Impact of directly acting-antivirals and behavior change due to the COVID 19 pandemic on HCV micro-elimination in MSM in Germany

doi:10.21203/rs.3.rs-3716276/v1

Introduction Directly-acting antivirals (DAA) are the cornerstone to reach HCV elimination. In men who have sex with men (MSM) with HIV coinfection, recently acquired HCV infection (RAHCV) is common. Sexual practices and reinfection rates may hamper micro-elimination despite high treatment rates. Methods The cohort included MSM with RAHCV from 2014 to 2021. The patients’ demographic, clinical, behavioral, and laboratory data were documented, as well as treatment and reinfection outcomes. Results 237 men with RAHCV were included, 216 (91%) were PLWH. Median age was 46 years (IQR: 39–52), median CD4 count was 660/mm3 (IQR: 527–835). The annual incidence of RAHCV remained between 0.28% and 0.43%, but dropped to 0.02% in 2021 during the onset of the COVID-pandemic almost reaching micro-elimination. The reinfection incidence was 15.5 per 100 patient-years (95%-CI: 12.6-18.8), reinfection was associated with use of crystal methamphetamine (p=0.032) and ketamine (p=0.042). 31.3% had multiple reinfections, four reinfections occurred in PrEP users. Conclusions High treatment and cure rates did not lead to HCV elimination. A change in sexual behavior, potentially imposed by COVID-19 restrictions, led to micro-elimination in the NoCo cohort. As RAHCV is prevalent in HIV-positive and -negative MSM, surveillance is necessary to consolidate elimination goals.

HCV incidence

DAA

WHO elimination goals

chemsex

reinfection

The availability of directly acting antivirals (DAA) against the hepatitis C virus (HCV) has radically changed the management of affected patients all over the world. As a consequence, the World Health Organization (WHO) has defined HCV elimination goals in its 2016 sector strategy(1): by 2030, an incidence drop of 80%, a treatment coverage of 80%, and a reduction of mortality by 65% compared to a 2015 baseline should be achieved. To date, only eleven countries are on track to achieve these elimination goals according to a recent modeling analysis(2). Germany is no longer among them due to an insufficient HCV treatment and diagnosis rate(3). In order to encourage stakeholders to reinforce HCV cure efforts in target populations on a local level, the concept of HCV micro-elimination has been suggested previously(4). Target populations may be those at-risk for ongoing HCV transmission, such as people who inject drugs (PWID) or men who have sex with men (MSM) living with HIV. Among the latter, high rates of HCV transmission and reinfection have been described in the last two decades(5), often in combination with sex practices involving multiple partners and recreational substance abuse (“Chemsex”). MSM living with HIV seem to be a promising target for a micro-elimination approach if the linkage to the health care system is good and in the absence of prescription restrictions for DAAs, and, exemplarily, the results from several European cohorts show steep reductions in incidence, potentially because broad and early DAA usage has contributed to cutting down ongoing transmission(6)(7)(8). However, a modeling study for MSM in Germany has suggested that scale-up of DAA treatment rates may not be sufficient to achieve elimination alone, but HCV treatment needed to be started earlier in the case of recently acquired HCV infection (RAHCV) and behavior that leads to HCV transmission would have to be changed(9). Eventually, it remains to date unknown which factor contributes most to HCV elimination in a setting with high treatment rates but of remaining high levels of at-risk behavior. The NoCo cohort study is a German multi-centric attempt to describe recently acquired HCV infection in MSM with or without HIV infection since the introduction of DAAs to study the epidemiology in this particular population, as well as clinical, virological and behavioral outcomes. As the COVID-19 pandemic and its containment measurements occurred during the NoCo recruitment period, their impact on the HCV epidemic in MSM in Germany was included into our analyses.

The NoCo cohort was established in April 2019 bringing together six German outpatient clinics for HIV and hepatitis care and HIV pre-exposure prophylaxis. The six sites are spread out over the country and have a history of collaborating in cohort studies (GECCO and PROBE-C), and provide care for roughly a fifth of the German HIV-infected MSM population.

NoCo is an ambidirectional cohort study, in which MSM were included if they had a diagnosis of recently acquired HCV infection since February 2014 (beginning of universal DAA treatment access in Germany). The cohort was ended on December 31st, 2021. HCV testing was performed at the respective physicians’ discretion and was in all centers routinely done biannually in HIV-positive MSM, or three to six-monthly in MSM with prior HCV infection to detect reinfection. Recently acquired HCV infection was defined as a documented HCV antibody seroconversion within 12 months prior HCV diagnosis, or a positive HCV RNA test with prior negative HCV RNA or antibody test within 12 months, or a documented liver enzyme elevation following an event considered high at risk for HCV transmission (needle sharing, anal intercourse) within six months. Recently acquired HCV reinfection was defined by a detectable HCV RNA after sustained virological response (SVR) or spontaneous clearance (two negative HCV RNA measures with an interval of 24 weeks), or HCV genotype switch within these timeframes, or detectable HCV RNA with phylogenetic proof of reinfection.

After written informed consent, the patient’s demographic, clinical, and laboratory data were documented in three-monthly intervals. The HCV infection incidence analysis was restricted to HIV-co-infected individuals, as data on the overall MSM population size in the centers was not available. NoCo participants filled-out a six-monthly risk behavior questionnaire that was used for a case-control study in collaboration with the London School of Hygiene and Tropical Medicine. Controls were non-HCV infected MSM from the participating centers (see behavioral study published by Schmidt AJ, et al.).

If willing, NoCo participants were included in an immunological sub-study to investigate T cell responses in HCV infection and reinfection in collaboration with the University of Freiburg (data not presented here), for which PBMC samples were collected in a longitudinal manner.

The clinical NoCo dataset was transferred to the University of California San Diego (UCSD), Biostatistics Research Center for statistical analysis. (S.J., F.H.) In collaboration with the Division of Infectious Diseases and Global Public Health

of UCSD (N.M.), where NoCo data was used to adapt a previously published HCV transmission model among HIV-diagnosed MSM to evaluate progress towards HCV elimination in Germany. The model has already been published(9).

Statistical analysis was performed using software R (version 3.6.1) (http://www.r-project.org). Descriptive summaries were provided for each variable overall and by HIV or HCV reinfection status. All statistical tests were two-sided with a significance level of 0.05. The Wilcoxon Rank Sum Test was applied for continuous variables and Fisher's Exact Test for categorical variables. Univariate logistic regression analysis was performed with reinfection status as the dependent variable. The reinfection incidence rate was calculated by dividing the number of reinfected events by the total number of follow-up person-years.

Overall, 237 men with recently acquired HCV infection were included between 2014 and 2021. Two hundred and six-teen (91%) occurred in HIV co-infected MSM, all but one were on antiretroviral therapy. Of the 21 men without HIV, 15 (71%) were on HIV pre-exposure prophylaxis (PrEP); 18/21 (86%) were diagnosed in 2018 or later.

At the time of HCV diagnosis, the median age was 46 years (interquartile range, IQR, 39 to 52), and the median time of HIV infection was 10.3 years (IQR 5.5 to 15.4). In HIV co-infected individuals, the median CD4 cell count was 660/mm³ (IQR 527 to 835), the median HIV viral load was 73 copies/mL (IQR 40 to 2150).

Most men were diagnosed through three to six-month routine HCV testing as part of regular HIV and/or STI check-ups (56.4%), followed by testing for ALT elevation (33.1%), 5.5% had an HCV-positive partner. Only four men (1.7%) had clinical symptoms that led to the diagnosis. The most common HCV genotype was 1a (58.7%), followed by 4d (16.5%), 3a (5.9%), or 4a (2.5%). Twenty patients (8.4%) had non-identifiable HCV subtypes. The median HCV viral load was 475,000 IU/mL (IQR: 66955-3.01x10⁶), and the median ALT level was 224 U/L (IQR 86 to 521). No patient suffered from hepatic decompensation during HCV diagnosis. Baseline characteristics are shown in table 1.

Risk factors for HCV acquisition

The majority of men (219, 92.4%) reported sexual contacts between men as the most likely mode of HCV transmission, followed by transmission through intravenous drug use in 3%, and sharing of paraphernalia for intranasal drug use in two men (0.8%).

Data on drug use within the last 12 months was only available in a subset of patients (52, 22%), but 15 (29%) of those men reported to use crystal methamphetamine, of these six (40%) via intravenous injection. Seven men (13.5%) reported ketamine use, and five (9.6%) declared mephedrone use for sexual enhancement.

A sexually transmitted infection preceded HCV diagnosis in 85 men (35.9%). Fifty-three men (23.9%) were diagnosed with syphilis, 20 (9%) with chlamydia or gonorrhea, respectively, and 6 (5.5%) with lymphogranuloma venereum within 12 months prior to HCV diagnosis.

Outcomes of HCV infection

Eighteen men (7.6%) cleared their HCV infection spontaneously, while 163 patients started DAA treatment (treatment regimens in supplementary table 1). In 47 patients (19.8%) treatment was not started by the time of the analysis, mainly because of the patient’s decision (36.2%) or health insurance/residency reasons (31.9%). Of those 137 men who had finished DAA treatment, all reached sustained virological response (SVR rate 100%). DAA treatment was started a median of 6.6 months (IQR: 4.0-9.3) after HCV diagnosis. Most patients were treated with sofosbuvir-ledipasvir or -velpatasvir (57.6%) or glecaprevir-pibrentasvir (27.6%); the complete list of treatments given in NoCo is shown in supplementary table 1.

HCV incidence in HIV-co-infected MSM

Between 8,212 and 10,228 HIV-positive MSM were annually in care in the six participating centers. Overall, 216 HIV-positive men with recently acquired HCV infection were included into the cohort between 2014 and 2021. The annual incidence of recently acquired HCV was 0.34% in 2014 and remained stable up to 2020 (0.28%). In 2021, the HCV incidence dropped to 0.02%, as only two HCV infections were documented. Compared to the incidence in 2015 (0.37%), this translates into a 94.6% drop in HCV incidence (Fig. 1). The number of HIV-positive men in care in 2021 was 10,228, the number of HCV PCR tests performed in NoCo participants was 515, and even higher than the pre-COVID-19 pandemic level of 339 in year 2019.

Risk factors for HCV reinfection and reinfection incidence

A total of eighty-eight men in the NoCo cohort had documented HCV reinfection (Table 2). Most reinfections were detected through routine HCV-PCR testing as part of regular HIV and/or STI check-ups (65.5%) or ALT elevation (26.4%), only 2.3% had clinical symptoms. Fifty-five men (68.8%) had one previous HCV infection, while 25 (31.3%) had multiple (maximum 5) HCV infection episodes. Four reinfections occurred in HIV-negative PrEP users who were demographically not different to HIV-positive individuals, except for being younger (39 vs 46 years, p = 0.003). HCV reinfection was independently associated with older age (odds ratio, OR 1.04 per year, p = 0.005), use of crystal methamphetamine (OR 5.3, p = 0.032) and use of ketamine (OR 7.1, p = 0.042). HIV infection itself was not associated with reinfection (Table 3).

Individuals with repeated HCV reinfection did not differ in clinical parameters, compared to individuals with one HCV reinfection episode.

Overall, in the 237 individuals within the NoCo cohort 103 episodes (more than one episode per individual allowed) of recently acquired HCV reinfection were documented. With an overall follow-up time of 665 person-years, the HCV reinfection incidence was 15.5 per 100 person-years (95% confidence interval, CI, 12.6 to 18.8).

The German NoCo cohort is the largest cohort worldwide of recently-acquired HCV infection in MSM from the DAA era. Most of these infections occurred in PLWH (216 out of 237, 91%). The six participating centers care for about one fifth of Germanys estimated MSM population living with HIV(10). The annual incidence of recently acquired HCV infection remained on a stable level of approximately 0.3–0.4% despite an unrestricted and broad, but delayed (see below) use of DAAs in Germany since 2014. Unlike in cohorts from neighboring European countries where a steep decline was related to reinforced DAA use(6)(7)(8), this finding could not be observed here. One explanation might be the delayed timing of DAA treatment: due to a restriction of DAA treatment approval to the chronic phase of HCV infection, most care providers in Germany refrained from early treatment, and consequently, the median delay between HCV diagnosis and treatment was 6.6 months. This may have led to a prolonged transmission window if risk behavior was maintained, which may potentially not have been the case in other countries where treatment might have been commenced earlier(11)(12). Further, the focus on RAHCV infection in NoCo restricts the analysis on a subgroup with the highest risk behavior and transmission rates, and policy makers in Germany ought to be well-advised to recommend early treatment in this specific population, even more so as response rates are excellent(13) and chances for spontaneous HCV clearance in PLWH are negligible(14).

In 2021, however, in the aftermath of the first lockdowns in response to the COVID-19 pandemic, a decline in the incidence of HCV infections of 94.6% was observed, virtually eliminating HCV in the NoCo cohort. Potentially, this finding may be explained with behavioral changes related to COVID-19 restrictions due to social distancing on an individual level and closure of venues and clubs that facilitate sexual encounters leading to HCV transmission. Although data on behavior change during lockdowns among MSM(15) is scarce and some studies even suggest an increase in individuals’ substance use(16)(17), an effect on sexual behavior in our cohort is possible (the NoCo behavioral sub-study is not part of this publication and is published simultaneously by Schmidt AJ, et al.). As the number of HCV RNA tests in NoCo remained stable during this period and the number of HIV-positive MSM in care remained high, an effect of reduced testing and treatment rate during the pandemic as described in other settings(18) seems unlikely here. Moreover, earlier modeling studies have suggested that behavior change may be needed to achieve HCV elimination(19), and the results from NoCo seem to confirm this, but it remains unclear if this effect proves to be sustainable(9).

As it has been undoubtedly demonstrated elsewhere(20), treatment rates were excellent, and, in NoCo, not a single treatment failure was documented, independently of the DAA regimen used. Our 100% SVR rate argues even more in favor of early treatment as suggested by international guidelines(21)(22).

Surprisingly, nearly 20% of men had not started treatment by the time of the analysis, mainly for the patients’ decision or health insurance constraints. It remains unknown to what extent these cases contribute to further maintain transmission, or if these men have been cured afterwards.

Over one third of HCV infections in NoCo were reinfections (103 episodes in 88 subjects, 37.1%), and HCV reinfection was associated with crystal methamphetamine and ketamine use. The incidence rate was as high as 15.5 per 100 patient-years. HCV reinfection is a common finding in cured HCV patients with ongoing risk behavior, especially in MSM(5), and HCV reinfection may challenge elimination efforts. Treatment rates have been high in reinfection in MSM even in the pre-DAA era(23), and our findings confirm high cure rates. Behavioral interventions on an individual level might be a strategy to reduce reinfection rates in this setting(24).

A minority of individuals in our cohort were HIV-negative MSM (9%), and most of them (71%) used HIV pre-exposure prophylaxis (PrEP). As the overall number of MSM in care in the participating centers is unknown, we were not able to perform an incidence analysis, and no specific demographic or virological factor was identified except for the fact that PLWH were older (mean 46 vs 39 years). Sexually acquired HCV infection in HIV uninfected MSM has been described in several cohorts(25)(26)(27) with viral clustering between HIV-positive and -negative subjects. In NoCo, cases in HIV-negative MSM started to increase in 2018, probably related to the wider use of PrEP in Germany, and increasing mixing between men on PrEP and men with HIV.

In over one third of patients, an STI preceded HCV diagnosis in the previous twelve months, in the majority of cases syphilis (62%), followed by chlamydia trachomatis or gonococcal infections. While an STI may be seen as an indicator (gonorrhoea/chlamydia) or even facilitator (syphilis/LGV) of HCV transmission, we would like to point out that most men in our study had not been STI-diagnosed just prior to HCV diagnosis, and no difference in the prevalence of STIs was seen prior or post HCV infection. Of note, most HCV diagnoses were made through routine testing (56%), and in only a third of cases due to elevated liver function tests, while only very few patients were clinically symptomatic. In a setting with high risk for HCV transmission, regular surveillance is needed to identify cases and to stay on track for HCV elimination goals.

Our study has some limitations. First of all, the NoCo cohort recruited from a primary care setting and cases were included at the centers’ discretion. We have no knowledge whether potential cases were missed or not included for other reasons. It is also possible that patients who cleared HCV spontaneously were not documented in the cohort, and in fact our reported spontaneous clearance rates are lower than in other studies reported to date(14).

Secondly, the patient data were taken from medical files based face-to-face interview and not from a standardized anonymous questionnaire. Especially behavioral data on illicit substance use may have therefore been underreported. However, NoCo is accompanied by a behavioral study arm and the results will be reported elsewhere.

Lastly, NoCo is not a comprehensive epidemiological study but a multi-centric clinical cohort. Trends seen here do not necessarily reflect the overall HIV-positive MSM population in Germany. However, we believe that due to the sizes and distribution of the participating centers, the results seen here are of general significance.

In conclusion, HCV micro-elimination in MSM in Germany is potentially not achievable through high treatment rates alone. Moreover, a substantial number of individuals opts out from antiviral treatment for several reasons. Early treatment and rapid viral clearance in at-risk individuals seem necessary to reduce transmission chains. Behavior changes enforced by COVID-19 lockdowns may have contributed largely to HCV micro-elimination in MSM in Germany, but this effect needs to be further elucidated. As RAHCV is mainly clinically inapparent and most men are diagnosed following routine testing during regular HIV or PrEP check-ups, screening efforts need to be maintained especially in high-risk individuals.

Acknowledgements:

The NoCo cohort was funded by a research grant from GILEAD Sciences (IN-DE-987-

4637). We would like to acknowledge all participating patients. A special thanks goes to

Nicole Gersbacher (Berlin) for her hard work as a study coordinator. Further we’d like to thank:

Berlin: Anna Maria Hamann, Stephan Grunwald, Bonn: Kathrin van Bremen, Malte Monin, Jan-Christian Wasmuth, Angelika Saidi, Martha Overschelp, Eva Schumacher Düsseldorf: Florian Berger, Hamburg: Susanne Terraf, Christian Hofmann, Münster: Sabine Offermann, Frankfurt: Gabi Knecht, Annette Haas. Clinovate, München: Stefan Preis.

Insitute for Immune Genetics Kaiserlautern: Martin Daeumer, Alexander Thielen.

University of Freiburg: Maike Hofmann, Charlotte Rennert. London School of Hygiene

and Tropical Medicine: Jason Doran, Ibrahim Sönmez, Peter Weatherburn.

Conflicts of interest:

AB has received honoraria for lectures and/or consultancies from Gilead Sciences, Janssen, MSD, ViiV Healthcare / GSK, Pfizer, and Astra Zeneca. CB has received honoraria for lectures and/or consultancies from AbbVie, Gilead Sciences, Janssen, MSD, ViiV Healthcare, and funding from DFG, DZIF, NEAT ID, Hector Stiftung, and Deutsche Leberstiftung. JKR has received honoraria for lectures and/or consultancies from AbbVie, Boehringer, MSD, Gilead Sciences, Janssen, ViiV Healthcare. NKM has received unrestricted research grants and honoraria from Gilead and Merck. PI has received research grants from Gilead Sciences (Noco and HDV Described), Abbott Laboratories, and speaker’s honoraria from Gilead Sciences, ViiV Healthcare, AbbVie. SC received personal fees and travel grants from Gilead Sciences, AbbVie, and ViiV Healthcare outside the submitted work. SM received honoraria for lectures and/or consultancies from AbbVie, Gilead Sciences, MSD, ViiV Healthcare, and travel grants from: AbbVie, Gilead Sciences. TL has received research grants from AbbVie, Gilead Sciences, Moderna, Heidelberger Immun, GSK/ ViiV Healthcare, MSD. The other authors declare no conflicts of interest.

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Table 1: Baseline characteristics of 237 men with recently acquired HCV infection

	Overall, n=237	HIV-positive, n=216	HIV-negative, n=21	p
Caucasian, n (%)	225 (94.9%)	204 (94.4%)	21 (100%)	0.607
Mean age, years (SD)	45.3 (9.57)	45.9 (9.5)	39.3 (8.28)	0.003
BMI, kg/m² (IQR)	23.2 (21.1- 25.0)	23.2 (21.1- 25.1)	23.2 (20.8- 24.4)	0.631
Duration HIV, years (IQR)	10.3 (5.5-15.4)	10.3 (5.5-15.4)	NA	-
On ART, n (%)	215 (91)	215 (99.5)	NA	-
On Prep, n (%)	15 (6)	NA	15 (71)	-
HIV viral load, copies per mL (IQR)	73 (40 -2150)	73 (40-2150)	NA	-
CD4 cell count, per mm3 (IQR)	660 (527-835)	660 (527- 835)	NA	-
Reason for HCV testing: ALT elevation Routine testing Partner with HCV	78 (33.1%) 133 (56.36%) 13 (5.51%)	70 (32.6%) 125 (58.14%) 10 (4.65%)	8 (38.1%) 8 (38.1%) 3 (14.29%)	0.073
HCV reinfection, n (%)	88 (37.13)	84 (38.89)	4 (19.05)	0.097
STI within 12 months prior HCV (n=222, n-pos=204, n-neg=18) Syphilis, n (%) Chlamydia infection, n (%) Gonorrhea infection, n (%)	53 (23.9) 20 (9) 20 (9)	51 (25) 19 (9) 17 (8)	2 (11) 1 (6) 3 (17)	0.254 >0.999 0.212
HCV RNA, IU/mL (IQR)	475,000 (66,955-3,005,882)	486,056 (81,062- 3,023,528)	270,000 (5895- 2,900,000)	0.359
HCV genotype 1a, n (%) 3a, n (%) 4d, n (%) GT or ST unknown	139 (59) 14 (6) 39 (16) 33 (14)	127 (59) 12 (6) 35 (16) 31 (14)	12 (57) 2 (10) 4 (19) 2 (10)	0.742
ALT, U/L (IQR)	224 (86-521)	222 (78-509)	224 (111-552)	0.607
Platelets, G/L (IQR)	222 (189-263)	217 (184-261)	260 (222-278)	0.010

BMI, body mass index; HIV, human immunodeficiency virus; ART, antiretroviral therapy; PrEP, pre-exposure prophylaxis; HCV, hepatitis C virus; ALT, alanine aminotransferase; STI, sexually transmitted infection; GT, HCV genotype; ST, HCV subtype

Table 2: Baseline characteristics of MSM with HCV reinfection

	Overall, n=88	HIV-positive, n=84	HIV-negative, n=4
Caucasian, n (%)	84 (95.5%)	80 (95.2%)	4 (100%)
Mean age, years (SD)	47.6 (8.54)	47.8 (8.58)	42.8 (6.45)
BMI, kg/m² (IQR)	22.5 (20.9- 24.3)	22.5 (20.9- 24.3)	20.7 (18.9-22.6)
On ART, n (%)	84 (100)	84 (100)	NA
On Prep, n (%)	4 (4.5)	NA	4 (100)
HIV viral load, copies per mL (IQR)	49.5 (37 - 101)	49.5 (37 - 101)	NA
CD4 cell count, per mm3 (IQR)	625 (518-789)	625 (518-789	NA
Reason for HCV testing: ALT elevation Routine testing Partner with HCV	23 (26.45) 57 (65.5%) 2 (2.3%)	22 (26.5%) 55 (66.3%) 1 (1.2%)	1 (25%) 2 (50%) 1 (25%)
Previous HCV episodes, n (%) 1 2 3 4 5	55 (68.8) 14 (17.5) 6 (7.5) 4 (5) 1 (1.3)	53 (68.8) 13 (16.9) 6 (7.8) 4 (5.2) 1 (1.3)	2 (66.7) 1 (33.3) NA NA NA
STI within 12 months prior HCV reinfection Syphilis, n (%) Chlamydia infection, n (%) Gonorrhea infection, n (%)	23 (26.8) 10 (11.6) 8 (9.3)	23 (27.7) 10 (12) 8 (9.6)	0 0 0
HCV RNA, IU/mL (IQR)	280,000 (20,204-1,200,000)	290,000 (14,450- 1,280,000)	270,000 (180,850-306,314)
Type of cure preceeding HCV episode, n (%) Spontaneous clearance SVR with DAA SVR with PEG/RBV unknown	12 (15) 39 (48.8) 26 (32.5) 33(3.8)	11 (14.3) 37 (48) 26 (33.8) 3 (3.9)	1 (33.3) 2 (66.7) 0 0
ALT, U/L (IQR)	129 (53-373)	121 (49-364)	482 (219-766)

BMI, body mass index; HIV, human immunodeficiency virus; ART, antiretroviral therapy; PrEP, pre-exposure prophylaxis; HCV, hepatitis C virus; ALT, alanine aminotransferase; STI, sexually transmitted infection; GT, SVR, sustained virological response

Table 3: Univariate logistic regression of HCV reinfection risk (selected variables)

Variable	OR	95% CI	p
Age	1.04	1.01-1.07	0.005
HIV coinfection	2.70	0.88-8.31	0.082
HCV transmission, IVDU MSM	1.28 0.72	0.28-5.85 0.27-1.90	0.75 0.51
STI prior to HCV, Syphilis Chlamydia Gonorrhea No STI	1.24 1.70 1.21 0.78	0.66-2.32 0.66-4.38 0.46-3.19 0.45-1.35	0.51 0.28 0.70 0.38
Substance use, Chrystal meth Ketamine	5.25 7.08	1.15-23.94 1.07-46.68	0.032 0.042

No competing interests reported.

supplementNoco.docx
Supplementary table 1: Treatment regimens used in the 163 men treated during the observation period between 2014 and 2021

Impact of directly acting-antivirals and behavior change due to the COVID 19 pandemic on HCV micro-elimination in MSM in Germany

Status:

Version 1

Abstract

Figures

Introduction

Methods

Results

Risk factors for HCV acquisition

Outcomes of HCV infection

HCV incidence in HIV-co-infected MSM

Risk factors for HCV reinfection and reinfection incidence

Discussion

Declarations

References

Tables

Additional Declarations

Supplementary Files

Status:

Version 1