Abstract
Background
Integrase strand transfer inhibitors (InSTIs) are recommended for first-line treatment of persons with human immunodeficiency virus (HIV). We identified risk factors, including ...baseline minor InSTI resistance mutations, for treatment failure of InSTI-based regimens.
Methods
We studied time-to-treatment failure and time to viral suppression among 1419 drug-naive patients in the Swiss HIV Cohort Study. We performed Cox regression models adjusted for demographic factors, baseline HIV RNA/CD4 cell counts, AIDS-defining events, and the type of InSTI. In 646 patients with a baseline genotypic resistance test of the integrase, we studied the impact of minor integrase resistance mutations.
Results
We observed 121 virological failures during 18 447 person-years of follow-up. A baseline viral load ≥100 000 copies/mL (multivariable hazard ratio mHR, 2.2; 95% confidence interval CI, 1.3–3.6) and an AIDS-defining event (mHR, 1.8; 95% CI. 1.1–3.0) were associated with treatment failure. CD4 counts between 200 and 500 cells/µL (mHR, 0.5; 95% CI, .3–.8) and >500 cells/µL (mHR, 0.4; 95% CI, .2–.7) were protective. Time to suppression was shorter in lower viral load strata (mHR, 0.7; 95% CI, .6–.8) and in dolutegravir-based therapy (mHR, 1.2; 95% CI, 1.0–1.4). Minor resistance mutations were found at baseline in 104 of 646 (16%) patients with no effect on treatment outcome.
Conclusions
Factors associated with treatment failure on InSTI-based first-line regimen remained similar to those of older treatments, in particular high viral load and low CD4 counts.
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
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
Objectives
We aimed to assess prevalence and age at menopause, identify factors associated with early menopause and explore the provision and utilization of healthcare in women living with HIV in ...Switzerland.
Methods
This was a retrospective Swiss HIV Cohort Study analysis from January 2010 to December 2018. Descriptive statistics to characterise the population and menopause onset. Logistic regression analysis to identify risk factors for early menopause.
Results
Of all women in the SHCS, the proportion of postmenopausal women tripled from 11.5% (n = 274) in 2010 to 36.1% (n = 961) in 2018. The median age at menopause was 50 years. Early menopause (< 45 years) occurred in 115 (10.2%) women and premature ovarian insufficiency (POI) (< 40 years) in 23 (2%) women. Early menopause was associated with black ethnicity (52.2% vs. 21.6%, p < 0.001), but not with HIV acquisition mode, CDC stage, viral suppression, CD4 cell count, hepatitis C, smoking or active drug use. While 92% of the postmenopausal women underwent a gynaecological examination during the 36 months before menopause documentation, only 27% received a bone mineral density measurement within 36 months after the last bleed and 11% were on hormone replacement therapy at the time of menopause documentation.
Conclusions
The median age of women living with HIV at menopause is around 2 years lower than that reported for HIV‐negative women in Switzerland. HIV care providers need to adapt their services to the requirements of the increasing number of women living with HIV transitioning through menopause. They should be able to recognize menopause‐associated symptoms and improve access to bone mineral density measurement as well as hormone replacement therapy.
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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
Objectives
We previously demonstrated an association between tenofovir disoproxil fumarate (TDF) and chronic liver enzyme elevation in the D:A:D study. The objective of the study was to assess ...changes in alanine aminotransferase (ALT) levels after switching from TDF to tenofovir alafenamide (TAF).
Methods
We included Swiss HIV Cohort Study participants who switched from TDF to TAF with two or more ALT values in the 24 months before and two or more values in the 24 months after replacing TDF with TAF. Individuals with replicating viral hepatitis were excluded. Uni‐ and multivariable linear mixed models were used to explore changes in ALT values associated with switching from TDF to TAF, and to assess potential modifying effects.
Results
A total of 1712 participants were included, contributing 6169 ALT values before and 5482 after switching. Median (interquartile range, IQR) age was 50 (42–57) years, and 75% were male. Median (IQR) ALT was 28 (22–38) U/L before and 24 (19–32) U/L after replacing TDF with TAF. ALT values decreased by 3.7 U/L (95% confidence interval: 3.2–4.2) after the switch. The median drop was larger in patients with chronic ALT elevation (defined as two or more elevated values for ≥ 6 months) compared with patients with normal ALT values (17.8 vs. 3.3 U/L, P < 0.001). We did not identify any major effect modifications of the ALT change with any of the potential variables studied.
Conclusions
Replacing TDF with TAF in HIV‐monoinfected people led to a significant decrease in ALT values. Findings were not significantly affected by known risk factors for hepatotoxicity.
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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
Introduction
In many countries, mortality due to suicide is higher among people living with HIV than in the general population. We aimed to analyse trends in suicide mortality before and after the ...introduction of triple combination antiretroviral therapy (cART), and to identify risk factors associated with death from suicide in Switzerland.
Methods
We analysed data from the Swiss HIV Cohort Study from the pre‐cART (1988‐1995), earlier cART (1996‐2008) and later cART (2009‐2017) eras. We used multivariable Cox regression to assess risk factors for death due to suicide in the ART era and computed standardized mortality ratios (SMRs) to compare mortality rates due to suicide among persons living with HIV with the general population living in Switzerland, using data from the Swiss National Cohort.
Results and Discussion
We included 20,136 persons living with HIV, of whom 204 (1.0%) died by suicide. In men, SMRs for suicide declined from 12.9 (95% CI 10.4‐16.0) in the pre‐cART era to 2.4 (95% CI 1.2‐5.1) in the earlier cART and 3.1 (95% CI 2.3‐4.3) in the later cART era. In women, the corresponding ratios declined from 14.2 (95% CI 7.9‐25.7) to 10.2 (3.8‐27.1) and to 3.3 (95% CI 1.5‐7.4). Factors associated with death due to suicide included gender (adjusted hazard ratio 0.58 (95% CI 0.38‐0.87) comparing women with men), nationality (1.95 (95% CI 1.34‐2.83) comparing Swiss with other), Centers for Disease Control and Prevention clinical stage (0.33 (95% CI 0.24‐0.46) comparing stage A with C), transmission group (2.64 (95% CI 1.71‐4.09) for injection drug use and 2.10 (95% CI 1.36‐3.24) for sex between men compared to other), and mental health (2.32 (95% CI 1.71‐3.14) for a history of psychiatric treatment vs. no history). There was no association with age.
Conclusions
Suicide rates have decreased substantially among people living with HIV in the last three decades but have remained about three times higher than in the general population since the introduction of cART. Continued emphasis on suicide prevention among men and women living with HIV is important.
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FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
Antiretroviral therapy has transformed HIV infection from a deadly into a chronic condition. Aging people with HIV (PWH) are at higher risk of polypharmacy, potential drug-drug interactions (DDIs), ...and potentially inappropriate medications (PIMs). This study aims to compare prescribed drugs, polypharmacy, and potential DDIs between young (<65 years old) and elderly (≥65 years old) PWH. The prevalence of PIMs was assessed in elderly.
PWH from 2 centers within the Swiss HIV Cohort Study were asked to fill in a form with all their current medications. Polypharmacy was defined as being on ≥5 non-HIV drugs. PIMs were evaluated using Beers criteria. Potential DDIs for the most prescribed therapeutic classes were screened with the Liverpool interaction database.
Among the 996 PWH included, 122 were ≥65 years old. Polypharmacy was more frequent in the elderly group (44% vs 12%). Medications and potential DDIs differed according to the age group: cardiovascular drugs and related potential DDIs were more common in the elderly group (73% of forms included ≥1 cardiovascular drug; 11% of cardiovascular drugs involved potential DDIs), whereas central nervous system drugs were more prescribed and involved in potential DDIs in younger PWH (26%, 11%). Potential DDIs were mostly managed through dosage adjustments. PIMs were found in 31% of the elderly group.
Potential DDIs remain common, and PIMs constitute an additional burden for the elderly. It is important that prescribers develop and maintain a proactive approach for the recognition and management of DDIs and other prescribing issues frequently encountered in geriatric medicine.
Factors influencing susceptibility to SARS-CoV-2 remain to be resolved. Using data of the Swiss HIV Cohort Study (SHCS) on 6,270 people with HIV (PWH) and serologic assessment for SARS-CoV-2 and ...circulating-human-coronavirus (HCoV) antibodies, we investigated the association of HIV-related and general parameters with SARS-CoV-2 infection.
We analyzed SARS-CoV-2 PCR-tests, COVID-19 related hospitalizations, and deaths reported to the SHCS between January 1, 2020 and December 31, 2021. Antibodies to SARS-CoV-2 and HCoVs were determined in pre-pandemic (2019) and pandemic (2020) bio-banked plasma and compared to HIV-negative individuals. We applied logistic regression, conditional logistic regression, and Bayesian multivariate regression to identify determinants of SARS-CoV-2 infection and Ab responses to SARS-CoV-2 in PWH.
No HIV-1-related factors were associated with SARS-CoV-2 acquisition. High pre-pandemic HCoV antibodies were associated with a lower risk of subsequent SARS-CoV-2 infection and with higher SARS-CoV-2 antibody responses upon infection. We observed a robust protective effect of smoking on SARS-CoV-2-infection risk (aOR= 0.46 0.38,0.56, p=2.6*10-14), which occurred even in previous smokers, and was highest for heavy smokers.
Our findings of two independent protective factors, smoking and HCoV antibodies, both affecting the respiratory environment, underscore the importance of the local immune milieu in regulating susceptibility to SARS-CoV-2.
Abstract
Background
Bacterial pneumonia is a leading reason for hospitalization among people with HIV (PWH); however, evidence regarding its drivers in the era of potent antiretroviral therapy is ...limited.
Methods
We assessed risk factors for bacterial pneumonia in the Swiss HIV Cohort Study using marginal models. We further assessed the relationship between risk factors and changes in bacterial pneumonia incidence using mediation analysis.
Results
We included 12927 PWH with follow-ups between 2008 and 2018. These patients had 985 bacterial pneumonia events during a follow-up of 100779 person-years. Bacterial pneumonia incidence significantly decreased from 13.2 cases/1000 person-years in 2008 to 6.8 cases/1000 person-years in 2018. Older age, lower education level, intravenous drug use, smoking, lower CD4-cell count, higher HIV load, and prior pneumonia were significantly associated with higher bacterial pneumonia incidence. Notably, CD4 cell counts 350–499 cells/μL were significantly associated with an increased risk compared to CD4 ≥ 500 cells/µL (adjusted hazard ratio, 1.39; 95% confidence interval, 1.01–1.89). Decreasing incidence over the last decade can be explained by increased CD4-cell counts and viral suppression and decreased smoking frequency.
Conclusions
Improvements in cascade of care of HIV and decrease in smoking may have mediated a substantial decrease in bacterial pneumonia incidence.
Bacterial pneumonia in people with HIV is associated with obstructive airway disease, proton pump inhibitors, CD4 cell count, viral load, smoking, and intravenous drug use. Improved HIV care and decreased smoking may have mediated reduced bacterial pneumonia incidence 2008–2018.
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