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New infections were associated with sharing chem‐sex drugs among MSM in Spain Among HIV+ has the potential to reseed the HCV epidemic and, consequently, preclude HCV elimination.
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Dec 26 2020 HIV Medicine - A Gonzalez-Serna,1 J Macias 1 R Palacios,2 C Gomez-Ayerbe,2 F Tellez,3 A Rivero-Juarez ,4 M Fernandez,1
J Santos,4 LM Real,1 CM Gonzalez-Domenech,2 J Gomez-Mateos,1 JA Pineda1 and On behalf of the HEPAVIR study group
in addition to the report I distributed from france on MSM & HCV increasing numbers this from Spain reports the same trend, decreasing HCV in other groups but increasing among MSM. Jules
"We have found a trend to a decrease in the incidence of RAHC among HIV‐infected patients in our area after 2016, with a steady incidence of residual cases afterwards. These episodes of RAHC were overwhelmingly observed among MSM who share chem‐sex drugs. Likewise, we found that HCV reinfections numerically decreased during the same time periods in parallel with primary infections.
In Spain, DAA therapy was administered if spontaneous clearance was not achieved, but since June 2017 all patients with HCV infection were candidates to receive DAA therapy without restrictions. In our study, we show a 52% decrease in RAHC among HIV‐infected patients after 2016. This relevant decrease in incidence of RAHC should be mostly attributable to a reduction in the burden of active HCV infections associated with unrestricted DAA treatment. Although these results are promising, residual incident RAHC cases and reinfections, are observed in our study after 2016. These RAHC cases have the potential to reseed the HCV epidemic and, consequently, preclude HCV elimination.
In conclusion, to achieve HCV elimination in Spain, the estimations of active HCV infections might need correction for the reseeding of the overall burden of HCV infection by RAHC. As virtually all HIV‐infected patients with HCV infections have been treated in our country, early detection by massive screening and immediate treatment of HIV‐uninfected MSM with HCV infection to access potential reservoirs of HCV is needed to keep Spain on track for HCV elimination by 2030.
Factors associated with RAHC
Several behavioural risk factors such as sharing chem‐sex drugs, two or more sexual partners during the last 6 months, never use condom during sex, group sex, use recreational drugs during sex and previous sexually transmitted infections (STIs) were associated with RAHC in the univariate analysis (Table 2). After multivariate analysis, only previous STIs, male gender and sharing chem‐sex drugs were identified as independently associated with RAHC.
HCV reinfections
Forty‐two patients showed positive anti‐HCV and undetectable HCV RNA at baseline and had at least one follow‐up visit afterwards. The characteristics of these patients at baseline are described in Table 3. Four (9.5%) of them were reinfected with HCV during the study period (Fig. 2). The characteristics of these four patients at baseline are described in Table 4. All reinfected patients were MSM with two or more sexual partners during the last 6 months and previous STIs. Most of them used recreational drugs during sex. All of them achieved sustained virological response (SVR) with DAA and subsequently were reinfected after achieving SVR. The incidence of reinfection per 100 py (IR 95% CI) was 25 (3.2-65) in 2016, 2.95 (0.1-14.5) in 2017, 0 (0-0) in 2018 and 2.94 (0.1-15.3) in 2019."
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Incidence of recently acquired hepatitis C virus infection among HIV‐infected patients in southern Spain
26 December 2020
Abstract
Objectives
Spain is close to HCV microelimination, so rates of recently acquired HCV infection (RAHC) should decrease. Nowadays, men who have sex with men (MSM) carry the highest risk of HCV acquisition. Our aim was to estimate the incidence of and the factors associated with RAHC, together with reinfection rates, among patients sexually infected by HIV.
Methods
Primary RAHC infection was diagnosed when anti‐HCV antibody seroconversion was documented. In anti‐HCV positive patients, initially without HCV viraemia, a diagnosis of reinfection was established if plasma HCV RNA was detected.
Results
All 350 patients tested negative for anti‐HCV at baseline and had at least one follow‐up visit. Among them, there were 16 RAHC cases from 2016 to 2019. RAHC incidence rates [IR (95% confidence interval, CI)] per 100 person‐years were 3.77 (0.5-12.9) in 2016, 1.85 (0.6-4.3) in 2017, 1.49 (0.4-3.8) in 2018 and 1.98 (0.6-4.5) in 2019. Only previous sexually transmitted infections [incidence rate ratio (IRR) = 18.23, 95% CI: 1.93-172.1; P = 0.011], male sex (IRR = 8.33, 95% CI: 1.38-54.15; P = 0.026) and sharing chem‐sex drugs (IRR: 4.93, 95% CI: 1.17-20.76; P = 0.030), were independently associated with RAHC. Four out of 42 (9.5%) patients became reinfected.
Conclusions
The incidence of RAHC among HIV‐infected patients showed a decrease after 2016, although a lower but steady incidence of residual cases still remains. HCV reinfections showed a similar pattern. New infections were associated with sharing chem‐sex drugs among MSM.
Introduction
In the last decade, numerous outbreaks of recently acquired hepatitis C virus infection (RAHC) have been described among people living with HIV (PLWH) worldwide, mainly in HIV‐positive men who have sex with men (MSM) [1-9]. The increased incidence of RAHC in HIV‐positive MSM has been attributed to several factors such as a higher hepatitis C virus (HCV) load in blood and semen [10], sexual practices with an increased risk of mucosal damage, the presence of ulcerative sexually transmitted diseases, a larger number of sexual partners and the use of chem‐sex [11].
Some studies conducted in very specific areas within the largest Spanish cities have reported an increase in the number of cases of RAHC among HIV‐infected MSM [1, 7, 12]. However, the number of RAHC episodes among PLWH in southern Spain remained stable until 2015 [13, 14], in spite of the fact that over one‐third of HIV‐infected subjects bore an active HCV coinfection [15]. This lack of RAHC outbreaks in southern Spain may reflect a different epidemiological situation in our area to what has been reported from other Spanish urban areas [1, 20] and in many European cities, as well as in Australia and the United States [3-6].
The direct‐acting antiviral drugs (DAAs) currently used yield sustained virological response rates of > 95% [16, 17]. The widespread use of DAAs in Spain may ultimately lead to the elimination of HCV in the country. Indeed, the Polaris Observatory reported that Spain is on track to eliminate HCV infection by 2030 [18]. Therefore, if the burden of HCV infection declines due to DAA use, a decrease of RAHC episodes during recent years should be observed in our area. Nowadays, MSM carry the highest risk of HCV acquisition [19]. Because of this, the expected decline in the incidence of RAHC should be primarily seen in this particular subset. Due to this, our aim was to estimate the incidence of RAHC and the factors associated with RAHC during recent years among PLWH in southern Spain infected through sexual intercourse. We also evaluated the rates of reinfections in those patients.
Study population
This study was a prospective cohort study conducted in four hospitals throughout Southern Spain. Eight hundred sixty‐one PLWH consecutively attended in the Infectious Diseases Units of the participating centers from January 2016 to December 2019 were analyzed. Of them, three hundred and fifty PLWH infected through sexual intercourse, i.e. MSM and PLWH infected through sexual intercourse who are not MSM (non‐MSM individuals), with at least 12 months of follow‐up and available serum samples were finally included in the study. PLWH infected by other routes, i.e. people who inject drugs (PWID), than through sexual intercourse were excluded. A questionnaire of behavioural risk factors and sexual practices associated with HCV infection was filled out for every patient at the first visit and every 12 months. All patients with at least one follow‐up visit were evaluated. HCV serum antibodies were determined, at the least, at baseline and every 12 months, and plasma HCV‐RNA was determined if seroconversion occurred during the follow‐up. For seropositive patients for anti‐HCV at baseline, plasma HCV‐RNA was determined, at the least, at baseline and every 12 months. The last participant was included in December 2018 in order to achieve 1‐year follow‐up.
Discussion
We have found a trend to a decrease in the incidence of RAHC among HIV‐infected patients in our area after 2016, with a steady incidence of residual cases afterwards. These episodes of RAHC were overwhelmingly observed among MSM who share chem‐sex drugs. Likewise, we found that HCV reinfections numerically decreased during the same time periods in parallel with primary infections.
The WHO goal is to eliminate viral hepatitis worldwide by 2030 [21]. According to the Polaris Observatory, Spain is in a leading position to achieve this objective [18]. One key aspect of HCV elimination is wide access to DAA combinations. In Spain, DAA therapy was administered if spontaneous clearance was not achieved, but since June 2017 all patients with HCV infection were candidates to receive DAA therapy without restrictions. In our study, we show a 52% decrease in RAHC among HIV‐infected patients after 2016. This relevant decrease in incidence of RAHC should be mostly attributable to a reduction in the burden of active HCV infections associated with unrestricted DAA treatment. Although these results are promising, residual incident RAHC cases and reinfections, are observed in our study after 2016. These RAHC cases have the potential to reseed the HCV epidemic and, consequently, preclude HCV elimination.
Our findings are in agreement with other studies that have reported a decrease in the incidence of RAHC after widespread treatment of HIV/HCV‐infected patients [22-24]. Thus, in the Netherlands, unrestricted DAA availability in the country was followed by a 51% decrease in the incidence of RAHC infections among HIV‐positive MSM, while the incidence of STIs increased during the same period of observation [22]. Similarly, in the Swiss HIV cohort, after intensive screening for HCV, the majority of HIV/HCV‐coinfected MSM received successful therapy and, as a consequence, a 49% reduction in incident RAHC was observed [23]. In the same way, in the UK, a 78% reduction in the incidence of RAHC episodes has been reported, after a peak in 2015, which coincides with wider access to DAAs in the UK [24]. However, HCV reinfection among HIV‐infected MSM in the UK remained challenging, probably because early treatment of HCV infection remained challenging, which is probably because second treatment of HCV infection was not permitted until September 2019 [25]. It is notable that, although all these studies show a decrease in the incidence of RAHC after wider access to DAAs, here we show for the first time that a low but steady incidence of HCV infections has been reached in our area after widespread treatment of HIV/HCV‐infected patients. Moreover, the IR in our study, all above 1 per 100 py, is comparable but higher than those in the studies mentioned earlier [22-24]. All these reports and our study fall short of WHO targets for reductions in new diagnoses to reach HCV elimination [21].
Given that DAA treatment is widely available in Spain, further reductions in the incidence of RAHC should have been observed in more recent years. Indeed, the prevalence of HIV‐infected patients with HCV viraemia has drastically decreased over time in our area, reaching HCV microelimination targets [26]. A possible explanation for our findings is that the sources of RAHC in recent years might be individuals outside the follow‐up of our practices. Thus, the undiagnosed fraction of active HCV infection was 29.4% according to the Spanish Ministry of Health in 2019 [27]. In the Swiss HIV Cohort, both international and domestic transmission networks were the source of HCV infections among HIV‐infected MSM [28]. In Spain, RAHC in HIV‐infected MSM followed in a single centre in Barcelona were linked to a large international HCV transmission network [1]. Therefore, incident RAHC among HIV‐infected MSM in our study could be related to transmission networks beyond our area.
We found that RAHC was linked to MSM with high‐risk sexual habits. Sexual transmission of HCV is not frequent among HIV‐infected patients [4]. However, certain MSM sexual practices, such as unprotected anal sex with bleeding, fisting and group sex, have been associated with HCV transmission [3, 29]. In addition to previous STIs, a marker of high‐risk sexual habits, we found that sharing chem‐sex drugs was independently associated with RAHC. HCV infection is strongly linked to parenteral exposure, with very high rates of transmission among people who share unsterile injection equipment [30]. Nowadays, sexualized injecting drug use is a high‐risk drug use pattern emerging among MSM [31]. In Spain, an anonymous online survey on sexual behaviour and recreational drug use among HIV‐infected MSM reported a rate of sexualized injecting drug use of 16% [32]. This relatively small group of sex‐enhancing drug users may ultimately maintain a residual rate of HCV infection among HIV‐infected MSM.
Providing behavioural interventions addressing high‐risk sexualized drug use practices should be part of a comprehensive HCV management in HIV‐infected MSM. However, drug addiction treatment programmes do not meet the needs of chem‐sex users. Specific behavioural and educational programmes are required, but such interventions may be difficult to implement because MSM using chem‐sex usually do not identify themselves as drug users [33]. Enrolment in HIV pre‐exposure prophylaxis (PrEP) programmes might reduce HCV incidence due to a reduction in risky behaviour [34], but they do not seem to achieve it, probably because HIV‐infected MSM and HIV‐negative MSM using PrEP share similar risk practices [35]. In fact, a recent study in a cohort of HIV‐negative MSM using PrEP in the Netherlands reported high IR of RAHC and of HCV reinfection, similar to the rates that we have found herein [36]. Mass screening at population level and linkage to care, with fast access to therapy for those with active HCV infection, is feasible, and it could be more successful than behavioural interventions, as proved with treatment‐as‐prevention for HIV infection [37].
This study might have some limitations. First, as episodes of RAHC are frequently asymptomatic [32], and tests were performed annually and spontaneous clearance is not an unlikely outcome [38], we cannot rule out the possibility that some reinfections could have gone unnoticed. However, this does not affect our main aim of estimating RAHC. In addition, most RAHC among HIV‐infected patients do not clear spontaneously [39]. Also, losses to follow‐up could bias our results toward patients with better adherence. In this sense, incidence of RAHC and/or reinfection might be even higher than that reported here. The prospective design, including a detailed questionnaire about sexual habits, is the main strength of the present study.
In conclusion, to achieve HCV elimination in Spain, the estimations of active HCV infections might need correction for the reseeding of the overall burden of HCV infection by RAHC. As virtually all HIV‐infected patients with HCV infections have been treated in our country, early detection by massive screening and immediate treatment of HIV‐uninfected MSM with HCV infection to access potential reservoirs of HCV is needed to keep Spain on track for HCV elimination by 2030.
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