooled estimate 64.4/100py (95%-CI: 48.4–85.6), I2 = 95.9%]. One Dutch  and the above-mentioned Australian cohort study  had comparable incidence rates [97.8/100py (95%-CI: 89.2–107.2) and 99.8/100py (95%-CI: 82.6–120.6), respectively]. Looking separately at the four cohort studies that fulfilled our quality criteria for the sensitivity analysis [28,29,34,51], our estimates ranged from 66.4/100py (95%-CI: 54.9–80.5) to 90.7/100py (95%-CI: 84.5–97.3), yielding an overall pooled estimate of 84.4/100py (95%-CI: 75.6–94.2, I2 = 68.3%).
Three placebo-controlled RCTs [24,26,43], one active-controlled RCT , one open-label RCT , and eight cohort studies [27,28,31–33,47,50,51] reported on incident cases of syphilis, comprising a total of 7771.5 person-years of follow-up. Two studies reported on participants infected rather than number of infections, and re-infections may have been unreported in these studies [44,50]. Considering all studies reporting on the incidence of syphilis, we calculated a pooled estimate of 9.2/100py (95%-CI: 7.7–10.9, I2 = 65.7). Incidence rates ranged from 1.8/100py (95%-CI: 0.3–12.9) in a cohort study of 15-to-17-year-old PrEP users  to 14.9/100py (95%-CI: 5.6–39.8) in an RCT of PrEP in 18 to 22 year old participants . As the person-years of follow-up were not directly reported in either of these two studies, these estimates should be treated with caution. Looking separately at cohort studies (i.e., in which all participants were on PrEP), the pooled estimate was 9.4/100py (95%-CI: 7.2–12.4, I2 = 68.2). Considering only the seven studies that met the quality criteria for our sensitivity analysis [25,27,28,31,43,47,51], we calculated a pooled estimate of 9.5/100py (95%-CI: 7.5–12.1, I2 = 79.7), see Fig 2. Looking separately at the estimates for different continents, the lowest pooled incidence rate was seen in studies that included participants from Latin America by majority [31,32,43] [7.4/100py (95%-CI: 6.7–8.2, I2 = 0.0)], and the highest incidence was seen in an Australian cohort study  [13.1/100py (95%-CI: 7.7–22.1)].
Gonorrhoea and chlamydia
Data on the incidence of gonorrhoea and chlamydia were reported in three placebo-controlled RCTs [23,24,26] one active-controlled RCT  one open-label RCT  and in eight cohort studies [27–29,33,45,47,50,51]. Grant et al. 2010 reported only testing for urethral gonorrhoea and chlamydia infection upon positive urine leukocyte esterase  and Lal et al. reported testing for genital gonorrhoea only upon clinical suspicion . For two studies, routine sampling did not include the throat  or it remained unclear, whether this site was included . In one cohort study, screening tests only included anal and pharyngeal sites for gonorrhoea, and anal and urethral sites for chlamydia . Three studies reported on persons infected, not on events of infection during follow-up [26,44,50]. In the following we have put the different anatomical locations in boldface to improve readability.
One cohort study reported data on the combined outcome of urethral gonorrhoea and/or chlamydia . In 179.5 person-years of follow-up, 32 cases of urethral STIs were diagnosed, leading to an incidence rate of 17.8/100py (95%-CI: 12.6–25.2).
Two placebo-controlled RCTs [23,24] and four cohort studies [29,33,45,51] reported data on urethral gonorrhoea, with an overall follow-up of 3626.4 person-years. The incidence of urethral gonorrhoea ranged from 1.3/100py (95%-CI: 0.9–1.8) in the RCT that only tested for urethral gonorrhoea upon positive leukocyte esterase to 6.4/100py (95%-CI: 3.1–13.5) in a retrospective Canadian cohort study. The pooled estimate was 3.3/100py (95%-CI: 1.6–7.0, I2 = 88.4%). Looking separately at cohort studies, the pooled estimate was 4.3/100py (95%-CI: 2.3–8.0, I2 = 72.1%). Considering only the three cohort studies that met the quality criteria for inclusion in the sensitivity analysis [29,45,51], the pooled estimate was 4.0/100py (95%-CI: 1.8–8.8, I2 = 81.3%).
For the outcome of urethral chlamydia, additionally to the six above-mentioned studies reporting on urethral gonorrhoea, one cohort study  reported data, resulting in a total of 3706.0 person-years of follow-up. Incidence rates ranged from 1.0/100py (95%-CI: 0.7–1.5) to 26.2/100py (95%-CI: 12.5–54.9), and the pooled estimate was 7.5/100py (95%-CI: 3.4–16.3, I2 = 94.9%). Among the cohort studies [27,29,33,45,51], heterogeneity was lower, yielding a pooled estimate of 9.2/100py (95%-CI: 7.2–11.7, I2 = 31.6%). Considering the four cohort studies that met the criteria for inclusion in the sensitivity analysis [27,29,45,51], the overall estimate for urethral chlamydia infection was 9.1/100py (95%-CI: 6.8–12.2, I2 = 48.7%).
Four studies reported on the combined incidence of rectal gonorrhoea and/or chlamydia [25,27,47,50], with an overall follow-up of 564.8 person-years. Incidence rates from these reports ranged from 38.3/100py (95%-CI: 31.2–46.9) in the PrEP group of an English open-label RCT  to 70.0/100py (95%-CI: 55.8–87.7) in an Australian cohort study . The two PrEP cohorts from the US [47,50] showed similar incidence rates [pooled estimate 51.9/100py (95%-CI: 43.1–62.5, I2 = 0)]. The pooled estimate from all studies was 52.6/100py (95%-CI: 39.6–69.7, I2 = 80.9%). Only considering the three studies that met the criteria for inclusion in the sensitivity analysis [25,27,47], the estimate for the incidence of rectal gonorrhoea and/or chlamydia was 51.1/100py (95%-CI: 36.5–71.5, I2 = 86.8%).
Five cohort studies reported the incidence of rectal gonorrhoea and rectal chlamydia separately [27,29,33,45,51]. For the outcome of rectal gonorrhoea, 1136.1 person-years of follow-up were available; for rectal chlamydia 1072.4 person-years. Incidence rates for rectal gonorrhoea ranged from 9.3/100py (95%-CI: 6.8–12.7) to 29.9/100py (95%-CI: 21.1–42.2), yielding a pooled estimate of 16.3/100py (95%-CI: 10.4–25.6, I2 = 87.2%). Considering the four studies [27,29,45,51] for sensitivity analysis only, the pooled estimate was 17.4/100py (95%-CI: 10.6–28.5, I2 = 89.8%). Incidence rates for rectal chlamydia ranged from 14.6/100py (95%-CI: 7.3–29.1) to 42.4/100py (95%-CI: 36.7–49.0). The pooled estimate was 30.3/100py (95%-CI: 21.9–42.0, I2 = 86.2%). Considering the four studies [27,29,45,51] for sensitivity analysis only, the pooled estimate for rectal chlamydia was 33.4/100py (95%-CI: 24.3–46.1, I2 = 86.8%). For both rectal gonorrhoea and rectal chlamydia, the separate analysis of geographic regions did not show less heterogeneous results.
One placebo-controlled RCT , one head-to-head RCT , one open-label RCT with data only derived from the PrEP group , and four cohort studies [27,28,45,51] reported on gonorrhoea and chlamydia of any of the body sites tested. The cumulative follow-up was 2093.2 and 2057.2 person-years, respectively. The incidence of gonorrhoea of any site ranged from 12.2/100py (95%-CI: 9.0–16.4) in an active-controlled RCT reporting the number of persons infected during follow-up rather than reporting the number of events of infection  to 43.0/100py (95%-CI: 37.5–49.3) in the US PrEP Demonstration Project . The pooled estimate from all studies reporting this outcome was 27.1/100py (95%-CI: 19.1–38.4, I2 = 94.1%), see Fig 3. Looking separately at cohort studies, the pooled estimate was 31.6/100py (95%-CI: 21.2–47.1, I2 = 91.3%). The heterogeneity of the incidence rates remained high when different geographic regions were pooled separately. Three studies [25,28,51] had incidence data easily accessible and reported applying proper screening procedures for these outcomes (nucleic acid amplification tests performed on anal and throat swabs and urine samples). Considering these studies only, the pooled estimate was 39.6/100py (95%-CI: 32.9–47.6, I2 = 57.6%).
Incidence rates are given as events per 100 person-years. CI, confidence interval.
For chlamydia of any site, incidence rates were similarly heterogeneous, ranging from 13.9/100py (95%-CI: 10.5–18.4) in the active-controlled RCT  to 48.5/100py (95%-CI: 37.0–63.7) in the Australian VicPrEP cohort . The pooled estimate was 30.2/100py (95%-CI: 21.4–42.5, I2 = 94.3%), see Fig 4. Looking separately at cohort studies, the pooled estimate was 40.5/100py (95%-CI: 31.0–52.9, I2 = 84.3%). Only considering studies that met the criteria for the sensitivity analysis, the pooled estimate was 41.8/100py (95%-CI: 33.9–51.5, I2 = 72.3%).
Mycoplasma and ureaplasma
No study reporting on the incidence of genital or rectal mycoplasma or ureaplasma infection was identified.
One placebo-controlled RCT , one open-label RCT , and seven cohort studies [30,46,48,50–53] reported data on the incidence of hepatitis C (HCV) during a cumulative follow-up of 3730.5 person-years. Of these studies, only five [25,30,46,51,52] reported using serology assays to screen for HCV at regular interviews. In the study by McCormack et al.  this applied only to participants who reported injecting or snorting drugs, fisting or the use of sex toys. The lowest HCV incidence was reported in a Canadian retrospective cohort study with zero events during 109 person-years of follow-up . The highest HCV incidence rate was reported for the Dutch AmPrEP cohort  and totalled 1.9/100py (95%-CI: 1.1–3.4). The overall estimate for HCV incidence was 1.3/100py (95%-CI: 1.0–1.8, I2 = 0.0). Looking separately at the cohort studies, the pooled estimate was almost identical. Although the incidence rate of HCV in European studies was twice the incidence rate in North American studies, the confidence intervals for these estimates overlapped, see Fig 5. Pooling data only from the sensitivity analysis sample [25,30,46] yielded a pooled estimate for HCV incidence of 1.2/100py (95%-CI: 0.8–1.8, I2 = 0.0).
Incidence rates are given as events per 100 person-years. CI, confidence interval.
One RCT  reported no incident cases of hepatitis B during 175 person-years of follow-up in the placebo group.
The incidence of hepatitis A was reported in one French cohort study . Six cases were diagnosed during a follow-up of 486 person-years, yielding an incidence rate of 1.2/100py (95%-CI: 0.6–2.8).
Participants with at least one STI and other STIs reported
Six studies reported on the outcome ‘participants diagnosed with at least one STI’, and one study each reported on anogenital warts, herpes simplex seroincidence, molluscum contagiosum and trichomonas. These data are reported in the online supplement (S2 File).
The present meta-analysis aimed to generate estimates for incidence rates for various STIs among MSM who engage in high-risk sexual behaviours, such as condomless anal intercourse with casual partners. The results indicate that the incidence rates for STIs in this subgroup of MSM are high. The incidence rate for a diagnosis with any STI was about 84/100py in the four cohort studies that met our criteria for higher-quality data. The bulk of diagnoses with any STI were due to chlamydia and gonorrhoea infections at different anatomical sites. Here, rectal gonorrhoea, chlamydia or both played a major role, with a pooled incidence rate of more than 50/100py. This is worrying given the rising levels of antimicrobial resistance seen especially in Neisseria gonorrhoea in recent years [7–11]. Although Mycoplasma genitalium infections have recently received increased attention as a difficult-to-treat STI  and epidemiological research partly supports screening for this infection in populations at higher risk, such as MSM [12,54–56], no corresponding incidence data were reported in the studies included in our meta-analysis.
Our overall estimate for the incidence rate of hepatitis C infections was 1.3/100py. This is substantially higher than the incidence of 0.4 per 1000 persons per year seen in HIV-uninfected MSM and even the incidence of 7.8 per 1000 persons per year seen in HIV-positive MSM reported in a recent meta-analysis that included both prospective and retrospective studies . Recent research suggests that only a proportion of the hepatitis C infections in this susceptible population are sexually transmitted and that practices involving intravenous or nasal drug use play an important role [58,59]. Due to the potentially severe sequelae and the high cost of treatment, our findings are worrying and suggest that policy makers may wish to consider redoubling efforts at primary prevention in those at highest risk (e.g. routine screening, needle exchange programmes).
In the one study reporting incidence data for hepatitis A, a rate of 1.2/100py was observed. While this is a high rate by any measure, it must be kept in mind that this French cohort study was conducted during an outbreak of hepatitis A among MSM in several European countries [60–65], including France . Nevertheless, these data underline the importance of increasing hepatitis A vaccination coverage in MSM, specifically in those who engage in sexual behaviour that puts them at high risk of acquiring HIV and other STIs.
Our study does not attempt to compare STI incidence rates among MSM taking PrEP versus MSM not taking PrEP. One such comparison has been performed previously . However, the validity of such studies is questionable . To be eligible to participate in clinical trials of PrEP, participants had to be at high risk of infection with HIV (and hence other STIs) already. Comparing this group of MSM to other MSM who are not at high risk, or to the overall population of MSM, will lead to predictable and meaningless results. Moreover, the frequent testing for STIs in the PrEP studies will lead to an increase in the number of detected STI diagnoses. Indeed, one of the PrEP cohort studies included reported that screening every six months instead of quarterly would have delayed diagnosis of STIs in 24% of the participants . A retrospective cohort study that compared the incidence of STIs in the year before PrEP initiation to the year after, found a significant increase only when the data were not adjusted for testing frequency . Two longitudinal studies comparing the incidence of STIs before PrEP initiation to that during PrEP intake have reported mixed results: in the first, which assessed the incidence of rectal STIs, no increase was seen , whereas in the second, a modest but significant increase in ‘any STI’ and Chlamydia infections was reported . Generally, the majority of studies included in our meta-analysis reported either a stable or decreased risk-behaviour and/or STI incidence during follow-up. This finding is supported by a recent case-crossover study .
Since the participants included in the studies benefit directly from their participation (free PrEP medication and STI testing), the follow-up may be more complete than in studies designed to assess STI incidence rates in susceptible sexual minorities. However, using data from PrEP trials and cohort studies to estimate STI incidence rates has a number of important limitations. First, the majority of studies included in our meta-analysis were not designed specifically to assess STI incidence rates. We have attempted to address this limitation with our sensitivity analysis. The results of this analysis generally support the validity of our approach. A second limitation is our inclusion of data from heterogeneous study designs, as well as different regions and populations of MSM. While participants included in double-blind placebo-controlled trials will not have known their group assignment, participants in the other types of studies, particularly in PrEP cohort studies, will all have been aware that they were using PrEP. This may have affected participants’ sexual risk taking behaviour and therefore their risk of acquiring STIs. We have accounted for this by building subgroups according to each of the different study designs and presenting the data separately for these where appropriate. Nevertheless, when interpreting the overall effect estimates, readers will need to bear this limitation in mind. The methodological and clinical heterogeneity is reflected by I-squared as a statistical tests for heterogeneity. This was often high, with values exceeding 75%. In a few cases, heterogeneity was substantially reduced when we analysed subgroups separately according to study design or region. While being at risk of acquiring HIV and therefore being eligible for PrEP was the common inclusion criterion for most of the studies, the actual risk behaviour of the participants may have varied between studies (and indeed over time) and may partly explain the heterogeneity of our results. Because the risk behaviour of participants in the included studies was not reported in ways that were consistent across the studies, comparing these risk behaviours is difficult and stratifying them in meaningful ways not feasible. Further factors, such as age and ethnicity of participants, may also partly explain high values of I-squared obtained for some of our pooled estimates.
If the limitations of our study are borne in mind, our estimates of STI incidence rates among MSM who are at high risk of STI infection can be helpful to policy makers and health professionals working in the fields of primary prevention and clinical care. For example, our estimates could be used to make recommendations on the frequency of STI screening and access to it in this susceptible population. Indeed, offering PrEP to this group of MSM may not only be a promising strategy to reduce the incidence of HIV. It could also help embed the target population into a comprehensive programme of frequent STI screening and treatment, potentially reducing the incidence and prevalence of STIs in the medium term, as predicted by a recent modelling study .
Despite the heterogeneous designs of the studies included in our meta-analysis and the heterogeneity of some of our results, our overall findings suggest that the incidence rates of various STIs among MSM who engage in high-risk sexual behaviour is high. The high rates of gonorrhoea, chlamydia and hepatitis C infections in the included cohort studies raise particular concerns. This subgroup of MSM can benefit from access to STI testing and treatment at close intervals. The use of PrEP is a highly effective means of preventing HIV infection and should be embedded in a comprehensive programme targeting primary and secondary prevention and treatment of other STIs.
S2 File. Online supplement.
Results on the outcomes ‘Participants diagnosed with at least one STI’, anogenital warts, herpes simplex and other STIs.
The authors would like to acknowledge and thank the following people: Dr Julia L. Marcus for supplying data on screening tests and screening test results for the Kaiser Permanente Northern California PrEP cohort, and Dr Christopher Cardwell and Dr Kari Tikkinen for providing advice on conducting the meta-analyses.
- 1. Newman L, Rowley J, Vander Hoorn S, Wijesooriya NS, Unemo M, Low N, et al. Global Estimates of the Prevalence and Incidence of Four Curable Sexually Transmitted Infections in 2012 Based on Systematic Review and Global Reporting. PLoS One. 2015;10(12):e0143304. pmid:26646541
- 2. Centers for Disease Control and Prevention. Sexually Transmitted Disease Surveillance 2016 Atlanta: U.S. Department of Health and Human Services; 2017 [cited 2 August 2018]. Available from: https://www.cdc.gov/std/stats16/CDC_2016_STDS_Report-for508WebSep21_2017_1644.pdf.
- 3. Bremer V, Dudareva-Vizule S, Buder S, an der Heiden M, Jansen K. Sexuell übertragbare Infektionen in Deutschland—Die aktuelle epidemiologische Lage. Bundesgesundheitsblatt. 2017;(60):948–57.
- 4. Public Health England. Sexually transmitted infections and screening for chlamydia in England, 2017. Health Protection Report. 2018;12(20).
- 5. Visser M, van Aar F, van Oeffelen AAM, van den Broek IVF, Op de Coul ELM, Hofstraat SHI, et al. Sexually transmitted infections including HIV, in the Netherlands in 2016 2017 [cited 2 August, 2018]. Available from: https://rivm.openrepository.com/rivm/bitstream/10029/620872/1/2017-0003.pdf.
- 6. Jansen K, Thamm M, Bock CT, Scheufele R, Kucherer C, Muenstermann D, et al. High Prevalence and High Incidence of Coinfection with Hepatitis B, Hepatitis C, and Syphilis and Low Rate of Effective Vaccination against Hepatitis B in HIV-Positive Men Who Have Sex with Men with Known Date of HIV Seroconversion in Germany. Plos One. 2015;10(11). doi: ARTN e0142515 pmid:26555244
- 7. Cole MJ, Spiteri G, Jacobsson S, Pitt R, Grigorjev V, Unemo M, et al. Is the tide turning again for cephalosporin resistance in Neisseria gonorrhoeae in Europe? Results from the 2013 European surveillance. Bmc Infect Dis. 2015;15. doi: ARTN 321 pmid:26259560
- 8. Eyre DW, Sanderson ND, Lord E, Regisford-Reimmer N, Chau K, Barker L, et al. Gonorrhoea treatment failure caused by a Neisseria gonorrhoeae strain with combined ceftriaxone and high-level azithromycin resistance, England, February 2018. Euro surveillance: bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin. 2018;23(27). Epub 2018/07/12. pmid:29991383
- 9. Chisholm SA, Wilson J, Alexander S, Tripodo F, Al-Shahib A, Schaefer U, et al. An outbreak of high-level azithromycin resistant Neisseria gonorrhoeae in England. Sexually transmitted infections. 2016;92(5):365–7. Epub 2015/11/26. pmid:26601852
- 10. Harris SR, Cole MJ, Spiteri G, Sanchez-Buso L, Golparian D, Jacobsson S, et al. Public health surveillance of multidrug-resistant clones of Neisseria gonorrhoeae in Europe: a genomic survey. The Lancet Infectious diseases. 2018;18(7):758–68. Epub 2018/05/20. pmid:29776807
- 11. Tacconelli E, Carrara E, Savoldi A, Harbarth S, Mendelson M, Monnet DL, et al. Discovery, research, and development of new antibiotics: the WHO priority list of antibiotic-resistant bacteria and tuberculosis. The Lancet Infectious diseases. 2018;18(3):318–27. Epub 2017/12/26. pmid:29276051
- 12. Couldwell DL, Jalocon D, Power M, Jeoffreys NJ, Chen SC, Lewis DA. Mycoplasma genitalium: high prevalence of resistance to macrolides and frequent anorectal infection in men who have sex with men in western Sydney. Sexually transmitted infections. 2018. Epub 2018/03/24. pmid:29567802
- 13. Allan-Blitz LT, Mokany E, Miller S, Wee R, Shannon C, Klausner JD. Prevalence of Mycoplasma genitalium and Azithromycin-Resistant Infections Among Remnant Clinical Specimens, Los Angeles. Sexually transmitted diseases. 2018. Epub 2018/03/07. pmid:29509566
- 14. Kelley CF, Vaughan AS, Luisi N, Sanchez TH, Salazar LF, Frew PM, et al. The Effect of High Rates of Bacterial Sexually Transmitted Infections on HIV Incidence in a Cohort of Black and White Men Who Have Sex with Men in Atlanta, Georgia. AIDS Research & Human Retroviruses. 2015;31(6):587–92. https://doi.org/10.1089/AID.2015.0013.
- 15. Bernstein KT, Marcus JL, Nieri G, Philip SS, Klausner JD. Rectal gonorrhea and chlamydia reinfection is associated with increased risk of HIV seroconversion. J Acquir Immune Defic Syndr. 2010;53(4):537–43. pmid:19935075
- 16. Chin-Hong PV, Husnik M, Cranston RD, Colfax G, Buchbinder S, Da Costa M, et al. Anal human papillomavirus infection is associated with HIV acquisition in men who have sex with men. Aids. 2009;23(9):1135–42. pmid:19390418
- 17. Galvin SR, Cohen MS. The role of sexually transmitted diseases in HIV transmission. Nat Rev Microbiol. 2004;2(1):33–42. pmid:15035007
- 18. Gama A, Martins MO, Dias S. HIV Research with Men who Have Sex with Men (MSM): Advantages and Challenges of Different Methods for Most Appropriately Targeting a Key Population. Aims Public Health. 2017;4(3):221–39. pmid:29546214
- 19. Magnani R, Sabin K, Saidel T, Heckathorn D. Review of sampling hard-to-reach and hidden populations for HIV surveillance. Aids. 2005;19:S67–S72.
- 20. Zhang D, Bi P, Hiller JE, Lv F. Web-based HIV/AIDS behavioral surveillance among men who have sex with men: Potential and challenges. Int J Infect Dis. 2008;12(2):126–31. pmid:17884663
- 21. Marcus U, Schmidt AJ, Kollan C, Hamouda O. The denominator problem: estimating MSM-specific incidence of sexually transmitted infections and prevalence of HIV using population sizes of MSM derived from Internet surveys. BMC public health. 2009;9:181. Epub 2009/06/13. pmid:19519889
- 22. Marcus U, Hickson F, Weatherburn P, Schmidt AJ. Estimating the size of the MSM populations for 38 European countries by calculating the survey-surveillance discrepancies (SSD) between self-reported new HIV diagnoses from the European MSM internet survey (EMIS) and surveillance-reported HIV diagnoses among MSM in 2009. BMC public health. 2013;13:919. Epub 2013/10/04. pmid:24088198
- 23. Grant RM, Lama JR, Anderson PL, McMahan V, Liu AY, Vargas L, et al. Preexposure chemoprophylaxis for HIV prevention in men who have sex with men. New England Journal of Medicine. 2010;363(27):2587–99. pmid:21091279
- 24. Hosek S, Siberry G, Bell M, Lally M, Kapogiannis B, Green K. The acceptability and feasibility of an HIV pre-exposure prophylaxis (PrEP) trial with young men who have sex with men (YMSM). Journal of Acquired Immune Deficiency Syndromes. 201;62(4):[447–56]. pmid:24135734
- 25. McCormack S, Dunn DT, Desai M, Dolling DI, Gafos M, Gilson R, et al. Pre-exposure prophylaxis to prevent the acquisition of HIV-1 infection (PROUD): Effectiveness results from the pilot phase of a pragmatic open-label randomised trial. The Lancet. 2016;387(10013):53–60.
- 26. Molina JM, Capitant C, Spire B, Pialoux G, Cotte L, Charreau I, et al. On-demand preexposure prophylaxis in men at high risk for HIV-1 infection. New England Journal of Medicine. 2015;373(23):2237–46. pmid:26624850
- 27. Lal L, Audsley J, Murphy DA, Fairley CK, Stoove M, Roth N, et al. Medication adherence, condom use and sexually transmitted infections in Australian preexposure prophylaxis users. Aids. 2017;31(12):1709–14. pmid:28700394
- 28. Liu AY, Cohen SE, Vittinghoff E, Anderson PL, Doblecki-Lewis S, Bacon O, et al. Preexposure prophylaxis for HIV infection integrated with municipal-and community-based sexual health services. JAMA Intern Med. 2016;176(1):75–84. pmid:26571482
- 29. Marcus JL, Hurley LB, Hare CB, Nguyen DP, Phengrasamy T, Silverberg MJ, et al. Preexposure Prophylaxis for HIV Prevention in a Large Integrated Health Care System: Adherence, Renal Safety, and Discontinuation. J Acquir Immune Defic Syndr. 2016;73(5):540–6. Epub 2016/11/17. pmid:27851714
- 30. Molina JM, Charreau I, Spire B, Cotte L, Chas J, Capitant C, et al. Efficacy, safety, and effect on sexual behaviour of on-demand pre-exposure prophylaxis for HIV in men who have sex with men: An observational cohort study. The Lancet HIV. 2017.
- 31. Grant RM, Anderson PL, McMahan V, Liu A, Amico KR, Mehrotra M, et al. Uptake of pre-exposure prophylaxis, sexual practices, and HIV incidence in men and transgender women who have sex with men: A cohort study. The Lancet Infectious Diseases. 2014;14(9):820–9. pmid:25065857
- 32. Grinsztejn B, Hoagland B, Moreira RI, Kallas EG, Madruga JV, Goulart S, et al. Retention, engagement, and adherence to pre-exposure prophylaxis for men who have sex with men and transgender women in PrEP Brasil: 48 week results of a demonstration study. The lancet HIV. 2018;5(3):e136–e45. pmid:29467098
- 33. Hosek SG, Landovitz RJ, Kapogiannis B, Siberry GK, Rudy B, Rutledge B, et al. Safety and Feasibility of Antiretroviral Preexposure Prophylaxis for Adolescent Men Who Have Sex With Men Aged 15 to 17 Years in the United States. Jama, Pediatr. 2017;05:05. pmid:28873128
- 34. Hosek SG, Rudy B, Landovitz R, Kapogiannis B, Siberry G, Rutledge B, et al. An HIV Preexposure Prophylaxis Demonstration Project and Safety Study for Young MSM. Journal of Acquired Immune Deficiency Syndromes. 2017;74(1):21–9. pmid:27632233
- 35. Volk JE, Marcus JL, Phengrasamy T, Blechinger D, Nguyen DP, Follansbee S, et al. No New HIV Infections With Increasing Use of HIV Preexposure Prophylaxis in a Clinical Practice Setting. Clin Infect Dis. 2015;61(10):1601–3. pmid:26334052
- 36. Celum C, Morrow RA, Donnell D, Hong T, Hendrix CW, Thomas KK, et al. Daily oral tenofovir and emtricitabine-tenofovir preexposure prophylaxis reduces herpes simplex virus type 2 acquisition among heterosexual HIV-1-uninfected men and women: a subgroup analysis of a randomized trial. Annals of Internal Medicine. 2014;161(1):11–9. pmid:24979446
- 37. Yousef F, Cardwell C, Cantwell MM, Galway K, Johnston BT, Murray L. The incidence of esophageal cancer and high-grade dysplasia in Barrett's esophagus: a systematic review and meta-analysis. American journal of epidemiology. 2008;168(3):237–49. pmid:18550563
- 38. Pesonen JS, Cartwright R, Mangera A, Santti H, Griebling TL, Pryalukhin AE, et al. Incidence and Remission of Nocturia: A Systematic Review and Meta-analysis. European urology. 2016;70(2):372–81. pmid:26905787
- 39. Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ. 2003;327(7414):557–60. pmid:12958120
- 40. Workowski KA, Bolan GA, Centers for Disease C, Prevention. Sexually transmitted diseases treatment guidelines, 2015. MMWR Recomm Rep. 2015;64(RR-03):1–137. pmid:26042815
- 41. Moher D, Liberati A, Tetzlaff J, Altman DG, Group P. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. J Clin Epidemiol. 2009;62(10):1006–12. pmid:19631508
- 42. Marcus JL, Glidden DV, McMahan V, Lama JR, Mayer KH, Liu AY, et al. Daily oral emtricitabine/tenofovir preexposure prophylaxis and herpes simplex virus type 2 among men who have sex with men. PLoS ONE. 2014;9 (3) (no pagination)(e91513). pmid:24637511
- 43. Solomon MM, Mayer KH, Glidden DV, Liu AY, McMahan VM, Guanira JV, et al. Syphilis predicts HIV incidence among men and transgender women who have sex with men in a preexposure prophylaxis trial. Clinical Infectious Diseases. 2014;59(7):1020–6. pmid:24928295
- 44. Gulick RM, Wilkin TJ, Chen YQ, Landovitz RJ, Amico KR, Young AM, et al. Phase 2 Study of the Safety and Tolerability of Maraviroc-Containing Regimens to Prevent HIV Infection in Men Who Have Sex With Men (HPTN 069/ACTG A5305). The Journal of infectious diseases. 2017;215(2):238–46. pmid:27811319
- 45. Bristow C, Moore DJ, Dube M, Calvo K, Ellorin E, Blumenthal J, et al. Sexually transmitted infections and adherence to PrEP. Topics in Antiviral Medicine. 2018;26(Supplement 1):469s–70s.
- 46. Cotte L, Cua E, Reynes J, Raffi F, Rey D, Delobel P, et al. Hepatitis C virus incidence in HIV-infected and in preexposure prophylaxis (PrEP)-using men having sex with men. Liver international: official journal of the International Association for the Study of the Liver. 2018. pmid:29959866
- 47. Golub SA, Pena S, Boonrai K, Douglas N, Hunt M, Radix A. STI data from community-based prep implementation suggest changes to CDC guidelines. Topics in Antiviral Medicine. 2016;24 (E-1):368.
- 48. Hoornenborg E, Coyer L, Achterbergh R, Van Der Loeff MS, Bruisten S, DeVries H, et al. High incidence of hepatitis C virus (re) infections among PrEP users in the Netherlands: Implications for prevention, monitoring and treatment. Journal of Viral Hepatitis. 2018;25(Supplement 2):192.
- 49. Hoornenborg E, Coyer LN, Achterbergh RC, Matser A, Davidovich U, Schim Van Der Loeff MF, et al. Incident HIV, hepatitis C and other STI in daily and event-driven PrEP users. Topics in Antiviral Medicine. 2018;26(Supplement 1):468s–9s.
- 50. Lalley-Chareczko L, Clark D, Conyngham SC, Zuppa A, Moorthy G, Mounzer K, et al. Delivery of TDF/FTC for Pre-Exposure Prophylaxis to Prevent HIV-1 Acquisition in Young Adult Men Who Have Sex with Men and Transgender Women of Color using a Urine Adherence Assay. Journal of acquired immune deficiency syndromes (1999). 2018. pmid:29905593
- 51. Nguyen V-K, Greenwald ZR, Trottier H, Cadieux M, Goyette A, Beauchemin M, et al. Incidence of sexually transmitted infections before and after preexposure prophylaxis for HIV. AIDS. 2018;32(4):523–30. pmid:29239887
- 52. Noret M, Balavoine S, Noret M, Pintado C, Siguier M, Brun A, et al. Daily or on demand oral TDF/FTC for HIV pre-exposure prophylaxis: experience from an hospital-based clinic in France. AIDS. 2018.
- 53. Volk JE, Marcus JL, Phengrasamy T, Bradley Hare C. Incident hepatitis C virus infections among users of HIV preexposure prophylaxis in a clinical practice setting. Clinical Infectious Diseases. 2015;60(11):1728–9. pmid:25694649
- 54. Bissessor M, Tabrizi SN, Bradshaw CS, Fairley CK, Hocking JS, Garland SM, et al. The contribution of Mycoplasma genitalium to the aetiology of sexually acquired infectious proctitis in men who have sex with men. Clinical microbiology and infection: the official publication of the European Society of Clinical Microbiology and Infectious Diseases. 2016;22(3):260–5. pmid:26686807
- 55. Manhart LE. Has the time come to systematically test for Mycoplasma genitalium? Sexually transmitted diseases. 2009;36(10):607–8. pmid:19734818
- 56. Baumann L, Cina M, Egli-Gany D, Goutaki M, Halbeisen FS, Lohrer GR, et al. Prevalence of Mycoplasma genitalium in different population groups: systematic review andmeta-analysis. Sexually transmitted infections. 2018;94(4):255–62. pmid:29440466
- 57. Ghisla V, Scherrer AU, Nicca D, Braun DL, Fehr JS. Incidence of hepatitis C in HIV positive and negative men who have sex with men 2000–2016: a systematic review and meta-analysis. Infection. 2017;45(3):309–21. pmid:28005195
- 58. Charre C, Cotte L, Kramer R, Miailhes P, Godinot M, Koffi J, et al. Hepatitis C virus spread from HIV-positive to HIV-negative men who have sex with men. PLoS One. 2018;13(1):e0190340. pmid:29293630
- 59. Tieu HV, Laeyendecker O, Nandi V, Rose R, Fernandez R, Lynch B, et al. Prevalence and mapping of hepatitis C infections among men who have sex with men in New York City. PLoS One. 2018;13(7):e0200269. pmid:30020960
- 60. Werber D, Michaelis K, Hausner M, Sissolak D, Wenzel J, Bitzegeio J, et al. Ongoing outbreaks of hepatitis A among men who have sex with men (MSM), Berlin, November 2016 to January 2017—linked to other German cities and European countries. Euro surveillance: bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin. 2017;22(5). pmid:28183391
- 61. Comelli A, Izzo I, Casari S, Spinetti A, Bergamasco A, Castelli F. Hepatitis A outbreak in men who have sex with men (MSM) in Brescia (Northern Italy), July 2016-July 2017. Le infezioni in medicina: rivista periodica di eziologia, epidemiologia, diagnostica, clinica e terapia delle patologie infettive. 2018;26(1):46–51.
- 62. Lanini S, Minosse C, Vairo F, Garbuglia A, Di Bari V, Agresta A, et al. A large ongoing outbreak of hepatitis A predominantly affecting young males in Lazio, Italy; August 2016—March 2017. PLoS One. 2017;12(11):e0185428. pmid:29125835
- 63. Rodriguez-Tajes S, Perpinan E, Caballol B, Lens S, Marino Z, Costa J, et al. Hepatitis A outbreak in Barcelona among men who have sex with men (MSM), January-June 2017: A hospital perspective. Liver Int. 2018;38(4):588–93. pmid:28980376
- 64. Freidl GS, Sonder GJ, Bovee LP, Friesema IH, van Rijckevorsel GG, Ruijs WL, et al. Hepatitis A outbreak among men who have sex with men (MSM) predominantly linked with the EuroPride, the Netherlands, July 2016 to February 2017. Euro surveillance: bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin. 2017;22(8). pmid:28251892
- 65. Beebeejaun K, Degala S, Balogun K, Simms I, Woodhall SC, Heinsbroek E, et al. Outbreak of hepatitis A associated with men who have sex with men (MSM), England, July 2016 to January 2017. Euro surveillance: bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin. 2017;22(5). pmid:28183392
- 66. Charre C, Ramiere C, Roque-Afonso AM, Chidiac C, Zoulim F, Godinot M, et al. Hepatitis A outbreak in HIV-infected MSM and in PrEP-using MSM despite a high level of immunity, Lyon, France, January to June 2017. Euro surveillance: bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin. 2017;22(48).
- 67. Kojima N, Davey DJ, Klausner JD. Pre-exposure prophylaxis for HIV infection and new sexually transmitted infections among men who have sex with men. Aids. 2016;30(14):2251–2. pmid:27314179
- 68. Harawa NT, Holloway IW, Leibowitz A, Weiss R, Gildner J, Landovitz RJ, et al. Serious concerns regarding a meta-analysis of preexposure prophylaxis use and STI acquisition. Aids. 2017;31(5):739–40. pmid:28225452
- 69. Parsons J, Rendina HJ, Whitfield T, Grov C. Changes in rectal STI incidence and behavioral HIV risk before, during, and after PrEP in a national sample of gay and bisexual men in the United States. International AIDS Conference; Amsterdam 2018.
- 70. Traeger M, Asselin J, Price B, Cornelisse V, Roth N, Willcox J, et al. Changes, Patterns and Predictors of Sexually Transmitted Infections in Gay and Bisexual Men Using PrEP—Interim Analysis from the PrEPX Study. International AIDS Conference; Amsterdam 2018.
- 71. Beymer MR, DeVost MA, Weiss RE, Dierst-Davies R, Shover CL, Landovitz RJ, et al. Does HIV pre-exposure prophylaxis use lead to a higher incidence of sexually transmitted infections? A case-crossover study of men who have sex with men in Los Angeles, California. Sexually transmitted infections. 2018;94(6):457–62. pmid:29487172
- 72. Jenness SM, Weiss KM, Goodreau SM, Gift T, Chesson H, Hoover KW, et al. Incidence of Gonorrhea and Chlamydia Following Human Immunodeficiency Virus Preexposure Prophylaxis Among Men Who Have Sex With Men: A Modeling Study. Clin Infect Dis. 2017;65(5):712–8. pmid:28505240