Search

BACKGROUND Hepatitis C virus (HCV) antigen testing is less expensive than quantitative RT-PCR but has lower sensitivity for very low viral loads (VLVL; HCV RNA ≤3,000 IU/ml). Currently the benefits of antigen testing for screening are discussed, but data on prevalence and outcomes of persons with VLVL are scarce. METHODS We assessed prevalence and predictors of VLVL by logistic regression in treatment-naive participants in the Swiss Hepatitis C Cohort Study. We analyzed if the last viral load after VLVL was low, compared cirrhosis and mortality in persons with and without VLVL, and evaluated the number of samples with VLVL that were reactive by antigen testing. RESULTS We included 2,533 treatment-naive persons with available quantitative HCV RNA testing results. Overall, 133 persons (5.3%) had a VLVL. Age 18-40 years, female gender and HIV coinfection were associated with VLVL. Of 72 persons with a viral load available after VLVL, 14% had a VLVL and 17% had spontaneous viral clearance. The prevalence and incidence of cirrhosis and mortality were comparable in persons with and without VLVL; all 24 persons with VLVL and cirrhosis had excessive alcohol consumption or immunosuppression. Overall 33% of samples with VLVL were reactive by antigen testing. CONCLUSIONS The frequency of VLVL was low. Among the persons who would probably be missed by antigen screening, some had a favorable disease course, but some had immunosuppression and liver cirrhosis. The benefit of HCV antigen testing for screening may be limited by the risk of missing patients with severe liver disease.

Background.With direct-acting antiviral agents (DAAs), mortality rates and causes of death among persons with hepatitis C virus (HCV) infection may change over time. However, the emergence of such trends may be delayed by the slow progression of chronic hepatitis C. To date, detailed analyses of cause-specific mortality among HCV-infected persons over time remain limited.Methods.We evaluated changes in causes of death among Swiss Hepatitis C Cohort Study (SCCS) participants from 2008 to 2016. We analyzed risk factors for all-cause and cause-specific mortality, accounting for changes in treatment, fibrosis stage, and use of injectable drugs over time. Mortality ascertainment was completed by linking lost-to-follow-up participants to the Swiss Federal Statistical Office death registry.Results.We included 4700 SCCS participants, of whom 478 died between 2008 and 2016. The proportion of unknown causes of death decreased substantially after linkage, from 42% to 10%. Leading causes of death were liver failure (crude death rate 4.4/1000 person-years), liver cancer (3.4/1000 person-years), and nonliver cancer (2.8/1000 person-years), with an increasing proportion of cancer-related deaths over time. Cause-specific analysis showed that persons with sustained virologic response were less at risk for liver-related mortality than those never treated or treated unsuccessfully.Conclusions.Although the expected decrease in mortality is not yet observable, causes of death among HCV-infected persons have evolved over time. With the wider use of DAAs, liver-related mortality is expected to decline in the future. Continued moni-toring of cause-specific mortality will remain important to assess the long-term effect of DAAs and design effective interventions.Keywords. cohort; hepatitis C; mortality; risk factors; Switzerland.

Late diagnosis and treatment may increase morbidity and mortality among persons with hepatitis C virus (HCV) infection. We included all participants of the Swiss Hepatitis C Cohort Study (SCCS). We used unadjusted and adjusted logistic and Cox regressions to determine the association between the geographic origin of the participants and the following outcomes: antiviral treatment status; sustained virologic response; cirrhosis at enrolment; incident cirrhosis; loss to follow-up (LTFU); and mortality. The analyses were adjusted for sex, baseline age, education, source of income, alcohol consumption, injection drug use (IDU), HCV genotype, HIV or HBV coinfection, duration of HCV infection, time since enrolment, cirrhosis, (type of) HCV treatment, and centre at enrolment. Among 5,356 persons, 1,752 (32.7%) were foreign-born. IDU was more common among Swiss- (64.1%) than foreign-born (36.6%) persons. Cirrhosis at enrolment was more frequent among foreign- than Swiss-born persons, reflecting the high frequency of cirrhosis among Italian-born persons who acquired HCV between 1950 and 1970 in Italian healthcare settings. Although antiviral treatment coverage was similar, the sustained viral response rate was increased and the mortality was lower among foreign-vs. Swiss-born persons, with the lowest mortality in persons from Asia/Oceania. LTFU was more frequent in persons from Germany, Eastern and Southern Europe, and the Americas. In conclusion, in Switzerland, a country with universal healthcare, geographic origin had no influence on hepatitis C treatment access, and the better treatment outcomes among foreign-born persons were likely explained by their lower prevalence of IDU and alcohol consumption than among Swiss-born persons.

Patients who start combination antiretroviral therapy (cART) during primary HIV-1 infection show a smaller HIV-1 latent reservoir, less immune activation and a smaller viral diversity compared to patients who start cART during chronic infection. We conducted a pilot study to test whether these properties would allow sustained virological suppression after simplification of cART to dolutegravir monotherapy.

BACKGROUND The incidence of anal cancer is high in HIV-positive men who have sex with men (MSM). We modeled the impact of screening strategies and combination antiretroviral therapy (cART) coverage on anal cancer incidence in Switzerland. METHODS Individual-based, dynamic simulation model parameterized with Swiss HIV Cohort Study (SHCS) and literature data. We assumed all men to be HPV infected. CD4 cell count trajectories were the main predictors of anal cancer. From 2016 we modeled cART coverage either as below 100% (corresponding to 2010-2015) or as 100%, and the following four screening strategies: (i) no screening, (ii) yearly anal cytology (Pap smears), (iii) yearly anoscopy and (iv) targeted anoscopy five years after CD4 count dropped below 200 cells/μl. RESULTS Median nadir CD4 cell count of 6,411 MSM increased from 229 cells/μl during 1980-89 to 394 cells/μl during 2010-15; cART coverage increased from 0% to 83.4%. Modeled anal cancer incidence peaked at 81.7/100,000 in 2009, plateaued 2010-2015 and decreased to 58.7 by 2030 with stable cART coverage, and to 52.0 with 100% cART coverage. With yearly cytology, incidence declined to 38.2/100,000 by 2030, with yearly anoscopy to 32.8 and with CD4 count guided anoscopy to 51.3. The numbers needed to screen over 15 years to prevent one anal cancer case (NNS) were 384 for yearly cytology, 313 for yearly anoscopy and 242 for CD4 count dependent screening. CONCLUSIONS Yearly screening of HIV-positive MSM may reduce anal cancer incidence substantially, with a NNS that is comparable to other screening interventions to prevent cancer.

Introduction Antibiotic resistant Neisseria gonorrhoeae (NG) is a global public health challenge; resistance has emerged to all antibiotics used for empirical treatment. In Switzerland, gonorrhoea reports increased from 404 in 2000 to 1895 in 2015, with about 40% in men who have sex with men (MSM). To our knowledge, no studies have examined factors associated with antibiotic resistant NG in Switzerland. Methods We enrolled MSM at clinics in Zürich and Bern from May 2015 to June 2016 presenting with symptoms suggestive of NG, partners of known cases or had a positive NG screening test. MSM completed an online questionnaire on social and behavioural factors and physicians completed a case report form. Specimens from pharynx, rectum and urethra were tested with a molecular test and culture. For culture positive specimens, the minimum inhibitory concentration (MIC) for different antibiotics was determined, using EUCAST 2017 resistance breakpoints for ciprofloxacin, ceftriaxone, cefixime and spectinomycin, and ≥2mg/L for azithromycin (as in a European study). We also examined reduced susceptibility to ceftriaxone (cutoff ≥0.016 mg/L). Cases were MSM with NG and MIC above the breakpoint, controls were MSM with NG and MIC less than or equal to the breakpoint. We used logistic regression to estimate odds ratios (OR) with 95% confidence intervals (CI). Results In total, 164/230 (71%) MSM were positive for NG; culture was positive in 118/164. We compared 45 (39%) cases with ciprofloxacin resistance with 73 controls. Cases were more likely than controls to have concurrent sexual partners (OR 2.2, 95%Cl 0.876.0, p=0.13), to have received oral sex (OR 5.3, 0.644.2, p=0.08), to have had sex abroad in the last three months (OR 2.3, 1.04.9, p=0.08) and for the most recent partner to be casual (OR 2.6, 0.88.5 p=0.08). One NG isolate was azithromycin resistant. No isolates were resistant to spectinomycin, cefixime or ceftriaxone; 21 (18%) had reduced susceptibility to ceftriaxone, but we found no associations with clinical or behavioural factors. Conclusions This study had a limited sample size but is the first in Switzerland to link behavioural factors with antibiotic resistant NG. Ciprofloxacin resistance was common in MSM and there is evidence of reduced susceptibility to ceftriaxone. Interventions for MSM to promote safer sex, especially whilst abroad, and enhanced surveillance of antimicrobial susceptibility could help to identify and control emerging resistance in NG.

BACKGROUND: Patterns of morbidity and mortality among human immunodeficiency virus (HIV)-infected individuals taking antiretroviral therapy are changing as a result of immune reconstitution and improved survival. We studied the influence of aging on the epidemiology of non-AIDS diseases in the Swiss HIV Cohort Study. METHODS: The Swiss HIV Cohort Study is a prospective observational cohort established in 1988 with continuous enrollment. We determined the incidence of clinical events (per 1000 person-years) from January 2008 (when a new questionnaire on non-AIDS-related morbidity was introduced) through December 2010. Differences across age groups were analyzed using Cox regression, adjusted for CD4 cell count, viral load, sex, injection drug use, smoking, and years of HIV infection. RESULTS: Overall, 8444 (96%) of 8848 participants contributed data from 40,720 semiannual visits; 2233 individuals (26.4%) were aged 50-64 years, and 450 (5.3%) were aged ≥65 years. The median duration of HIV infection was 15.4 years (95% confidence interval [CI], 9.59-22.0 years); 23.2% had prior clinical AIDS. We observed 994 incident non-AIDS events in the reference period: 201 cases of bacterial pneumonia, 55 myocardial infarctions, 39 strokes, 70 cases of diabetes mellitus, 123 trauma-associated fractures, 37 fractures without adequate trauma, and 115 non-AIDS malignancies. Multivariable hazard ratios for stroke (17.7; CI, 7.06-44.5), myocardial infarction (5.89; 95% CI, 2.17-16.0), diabetes mellitus (3.75; 95% CI, 1.80-7.85), bone fractures without adequate trauma (10.5; 95% CI, 3.58-30.5), osteoporosis (9.13; 95% CI, 4.10-20.3), and non-AIDS-defining malignancies (6.88; 95% CI, 3.89-12.2) were elevated for persons aged ≥65 years. CONCLUSIONS: Comorbidity and multimorbidity because of non-AIDS diseases, particularly diabetes mellitus, cardiovascular disease, non-AIDS-defining malignancies, and osteoporosis, become more important in care of HIV-infected persons and increase with older age.

BACKGROUND Switzerland recommends individuals who originate from high-prevalence countries to be screened for hepatitis C virus (HCV) infection. However, not all these persons are equally at risk. We thus aimed to describe the number and characteristics of persons with HCV infection born outside of Switzerland. METHODS We compared characteristics of anti-HCV-positive individuals in the Swiss Hepatitis C Cohort Study (SCCS) and of HCV cases reported to the Federal Office of Public Health (FOPH), with those of the general population in Switzerland. Persons who inject drugs (PWID) and persons who do not inject drugs (non-PWID) were compared by age groups for different countries of origin (represented by ≥1% of participants in the SCCS or FOPH). RESULTS We included 4,199 persons from the SCCS and 26,610 cases from the FOPH. Both groups had similar characteristics. In both data sources non-PWID were more frequent in foreign-born than in Swiss-born persons (63% versus 34% in the SCCS). The only subgroup with a clearly higher proportion both in the SCCS and FOPH than in the general population were persons over 60 years from Italy and Spain, with a 3.7- and 2.8-fold increase in the SCCS. These persons were non-PWID (99%), less frequently HIV- and anti-HBc positive and more often female than PWID from Italy and Spain; cirrhosis at enrolment was frequent (31%). Their HCV genotypes were consistent with those observed in elderly non-PWID of their birth countries. In the FOPH a higher proportion than in the general population was also seen for cases from Georgia and Russia. CONCLUSION The identification of subgroups in which HCV infection is particularly frequent might allow for better targeting HCV screening among foreign-born persons in Switzerland and elsewhere.

OBJECTIVES: Inequalities and inequities in health are an important public health concern. In Switzerland, mortality in the general population varies according to the socio-economic position (SEP) of neighbourhoods. We examined the influence of neighbourhood SEP on presentation and outcomes in HIV-positive individuals in the era of combination antiretroviral therapy (cART). METHODS: The neighbourhood SEP of patients followed in the Swiss HIV Cohort Study (SHCS) 2000-2013 was obtained on the basis of 2000 census data on the 50 nearest households (education and occupation of household head, rent, mean number of persons per room). We used Cox and logistic regression models to examine the probability of late presentation, virologic response to cART, loss to follow-up and death across quintiles of neighbourhood SEP. RESULTS: A total of 4489 SHCS participants were included. Presentation with advanced disease [CD4 cell count

Although persons infected with human immunodeficiency virus (HIV), particularly men who have sex with men, are at excess risk for anal cancer, it has been difficult to disentangle the influences of anal exposure to human papillomavirus (HPV) infection, immunodeficiency, and combined antiretroviral therapy. A case-control study that included 59 anal cancer cases and 295 individually matched controls was nested in the Swiss HIV Cohort Study (1988-2011). In a subset of 41 cases and 114 controls, HPV antibodies were tested. A majority of anal cancer cases (73%) were men who have sex with men. Current smoking was significantly associated with anal cancer (odds ratio (OR) = 2.59, 95% confidence interval (CI): 1.25, 5.34), as were antibodies against L1 (OR = 4.52, 95% CI: 2.00, 10.20) and E6 (OR = ∞, 95% CI: 4.64, ∞) of HPV16, as well as low CD4+ cell counts, whether measured at nadir (OR per 100-cell/μL decrease = 1.53, 95% CI: 1.18, 2.00) or at cancer diagnosis (OR per 100-cell/μL decrease = 1.24, 95% CI: 1.08, 1.42). However, the influence of CD4+ cell counts appeared to be strongest 6-7 years prior to anal cancer diagnosis (OR for

HIV-infected women are at increased risk of cervical intra-epithelial neoplasia (CIN) and invasive cervical cancer (ICC), but it has been difficult to disentangle the influences of heavy exposure to HPV infection, inadequate screening, and immunodeficiency. A case-control study including 364 CIN2/3 and 20 ICC cases matched to 1,147 controls was nested in the Swiss HIV Cohort Study (1985-2013). CIN2/3 risk was significantly associated with low CD4+ cell counts, whether measured as nadir (odds ratio (OR) per 100-cell/μL decrease=1.15, 95% CI: 1.08, 1.22), or at CIN2/3 diagnosis (1.10, 95% CI: 1.04, 1.16). An association was evident even for nadir CD4+ 200-349 versus ≥350 cells/μL (OR=1.57, 95% CI: 1.09, 2.25). After adjustment for nadir CD4+, a protective effect of >2-year cART use was seen against CIN2/3 (OR versus never cART use=0.64, 95% CI: 0.42, 0.98). Despite low study power, similar associations were seen for ICC, notably with nadir CD4+ (OR for 50 versus >350 cells/μL= 11.10, 95% CI: 1.24, 100). HPV16-L1 antibodies were significantly associated with CIN2/3, but HPV16-E6 antibodies were nearly exclusively detected in ICC. In conclusion, worsening immunodeficiency, even at only moderately decreased CD4+ cell counts (200-349 CD4+ cells/μL), is a significant risk factor for CIN2/3 and cervical cancer. This article is protected by copyright. All rights reserved.

BACKGROUND AND AIMS Hepatitis C (HCV) is a leading cause of morbidity and mortality in people who live with HIV. In many countries, access to direct acting antiviral agents to treat HCV is restricted to individuals with advanced liver disease (METAVIR stage F3 or F4). Our goal was to estimate the long term impact of deferring HCV treatment for men who have sex with men (MSM) who are coinfected with HIV and often have multiple risk factors for liver disease progression. METHODS We developed an individual-based model of liver disease progression in HIV/HCV coinfected men who have sex with men. We estimated liver-related morbidity and mortality as well as the median time spent with replicating HCV infection when individuals were treated in liver fibrosis stages F0, F1, F2, F3 or F4 on the METAVIR scale. RESULTS The percentage of individuals who died of liver-related complications was 2% if treatment was initiated in F0 or F1. It increased to 3% if treatment was deferred until F2, 7% if it was deferred until F3 and 22% if deferred until F4. The median time individuals spent with replicating HCV increased from 5 years if treatment was initiated in F2 to almost 15 years if it was deferred until F4. CONCLUSIONS Deferring HCV therapy until advanced liver fibrosis is established could increase liver-related morbidity and mortality in HIV/HCV coinfected individuals, and substantially prolong the time individuals spend with replicating HCV infection.

Anal cancer is common among people infected with human immunodeficiency virus (HIV). This cancer is caused by human papillomavirus, and immunosuppression likely contributes to its development. In this issue of the Journal, Bertisch et al. (Am J Epidemiol. 2013;178(6):877–884) present the results of a case-control study of anal cancer among HIV-infected people in Switzerland. They demonstrate that anal cancer risk is increased in association with a low CD4+ cell count (a clinical measurement of immune status). In particular, HIV-induced immunosuppression was most severe among cases approximately 6–7 years prior to the diagnosis of anal cancer. A plausible biological interpretation is that immunosuppression is important at an early stage of the development of anal cancer, but that the neoplastic process becomes irreversible over time with persistent human papillomavirus infection and genetic damage. With current efforts to provide earlier combination antiretroviral therapy to HIV-infected people, anal cancer incidence may start to decline. Bertisch et al. also demonstrate a strong association between serum antibodies against the human papillomavirus type 16 protein E6 and anal cancer risk, highlighting the role of this viral oncoprotein in carcinogenesis. Additional biomarkers could help refine clinical approaches to anal cancer screening and prevention for the HIV-infected population.