Objectives
Gender‐specific data on the outcome of combination antiretroviral therapy (cART) are a subject of controversy. We aimed to compare treatment responses between genders in a setting of equal ...access to cART over a 14‐year period.
Methods
Analyses included treatment‐naïve participants in the Swiss HIV Cohort Study starting cART between 1998 and 2011 and were restricted to patients infected by heterosexual contacts or injecting drug use, excluding men who have sex with men.
Results
A total of 3925 patients (1984 men and 1941 women) were included in the analysis. Women were younger and had higher CD4 cell counts and lower HIV RNA at baseline than men. Women were less likely to achieve virological suppression < 50 HIV‐1 RNA copies/mL at 1 year (75.2% versus 78.1% of men; P = 0.029) and at 2 years (77.5% versus 81.1%, respectively; P = 0.008), whereas no difference between sexes was observed at 5 years (81.3% versus 80.5%, respectively; P = 0.635). The probability of virological suppression increased in both genders over time (test for trend, P < 0.001). The median increase in CD4 cell count at 1, 2 and 5 years was generally higher in women during the whole study period, but it gradually improved over time in both sexes (P < 0.001). Women also were more likely to switch or stop treatment during the first year of cART, and stops were only partly driven by pregnancy. In multivariate analysis, after adjustment for sociodemographic factors, HIV‐related factors, cART and calendar period, female gender was no longer associated with lower odds of virological suppression.
Conclusions
Gender inequalities in the response to cART are mainly explained by the different prevalence of socioeconomic characteristics in women compared with men.
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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. Human immunodeficiency virus (HIV)–infected persons may be at increased risk for developing type 2 diabetes mellitus because of viral coinfection and adverse effects of treatment. ...Methods. We studied associations of new-onset diabetes mellitus with hepatitis B virus and hepatitis C virus coinfections and antiretroviral therapy in participants in the Swiss HIV Cohort Study, using Poisson regression. Results. A total of 123 of 6513 persons experienced diabetes mellitus during 27,798 person-years of follow-up (PYFU), resulting in an incidence of 4.4 cases per 1000 PYFU (95% confidence interval CI, 3.7–5.3 cases per 1000 PYFU). An increased incidence rate ratio (IRR) was found for male subjects (IRR, 2.5; 95% CI, 1.5–4.2), older age (IRR for subjects >60 years old, 4.3; 95% CI, 2.3–8.2), black (IRR, 2.1; 95% CI, 1.1–4.0) and Asian (IRR, 4.9; 95% CI, 2.2–10.9) ethnicity, Centers for Disease Control and Prevention disease stage C (IRR, 1.6; 95% CI, 1.04–2.4), and obesity (IRR, 4.7; 95% CI, 3.1–7.0), but results for hepatitis C virus infection or active hepatitis B virus infection were inconclusive. Strong associations were found for current treatment with nucleoside reverse-transcriptase inhibitors (IRR, 2.22; 95% CI, 1.11–4.45), nucleoside reverse-transcriptase inhibitors plus protease inhibitors (IRR, 2.48; 95% CI, 1.42–4.31), and nucleoside reverse-transcriptase inhibitors plus protease inhibitors and nonnucleoside reverse-transcriptase inhibitors (IRR, 3.25; 95% CI, 1.59–6.67) but were not found for treatment with nucleoside reverse-transcriptase inhibitors plus nonnucleoside reverse-transcriptase inhibitors (IRR, 1.47; 95% CI, 0.77–2.82). Conclusions. In addition to traditional risk factors, current treatment with protease inhibitor– and nucleoside reverse-transcriptase inhibitor–containing regimens was associated with the risk of developing type 2 diabetes mellitus. Our study did not find a significant association between viral hepatitis infection and risk of incident diabetes.
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.
Objectives
The aim of the study was to assess the feasibility of a national pre‐exposure prophylaxis (PrEP) programme using smartphone‐compatible data collection.
Methods
This was a multicentre ...cohort study (NCT03893188) enrolling individuals interested in PrEP in Switzerland. All centres participate in the SwissPrEPared programme, which uses smartphone‐compatible data collection. Feasibility was assessed after centres had enrolled at least one participant. Participants were HIV‐negative individuals presenting for PrEP counselling. Outcomes were participation (number enrolled/number eligible), enrolment rates (number enrolled per month), retention at first follow‐up (number with first follow‐up/number enrolled), and uptake (proportion attending first visit as scheduled). Participant characteristics were compared between those retained after baseline assessment and those who dropped out.
Results
Between April 2019 and January 2020, 987 individuals were assessed for eligibility, of whom 969 were enrolled (participation: 98.2%). The median enrolment rate was 86 per month interquartile range (IQR) 52–137. Retention at first follow‐up and uptake were both 80.7% (782/969 and 532/659, respectively). At enrolment, the median age was 40 (IQR 33–47) years, 95% were men who have sex with men, 47% had a university degree, and 75.5% were already taking PrEP. Most reported multiple casual partners (89.2%), previous sexually transmitted infections (74%) and sexualized drug use (73.1%). At baseline, 25.5% tested positive for either syphilis, gonorrhoea or chlamydia. Participants who dropped out were at lower risk of HIV infection than those retained after baseline assessment.
Conclusions
In a national PrEP programme using smartphone‐compatible data collection, participation, retention and uptake were high. Participants retained after baseline assessment were at considerable risk of HIV infection. Younger, less educated individuals were underrepresented in the SwissPrEPared cohort.
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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. Data on the incidence of hepatitis C virus (HCV) infection among human immunodeficiency virus (HIV)–infected persons are sparse. It is controversial whether and how frequently HCV is ...transmitted by unprotected sexual intercourse. Methods. We assessed the HCV seroprevalence and incidence of HCV infection in the Swiss HIV Cohort Study between 1988 and 2004. We investigated the association of HCV seroconversion with mode of HIV acquisition, sex, injection drug use (IDU), and constancy of condom use. Data on condom use or unsafe sexual behavior were prospectively collected between 2000 and 2004. Results. The overall seroprevalence of HCV infection was 33% among a total of 7899 eligible participants and 90% among persons reporting IDU. We observed 104 HCV seroconversions among 3327 participants during a total follow-up time of 16,305 person-years, corresponding to an incidence of 0.64 cases per 100 person-years. The incidence among participants with a history of IDU was 7.4 cases per 100 person-years, compared with 0.23 cases per 100 person-years in patients without such a history (P < .001). In men who had sex with men (MSM) without a history of IDU who reported unsafe sex, the incidence was 0.7 cases per 100 person-years, compared with 0.2 cases per 100 person-years in those not reporting unsafe sex (P = .02), corresponding to an incidence rate ratio of 3.5 (95% confidence interval, 1.2–10.0). The hazard of acquiring HCV infection was elevated among younger participants who were MSM. Conclusions. HCV infection incidence in the Swiss HIV Cohort Study was mainly associated with IDU. In HIV-infected MSM, HCV infection was associated with unsafe sex.
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
An abstract of the study of Gaudio et. al. about the novel BTK and PI3K-delta inhibitors acalabrutinib (ACP-196) and ACP-319 show activity in pre-clinical B-cell lymphoma models is presented. Among ...other things BTK and PI3K-delta inhibitors are among the most promising classes of anti-lymphoma agents, as demonstrated by the FDA approval of ibrutinib and idelalisib. Acalabrutinib (ACP-196) and ACP-319 are novel BTK and PIK3-delta selective inhibitors, respectively, under clinical evaluation. Acalabrutinib and ACP-319 showed both in vitro and in vivo anti-lymphoma activity. In vitro synergism was observed in some cell lines where single agent activity of either agent was modest or absent. Further preclinical and clinical studies are suggested.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
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
To assess the association of CYP2B6 allelic diversity with efavirenz (EFV) pharmacokinetics, we performed extensive genotyping of 15 relevant single nucleotide polymorphism in 169 study participants, ...and full resequencing of CYP2B6 in individuals with abnormal EFV plasma levels. Seventy‐seven (45.5%) individuals carried a known (CYP2B6★6,★11,★15, or ★18) or new loss/diminished‐function alleles. Resequencing defined two new loss‐of‐function alleles: allele ★27 (marked by 593T>C M198T), that results in 85% decrease in enzyme activity and allele ★28 (marked by 1132C>T), that results in protein truncation at arginine 378. Median AUC levels were 188.5 μg h/ml for individuals homozygous for a loss/diminished‐function allele, 58.6 μg h/ml for carriers, and 43.7 μg h/ml for noncarriers (P<0.0001). Individuals with a poor metabolizer genotype had a likelihood ratio of 35 (95% CI, 11–110) of presenting very high EFV plasma levels. CYP2B6 poor metabolizer genotypes explain to a large extent EFV pharmacokinetics and identify individuals at risk of extremely elevated EFV plasma levels.
Clinical Pharmacology & Therapeutics (2007) 81, 557–566. doi:10.1038/sj.clpt.6100072; published online 18 January 2007
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, 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
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