The advent of highly active antiretroviral therapy (HAART) in 1996 led to a decrease in the incidence of Kaposi's sarcoma (KS) and non-Hodgkin's lymphoma (NHL), but not of other cancers, among people ...with HIV or AIDS (PWHA). It also led to marked increases in their life expectancy.
We conducted a record-linkage study between the Swiss HIV Cohort Study and nine Swiss cantonal cancer registries. In total, 9429 PWHA provided 20,615, 17,690, and 15,410 person-years in the pre-, early-, and late-HAART periods, respectively. Standardised incidence ratios in PWHA vs the general population, as well as age-standardised, and age-specific incidence rates were computed for different periods.
Incidence of KS and NHL decreased by several fold between the pre- and early-HAART periods, and additionally declined from the early- to the late-HAART period. Incidence of cancers of the anus, liver, non-melanomatous skin, and Hodgkin's lymphoma increased in the early- compared with the pre-HAART period, but not during the late-HAART period. The incidence of all non-AIDS-defining cancers (NADCs) combined was similar in all periods, and approximately double that in the general population.
Increases in the incidence of selected NADCs after the introduction of HAART were largely accounted for by the ageing of PWHA.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, SIK, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Summary
In order to accurately assess the burden of hepatitis C (HCV) and develop effective interventions, we must understand the magnitude and trends of mortality related to the disease. In the ...United States, HCV‐related mortality is continuously increasing. We have no comparable data for Switzerland and other European countries, although a modelling study predicted a similar increase. We analysed time trends (1 January 1995‐31 December 2014) in HCV‐specific mortality rates in the Swiss general population using the death registry of the Swiss Federal Statistical Office (SFSO). We compared HCV‐related mortality to HIV‐related and hepatitis B (HBV)‐related mortality. To determine potential under‐reporting in HCV‐related mortality, we probabilistically linked the SFSO data to persons who died in the Swiss Hepatitis C Cohort Study (SCCS). SFSO data showed that HCV‐related mortality more than doubled between 1995 and 2003, but has since stabilized at ~2.5/100 000 person‐years. Since 2000, HCV‐related mortality has been higher than HIV‐related mortality and was about fivefold higher in 2014. HBV‐related mortality remained low at ~0.5/100 000 person‐years. Of 4556 persons in the SCCS, 421 have died and 86.2% could be linked to the death registry. According to the SCCS, 133 deaths were HCV‐related. HCV was not mentioned on the SFSO death certificate of 45% of these (n = 60/133). In conclusion, HCV‐related mortality remained constant, possibly because quality of care was high, or because of under‐reporting or because mortality has not yet increased. However, HCV‐related mortality is now much higher than HIV‐ and HBV‐related mortality, and under‐reporting was common.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
Background: Persons infected with human immunodeficiency virus (HIV) have an increased risk for several cancers, but the influences of behavioral risk factors, such as smoking and intravenous drug ...use, and highly active antiretroviral therapy (HAART) on cancer risk are not clear. Methods: Patient records were linked between the Swiss HIV Cohort Study and Swiss cantonal cancer registries. Observed and expected numbers of incident cancers were assessed in 7304 persons infected with HIV followed for 28 836 person-years. Relative risks for cancer compared with those for the general population were determined by estimating cancer registry–, sex-, age-, and period-standardized incidence ratios (SIRs). Results: Highly elevated SIRs were confirmed in persons infected with HIV for Kaposi sarcoma (KS) (SIR = 192, 95% confidence interval CI = 170 to 217) and non-Hodgkin lymphoma (SIR = 76.4, 95% CI = 66.5 to 87.4). Statistically significantly elevated SIRs were also observed for anal cancer (SIR = 33.4, 95% CI = 10.5 to 78.6); Hodgkin lymphoma (SIR = 17.3, 95% CI = 10.2 to 27.4); cancers of the cervix (SIR = 8.0, 95% CI = 2.9 to 17.4); liver (SIR = 7.0, 95% CI = 2.2 to 16.5); lip, mouth, and pharynx (SIR = 4.1, 95% CI = 2.1 to 7.4); trachea, lung, and bronchus (SIR = 3.2, 95% CI = 1.7 to 5.4); and skin, nonmelanomatous (SIR = 3.2, 95% CI = 2.2 to 4.5). In HAART users, SIRs for KS (SIR = 25.3, 95% CI = 10.8 to 50.1) and non-Hodgkin lymphoma (SIR = 24.2, 95% CI = 15.0 to 37.1) were lower than those for nonusers (KS SIR = 239, 95% CI = 211 to 270; non-Hodgkin lymphoma SIR = 99.3, 95% CI = 85.8 to 114). Among HAART users, however, the SIR (although not absolute numbers) for Hodgkin lymphoma (SIR = 36.2, 95% CI = 16.4 to 68.9) was comparable to that for KS and non-Hodgkin lymphoma. No clear impact of HAART on SIRs emerged for cervical cancer or non–acquired immunodeficiency syndrome-defining cancers. Cancers of the lung, lip, mouth, or pharynx were not observed among nonsmokers. Conclusion: In persons infected with HIV, HAART use may prevent most excess risk of KS and non-Hodgkin lymphoma, but not that of Hodgkin lymphoma and other non–acquired immunodeficiency syndrome-defining cancers. No cancers of the lip, mouth, pharynx, or lung were observed in nonsmokers.
Abstract
Background
Coronary artery disease (CAD) events have been associated with certain antiretroviral therapy (ART) agents. In contrast, the influence of ART on subclinical atherosclerosis is not ...clear. The study objective was to assess the association between individual ART agents and the prevalence and extent of subclinical CAD.
Methods
Coronary artery calcium (CAC) scoring and coronary computed tomography angiography (CCTA) were performed in ≥45-year-old Swiss Human Immunodeficiency Virus Cohort Study participants. The following subclinical CAD endpoints were analyzed separately: CAC score >0, any plaque, calcified plaque, noncalcified/mixed plaque, segment involvement score (SIS), and segment severity score (SSS). Logistic regression models calculated by inverse probability of treatment weights (IPTW) were used to explore associations between subclinical CAD and cumulative exposure to the 10 most frequently used drugs.
Results
There were 403 patients who underwent CCTA. A CAC score >0 was recorded in 188 (47%), any plaque in 214 (53%), calcified plaque in 151 (38%), and noncalcified/mixed plaque in 150 (37%) participants. A CAC score >0 was negatively associated with efavirenz (IPTW adjusted odds ratio per 5 years 0.73, 95% confidence interval CI 0.56–0.96), tenofovir disoproxil fumarate (0.68, 95% CI 0.49–0.95), and lopinavir (0.64, 95% CI 0.43–0.96). Any plaque was negatively associated with tenofovir disoproxil fumarate (0.71, 95% CI 0.51–0.99). Calcified plaque was negatively associated with efavirenz (0.7, 95% CI 0.57–0.97). Noncalcified/mixed plaque was positively associated with abacavir (1.46, 95% CI 1.08–1.98) and negatively associated with emtricitabine (0.67, 95% CI 0.46–0.99). For SSS and SIS, we found no association with any drug.
Conclusions
An increased risk of noncalcified/mixed plaque was only found in patients exposed to abacavir. Emtricitabine was negatively associated with noncalcified/mixed plaque, while tenofovir disoproxil fumarate and efavirenz were negatively associated with any plaque and calcified plaque, respectively.
In this prospective coronary computed tomography angiography study among human immunodeficiency virus–positive participants, noncalcified/mixed plaque was only positively associated with abacavir. Emtricitabine, tenofovir disoproxil fumarate, and efavirenz were negatively associated with noncalcified/mixed plaque, any plaque, and calcified plaque, respectively.
In people with human immunodeficiency virus (PWH), it is unknown whether genetic background associates with rapid progression of kidney dysfunction (ie, estimated glomerular filtration rate eGFR ...decrease of >5mL/min/1.73m2 per year for ≥3 consecutive years).
We obtained univariable and multivariable hazard ratios (HR) for rapid progression, based on the clinical D:A:D chronic kidney disease (CKD) risk score, antiretroviral exposures, and a polygenic risk score based on 14 769 genome-wide single nucleotide polymorphisms in white Swiss HIV Cohort Study participants.
We included 225 participants with rapid progression and 3378 rapid progression-free participants. In multivariable analysis, compared to participants with low D:A:D risk, participants with high risk had rapid progression (HR = 1.82 95% CI, 1.28-2.60). Compared to the first (favorable) polygenic risk score quartile, participants in the second, third, and fourth (unfavorable) quartiles had rapid progression (HR = 1.39 95% CI, 0.94-2.06, 1.52 95% CI, 1.04-2.24, and 2.04 95% CI, 1.41-2.94, respectively). Recent exposure to tenofovir disoproxil fumarate was associated with rapid progression (HR = 1.36 95% CI, 1.06-1.76).
An individual polygenic risk score is associated with rapid progression in Swiss PWH, when analyzed in the context of clinical and antiretroviral risk factors.
Summary
Increasing access to direct‐acting antiviral (DAA) treatment for hepatitis C virus (HCV) infection and decelerating the rise in high‐risk behaviour over the next decade could curb the HCV ...epidemic among HIV‐positive men who have sex with men (MSM). We investigated if similar outcomes would be achieved by short‐term intensive interventions like the Swiss‐HCVree‐trial. We used a HCV transmission model emulating two 12‐months intensive interventions combining risk counselling with (i) universal DAA treatment (pangenotypic intervention) and (ii) DAA treatment for HCV genotypes 1 and 4 (replicating the Swiss‐HCVree‐trial). To capture potential changes outside intensive interventions, we varied time from HCV infection to treatment in clinical routine and overall high‐risk behaviour among HIV‐positive MSM. Simulated prevalence dropped from 5.5% in 2016 to ≤2.0% over the intervention period (June/2016‐May/2017) with the pangenotypic intervention, and to ≤3.6% with the Swiss‐HCVree‐trial. Assuming time to treatment in clinical routine reflected reimbursement restrictions (METAVIR ≥F2, 16.9 years) and stable high‐risk behaviour in the overall MSM population, prevalence in 2025 reached 13.1% without intensive intervention, 11.1% with the pangenotypic intervention and 11.8% with the Swiss‐HCVree‐trial. If time to treatment in clinical routine was 2 years, prevalence in 2025 declined to 4.8% without intensive intervention, to 2.8% with the pangenotypic intervention, and to 3.5% with the Swiss‐HCVree‐trial. In this scenario, the pangenotypic intervention and the Swiss‐HCVree‐trial reduced cumulative (2016‐2025) treatment episodes by 36% and 24%, respectively. Therefore, intensive interventions could reduce future HCV treatment costs and boost the benefits of long‐term efforts to prevent high‐risk behaviour and to reduce treatment delay. But if after intensive interventions treatment is deferred until F2, short‐term benefits of intensive interventions would dissipate in the long term.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
Immunodeficiency and AIDS-related pulmonary infections have been suggested as independent causes of lung cancer among HIV-infected persons, in addition to smoking.
A total of 68 lung cancers were ...identified in the Swiss HIV Cohort Study (SHCS) or through linkage with Swiss Cancer Registries (1985-2010), and were individually matched to 337 controls by centre, gender, HIV-transmission category, age and calendar period. Odds ratios (ORs) were estimated by conditional logistic regression.
Overall, 96.2% of lung cancers and 72.9% of controls were ever smokers, confirming the high prevalence of smoking and its strong association with lung cancer (OR for current vs never=14.4, 95% confidence interval (95% CI): 3.36-62.1). No significant associations were observed between CD4+ cell count and lung cancer, neither when measured within 1 year (OR for <200 vs ≥500=1.21, 95% CI: 0.49-2.96) nor further back in time, before lung cancer diagnosis. Combined antiretroviral therapy was not significantly associated with lung cancer (OR for ever vs never=0.67, 95% CI: 0.29-1.52), and nor was a history of AIDS with (OR=0.49, 95% CI: 0.19-1.28) or without (OR=0.53, 95% CI: 0.24-1.18) pulmonary involvement.
Lung cancer in the SHCS does not seem to be clearly associated with immunodeficiency or AIDS-related pulmonary disease, but seems to be attributable to heavy smoking.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, SIK, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Reluctance has been expressed about treating chronic hepatitis C in active intravenous (IV) drug users (IDUs), and this is found in both international guidelines and routine clinical practice. ...However, the medical literature provides no evidence for an unequivocal treatment deferral of this risk group. We retrospectively analyzed the direct effect of IV drug use on treatment outcome in 500 chronic hepatitis C patients enrolled in the Swiss Hepatitis C Cohort Study. Patients were eligible for the study if they had their serum hepatitis C virus (HCV) RNA tested 6 months after the end of treatment and at least one visit during the antiviral therapy, documenting the drug use status. Five hundred patients fulfilled the inclusion criteria (199 were IDU and 301 controls). A minimum exposure to 80% of the scheduled cumulative dose of antivirals was reached in 66.0% of IDU and 60.5% of controls (P = NS). The overall sustained virological response (SVR) rate was 63.6%. Active IDU reached a SVR of 69.3%, statistically not significantly different from controls (59.8%). A multivariate analysis for treatment success showed no significant negative influence of active IV drug use. In conclusion, our study shows no relevant direct influence of IV drugs on the efficacy of anti‐HCV therapy among adherent patients.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
Background & Aims
Hepatitis C virus (HCV) therapies with interferon‐free second‐generation direct‐acting antivirals (DAAs) are highly effective and well tolerated. They have the potential to increase ...treatment eligibility and efficacy in HIV‐infected patients. We assessed the impact of DAAs on treatment uptake and efficacy, as well as its impact on the burden of liver disease in the Swiss HIV Cohort Study (SHCS).
Methods
We describe clinical and virological characteristics of patients treated with second‐generation DAAs. We compared treatment incidence, sustained virological response (SVR)12 and liver fibrosis stages between three time periods: period 1, 01/2009‐08/2011 (prior to the availability of DAAs); period 2, 09/2011‐03/2014 (first generation DAAs); period 3, 04/2014‐12/2015 (second generation DAAs).
Results
At the beginning of the third period, 876 SHCS participants had a chronic HCV infection of whom 180 (20%) started treatment with a second‐generation DAA. Three‐quarters of them had advanced liver fibrosis (Metavir ≥ F3) of whom 80% were cirrhotics. SVR12 was achieved in 173/180 (96%) patients, three patients died and four experienced a virological failure. Over the three time periods, treatment uptake (4.5/100 py, 5.7/100 py, 22.4/100 py) and efficacy (54%, 70%, 96% SVR12) continuously increased. The proportion of cirrhotic patients with replicating HCV infection in the SHCS declined from 25% at the beginning to 12% at the end of the last period.
Conclusions
After the introduction of second‐generation DAAs, we observed an increase in treatment uptake and efficacy which resulted in a significant reduction in the number of cirrhotic patients with a replicating HCV infection in the SHCS.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
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