Adherence to Post-Exposure Prophylaxis (PEP) and Incidence of HIV Seroconversion in a Major North American Cohort

Abstract

Background

There is limited evidence on the efficacy of post-exposure prophylaxis (PEP) for sexual exposures. We sought to determine the factors associated with adherence to treatment and describe the incidence of PEP failures in a Montreal clinic.

Methods

We prospectively assessed all patients consulting for PEP following sexual exposures from October 2000 to July 2014. Patients were followed at 4 and 16 weeks after starting PEP. Treatment adherence was determined by self-report at week 4. Multivariable logistic regression was used to estimate the factors predicting adherence to treatment.

Results

3547 PEP consults were included. Patients were mainly male (92%), MSM (83%) and sought PEP for anal intercourse (72%). Seventy-eight percent (n = 2772) of patients received a prescription for PEP, consisting of Tenofovir/Emtracitabine (TVD) + Lopinavir/Ritonavir (LPV) in 74% of cases, followed by Zidovudine/Lamivudine (CBV) + LPV (10%) and TVD + Raltegravir (RAL) (8%). Seventy percent of patients were adherent to treatment. Compared to TVD+LPV, patients taking CBV+LPV were less likely to adhere to treatment (OR 0.58, 95% CI 0.44–0.75), while no difference was observed for patients taking TVD+RAL (OR 1.15, 95% CI 0.83–1.59). First-time PEP consults, older and male patients were also more adherent to treatment. Ten treated patients seroconverted (0.37%) during the study period, yet only 1 case can be attributed to PEP failure (failure rate = 0.04%).

Conclusion

PEP regimen was associated with treatment adherence. Patients were more likely to be adherent to TVD-based regimens. Ten patients seroconverted after taking PEP; however, only 1 case was a PEP failure as the remaining patients continued to engage in high-risk behavior during follow-up. One month PEP is an effective preventive measure to avoid HIV infection.

About the Authors:

Réjean Thomas

Affiliation: Clinique médicale l’Actuel, Montreal, Quebec, Canada

Chrissi Galanakis

Affiliation: Clinique médicale l’Actuel, Montreal, Quebec, Canada

Sylvie Vézina

Affiliation: Clinique médicale l’Actuel, Montreal, Quebec, Canada

Danièle Longpré

Affiliation: Clinique médicale l’Actuel, Montreal, Quebec, Canada

Michel Boissonnault

Affiliation: Clinique médicale l’Actuel, Montreal, Quebec, Canada

Emmanuelle Huchet

Affiliation: Clinique médicale l’Actuel, Montreal, Quebec, Canada

Louise Charest

Affiliation: Clinique médicale l’Actuel, Montreal, Quebec, Canada

Daniel Murphy

Affiliation: Clinique médicale l’Actuel, Montreal, Quebec, Canada

Benoît Trottier

Affiliation: Clinique médicale l’Actuel, Montreal, Quebec, Canada

Nimâ Machouf

* E-mail: [email protected]

Affiliation: Clinique médicale l’Actuel, Montreal, Quebec, Canada

Introduction

The estimated risk of HIV transmission via sexual intercourse ranges from 0.2 to 1.4% depending on the type of exposure, with receptive anal intercourse having the greatest risk of HIV acquisition [1–4]. The indication of Post-Exposure Prophylaxis (PEP) following sexual exposures has been recommended by various international guidelines though current evidence on PEP efficacy regarding these exposures is sparse and most research supporting its use stems from animals models and observational studies on mother-to-child transmission and occupational exposures [3, 5–8].

Adherence and continued high-risk sexual behaviors are both key determinants of PEP efficacy [3]. However, treatment completion rates are inconsistent across the literature and vary according to exposure, population and study type [9–15]. Moreover, though studies have described the incidence of HIV infection following PEP use for non-occupational exposures, it is unclear whether the seroconversions that occurred are the result of PEP failure or continued exposure to HIV [16, 17]. While a 28-day regimen of PEP administered within 72 hours of the exposure may prevent HIV infection, its effectiveness for sexual exposures remains unknown [6, 18, 19]. As poor adherence and re-exposure to HIV limit the assessment of PEP efficacy, determining the factors associated with the latter is crucial.

In this article we aimed to: 1) describe the population presenting for PEP following sexual exposures at our clinic; 2) determine the factors associated with adherence to PEP treatment and 3) document the incidence of the seroconversions from treatment failures.

Methods

Study Design and Participants

Clinique médicale L’Actuel is a community clinic specialized in HIV that has been providing PEP for non-occupational exposures since 2000 and receives 40–50 consultations each month. It has one of the largest cohorts of PEP users in Canada with over 4000 consultations to date. We conducted a prospective observational study of all patients presenting for PEP following a sexual exposure from October 2000 to July 2014. We prospectively assessed all patients seeking PEP at their initial visit. Patients refusing consent and those presenting for non-sexual exposures were excluded from the study.

Clinical Protocol

Initial Patient Evaluation.

Upon presentation at the clinic, information regarding the sexual exposure, consultation delay, the source and the patient’s history of at-risk behavior was evaluated by a triage nurse. Patients were also explained the follow-up procedure and provided counseling on antiretroviral (ARV) therapy. HIV rapid testing (INSTI), MEIA screening for HIV antibodies and antigen p24 tests (Abbott ARCHITECT ® HIV Ag/Ab Combo) were offered to patients and their partners, if present at the consultation. Patients were then examined by a physician, attributed an exposure risk (negligible, moderate or high) and indicated a treatment accordingly. Advice on ARV use and STD counseling was also provided to patients at this time.

Treatment.

Patients were prescribed a 28-day ARV regimen consisting mainly of 2 NRTIs and a third agent (protease inhibitor or integrase inhibitor). Treatment was not indicated for patients who presented 72 hours or more after the exposure, for those with a negligible risk of infection or for those testing HIV positive at baseline.

Follow-up and Adherence.

Patients receiving treatment had scheduled follow-up visits at 4 weeks (end of treatment) and 12 weeks after the initial PEP consultation. Prior to 2009, the PEP protocol consisted of 8 visits over a 6-month follow-up period (24 weeks). From 2009 to February 2014, the PEP follow-up changed to 3 visits over a 4-month period (16 weeks). Thus, for the purpose of this study, we used the information collected at baseline, week 4 and either week 12, 16 or 24 depending on the year of the PEP consult.

Information on treatment adherence, side-effects and ongoing at-risk sexual behavior was collected and HIV testing was performed at each follow-up visit. Patients were considered adherent to treatment if they did not miss more than 5 doses during their month-long treatment. Ongoing at-risk sexual practices were defined as unprotected anal sexual intercourse, fellatio with receptive ejaculation or any other behavior the physician evaluated to be high risk.

Sexual Exposure

We collected information on the type of intercourse (e.g. anal, vaginal, fellatio, with or without ejaculation, receptive or insertive), condom use, drug and alcohol use at the time of exposure, relationship with the source, HIV status of the source and the risk status of the source. HIV status was defined as positive, negative (if the source was tested at the visit), or unknown with either low or high risk of being HIV positive. A source was considered high risk if they belonged to the following groups: men who have sex with men (MSM), sex workers, from endemic regions, hemophiliacs or intravenous drug users.

Ethical Considerations

Ethical approval was provided by the Veritas Independent Review Board. Patients provided written consent to the use of their clinical data for research purposes on post-exposure prophylaxis.

Statistical Analysis

Statistical analysis was performed using SPSS version 17.0 (IBM, USA). Multivariable logistic regression was used to estimate the factors predicting adherence to treatment. Intent-to-treat analysis was applied to treatment adherence. P-values less than 0.05 were considered statistically significant.

Results

As of July 1^st 2014, we received 3700 PEP consultations. Among the consultations, 153 were excluded: 74 patients refused consent, 7 patients left the consultation before they could be evaluated by a physician, and 72 consultations were for non-sexual exposures. A total of 3547 consultations were included in this study.

Patients consulting for sexual PEP were primarily male (92%), MSM (83%) and university educated (49%) with a mean age of 34.6 (SD 10.2). It was the first consultation for 70% of patients, 25% had 2–4 PEP consultations and only 3% of patients had 5 or more PEP episodes. Forty-three percent of patients were intoxicated at the time of exposure and two-thirds of patients had sexual relations with an unknown source (Table 1). Among exposures where the patient was familiar with the source, the source was known to be HIV+ in 64% of cases, whereas 15% tested HIV-negative and 21% had unknown HIV statuses. The risk of the exposure was considered moderate to high in 81% of cases. Anal intercourse was the most common type of exposure (n = 2560, 72%), followed by fellatio (n = 1607, 45%), receiving fellatio (n = 1188, 33%) and vaginal intercourse (n = 542, 15%). Over half (54%) of anal intercourse was receptive, 56% of which was unprotected. Likewise, 51% of insertive anal intercourse and 43% of vaginal intercourse was unprotected. All except 51 (1%) patients consulted within the 72-hour delay following the exposure.

[Figure omitted. See PDF.]

Table 1. Patient and exposure characteristics (N = 3547).

https://doi.org/10.1371/journal.pone.0142534.t001

Among the 3547 consults, 2772 (78%) patients received a prescription for PEP (Table 2). Patients were mainly prescribed 2 NRTIs and a protease inhibitor, consisting of Tenofovir/Emtacitabine (TVD) + Lopinavir/Ritonavir (LPV) (74%) or Zidovudine/Lamivudine (CBV) + LPV (10%). TVD + Raletegravir (RAL) was prescribed in 8% of cases. The exposure risk was perceived as moderate to high in 96% of cases where treatment was indicated (data not shown). However, only 2731 patients were treated as 41 stopped their treatment prematurely as the source tested HIV negative and no window period was suspected. Of the 2731 treated patients, 69% completed their entire prescribed treatment, 2% missed more than 5 doses, 4% discontinued prophylaxis and 1% switched to a different regimen, while 16% were lost to follow-up and 8% has missing information. Side effects were the main reason for discontinuation and regimen switching (70% and 90% respectively).

[Figure omitted. See PDF.]

Table 2. PEP regimen prescribed (N = 2772).

https://doi.org/10.1371/journal.pone.0142534.t002

Overall, 1902 (70%, OT = 87%) patients were adherent to treatment (Table 3). Patients taking TVD-based regimens adhered more to treatment than those on CBV-based or other regimens (72% adherent vs. 60% and 59%, p <0.001). Compared to patients who received TVD+LPV, patients taking CBV+LPV were less likely to adhere to treatment (OR 0.58, 95% CI 0.44–0.76). Patients taking TVD+RAL, however, were as likely as those taking TVD+LPV to be adherent to treatment (OR 1.15, 95% CI 0.83–1.59). First-time PEP consults, older and male patients also tend to adhere more to treatment (Table 4).

[Figure omitted. See PDF.]

Table 3. Adherence to prescribed PEP regimen (N = 2731).

https://doi.org/10.1371/journal.pone.0142534.t003

[Figure omitted. See PDF.]

Table 4. Factors associated with adherence to PEP regimen (N = 2731).

https://doi.org/10.1371/journal.pone.0142534.t004

Seroconversion

Eleven patients seroconverted within the follow-up period of the PEP protocol. One patient, however, was not treated as the source was presumed to be HIV-negative. As such, 10 of the 2731 treated patients could be possible treatment failures (0.37%). Nevertheless, 9 (90%) of the 10 treated cases continued to exhibit high-risk behavior following treatment; therefore, only one case can be considered a pure treatment failure (0.04%). Characteristics of these cases are presented in Table 5. Seroconverted patients had a mean age of 31 years (SD 9.1) and were all male and MSM. It was the first PEP episode for 9 (82%) patients and 6 (55%) consulted within the first 24 hours of the exposure. The main indication for PEP was unprotected anal intercourse (82% receptive, 27% insertive). One patient had no recollection of the exposure and eight (73%) patients were intoxicated at the time of exposure. All treated patients completed treatment; 9 (90%) were compliant and one case has no information on treatment adherence.

[Figure omitted. See PDF.]

Table 5. Characteristics of seroconverted cases (N = 11).

https://doi.org/10.1371/journal.pone.0142534.t005

Discussion

Patients presenting at our clinic are young MSM seeking PEP following high-risk sexual exposures. Unprotected anal intercourse with a source of unknown HIV status was the most common type of exposure among PEP consults. Over half of patients did not use condoms during anal intercourse; a trend that has been reported in other studies [20, 21]. While PEP awareness and utilization have been described as low [22–26], patients in this study seem to be knowledgeable with regards to HIV prophylaxis as almost half consulted within 24 hours of the exposure.

Adherence in this study (70%) was consistent with other PEP completion rates reported in the literature [9, 10, 12, 15, 21, 26, 27]. Treatment regimen was significantly associated with PEP adherence. Among the 3 main regimens prescribed, patients taking CBV+LPV were less likely to adhere to treatment as compared to TVD+LPV regimens and there was no difference in adherence between TVD+LPV and TVD+RAL. Our results indicate that tolerability may be an important factor in improving adherence to PEP. For instance, the observed increase in PEP completion with TVD-based regimens is likely due to the better tolerability of the TDF/FTC backbone [28–31]. Moreover, studies examining PEP regimens consisting of TVD + RAL have also demonstrated fewer side effects among patients taking CBV-based regimens [32] and showed no difference in adherence when compared to TVD alone [13]. Though it is also suggested that 2-drug regimens are associated with improved PEP adherence in terms of pill burden and dosing [3, 9, 21], the latter do not seem to be factors in our patient population as very few patients were prescribed dual therapy. Additional studies are required to assess the effects of pill burden and tolerability of new PEP regimen combinations on treatment adherence.

Moreover, less than 1% of patients seen over the course of 14 years seroconverted following PEP. Though 10 treated patients seroconverted during the study period, we can only attribute one of these cases to possible treatment failure as only one patient reported no additional high-risk exposures. Nevertheless, the possibility remains that other exposures prior to PEP consultation may have resulted in seroconversion. The rate of seroconversion in this study was comparable to other studies on PEP efficacy [12, 17, 19, 26, 33–35]. As in our study, only a small portion of seroconversions were considered PEP failures as the patients continued to exhibit ongoing high-risk sexual behaviors [12, 17, 19, 34]. A longitudinal study of HIV infection after PEP use had 39 (4.4%) cases seroconvert (HIV incidence rate 2.2 infections per 100 person-years) over a 16 year period with the majority of cases seroconverting outside the standard PEP follow-up period [36]. These findings suggest that the seroconversions observed were not due to PEP failure but other high-risk exposures to HIV [36]. As PEP users are at greater risk of subsequent HIV infection given their propensity of continued at-risk behavior, patients should consider pre-exposure prophylaxis (PrEP) as an alternative prevention strategy. Daily PrEP use would be particularly beneficial for a third of patients in this study with repeat PEP episodes. A combination of risk reducing behavioral interventions and prophylaxis may therefore be more beneficial to patients than PEP alone [27, 37].

This study had several limitations. Adherence and re-exposure were measured by self-report, thereby being potentially susceptible to social desirability bias as patients may not have been forthcoming to their physicians about their behavioral practices and treatment compliance. Adherence data was missing for several patients. Though intent-to-treat analysis was used to compensate for the missing data, we may have underestimated the proportion of patients adhering to treatment. Some patients inconsistently attended the scheduled follow-up visits for HIV testing, limiting our ability to accurately determine the time of seroconversion. We were also unable to adjust for other factors which may have influenced treatment indication and regimen selection.

Conclusions

PEP regimen was significantly associated with adherence to treatment. Patients were more likely to be adherent to TVD-based regimens which are known to have better tolerability than CBV-based regimens. Ten patients seroconverted during the follow-up period after taking PEP; however, only a single case of PEP failure was observed as the remaining cases did not reduce at-risk behaviors and increased possible re-exposure to HIV. PEP is therefore a successful method to prevent HIV infection after sexual exposure. This study also underlines the impact of a global approach, including a close and multidisciplinary follow-up, as a key component of the PEP protocol.

Acknowledgments

The authors would like to thank Martha Cadieux and Maliheh Vaziri for data entry and data management.

Author Contributions

Conceived and designed the experiments: NM CG. Performed the experiments: RT BT SV EH DL LC MB. Analyzed the data: CG NM. Wrote the paper: RT BT CG NM. Manuscript review and clinical input: SV DL MB EH LC DM.

Citation: Thomas R, Galanakis C, Vézina S, Longpré D, Boissonnault M, Huchet E, et al. (2015) Adherence to Post-Exposure Prophylaxis (PEP) and Incidence of HIV Seroconversion in a Major North American Cohort. PLoS ONE 10(11): e0142534. https://doi.org/10.1371/journal.pone.0142534

References

1. Baggaley RF, White RG, Boily MC. HIV transmission risk through anal intercourse: systematic review, meta-analysis and implications for HIV prevention. Int J Epidemiol. 2010;39(4):1048–63. pmid:20406794

2. Jin F, Jansson J, Law M, Prestage GP, Zablotska I, Imrie JC, et al. Per-contact probability of HIV transmission in homosexual men in Sydney in the era of HAART. AIDS. 2010;24(6):907–13. pmid:20139750

3. Sultan B, Benn P, Waters L. Current perspectives in HIV post-exposure prophylaxis. HIV/AIDS (Auckl). 2014;6:147–58.

4. Patel P, Borkowf CB, Brooks JT, Lasry A, Lansky A, Mermin J. Estimating per-act HIV transmission risk: a systematic review. AIDS. 2014;28(10):1509–19. pmid:24809629

5. Barber TJ, Benn PD. Postexposure prophylaxis for HIV following sexual exposure. Curr Opin HIV AIDS. 2010;5(4):322–6. pmid:20543608

6. Benn P, Fisher M, Kulasegaram R, Bashh , Group PGWGCE. UK guideline for the use of post-exposure prophylaxis for HIV following sexual exposure (2011). Int J STD AIDS. 2011;22(12):695–708. pmid:22174049

7. Cardo DM, Culver DH, Ciesielski CA, Srivastava PU, Marcus R, Abiteboul D, et al. A case-control study of HIV seroconversion in health care workers after percutaneous exposure. Centers for Disease Control and Prevention Needlestick Surveillance Group. N Engl J Med. 1997;337(21):1485–90. pmid:9366579

8. Irvine C, Egan KJ, Shubber Z, Van Rompay KK, Beanland RL, Ford N. Efficacy of HIV Postexposure Prophylaxis: Systematic Review and Meta-analysis of Nonhuman Primate Studies. Clin Infec Dis. 2015;60 (Suppl 3):S165–9.

9. Oldenburg CE, Barnighausen T, Harling G, Mimiaga MJ, Mayer KH. Adherence to post-exposure prophylaxis for non-forcible sexual exposure to HIV: a systematic review and meta-analysis. AIDS Behav. 2014;18(2):217–25. pmid:23877791

10. Ford N, Irvine C, Shubber Z, Baggaley R, Beanland R, Vitoria M, et al. Adherence to HIV postexposure prophylaxis: a systematic review and meta-analysis. AIDS. 2014;28(18):2721–7. pmid:25493598

11. Bogoch II, Scully EP, Zachary KC, Yawetz S, Mayer KH, Bell CM, et al. Patient attrition between the emergency department and clinic among individuals presenting for HIV nonoccupational postexposure prophylaxis. Clin Infect Dis. 2014;58(11):1618–24. pmid:24723288

12. Gulholm T, Jamani S, Poynten IM, Templeton DJ. Non-occupational HIV post-exposure prophylaxis at a Sydney metropolitan sexual health clinic. Sexl Health. 2013;10(5):438–41.

13. McAllister J, Read P, McNulty A, Tong WWY, Ingersoll A, Carr A. Raltegravir-emtricitabine-tenofovir as HIV nonoccupational post-exposure prophylaxis in men who have sex with men: safety, tolerability and adherence. HIV Med. 2014;15(1):13–22. pmid:24007390

14. Krause KH, Lewis-O'Connor A, Berger A, Votto T, Yawetz S, Pallin DJ, et al. Current practice of HIV postexposure prophylaxis treatment for sexual assault patients in an emergency department. Womens Health Issues. 2014;24(4):e407–12. pmid:24981399

15. Lunding S, Katzenstein T, Kronborg G, Lindberg J, Jensen J, Nielsen H, et al. Danish post-exposure prophylaxis (PEP) registry: 10 years experience with the use of PEP following HIV exposure. Poster presented at: 4th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention; 2007 July 22–25, Sydney, Australia.

16. Heuker J, Sonder GJ, Stolte I, Geskus R, van den Hoek A. High HIV incidence among MSM prescribed postexposure prophylaxis, 2000–2009: indications for ongoing sexual risk behaviour. AIDS. 2012;26(4):505–12. pmid:22156963

17. Tissot F, Erard V, Dang T, Cavassini M. Nonoccupational HIV post-exposure prophylaxis: a 10-year retrospective analysis. HIV Med. 2010;11(9):584–92. pmid:20345883

18. Bryant J, Baxter L, Hird S. Non-occupational postexposure prophylaxis for HIV: a systematic review. Health Technol Assess. 2009;13(14):iii, ix-x, 1–60. pmid:19236820

19. Roland ME, Neilands TB, Krone MR, Katz MH, Franses K, Grant RM, et al. Seroconversion following nonoccupational postexposure prophylaxis against HIV. Clin Infect Dis. 2005;41(10):1507–13. pmid:16231265

20. Casalino E, Choquet C, Leleu A, Hellmann R, Wargon M, Juillien G, et al. Trends in condom use and risk behaviours after sexual exposure to HIV: a seven-year observational study. PloS One. 2014;9(8):e104350. pmid:25157477

21. Jain S, Oldenburg CE, Mimiaga MJ, Mayer KH. Longitudinal Trends in HIV Nonoccupational Postexposure Prophylaxis Use at a Boston Community Health Center Between 1997 and 2013. J Acquir Immune Defic Syndr. 2015;68(1):97–101. pmid:25321180

22. Joshi M, Basra A, McCormick C, Webb H, Pakianathan M. Post-exposure prophylaxis after sexual exposure (PEPSE) awareness in an HIV-positive cohort. Int J STD AIDS. 2014;25(1):67–9. pmid:23970629

23. Rodriguez AE, Castel AD, Parish CL, Willis S, Feaster DJ, Kharfen M, et al. HIV medical providers' perceptions of the use of antiretroviral therapy as nonoccupational postexposure prophylaxis in 2 major metropolitan areas. J Acquir Immune Defic Syndr. 2013;64 (Suppl 1):S68–79. pmid:24126450

24. Fernandez-Balbuena S, Belza MJ, Castilla J, Hoyos J, Rosales-Statkus ME, Sanchez R, et al. Awareness and use of nonoccupational HIV post-exposure prophylaxis among people receiving rapid HIV testing in Spain. HIV Med. 2013;14(4):252–7. pmid:23088284

25. Mehta SA, Silvera R, Bernstein K, Holzman RS, Aberg JA, Daskalakis DC. Awareness of post-exposure HIV prophylaxis in high-risk men who have sex with men in New York City. Sex Transm Infect. 2011;87(4):344–8. pmid:21357600

26. McDougal SJ, Alexander J, Dhanireddy S, Harrington RD, Stekler JD. Non-occupational post-exposure prophylaxis for HIV: 10-year retrospective analysis in Seattle, Washington. PloS One. 2014;9(8):e105030. pmid:25140868

27. Landovitz RJ, Fletcher JB, Inzhakova G, Lake JE, Shoptaw S, Reback CJ. A novel combination HIV prevention strategy: post-exposure prophylaxis with contingency management for substance abuse treatment among methamphetamine-using men who have sex with men. AIDS Patient Care STDs. 2012;26(6):320–8. pmid:22680280

28. Gallant JE, DeJesus E, Arribas JR, Pozniak AL, Gazzard B, Campo RE, et al. Tenofovir DF, emtricitabine, and efavirenz vs. zidovudine, lamivudine, and efavirenz for HIV. N Engl J Med. 2006;354(3):251–60. pmid:16421366

29. Arribas JR, Pozniak AL, Gallant JE, Dejesus E, Gazzard B, Campo RE, et al. Tenofovir disoproxil fumarate, emtricitabine, and efavirenz compared with zidovudine/lamivudine and efavirenz in treatment-naive patients: 144-week analysis. J Acquir Immune Defic Syndr. 2008;47(1):74–8. pmid:17971715

30. Cai J, Xiao J, Zhang Q. Side effects and tolerability of post-exposure prophylaxis with zidovudine, lamivudine, and lopinavir/ritonavir: a comparative study with HIV/AIDS patients. Chin Med J (Engl.). 2014;127(14):2632–6.

31. Tosini W, Muller P, Prazuck T, Benabdelmoumen G, Peyrouse E, Christian B, et al. Tolerability of HIV postexposure prophylaxis with tenofovir/emtricitabine and lopinavir/ritonavir tablet formulation. AIDS. 2010;24(15):2375–80. pmid:20729709

32. Mayer KH, Mimiaga MJ, Gelman M, Grasso C. Raltegravir, tenofovir DF, and emtricitabine for postexposure prophylaxis to prevent the sexual transmission of HIV: safety, tolerability, and adherence. J Acqui Immune Defic Syndr. 2012;59(4):354–9.

33. McCarty EJ, Quah S, Maw R, Dinsmore WW, Emerson CR. Post-exposure prophylaxis following sexual exposure to HIV: a seven-year retrospective analysis in a regional centre. Int J STD AIDS. 2011;22(7):407–8. pmid:21729962

34. Chan ACH, Gough K, Yoong D, Dimeo M, Tan DHS. Non-occupational post-exposure prophylaxis for HIV at St Michael's Hospital, Toronto: a retrospective review of patient eligibility and clinical outcomes. Int J STD AIDS. 2013;24(5):393–7. pmid:23970708

35. Vives N, Almeda J, Contreras CA, Garcia F, Campins M, Casabona J, et al. Use of non-occupational HIV post-exposure prophylaxis in Spain (2001–2005). Enferm Infecc Microbiol Clin. 2008;26(9):546–51. pmid:19100173

36. Jain S, Oldenburg CE, Mimiaga MJ, Mayer KH. Subsequent HIV Infection Among Men Who Have Sex with Men Who Used Non-Occupational Post-Exposure Prophylaxis at a Boston Community Health Center: 1997–2013. AIDS Patient Care STDs. 2015;29(1):20–5. pmid:25369451

37. Dilley JW, Woods WJ, Loeb L, Nelson K, Sheon N, Mullan J, et al. Brief cognitive counseling with HIV testing to reduce sexual risk among men who have sex with men: results from a randomized controlled trial using paraprofessional counselors. J Acquir Immune Defic Syndr. 2007;44(5):569–77. pmid:17310937