Pre-exposure prophylaxis for HIV with oral tenofovir disoproxil fumarate/emtricitabine in men who have sex with men: Slovenian national demonstration project

Abstract

Prevalence of HIV in Slovenia is low, and men who have sex with men (MSM) have the highest risk for infection. Rates of enrolment into HIV care, initiation of antiretroviral therapy and reaching an undetectable viral load in HIV-infected patients are very high. Prevention of HIV infection for MSM with PrEP is not formally available in Slovenia. The aim of this study was to demonstrate possible implementation of PrEP in Slovenia. Sixty-nine (n = 69) MSM with increased risk for HIV received PrEP with oral tenofovir disproxil fumarate /emtricitabine and acquisition were followed for a mean of 566.6 days. They had 71 episodes of STIs (incidence 61.7 per 100 person-years). No one got acquired HIV infection. Estimated glomerular filtration rate (EGFR) was significantly lower 4 (p = 0.014) and 19 (p = 0.021) months after inclusion; however, there was no clinically significant renal failure (mean EGFR 110–115 mL/min). Self-reported body weight significantly increased after 7 months (p < 0.05). Overall EGFR and self-reported body weight did not change significantly. No significant change in adherence (overall mean 81.0%; 95% CI 77.5%–84.6%; p = 0.728), condom use (p = 0.077) and number of sexual partners (overall mean 2.36 per 30 days; 95% CI 2.06 to 2.65; p = 0.235) was found throughout the study. Participants reported 110 graded adverse effects (AE), 104 (94.5%) grade 1–2 and 6 (5.5%) grade 3–4. No participant discontinued PrEP due to AE. The study showed successful implementation of PrEP among MSM at high risk for HIV infection in Slovenia. Based on the results of our study, PrEP should be formally available in Slovenia.

Keywords

Prevention HIV Europe men who have sex with men antiretroviral therapy

Introduction

Pre-exposure prophylaxis (PrEP) of HIV with oral tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) was introduced in the early 2010s and has shown high efficacy in HIV prevention among men who have sex with men (MSM).^1–4 The European Centre for Disease Control (ECDC) and the World Health Organization (WHO) recommended, in 2015 and 2016, respectively, PrEP as part of a combination strategy to end the HIV pandemic.^5,6 By the end of 2019, >30 countries worldwide implemented PrEP either through national health services, in specific healthcare settings or via pilot/research/demonstration projects.⁷

Slovenia is a country with low HIV prevalence. From 2010 up to 20 November 2020, the yearly HIV incidence ranged from 2.9/100,000 inhabitants in 2016 to 1.3/100,000 inhabitants in 2020. In comparison, the average HIV incidence in the European Union and the European Economic Area was 5.1/100,000 inhabitants in 2018. The predominantly affected group in Slovenia is MSM.⁸

The core of HIV prevention among MSM in Slovenia has been safe sex education, good access to HIV and sexually transmitted infection (STI) testing, counselling within the MSM community, early linkage to care and early treatment of people living with HIV.⁹ The HIV National Strategy from 2017 to 2025 recommends implementation of post-exposure prophylaxis (PEP) and PrEP.⁹ In 2020, 704 HIV patients were involved in care, 92% were on therapy and of those 96% were undetectable; PEP is available through infectious diseases outpatient services.⁸ PrEP was not formally available in Slovenia due to insufficient information on PrEP implementation. This demonstration project enabled formal PrEP for MSM at highest risk for HIV infection.

The objectives of the study were to provide information for the national stakeholders on possible implementation of PrEP for MSM in Slovenia, to demonstrate the presence of MSM willing to participate in such a preventive programme and to monitor adherence and safety of PrEP, incidence of STIs, and use of alcohol and drugs at sexual intercourse in this population.

Methods

We conducted a prospective single centre demonstration study assessing possible PrEP delivery in Slovenia. The participants were recruited through social media, nongovernmental organisations, STI outpatient services, HIV anonymous testing sites and oral dissemination in the MSM community. MSM age ≥18 years with ≥1 inclusion criteria in the previous 12 months (self-reported condomless anal sex, a diagnosed STI or any use of PEP) were included. The exclusion criteria were a positive fourth generation HIV test at inclusion (tested <7 days prior to inclusion), estimated glomerular filtration rate (EGFR) <60 mL/min, use of medications influencing renal function, chronic liver disease, HBsAg/anti-HBc positive, current PEP use, and conditions/diseases influencing adherence or safety. The participants used TDF/FTC 245/200 mg in tablet form. The regimen was ‘on demand’: 2 tablets 2–24 h before sex (or 1 tablet if they took ≥1 tablet in the previous 1–6 days), following 1 tablet QD until 48 h after the last sex (2 + 1 + 1).³ Participants with frequent risk of exposure were counselled to switch to daily regimen. Following the inclusion visit (V0), they were assessed after 1 (V1M), 4 (V4M), 7 (V7M), 10 (V10M), 13 (V13M), 16 (V16M) and 19 (V19M) months. The study drug was dispensed by the researchers at visits until V16M. Safer sex counselling was offered at each visit.

At every visit, self-reported body weight, number of sexual encounters (with differentiation between with/without condom, insertive/receptive and anal/oral), number of sexual partners (without differentiation of the type of sexual partner and steady vs. non-steady) and condom, drug and alcohol use were collected for the period of 12 months before V0 and thereafter for the period in-between two visits. Participants kept monthly diaries on PrEP, sex, drug and alcohol use and adverse effects (AE). Condom, drug and alcohol use were measured by self-reported percentage of episodes of anal sexual intercourse (below 50%, about 50%, about 75% or about 100%) with a condom or with consumption of drugs/alcohol. The participants reported all STIs diagnosed prior to V0 and those diagnosed elsewhere during the study. Laboratory assessment of renal function, liver enzymes, analysis of urine, fourth generation HIV test, HBsAg, anti-HBs, anti-HBc, anti-HCV, VDRL and TPHA/TPPA, and PCR test on separate swabs of urethra, rectum and pharynx for Chlamydia trachomatis and Neisseria gonorrhoeae were performed. Grading of AE was done with the Division of AIDS (DAIDS) Table.¹⁰ See Supplementary Appendix Table 1) for the detailed study protocol.

Renal function was assessed by measurement of serum creatinine and calculation of EGFR in mL/min (Cockcroft–Gault equation adjusted to the ideal body weight). Self-reported adherence to PrEP was defined as the proportion of episodes of sexual intercourse with appropriate timing and dosing of TDF/FTC (2 + 1 + 1) and calculated from the monthly diaries. The incidence of STIs was calculated as the sum of STIs diagnosed elsewhere and STIs confirmed at the study visits (excluding all viral hepatitis) and was adjusted for time in the study (mean duration from first to final visit). All newly diagnosed STIs were treated according to guidelines.

The statistical analysis with Microsoft^® Excel^® for Microsoft 365 MSO (16.0.13328.20262) was done using descriptive statistics, paired two sample test for means, one-tailed p-value for self-reported body weight and EGFR (comparing values at specific visit to V0) and single factor ANOVA for overall self-reported body weight, EGFR, adherence, number of sexual partners and condom, alcohol and drug use.

The study was approved by the National Medical Ethics Committee (approval number 0120-15/2018/10), and written informed consent was obtained from all participants.

Results

From 7 August 2018 until 24 December 2018, we included 74 MSM. Date of the final visit was 9 October 2020; average follow-up time was 566.6 days. Five participants were excluded after V0 because one participant was newly diagnosed with HIV, three participants had current or previous infections with HBV and one participant had decreased renal function. The baseline characteristics of the 69 remaining participants are presented in Table 1.

Table 1.

Baseline characteristics of the participants.

Characteristics
Age, years (IQR), n = 69	35.9 (28.6–41.9)
Self-reported weight, kg (IQR), n = 68	79.9 (73.8–85.0)
Inclusion criteria in previous 12 months
Condomless anal sex, n (%), n = 69	64 (92.8)
STI, n (%), n = 69	17 (24.6)
PEP, n (%), n = 69	8 (11.6)
Sex in the previous 12 months
Receptive or insertive anal intercourse with condom, mean n (range), n = 58	53 (0–200)
Receptive or insertive anal intercourse without condom, mean n (range), n = 59	44 (0–100)
Oral sex, mean n (range), n = 58	56 (0–119)
PEP before inclusion, n (%), n = 69	17 (24.6)
PrEP before inclusion, n (%), n = 69	9 (13.0)
Lifelong self-reported STIs before inclusion
Overall, n (%, range)	45 (65.2, 0–5)
Syphilis, n (%), n = 69	16 (23.2)
Gonorrhoea, n (%), n = 69	25 (36.2)
Chlamydia trachomatis infection, n (%), n = 69	16 (23.2)
LGV, n (%), n = 69	1 (1.4)
HSV infection, n (%), n = 69	2 (2.9)
HPV infection, n (%), n = 69	15 (21.7)
Past or current HCV infection, n (%), n = 69	1 (1.4)
Trichomonas vaginalis infection, n (%), n = 69	1 (1.4)

n: number; IQR: interquartile range; STI: sexually transmitted infection; PEP: post-exposure prophylaxis; PrEP: pre-exposure prophylaxis; LGV: lymphogranuloma venereum; HSV: herpes simplex virus; HPV: human papilloma virus; HCV: hepatitis C virus.

During the study, 71 episodes (41 in the study and 30 elsewhere) of STIs in 36 different participants were diagnosed (gonorrhoea 32, C. trachomatis infection 20, syphilis 9, Mycoplasma genitalium 4, HCV 3, HAV 1, HBV 1 and unspecified urethritis 1). HBV infection was diagnosed between V16M and V19M. All three HCV infections were newly acquired, diagnosed by positive anti-HCV in participants previously negative and confirmed by PCR tests. The estimated yearly incidence of STIs (excluding HAV, HBV and HCV) adjusted for the period in the study was 61.7 per 100 person-years. None of the 69 included MSM tested positive for HIV during the study.

Self-reported body weight significantly increased after V7M (in comparison to V0). EGFR (in comparison to V0) was significantly lower at V4M and V19M; however, there was no clinically significant renal failure, and no participant was excluded due to renal failure (Table 2). Overall self-reported body weight and EGFR did not change significantly. Proteinuria was transitionally detected in 9 participants (Table 2). The mean adherence was 81.0% (95% CI 77.5–84.6), and the mean number of sexual partners per 30 days was 2.36 (95% CI 2.06–2.65) (Table 2). Reported alcohol (p = 0.765) and drug (p = 0.975) use did not change throughout the study period (Table 2). See Supplementary Appendix Table 2 for detail on attendance, time period, answer availability and tests performed.

Table 2.

Self-reported body weight, serum creatinine, EGFR, proteinuria, adherence, condom use and number of sexual partners.

	V0	V1M	V4M	V7M	V10M	V13M	V16M	V19M
Self-reported body weight
Mean, kg	79.9	79.4	79.6	79.6	82.2	79.2	81.2	81.0
Median, kg	78.5	78.0	80.0	79.0	80.5	79.0	80.0	80.0
IQR, kg	73.8–85.0	71.0–83.5	72.8–85.0	70.5–85.5	73.5–86.5	73.5–85.0	75.0–86.0	73.5–85.0
p value, mean^a	—	0.128	0.129	0.018	0.001	0.030	0.002	0.000
p value, mean	0.926
Serum creatinine
Mean, µmol/L	86.5	88.2	88.3	87.7	87.2	87.9	86.6	88.0
Median, µmol/L	84.5	87.5	89.0	84.0	87.5	84.0	86.0	86.5
IQR, µmol/L	78.8–90.5	80.0–95.3	80.0–95.5	80.0–93.0	82.0–93.0	80.0–94.5	80.3–90.8	81.0–92.3
Range	66–121	67–120	65–108	60–139	66–115	66–118	64–112	64–127
EGFR
Mean, mL/min	115	113	112	112	112	110	112	111
Median, mL/min	115	111	111	112	112	110	109	111
IQR, mL/min	99.4–129.3	97.0–125.0	97.2–119.0	101.4–123.0	98.9–122.6	97.0–123.2	99.8–120.8	96.5–121.7
Range	76–180	83–169	76–158	69–183	87–159	80–157	83–157	79–145
p value, mean^a	—	0.105	0.014	0.068	0.057	0.084	0.308	0.021
p value, mean	0.890
Proteinuria
Number	0	1	0	5	4	2	1	2
Adherence
Mean	—	0.77	0.81	0.80	0.81	0.87	0.81	—
Median	—	1.00	1.00	0.96	1.00	1.00	1.00	—
IQR	—	0.60–1.00	0.72–1.00	0.70–1.00	0.81–1.00	0.96–1.00	0.83–1.00	—
p value, mean		0.728
Condom use
Less than 50%	24.2	48.3	45.8	50.0	48.3	49.0	56.5	37.9
About 50%	9.1	13.3	18.6	12.5	20.7	15.7	23.9	10.3
About 75%	63.6	18.3	16.9	23.2	15.5	23.5	8.7	24.1
About 100%	3.0	20.0	18.6	14.3	15.5	11.8	10.9	27.6
p value	0.077
Number of sexual partners per 30 days
Mean	—	3.25	2.69	2.59	2.02	2.75	2.04	1.20
Median	—	2.50	1.88	1.98	1.57	1.76	1.48	0.99
IQR	—	1.22–4.29	0.67–3.38	0.79–3.66	1.19–2.97	1.05–3.35	0.91–3.23	0.39–1.22
p value, mean		0.235^b
p value, mean		0.025^c

IQR: interquartile range; EGFR: estimated glomerular filtration rate.

^a In comparison to V0.

^b Calculated for V1M-V16M.

^c Calculated for V1M-V19M.

The proportion of participants with ≥1 AE was highest at V10M 35.6%. The majority (104, 94.5%) of graded AE were mild to moderate (grade 1–2), and 6 (5.5%) AE were grade ≥3. All liver-related AE grade ≥3 were caused by acute viral hepatitis. No participants left the study because of AE. Details on AE are presented in Table 3.

Table 3.

Adverse effects.

	V1M	V4M	V7M	V10M	V13M	V16M	V19M	Sum
Number of participants with ≥1 AE, (%)	20 (30.8)	21 (32.8)	15 (24.6)	21 (35.6)	18 (34.6)	13 (26.0)	10 (16.7)	—
Diarrhoea, grade 1–2	5	3	1	1	0	0	0	10
Diarrhoea, grade 3–4	0	0	0	0	0	1	0	1
Fatigue, grade 1–2	4	1	0	2	2	0	0	9
AST or ALT elevation,^a grade 1–2 (1.25–5.0 × ULN)	4	7	4	8^b	5	7	4	39
AST or ALT elevation,^a grade 3–4 (>5.0 × ULN)	0	0	0	0	3^c	0	1^d	4
Serum creatinine elevation,^a grade 1–2 (1.1–1.8 × ULN)	0	4	4	3	6	2	3	22
Mood change, grade 1–2	1	0	0	0	0	0	0	1
Nausea, grade 1–2	8	4	2	5	2	1	0	22
Nausea, grade 3–4	0	0	0	0	0	0	1	1
Vomiting, grade 1–2	0	0	0	0	1	0	0	1
Other (not graded)^e	8	6	6	2	2	4	0	28

AE: adverse effects; AST: aspartate aminotransferase; ALT: alanine aminotransferase; ULN: upper limit normal.

^a Excluding participants with same grade elevation at V0.

^b 1 participant had hepatitis C virus infection.

^c 3 participants had hepatitis C virus infection.

^d 1 participant had hepatitis B virus infection.

^e Vertigo, headache, myalgia, bone pain, other neurological symptoms, other gastrointestinal symptoms, malaise, chest pain, kidney stones, tachycardia, cold, unspecified.

Discussion

Before this study, formal PrEP for MSM in Slovenia was not available. With the study, we demonstrated the need and feasibility of such a preventive programme in Slovenia, as 69 MSM were successfully included. The participants were at increased risk for HIV infection, as they had frequent condomless anal sex (92.8%), high numbers of sexual partners (2.36 per month) and had extremely high incidence of STIs (61.7 per 100 person-years); incidence in Slovenia in 2018 was 0.07 per 100 person-years.¹¹ Multiple factors affected this high incidence. As the majority of extragenital gonorrhoea and C. trachomatis infections are asymptomatic, regular screening for STIs in the study would yield higher incidence in comparison to the general population, that is not regularly screened.¹² Also, the inclusion criteria describe sexual behaviour with higher risk for STIs. Although the incidence was high in comparison to the general population, similar incidence rates were demonstrated by others (e.g. AMPrEP).^13,14 After conclusion of the study, PrEP was not available to the high risk MSM, which resulted in one HIV infection.

The number of sexual partners was lower than in the PROUD study (≈10 per month) or the IPERGAY study (≈4 per month); however, it might be underestimated as this was not included in the primary protocol and the last visits were often done during the SARS-CoV-2 epidemic.^2,3 There was no significant change in the number of sexual partners or condom use throughout the study (excluding data at V19M due to the SARS-CoV-2 epidemic which introduced measures to limit spread of the virus). From March until May 2020, these measures in Slovenia included closure of public transport, schools, nonessential shops, bars, clubs and restaurants, introduction of police curfew, banned gatherings and restriction of movement outside of the municipality of residence; from May until the end of the study, most of the restrictions were lifted. Effect of the introduced measures is shown through the significant decrease in the number of sexual partners at V19M.

During the study, we did not encounter AE requiring exclusion of participants from the study. The majority of the 110 graded AE were grade 1–2 (94.5%), and only 6 (5.5%) were grade 3–4 (one nausea, one diarrhoea and four grade 3–4 liver AE all caused by viral hepatitis). This safety is supported by other studies.¹⁵ Although EGFR was significantly lower at V4M and V19M, this statistical significance did not translate into clinically significant renal failure and no participant had EGFR <60 mL/min. There were also no grade 3–4 serum creatinine elevations. Self-reported body weight significantly increased from V7M onwards and was highest at V10M (+2.9% from V0); similar increase at 96 weeks however was found in a Californian study.¹⁶ Increase in body weight could result from many factors (e.g. ageing, seasonal variability and lockdown) and cannot be directly attributed to TDF/FTC. Safety of PrEP is also supported by the fact that the overall EGFR and self-reported body weight did not significantly change.

Adherence is crucial for efficacy. In the substudy of Partners trial, >80% adherence was associated with 100% efficacy (95% CI 83.7–100). In our study, self-reported adherence to PrEP was estimated at 81.0% overall and did not significantly change throughout the study, although proper dosing was discussed at every visit. Participants with more opportunities for PrEP transitioned from ‘on-demand’ to daily PrEP. Comparison of adherence to other studies is difficult because of different methodology and their subjective component. With this in mind, we demonstrated similar self-reported adherence to others.^17,18

Estimation of PrEP efficacy was not the objective of this study, as this was done by others on a higher number of participants^1–3; however, we have demonstrated that there is a group of MSM in Slovenia with increased risk for HIV infection, who would benefit from such a programme. In this group, PrEP was safe and properly used. Participation of MSM with increased risk for HIV in such a programme could also provide an important point of access to STI testing, could improve their sexual health and could have measurable public health impact.

Major limitations of our study were small number of participants and self-reported (not measured) body weight and height. More detailed grading of all AE could shed more light on this subject, and in future research, differentiation between symptomatic and asymptomatic gonorrhoea and C. trachomatis infection should be done. There was also the effect of the SARS-CoV-2 epidemic with social distancing, lockdown and decreased availability of our services at V16M and V19M.

Supplemental Material

sj-pdf-1-std-10.1177_09564624211019876 – Supplemental Material for Pre-exposure prophylaxis for HIV with oral tenofovir disoproxil fumarate/emtricitabine in men who have sex with men: Slovenian national demonstration project

Supplemental Material, sj-pdf-1-std-10.1177_09564624211019876 for Pre-exposure prophylaxis for HIV with oral tenofovir disoproxil fumarate/emtricitabine in men who have sex with men: Slovenian national demonstration project by Blaž Pečavar, Barbara Kokošar Ulčar, Manja Kordiš, Maja Pleško, Gabriele Turel, Tomaž Vovko and Janez Tomažič in International Journal of STD & AIDS

Footnotes

Acknowledgements

We would like to thank all participants for their participation in this study. We also acknowledge important contribution of our nursing and administrative staff.

Declaration of conflicting interests

The author(s) declared no potential conflicts of interest with respect to the research, authorship and/or publication of this article.

Funding

The author(s) disclosed receipt of the following financial support for the research, authorship and/or publication of this article: This work was supported by the Ministry of Health, Republic of Slovenia and the Slovenian Research Agency (project number V3-1717).

ORCID iDs

Blaž Pečavar

Gabriele Turel

Supplemental material

Supplemental material for this article is available online.

References

Grant

Lama

Anderson

, et al. Preexposure chemoprophylaxis for HIV prevention in men who have sex with men. N Engl J Med 2010; 30(27): 2587–2599.

McCormack

Dunn

Desai

, 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. Lancet 2016; 387(10013): 53–60.

Molina

J-M

Capitant

Spire

, et al. On-demand preexposure prophylaxis in men at high risk for HIV-1 infection. N Engl J Med 2015; 3(23): 2237–2246.

Spinner

Boesecke

Zink

, et al. HIV pre-exposure prophylaxis (PrEP): a review of current knowledge of oral systemic HIV PrEP in humans. Infection 2016; 44(2): 151–158.

World Health Organization . Consolidated guidelines on HIV prevention, diagnosis, treatment and care for key populations, http://proxy.library.carleton.ca/loginurl=https://www.deslibris.ca/ID/10063272 (2016, accessed 7 November 2020).

European Centres for Disease Control and Prevention . Pre-exposure prophylaxis to prevent HIV among MSM in Europe, https://www.ecdc.europa.eu/en/news-events/pre-exposure-prophylaxis-prevent-hiv-among-msm-europe (2015, accessed 18 March 2021).

Hayes

Azad

Gowar

, et al. Pre-exposure prophylaxis for HIV prevention in Europe and Central Asia monitoring implementation of the dublin declaration on partnership to fight HIV/AIDS in Europe and Central Asia – 2018/19 progress report, ECDC evidence brief, https://www.ecdc.europa.eu/sites/default/files/documents/HIV-pre-exposure-prophylaxis-evidence-2019_0.pdf (2019, accessed 7 November 2020).

Nacionalni inštitut za javno zdravje . Okužba s HIV v Sloveniji Podatki o prijavljenih primerih do vključno 20, novembra 2020, https://www.nijz.si/sites/www.nijz.si/files/uploaded/okuzba_s_hiv_v_si_do_vkljucno_ 20.11.2020.pdf (2020, accessed 18 March 2021).

Ministrstvo za zdravje . Strategija preprečevanja in obvladovanja okužbe s HIV 2017 – 2025, https://www.gov.si/assets/ministrstva/MZ/DOKUMENTI/Preventiva-in-skrb-za-zdravje/nalezljive-bolezni/nac-strat-HIV-2017.pdf (2017, accessed 18 March 2021).

10.

Division of AIDS National Institute of Allergy and Infectious Diseases National Institutes of Health US Department of Health and Human Services . Table for grading the severity of adult and pediatric adverse events corrected version 2, https://rsc.niaid.nih.gov/sites/default/files/daidsgradingcorrectedv21.pdf (2017, accessed 7 November 2020).

11.

Klavs

Kustec

Kosmač

. Spolno prenesene okužbe v Sloveniji: letno poročilo, https://www.nijz.si/sites/www.nijz.si/files/uploaded/spo_letno_porocilo_2018.pdf (2018, accessed November 2020).

12.

Chan

Robinette

Montgomery

, et al. Extragenital infections caused by Chlamydia trachomatis and Neisseria gonorrhoeae: a review of the literature. Infect Dis Obstet Gynecol 2016; 2016: 1–17.

13.

Hoornenborg

Coyer

Achterbergh

RCA

, et al. Sexual behaviour and incidence of HIV and sexually transmitted infections among men who have sex with men using daily and event-driven pre-exposure prophylaxis in AMPrEP: 2 year results from a demonstration study. Lancet HIV 2019; 6(7): e447–e455.

14.

Ong

Baggaley

, et al. Global epidemiologic characteristics of sexually transmitted infections among individuals using preexposure prophylaxis for the prevention of HIV infection: a systematic review and meta-analysis. JAMA Netw Open 2019; 11(12): e1917134.

15.

Pilkington

Hill

Hughes

, et al. How safe is TDF/FTC as PrEP? A systematic review and meta-analysis of the risk of adverse events in 13 randomised trials of PrEP. J Virus Erad 2018; 1(4): 215–224.

16.

Glidden

Mulligan

McMahan

, et al. Metabolic effects of preexposure prophylaxis with coformulated tenofovir disoproxil fumarate and emtricitabine. Clin Infect Dis 2018; 18(3): 411–419.

17.

Chou

Evans

Hoverman

, et al. Preexposure prophylaxis for the prevention of hiv infection: evidence report and systematic review for the us preventive services task force. JAMA 2019; 11(22): 2214.

18.

Sidebottom

Ekström

Strömdahl

. A systematic review of adherence to oral pre-exposure prophylaxis for HIV - how can we improve uptake and adherence? BMC Infect Dis 2018; 16(1): 581.

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