Publications by authors named "Matthias Cavassini"

330 Publications

HIV testing in termination of pregnancy and colposcopy services: a scoping review.

Sex Transm Infect 2021 Sep 20. Epub 2021 Sep 20.

Service of Infectious Diseases, Lausanne University Hospital, Lausanne, Switzerland

Background: Women and girls are relatively under-represented across the HIV treatment cascade. Two conditions unique to women, pregnancy and cervical cancer/dysplasia, share a common acquisition mode with HIV. This scoping review aimed to explore HIV testing practices in voluntary termination of pregnancy (TOP) and colposcopy services.

Methods: The scoping review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews. We searched articles published up to 20 December 2020 using three electronic databases (PubMed/Medline, Embase, Google Scholar) and including the keywords "HIV Testing", "Abortion, Induced", "Colposcopy", "HIV screen*" and "termination of pregnancy".

Results: A total of 1496 articles were identified, of which 55 met the inclusion criteria. We included studies providing background HIV prevalence in addition to prevalence in the study population and studies of women seeking TOP rather than presenting with TOP complications. This limited our review to high-income, low HIV prevalence settings. We observed two study phases: studies pre-antiretroviral therapy (ART) using unlinked anonymous testing data and examining HIV risk factors associated with positive HIV tests and studies post-ART using routine testing data and exploring HIV testing uptake. HIV prevalence was estimated at >0.2% in most TOP settings and >1% (range 1.7%-11.4%) in colposcopy services. Many TOP providers did not have local HIV testing policies and HIV testing was not mentioned in many specialist guidelines. Testing uptake was 49%-96% in TOP and 23%-75% in colposcopy services.

Conclusion: Given the estimated HIV prevalence of >0.1% among women attending TOP and colposcopy services, HIV testing would be economically feasible to perform in high-income settings. Explicit testing policies are frequently lacking in these two settings, both at the local level and in specialist guidelines. Offering HIV testing regardless of risk factors could normalise testing, reduce late HIV presentation and create an opportunity for preventive counselling.
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http://dx.doi.org/10.1136/sextrans-2021-055111DOI Listing
September 2021

Long-acting antiretrovirals: a new era for the management and prevention of HIV infection.

J Antimicrob Chemother 2021 Sep 9. Epub 2021 Sep 9.

Service and Laboratory of Clinical Pharmacology, Department of Laboratory Medicine and Pathology, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.

The long-acting antiretroviral cabotegravir and rilpivirine combination has just received FDA, EMA and Health Canada approval. This novel drug delivery approach is about to revolutionize the therapy of people living with HIV, decreasing the 365 daily pill burden to only six intramuscular injections per year. In addition, islatravir, a first-in-class nucleoside reverse transcriptase translocation inhibitor, is intended to be formulated as an implant with a dosing interval of 1 year or more. At present, long-acting antiretroviral therapies (LA-ARTs) are given at fixed standard doses, irrespectively of the patient's weight and BMI, and without consideration for host genetic and non-genetic factors likely influencing their systemic disposition. Despite a few remaining challenges related to administration (e.g. pain, dedicated medical procedure), the development and implementation of LA-ARTs can overcome long-term adherence issues by improving patients' privacy and reducing social stigma associated with the daily oral intake of anti-HIV treatments. Yet, the current 'one-size-fits-all' approach does not account for the recognized significant inter-individual variability in LA-ART pharmacokinetics. Therapeutic drug monitoring (TDM), an important tool for precision medicine, may provide physicians with valuable information on actual drug exposure in patients, contributing to improve their management in real life. The present review aims to update the current state of knowledge on these novel promising LA-ARTs and discusses their implications, particularly from a clinical pharmacokinetics perspective, for the future management and prevention of HIV infection, issues of ongoing importance in the absence of curative treatment or an effective vaccine.
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http://dx.doi.org/10.1093/jac/dkab324DOI Listing
September 2021

High-dimensional immune phenotyping of blood cells by mass cytometry in patients infected with hepatitis C virus.

Clin Microbiol Infect 2021 Aug 30. Epub 2021 Aug 30.

Infectious Diseases Service, Department of Medicine, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland. Electronic address:

Objectives: Chronic hepatitis C virus (HCV) infection affects the immune system. Whether elimination of HCV with direct-acting antivirals (DAA) restores immunity is unclear. We used mass cytometry to get a broad and in-depth assessment of blood cell populations of patients with chronic HCV before and after DAA therapy.

Methods: Before and 12 weeks after sustained virological response (SVR12) to DAA therapy, 22 cell populations were analysed by mass cytometry in blood collected from ten healthy control individuals and 20 HCV-infected patients with (ten patients) or without (ten patients) human immunodeficiency virus (HIV) infection.

Results: HCV infection altered the frequency of 14/22 (64%) blood cell populations. At baseline, the frequencies (median, interquartile range (IQR); control, HCV, HCV/HIV) of intermediate monocytes (1.2, IQR 0.47-1.46; 1.76, IQR 0.83-2.66; 0.78, IQR 0.28-1.77), non-classical monocytes (1.11, IQR 0.49-1.26; 0.9, IQR 0.18-0.99; 0.54, IQR 0.28-1.77), conventional dendritic cells type 2 (0.55, IQR 0.35-0.59; 0.31, IQR 0.16-0.38; 0.19, IQR 0.11-0.36) and CD56 natural killer cells (8.08, IQR 5.34-9.79; 4.72, IQR 2.59-6.05) 3.61, IQR 2.98-5.07) were reduced by 35% to 65%, particularly in HCV/HIV co-infected patients. In contrast, activated double-negative T cells (0.07, IQR 0.06-0.10; 0.10, IQR 0.09-0.19; 0.19, IQR 0.12-0.25), activated CD4 T cells (0.28, IQR 0.21-0.36; 0.56, IQR 0.33-0.77; 0.40, IQR 0.22-0.53) and activated CD8 T cells (0.23, IQR 0.14-0.42; 0.74, IQR 0.30-1.65; 0.80, IQR 0.58-1.16) were increased 1.4 to 3.5 times. Upon stimulation with Toll-like receptor ligands, the expression of cytokines was up-regulated in 7/9 (78%) and 17/19 (89%) of the conditions in HCV- and HCV/HIV-infected patients, respectively. Most alterations persisted at SVR12.

Conclusions: Chronic HCV and HCV/HIV infections induce profound and durable perturbations of innate and adaptive immune homeostasis.
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http://dx.doi.org/10.1016/j.cmi.2021.08.018DOI Listing
August 2021

Neurocognitive course at two-year follow-up in the neurocognitive assessment in the metabolic and aging cohort (NAMACO) study.

AIDS 2021 Aug 19. Epub 2021 Aug 19.

Service of Infectious Diseases, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland Department of Infectious Diseases and Hospital Epidemiology, Universitätsspital Zurich, University of Zurich, Zurich, Switzerland Laboratory of Neuroimmunology, Research Centre of clinical neurosciences, Department of clinical neurosciences, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland University Department of Medicine, Kantonsspital Bruderholz, University of Basel, Bruderholz, Switzerland Department of Infectious Diseases and Hospital Epidemiology, Universitätsspital Basel, University of Basel, Basel, Switzerland Memory Clinic, Felix Platter Hospital, University Center for Medicine of Aging, Basel, Switzerland Department of Infectious Diseases, Bern University Hospital, University of Bern, Bern, Switzerland Department of Neurology, Bern University Hospital, University of Bern, Bern, Switzerland HIV unit, Infectious Diseases Division, Department of Medicine, University Hospital of Geneva, Geneva, Switzerland Department of Neurology, University Hospital of Geneva and Faculty of Medicine, Geneva, Switzerland Division of Infectious Diseases and Hospital Epidemiology Division, Kantonsspital St. Gallen, St. Gallen, Switzerland Department of Neurology, Kantonsspital St. Gallen, St. Gallen, Switzerland Infectious Diseases Division, Ospedale Regionale di Lugano, Lugano, Switzerland Department of Neurology, Neurocentre of Southern Switzerland, Ospedale Civico, Lugano, Switzerland Neuropsychology Unit, Department of Neurology, Universitätsspital Zurich, University of Zurich, Zurich, Switzerland Service of Neurology, Department of Clinical Neurosciences, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.

Objective: To examine neurocognitive course over time among people with well-treated HIV.

Design: The Neurocognitive Assessment in the Metabolic and Aging Cohort (NAMACO) study is an ongoing, prospective, longitudinal, multicenter and multilingual study within the Swiss HIV Cohort Study (SHCS). Participants undergo neuropsychological assessment at baseline and two-yearly follow-up.

Setting: Seven SHCS centers.

Subjects: Patients aged ≥45 years enrolled in the SHCS with fluency in the local language (French, German or Italian) and agreeing to participate in the NAMACO study: 981 participants at baseline, 720 at two-year follow-up of whom 644 had complete data sets.

Intervention: Standardized neuropsychological assessment at baseline and two-year follow-up.

Main Outcome Measure: Neurocognitive performance using Frascati criteria and mean z-scores.

Results: Four participants (of 644, 0.6%) had plasma HIV-1 RNA > 50 copies/mL; median CD4 count was 660 cells/μL. According to Frascati criteria, 204 participants (31.7%) had neurocognitive impairment (NCI) at baseline. NCI severity in these participants changed little over two years and comprehensive models based on Frascati criteria were not feasible. Examining mean z-scores, however, we observed neurocognitive stability or improvement over two years in five of seven neurocognitive domains assessed. Age ≥65 years (p = 0.02) and cognitive complaints (p = 0.004) were associated with neurocognitive decline, while black race (p = 0.01) and dolutegravir treatment (p = 0.002) were associated with improvement.

Conclusion: Frascati criteria were less sensitive in measuring NCI change and therefore unsuitable for following neurocognitive course in our cohort of people with well-treated HIV. Examining neurocognitive course by mean z-score change, we observed stability or improvement.
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http://dx.doi.org/10.1097/QAD.0000000000003057DOI Listing
August 2021

Forgiveness of Dolutegravir-Based Triple Therapy Compared With Older Antiretroviral Regimens: A Prospective Multicenter Cohort of Adherence Patterns and HIV-RNA Replication.

Open Forum Infect Dis 2021 Jul 1;8(7):ofab316. Epub 2021 Jul 1.

Department of Infectious Diseases, Regional Hospital, Orléans, France.

Background: For many people with HIV (PWH), taking antiretroviral therapy (ARV) every day is difficult.

Methods: Average adherence (Av-Adh) and log-transformed treatment interruption (TI) to ARV were prospectively measured over 6 months using electronic drug monitoring (EDM) in several cohorts of PWH. Multivariate linear regression models including baseline confounders explored the influence of EDM-defined adherence ( ) on 6-month log HIV-RNA. Multivariate logistic regression models were used to compare the risk of HIV-RNA detection (VR) within subgroups stratified by lower (≤95%) and higher (>95%) Av-Adh.

Results: Three hundred ninety-nine PWH were analyzed with different ARVs: dolutegravir (n = 102), raltegravir (n = 90), boosted PI (bPI; n = 107), and NNRTI (n = 100). In the dolutegravir group, the influence of adherence pattern measures on for HIV-RNA levels was marginal (+2%). Av-Adh, TI, and Av-Adh × TI increased the for HIV-RNA levels by 54% and 40% in the raltegravir and bPI treatment groups, respectively. TI increased the for HIV-RNA levels by 36% in the NNRTI treatment group. Compared with the dolutegravir-based regimen, the risk of VR was significantly increased for raltegravir (adjusted odds ratio [aOR], 45.6; 95% CI, 4.5-462.1; = .001), NNRTIs (aOR, 24.8; 95% CI, 2.7-228.4; = .005), and bPIs (aOR, 28.3; 95% CI, 3.4-239.4; = .002) in PWH with Av-Adh ≤95%. Among PWH with >95% Av-Adh, there were no significant differences in the risk of VR among the different ARVs.

Conclusions: These findings support the concept that dolutegravir in combination with 2 other active ARVs achieves greater virological suppression than older ARVs, including raltegravir, NNRTI, and bPI, among PWH with lower adherence.
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http://dx.doi.org/10.1093/ofid/ofab316DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8297697PMC
July 2021

Seasonal trivalent inactivated influenza vaccine with topical imiquimod in immunocompromised patients: A randomized controlled trial.

J Infect 2021 09 21;83(3):354-360. Epub 2021 Jul 21.

Transplantation Center, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland; Service of Infectious Diseases, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.

Background: The effect of the Toll-like receptor 7 agonist imiquimod before intradermal (ID) or intramuscular (IM) influenza vaccine in immunocompromised hosts is unknown.

Methods: In this open-label randomized controlled trial, kidney transplant recipients (KT) and people living with HIV (PLWH) were randomized to receive IM trivalent inactivated influenza vaccine alone (IM), IM vaccine after topical imiquimod (imi+IM) or ID vaccine after topical imiquimod (imi+ID). Immunogenicity was assessed by hemagglutination inhibition assay. The primary outcome was vaccine response, defined as seroconversion to at least one viral strain at day 21.

Results: Seventy patients (35 KT and 35 PLWH) received IM (24), imi+IM (22), or imi+ID (24) vaccine. Vaccine response was 61% (14/23) with IM, 59% (13/22) with imi+IM, and 65% (15/23) with imi+ID vaccine (P = 0.909). Vaccine response was associated with HIV infection compared to kidney transplantation (adjusted-OR 3.74, 95% CI 1.25 - 11.23, P = 0.019), but not with imiquimod application nor ID injection. After vaccination, seroprotection to all viral strains was 79% (19/24) with IM, 68% (15/22) with imi+IM, and 70% (16/23) with imi+ID (P = 0.657). We did not observe any vaccine-related severe adverse event.

Conclusions: In our study, topical imiquimod did not improve the immunogenicity of influenza vaccine in KT and in PLWH.
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http://dx.doi.org/10.1016/j.jinf.2021.07.010DOI Listing
September 2021

Identifying and Characterizing Trans women in the Swiss HIV Cohort Study as an Epidemiologically Distinct Risk Group.

Clin Infect Dis 2021 Jul 20. Epub 2021 Jul 20.

Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, Zurich, Switzerland.

Background: As trans women are disproportionately affected by the HIV epidemic, and are still understudied, we aimed to identify and characterize the trans women in the Swiss HIV Cohort Study (SHCS).

Methods: A combination of criteria from pre-existing cohort data was used to identify trans women. Information on socioeconomic factors, clinical data, risk behaviors, and mental health was collected. We also described their phylogenetic patterns within HIV transmission networks in relation to other risk groups.

Results: We identified 89 trans women out of a total 20925 cohort participants. Trans women were much more likely to be Asian (30.3%) and Hispanic (15.7%) compared to men-who-have-sex with-men/MSM (2.5% and 4.1%, P value<0.001) and cis heterosexual (HET) women (7.0% and 3.3%, P value<0.001). Trans women were more similar to cis HET women in some measures like education level (post-secondary education attainment: 22.6% and 20.7% [P value =0.574], vs. 46.5% for MSM [P value<0.001]), while being more similar to MSM for measures like prior syphilis diagnosis (36.0% and 44.0% [P value=0.170], vs. 6.7% for cis HET women [P value <0.001]). 11.2% of trans women have been priorly hospitalized for psychological reasons, compared to 4.2% of MSM (P value=0.004) and 5.1% of cis HET women (P value=0.025). An analysis of transmission clusters containing trans women suggested greater affinity within the transmission networks to MSM compared to cis HET women.

Conclusions: Trans women are epidemiologically distinct in the setting of the Swiss HIV epidemic, warranting better identification and study to better serve this underserved risk group.
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http://dx.doi.org/10.1093/cid/ciab628DOI Listing
July 2021

Increasing Frequency and Transmission of HIV-1 Non-B Subtypes among Men Who Have Sex with Men in the Swiss HIV Cohort Study.

J Infect Dis 2021 Jul 14. Epub 2021 Jul 14.

Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, 8091 Zurich, Switzerland.

Background: In Switzerland, HIV-1 transmission among men who have sex with men (MSM) has been dominated by subtype B, whilst non-B subtypes are commonly attributed to infections acquired abroad among heterosexuals. Here, we evaluated the temporal trends of non-B subtypes and the characteristics of molecular transmission clusters (MTCs) among MSM.

Methods: Sociodemographic and clinical data and partial pol sequences were obtained from participants enrolled in the Swiss HIV Cohort Study (SHCS). For non-B subtypes, maximum likelihood trees were constructed, from which Swiss MTCs were identified and analysed by transmission group.

Results: Non-B subtypes were identified in 8.1% (416/5,116) of MSM participants. CRF01_AE was the most prevalent strain (3.5%), followed by A (1.2%), F (1.1%), CRF02_AG (1.1%), C (0.9%), and G (0.3%). Between 1990 and 2019, an increase in the proportion of newly diagnosed individuals (0/123[0%] to 11/32 [34%]) with non-B subtypes in MSM was found. Across all non-B subtypes, the majority of MSM MTCs were European. Larger MTCs were observed for MSM than heterosexuals.

Conclusions: We found a substantial increase in HIV-1 non-B subtypes among MSM in Switzerland and the occurrence of large MTCs, highlighting the importance of molecular surveillance in guiding public health strategies targeting the HIV-1 epidemic.
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http://dx.doi.org/10.1093/infdis/jiab360DOI Listing
July 2021

EBV-positive large B-cell lymphoma with an unusual intravascular presentation and associated haemophagocytic syndrome in an HIV-positive patient: report of a case expanding the spectrum of EBV-positive immunodeficiency-associated lymphoproliferative disorders.

Virchows Arch 2021 Jun 19. Epub 2021 Jun 19.

Institute of Pathology, Department of Laboratory Medicine and Pathology, Lausanne, University Hospital (CHUV) and Lausanne University (UNIL), Rue du Bugnon 25, CH-1011, Lausanne, Switzerland.

Intravascular large B-cell lymphoma is a rare and aggressive EBV-negative large B-cell lymphoma with a dismal outcome. Here, we describe the case of a 76-year-old HIV-positive patient with an acute presentation of systemic symptoms and rapidly fatal outcome. Autopsy revealed a disseminated large B-cell lymphoma with an intravascular distribution involving the liver, lymph nodes, spleen, and bone marrow and associated to fibrin thrombi in hepatic capillary haemangiomas. The neoplastic B cells (CD79a + / - , CD20 + / - , CD30 + , MUM1 + , PD-L1 +) showed a Hodgkin and Reed-Sternberg-like morphology and were EBV-positive with a latency type II (LMP1 + , EBNA2-). Haemophagocytosis was documented in the bone marrow and lymph nodes. This case illustrates the diagnostic challenges of large B-cell lymphoma with intravascular presentation. We found only five other cases of EBV-positive large B-cell lymphoma with an intravascular presentation in the literature, three of which had an underlying immunodeficiency adding to the broad spectrum of EBV-associated lymphoma in the setting of immunosuppression.
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http://dx.doi.org/10.1007/s00428-021-03142-1DOI Listing
June 2021

Coronary Artery Disease-associated and Longevity-associated Polygenic Risk Scores for Prediction of Coronary Artery Disease Events in Persons Living with HIV: The Swiss HIV Cohort Study.

Clin Infect Dis 2021 Jun 6. Epub 2021 Jun 6.

University Department of Medicine and Infectious Diseases Service, Kantonsspital Baselland, University of Basel, Bruderholz, Switzerland.

Background: Coronary artery disease (CAD) is in part genetically determined. Aging is accentuated in people with HIV (PLWH). It is unknown whether genetic CAD event prediction in PLWH is improved by applying individual polygenic risk scores (PRS) and by considering genetic variants associated with successful aging and longevity.

Methods: In Swiss HIV Cohort Study participants of self-reported European descent, we determined univariable and multivariable odds ratios (OR) for CAD events, based on traditional CAD risk factors, adverse antiretroviral exposures, and different validated genome-wide PRS. PRS were built from CAD-associated single nucleotide polymorphisms (SNPs), longevity-associated SNPs, or both.

Results: We included 269 cases with CAD events between 2000-2017 (Median age 54 years, 87% male, 82% with suppressed HIV RNA) and 567 event-free controls. Clinical (i.e. traditional and HIV-related) risk factors, and PRS built from CAD-associated SNPs, longevity-associated SNPs, or both, each contributed independently to CAD events (p<0.001). Participants with the most unfavorable clinical risk factor profile (top quintile) had adjusted CAD-OR=17.82 (8.19-38.76), compared to participants in the bottom quintile. Participants with the most unfavorable CAD-PRS (top quintile) had adjusted CAD-OR=3.17 (1.74-5.79), compared to the bottom quintile. After adding longevity-associated SNPs to the CAD-PRS, participants with the most unfavorable genetic background (top quintile) had adjusted CAD-OR=3.67 (2.00-6.73), compared to the bottom quintile.

Conclusions: In Swiss PLWH, CAD prediction based on traditional and HIV-related risk factors was superior to genetic CAD prediction based on longevity- and CAD-associated PRS. Combining traditional, HIV-related and genetic risk factors provided the most powerful CAD prediction.
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http://dx.doi.org/10.1093/cid/ciab521DOI Listing
June 2021

Systematic screening of viral and human genetic variation identifies antiretroviral resistance and immune escape link.

Elife 2021 06 1;10. Epub 2021 Jun 1.

Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.

Background: Considering the remaining threat of drug-resistantmutations (DRMs) to antiretroviral treatment (ART) efficacy, we investigated how the selective pressure of human leukocyte antigen (HLA)-restricted cytotoxic T lymphocytes drives certain DRMs' emergence and retention.

Methods: We systematically screened DRM:HLA class I allele combinations in 3997 ART-naïve Swiss HIV Cohort Study (SHCS) patients. For each pair, a logistic regression model preliminarily tested for an association with the DRM as the outcome. The three HLA:DRM pairs remaining after multiple testing adjustment were analyzed in three ways: cross-sectional logistic regression models to determine any HLA/infection time interaction, survival analyses to examine if HLA type correlated with developing specific DRMs, and via NetMHCpan to find epitope binding evidence of immune escape.

Results: Only one pair, RT-E138:HLA-B18, exhibited a significant interaction between infection duration and HLA. The survival analyses predicted two pairs with an increased hazard of developing DRMs: RT-E138:HLA-B18 and RT-V179:HLA-B35. RT-E138:HLA-B18 exhibited the greatest significance in both analyses (interaction term odds ratio [OR] 1.169 [95% confidence interval (CI) 1.075-1.273]; p-value<0.001; survival hazard ratio 12.211 [95% CI 3.523-42.318]; p-value<0.001). The same two pairs were also predicted by netMHCpan to have epitopic binding.

Conclusions: We identified DRM:HLA pairs where HLA presence is associated with the presence or emergence of the DRM, indicating that the selective pressure for these mutations alternates direction depending on the presence of these HLA alleles.

Funding: Funded by the Swiss National Science Foundation within the framework of the SHCS, and the University of Zurich, University Research Priority Program: Evolution in Action: From Genomes Ecosystems, in Switzerland.
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http://dx.doi.org/10.7554/eLife.67388DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8169104PMC
June 2021

[Fecal microbiota transplantation: from the evidence to the realty of the field].

Rev Med Suisse 2021 Apr;17(734):726-731

Service des maladies infectieuses, CHUV, 1011 Lausanne.

In clinical practice, fecal microbiota transplantation (FMT) has been established as an unparalleled therapy to date for multiple recurrent Clostridioides difficile infections (CDI). The implementation of the FMT in practice requires a significant investment to meet legal, security and financial requirements. Research on the microbiota is booming and multiple investigations on FMT in indications other than CDI are ongoing.
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April 2021

Pharmacokinetic parameters and weight change in HIV patients newly switched to dolutegravir-based regimens in SIMPL'HIV clinical trial.

Br J Clin Pharmacol 2021 Mar 25. Epub 2021 Mar 25.

HIV/AIDS Unit, Department of Infectious Diseases, Geneva University Hospitals and the University of Geneva Faculty of Medicine, Geneva, Switzerland.

This study aims to evaluate the association between dolutegravir (DTG) pharmacokinetic parameters and weight changes in treatment-experienced people with HIV (PWHIV) from the Simpl'HIV study newly switched to a dual DTG-based regimen. We used multivariable linear regressions to evaluate the association between DTG pharmacokinetic parameters at week 48 (derived using an established model) and weight change between week 0 and week 48. We adjusted our model for potential confounders including CD4 nadir, female sex, African origin, age, weight at week 0 and presence of a non-nucleoside reverse transcriptase inhibitor-based regimen before switch to DTG. The analysis included data from 39 PWHIV. An average significant weight gain of 2.4 kg was observed between baseline and week 48. DTG plasma exposure was not significantly associated with weight gain, even after adjusting for potential confounders (P = .9). We found no significant association between DTG pharmacokinetic parameters and weight gain amongst PWHIV newly switched to a DTG-based dual regimen.
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http://dx.doi.org/10.1111/bcp.14832DOI Listing
March 2021

Weight and Metabolic Changes After Switching From Tenofovir Disoproxil Fumarate to Tenofovir Alafenamide in People Living With HIV : A Cohort Study.

Ann Intern Med 2021 06 16;174(6):758-767. Epub 2021 Mar 16.

Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland (B.S., C.M., H.F., G.W., A.R.).

Background: Tenofovir-based antiretroviral therapy (ART) has become first-line in all major HIV treatment guidelines. Compared with tenofovir disoproxil fumarate (TDF), tenofovir alafenamide (TAF) has a favorable renal and bone safety profile, but concerns about metabolic complications remain.

Objective: To assess weight changes, the development of overweight/obesity, and changes in lipid levels 18 months after replacing TDF with TAF.

Design: Cohort study.

Setting: 5 university hospitals, affiliated hospitals, and private physicians in Switzerland.

Participants: 4375 adults living with HIV who received TDF-containing ART for 6 months or longer.

Measurements: Changes in weight and lipid levels were assessed using mixed-effect models. Differences in proportions of newly overweight/obese participants were calculated using 2-proportions tests.

Results: 4375 individuals were included, with follow-up between 1 January 2016 and 31 July 2019. Median age was 50 years (interquartile range, 43 to 56 years), 25.9% were female, and 51.7% had a normal body mass index (BMI); 3484 (79.6%) switched to TAF and 891 (20.4%) continued TDF. After 18 months, switching to TAF was associated with an adjusted mean weight increase of 1.7 kg (95% CI, 1.5 to 2.0 kg), compared with 0.7 kg (CI, 0.4 to 1.0 kg) with the continued use of TDF (between-group difference, 1.1 kg [CI, 0.7 to 1.4 kg]). Among individuals with a normal BMI, 13.8% who switched to TAF became overweight/obese, compared with 8.4% of those continuing TDF (difference, 5.4 percentage points [CI, 2.1 to 8.8 percentage points]). Switching to TAF led to increases in adjusted mean total cholesterol (0.25 mmol/L [9.5 mg/dL]), high-density lipoprotein cholesterol (0.05 mmol/L [1.9 mg/dL]), low-density lipoprotein cholesterol (0.12 mmol/L [4.7 mg/dL]), and triglyceride (0.18 mmol/L [16.1 mg/dL]) levels after 18 months.

Limitation: Short follow-up, small subgroup analyses, and potential residual confounding.

Conclusion: Replacing TDF with TAF is associated with adverse metabolic changes, including weight increase, development of obesity, and worsening serum lipid levels.

Primary Funding Source: Swiss National Science Foundation.
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http://dx.doi.org/10.7326/M20-4853DOI Listing
June 2021

Alcohol consumption and neurocognitive deficits in people with well-treated HIV in Switzerland.

PLoS One 2021 2;16(3):e0246579. Epub 2021 Mar 2.

Infectious Diseases Service, Lausanne University Hospital, Lausanne, Switzerland.

Background: Hazardous alcohol consumption and HIV infection increase the risk of neurocognitive impairment (NCI). We examined the association between alcohol consumption and specific neurocognitive domain function in people with HIV (PWH) taking modern antiretroviral therapy.

Methods: The Neurocognitive Assessment in the Metabolic and Aging Cohort (NAMACO) study is a prospective, longitudinal, multicentre and multilingual (French, German and Italian) study of patients aged ≥45 years old enrolled in the Swiss HIV Cohort Study (SHCS). Baseline data from 981 study participants were examined. Five neurocognitive domains were evaluated: motor skills, speed of information processing, attention/working memory, executive function and verbal episodic memory. NCI was examined as binary (presence/absence) and continuous (mean z-score) outcomes against Alcohol Use Disorders Identification Test for Consumption (AUDIT-C) scores using logistic and linear regression models, respectively.

Results: Most participants (96.2%) had undetectable viral loads and 64% were aged >50 years old. Hazardous alcohol consumption was observed in 49.4% of participants and binge drinking in 4.2%. While alcohol consumption frequency and quantity were not associated with NCI, the practice of binge drinking was significantly associated with impaired motor skills and overall neurocognitive function in both binary (odds ratio, OR ≥2.0, P <0.05) and continuous (mean z-score difference -0.2 to -0.4, P ≤0.01) outcomes. A significant U-shaped distribution of AUDIT-C score was also observed for motor skills and overall neurocognitive function.

Conclusions: In this cohort of PWH with well-controlled HIV infection, NCI was associated with the practice of binge drinking rather than alcohol consumption frequency or quantity. Longitudinal analysis of alcohol consumption and NCI in this population is currently underway.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0246579PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7924787PMC
August 2021

The influence of human genetic variation on Epstein-Barr virus sequence diversity.

Sci Rep 2021 Feb 25;11(1):4586. Epub 2021 Feb 25.

School of Life Sciences, EPFL, Lausanne, Switzerland.

Epstein-Barr virus (EBV) is one of the most common viruses latently infecting humans. Little is known about the impact of human genetic variation on the large inter-individual differences observed in response to EBV infection. To search for a potential imprint of host genomic variation on the EBV sequence, we jointly analyzed paired viral and human genomic data from 268 HIV-coinfected individuals with CD4 + T cell count < 200/mm and elevated EBV viremia. We hypothesized that the reactivated virus circulating in these patients could carry sequence variants acquired during primary EBV infection, thereby providing a snapshot of early adaptation to the pressure exerted on EBV by the individual immune response. We searched for associations between host and pathogen genetic variants, taking into account human and EBV population structure. Our analyses revealed significant associations between human and EBV sequence variation. Three polymorphic regions in the human genome were found to be associated with EBV variation: one at the amino acid level (BRLF1:p.Lys316Glu); and two at the gene level (burden testing of rare variants in BALF5 and BBRF1). Our findings confirm that jointly analyzing host and pathogen genomes can identify sites of genomic interactions, which could help dissect pathogenic mechanisms and suggest new therapeutic avenues.
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http://dx.doi.org/10.1038/s41598-021-84070-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7907281PMC
February 2021

The association between depressive symptoms and neurocognitive impairment in people with well-treated HIV in Switzerland.

Int J STD AIDS 2021 07 25;32(8):729-739. Epub 2021 Feb 25.

Infectious Diseases Service, 30635Lausanne University Hospital, Lausanne, Switzerland.

Background: Depression may contribute to neurocognitive impairment (NCI) in people with HIV (PWH). Attributing NCI to depression rather than to HIV is complicated as depression may be both a causal factor and an effect of NCI. This study aimed to determine the association between depressive symptoms and NCI among PWH with well-controlled infection.

Methods: The Neurocognitive Assessment in the Metabolic and Ageing Cohort study is an ongoing, prospective, longitudinal study of PWH aged ≥45 years old nested within the Swiss HIV Cohort Study. Neurocognitive Assessment in the Metabolic and Ageing Cohort study participants underwent neurocognitive assessment and grading of depressive symptoms using the Centre for Epidemiological Studies Depression Scale. Neurocognitive impairment categories were defined using Frascati criteria. Participants with NCI related to neurological or psychiatric confounders other than depression were excluded. The cross-sectional association between the Centre for Epidemiological Studies Depression score and neurocognitive impairment was examined taking Centre for Epidemiological Studies Depression score as a continuous variable and then as a binary variable using two score thresholds, 16 and 27.

Results: Excluding 79 participants with confounding factors, 902 participants were studied: 81% were men; 96% had plasma viral loads <50 copies/ml; 35% had neurocognitive impairment; 28% had Centre for Epidemiological Studies Depression scores ≥16. Higher Centre for Epidemiological Studies Depression scores were associated with female sex ( = 0.0003), non-Caucasian origin ( = 0.011) and current/past intravenous drug use ( = 0.002). Whilst neurocognitive impairment was associated with higher Centre for Epidemiological Studies Depression scores, the Centre for Epidemiological Studies Depression score was a poor predictor of having neurocognitive impairment (area under the ROC curve 0.604). Applying a Centre for Epidemiological Studies Depression score threshold of 16 predicted the presence of neurocognitive impairment with a sensitivity of 38.3% (specificity 77.2%), increasing the threshold to 27 lowered sensitivity to 15.4% (specificity 93.6%).

Conclusion: In this large cohort of PWH in Switzerland, we did not observe a Centre for Epidemiological Studies Depression score threshold that was sensitive in predicting neurocognitive impairment. As neurocognitive impairment was however associated with higher Centre for Epidemiological Studies Depression scores, the data support the screening for and treatment of depression among PWH diagnosed with neurocognitive impairment.
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http://dx.doi.org/10.1177/0956462420987434DOI Listing
July 2021

Data linkage to evaluate the long-term risk of HIV infection in individuals seeking post-exposure prophylaxis.

Nat Commun 2021 02 22;12(1):1219. Epub 2021 Feb 22.

Division of Infectious Diseases and Hospital Epidemiology, University Hospital of Zurich, Zurich, Switzerland.

Evidence on the long-term risk of HIV infection in individuals taking HIV post-exposure prophylaxis remains limited. In this retrospective data linkage study, we evaluate the occurrence of HIV infection in 975 individuals who sought post-exposure prophylaxis in a tertiary hospital between 2007 and 2013. Using privacy preserving probabilistic linkage, we link these 975 records with two observational databases providing data on HIV events (Zurich Primary HIV Infection study and the Swiss HIV Cohort Study). This enables us to identify 22 HIV infections and to obtain long-term follow-up data, which reveal a median of 4.1 years between consultation for post-exposure prophylaxis and HIV diagnosis. Even though men who have sex with men constitute only 35.8% of those seeking post-exposure prophylaxis, all 22 events occur in this subgroup. These findings should strongly encourage early consideration of pre-exposure prophylaxis in men who have sex with men after a first episode of post-exposure prophylaxis.
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http://dx.doi.org/10.1038/s41467-021-21485-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7900236PMC
February 2021

Association of Incomplete Adherence to Antiretroviral Therapy With Cardiovascular Events and Mortality in Virologically Suppressed Persons With HIV: The Swiss HIV Cohort Study.

Open Forum Infect Dis 2021 Feb 21;8(2):ofab032. Epub 2021 Jan 21.

University of Basel, Basel, Switzerland.

Background: Incomplete antiretroviral therapy (ART) adherence, even if sufficient to maintain viral suppression, is associated with enhanced inflammation in persons with HIV (PWH). However, its clinical implications remain unknown.

Methods: PWH enrolled in the Swiss HIV Cohort Study without a history of cardiovascular disease (CVD) who initiated ART between 2003 and 2018 and had viral suppression (<50 copies/mL) for ≥6 months were evaluated. The association between incomplete self-reported ART adherence (≥1 or ≥2 missed doses in the last month) and (1) any CVD event (myocardial infarction, revascularization, cerebral hemorrhage, stroke, and/or death due to CVD event) or (2) non-CVD-related death was evaluated using adjusted Cox proportional hazards models.

Results: A total of 6971 PWH (74% male) were included in the analysis (median age [interquartile range {IQR}], 39 [32-47] years). The median (IQR) follow-up was 8 (4-11) years, with 14 (8-23) adherence questionnaires collected per participant. In total, 205 (3%) participants experienced a CVD event, and 186 (3%) died a non-CVD-related death. In an adjusted competing risk model where missing data were imputed, missing ≥1 ART dose showed an increased, but not statistically significant, risk for CVD events (hazard ratio [HR], 1.23; 95% CI, 0.85-1.79;  = .28). Non-CVD-related mortality showed a statistically significantly increased risk with missing ≥1 ART dose (HR, 1.44; 95% CI, 1.00-2.07;  = .05) and missing ≥2 ART doses (HR, 2.21; 95% CI, 1.37-3.57;  = .001).

Conclusions: Incomplete ART adherence was significantly associated with an increased risk for non-CVD-related mortality in PWH with virologic suppression. This highlights the potential role of nonadherence to ART as a driver of non-AIDS clinical outcomes.
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http://dx.doi.org/10.1093/ofid/ofab032DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7880264PMC
February 2021

Population pharmacokinetic modelling to quantify the magnitude of drug-drug interactions between amlodipine and antiretroviral drugs.

Eur J Clin Pharmacol 2021 Jul 16;77(7):979-987. Epub 2021 Jan 16.

Centre for Research and Innovation in Clinical Pharmaceutical Sciences, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.

Purpose: Drug-drug interactions (DDIs) with antiretroviral drugs (ARVs) represent an important issue in elderly people living with HIV (PLWH). Amlodipine is a commonly prescribed antihypertensive drug metabolized by CYP3A4, thus predisposed to a risk of DDIs. Guidance on the management of DDIs is mostly based on theoretical considerations derived from coadministration with other CYP3A4 inhibitors. This study aimed at characterizing the magnitude of DDIs between amlodipine and ARV drugs in order to establish dosing recommendations.

Methods: A population pharmacokinetic analysis was developed using non-linear mixed effect modelling (NONMEM) and included 163 amlodipine concentrations from 55 PLWH. Various structural and error models were compared to characterize optimally the concentration-time profile of amlodipine. Demographic and clinical characteristics as well as comedications were tested as potential influential covariates. Model-based simulations were performed to compare amlodipine exposure (i.e. area under the curve, AUC) between coadministered ARV drugs.

Results: Amlodipine concentration-time profile was best described using a one-compartment model with first-order absorption and a lag-time. Amlodipine apparent clearance was influenced by both CYP3A4 inhibitors and efavirenz (CYP3A4 inducer). Model-based simulations revealed that amlodipine AUC increased by 96% when coadministered with CYP3A4 inhibitors, while efavirenz decreased drug exposure by 59%.

Conclusion: Coadministered ARV drugs significantly impact amlodipine disposition in PLWH. Clinicians should adjust amlodipine dosage accordingly, by halving the dosage in PLWH receiving ARV with inhibitory properties (mainly ritonavir-boosted darunavir), whereas they should double amlodipine doses when coadministering it with efavirenz, under appropriate monitoring of clinical response and tolerance.
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http://dx.doi.org/10.1007/s00228-020-03060-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8184532PMC
July 2021

[HIV in the time of COVID-19 : the meeting between two pandemics].

Rev Med Suisse 2021 Jan;17(720-1):95-101

Service des maladies infectieuses, CHUV, 1011 Lausanne.

The current COVID-19 pandemic is the main topic of news worldwide by its magnitude and consequences across the entire planet. From a medical point of view, several risk factors for developing severe illness have been reported in the literature, notably an immunosuppressed status. For people living with HIV, several questions have been raised concerning not only their vulnerability, but also in relation to an eventual protection conferred by antiretroviral therapy. This article will address these two pandemics by looking at the potential impact of SARS-CoV-2 on people living with HIV and, in parallel, exploring similarities and differences in terms of treatment, potential for recovery, prevention and their impact on clinical research. We review also future novel therapies for the treatment of HIV.
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January 2021

The relationship of smoking and unhealthy alcohol use to the HIV care continuum among people with HIV in an integrated health care system.

Drug Alcohol Depend 2021 02 8;219:108481. Epub 2021 Jan 8.

Kaiser Permanente Northern California, Oakland, CA, USA.

Introduction: Smoking tobacco and unhealthy alcohol use may negatively influence HIV care continuum outcomes but have not been examined in combination.

Methods: Participants were people with HIV (PWH) in Kaiser Permanente Northern California. Predictors included smoking status and unhealthy alcohol use (exceeding daily and/or weekly limits) reported by patients during primary care screening (index date). Outcomes were based on not achieving the following steps in the care continuum: linkage to HIV care (≥1 visit within 90 days of newly identified HIV diagnosis), retention (2+ in-person visits, 60+ days apart) and HIV RNA control (<75 copies/mL). Adjusted odds ratios (ORs) were obtained from separate logistic regression models for each outcome associated with smoking and unhealthy alcohol use independently and combined.

Results: The overall sample (N = 8958) had a mean age of 48.0 years; was 91.3 % male; 54.0 % white, 17.6 % Latino, 15.1 % black, and 9.6 % other race/ethnicity. Smoking was associated with higher odds of not being linked to HIV care (OR = 1.60 [95 % CI 1.03-2.48]), not retained (OR = 1.30 [95 % CI 1.13-1.50]), and HIV RNA not in control (OR = 1.91 [95 % CI 1.60-2.27]). Alcohol measures were not independently associated with outcomes. The combination of unhealthy alcohol use and smoking (versus neither) was associated with higher odds of not being linked to care (OR = 2.83 [95 % CI 1.40-5.71]), although the interaction did not reach significance (p = 0.18).

Conclusions: In this large sample of PWH in an integrated health care system, smoking, both independently and in combination with unhealthy alcohol use, was associated with worse HIV care continuum outcomes.
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http://dx.doi.org/10.1016/j.drugalcdep.2020.108481DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7869693PMC
February 2021

Epidemiology of sexually transmitted infections among female sex workers in Switzerland: a local, exploratory, cross-sectional study.

Swiss Med Wkly 2020 Dec 30;150:w20357. Epub 2020 Dec 30.

Department of Vulnerable Populations and Social Medicine, Centre for Primary Care and Public Health, Lausanne, Switzerland.

Female sex workers are often considered highly vulnerable to sexually transmitted infections (STIs). However, data on STI epidemiology in female sex workers are lacking in Switzerland. Our main goal was to evaluate the prevalence of six STIs (human immunodeficiency virus [HIV], hepatitis B, hepatitis C, Chlamydia trachomatis, Neisseria gonorrhoeae and syphilis) among local female sex workers in Lausanne. A local, exploratory, cross-sectional study was conducted on a convenience sample of adult (≥18 years) Female sex workers in Lausanne, Switzerland, from 1 April 2015 to 31 December 2016. female sex workers who worked in street sex venues, massage parlours and brothels were approached for recruitment by a local non-governmental organisation. They were then invited to present at the Lausanne University Hospital, where they were offered a free STI screening and hepatitis A and B vaccination. We enrolled 96 female sex workers. They were predominantly undocumented immigrants (60%) from Africa and Eastern Europe with no health insurance; only one participant (1%) was Swiss born. During the study, 15 (16%; 95% confidence interval [CI] 9–23%) participants were newly confirmed to have an STI: six (6%; 95% CI 1–11%) had C. trachomatis, five (5%; 95% CI 0.6-9%) latent syphilis and four (4%; 95% CI 0.1–8%) hepatitis B (three with chronic active infection and one with past exposure). No human immunodeficiency virus (HIV) infections were newly diagnosed among the participants. Nineteen (20%) of the female sex workers were already vaccinated against hepatitis B, and 73 (76%) initiated vaccination against hepatitis A and hepatitis B during the study. Forty-four (46%) of the female sex workers required translation and assistance from social services.
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http://dx.doi.org/10.4414/smw.2020.20357DOI Listing
December 2020

Analysis of inappropriate prescribing in elderly patients of the Swiss HIV Cohort Study reveals gender inequity.

J Antimicrob Chemother 2021 02;76(3):758-764

University of Basel, Basel, Switzerland.

Background: The extent of inappropriate prescribing observed in geriatric medicine has not been thoroughly evaluated in people ageing with HIV. We determined the prevalence of and risk factors for inappropriate prescribing in individuals aged ≥75 years enrolled in the Swiss HIV Cohort Study.

Methods: Retrospective review of medical records was performed to gain more insights into non-HIV comorbidities. Inappropriate prescribing was screened using the Beers criteria, the STOPP/START criteria and the Liverpool drug-drug interactions (DDIs) database.

Results: For 175 included individuals, the median age was 78 years (IQR 76-81) and 71% were male. The median number of non-HIV comorbidities was 7 (IQR 5-10). The prevalence of polypharmacy and inappropriate prescribing was 66% and 67%, respectively. Overall, 40% of prescribing issues could have deleterious consequences. Prescribing issues occurred mainly with non-HIV drugs and included: incorrect dosage (26%); lack of indication (21%); prescription omission (drug not prescribed although indicated) (17%); drug not appropriate in elderly individuals (18%) and deleterious DDIs (17%). In the multivariable logistic regression, risk factors for prescribing issues were polypharmacy (OR: 2.5; 95% CI: 1.3-4.7), renal impairment (OR: 2.7; 95% CI: 1.4-5.1), treatment with CNS-active drugs (OR: 2.1; 95% CI: 1.1-3.8) and female sex (OR: 8.3; 95% CI: 2.4-28.1).

Conclusions: Polypharmacy and inappropriate prescribing are highly prevalent in elderly people living with HIV. Women are at higher risk than men, partly explained by sex differences in the occurrence of non-HIV comorbidities and medical care. Medication reconciliation and periodic review of prescriptions by experienced physicians could help reduce polypharmacy and inappropriate prescribing in this vulnerable, growing population.
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http://dx.doi.org/10.1093/jac/dkaa505DOI Listing
February 2021

Impact of rosuvastatin on atherosclerosis in people with HIV at moderate cardiovascular risk: a randomised, controlled trial.

AIDS 2021 03;35(4):619-624

Division of Infectious Diseases, HIV/AIDS Unit, Geneva University Hospitals, Geneva, Switzerland.

Background: People living with HIV-1 (PLHIV) are at increased risk for cardiovascular disease.

Objective: This study aimed to determine if PLHIV would benefit from starting statins at a lower threshold than currently recommended in the general population.

Design: A double-blind multicentre, randomised, placebo-controlled trial was performed.

Methods: Participants (n = 88) with well controlled HIV, at moderate cardiovascular risk (Framingham score of 10-15%), and not recommended for statins were recruited from Australia and Switzerland. They were randomized 1 : 1 to rosuvastatin (n = 44) 20 mg daily, 10 mg if co-administered with ritonavir/cobicistat-boosted antiretroviral therapy, or placebo (n = 40) for 96 weeks. Assessments including fasting blood collection and carotid--intima media thickness (CIMT) were performed at baseline, and weeks 48 and 96. The primary outcome was the change from baseline to week 96 in CIMT (clinicaltrials.gov: NCT01813357).

Results: Participants were predominantly men [82 (97.6%); mean age 54 years (SD 6.0)]. At 96 weeks, there was no difference in the progression of CIMT between the rosuvastatin (mean 0.004 mm, SE 0.0036) and placebo (0.0062 mm, SE 0.0039) arms (P = 0.684), leading to no difference in CIMT levels between groups at week 96 [rosuvastatin arm, 0.7232 mm (SE 0.030); placebo arm 0.7785 mm (SE 0.032), P = 0.075].Adverse events were common (n = 146) and predominantly in the rosuvastatin arm [108 (73.9%)]. Participants on rosuvastatin were more likely to cease study medication because of an adverse event [7 (15.9%) vs. 2 (5.0%), P = 0.011].

Conclusion: In PLHIV, statins prescribed at a lower threshold than guidelines did not lead to improvements in CIMT but was associated with significant adverse events.
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http://dx.doi.org/10.1097/QAD.0000000000002764DOI Listing
March 2021

Increased CHIP Prevalence Amongst People Living with HIV.

medRxiv 2020 Nov 7. Epub 2020 Nov 7.

People living with human immunodeficiency virus (PLWH) have significantly increased risk for cardiovascular disease in part due to inflammation and immune dysregulation. Clonal hematopoiesis of indeterminate potential (CHIP), the age-related acquisition and expansion of hematopoietic stem cells due to leukemogenic driver mutations, increases risk for both hematologic malignancy and coronary artery disease (CAD). Since increased inflammation is hypothesized to be both a cause and consequence of CHIP, we hypothesized that PLWH have a greater prevalence of CHIP. We searched for CHIP in multi-ethnic cases from the Swiss HIV Cohort Study (SHCS, n=600) and controls from the Atherosclerosis Risk in the Communities study (ARIC, n=8,111) from blood DNA-derived exome sequences. We observed that HIV is associated with increased CHIP prevalence, both in the whole study population and in a subset of 230 cases and 1002 matched controls selected by propensity matching to control for demographic imbalances (SHCS 7%, ARIC 3%, p=0.005). Additionally, unlike in ARIC, ASXL1 was the most commonly implicated mutated CHIP gene. We propose that CHIP may be one mechanism through which PLWH are at increased risk for CAD. Larger prospective studies should evaluate the hypothesis that CHIP contributes to the excess cardiovascular risk in PLWH.
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http://dx.doi.org/10.1101/2020.11.06.20225607DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7654930PMC
November 2020

Efficacy and safety of dolutegravir plus emtricitabine versus standard ART for the maintenance of HIV-1 suppression: 48-week results of the factorial, randomized, non-inferiority SIMPL'HIV trial.

PLoS Med 2020 11 10;17(11):e1003421. Epub 2020 Nov 10.

HIV/AIDS Unit, Department of Infectious Diseases, Geneva University Hospitals, Geneva, Switzerland.

Background: Dolutegravir (DTG)-based dual therapy is becoming a new paradigm for both the initiation and maintenance of HIV treatment. The SIMPL'HIV study investigated the outcomes of virologically suppressed patients on standard combination antiretroviral therapy (cART) switching to DTG + emtricitabine (FTC). We present the 48-week efficacy and safety data on DTG + FTC versus cART.

Methods And Findings: SIMPL'HIV was a multicenter, open-label, non-inferiority randomized trial with a factorial design among treatment-experienced people with HIV in Switzerland. Participants were enrolled between 12 May 2017 and 30 May 2018. Patients virologically suppressed for at least 24 weeks on standard cART were randomized 1:1 to switching to DTG + FTC or to continuing cART, and 1:1 to simplified patient-centered monitoring versus standard monitoring. The primary endpoint was the proportion of patients virologically suppressed with <100 copies/ml through 48 weeks. The secondary endpoints included virological suppression at 48 weeks according to the US Food and Drug Administration (FDA) snapshot analysis. Non-inferiority of DTG + FTC versus cART for viral suppression was assessed using a stratified Mantel-Haenszel risk difference, with non-inferiority declared if the lower bound of the 95% confidence interval was greater than -12%. Adverse events were monitored to assess safety. Quality of life was evaluated using the PROQOL-HIV questionnaire. Ninety-three participants were randomized to DTG + FTC, and 94 individuals to cART. Median nadir CD4 count was 246 cells/mm3; median age was 48 years; 17% of participants were female. DTG + FTC was non-inferior to cART. The proportion of patients with viral suppression (<100 copies/ml) through 48 weeks was 93.5% in the DTG + FTC arm and 94.7% in the cART arm in the intention-to-treat population (risk difference -1.2%; 95% CI -7.8% to 5.6%). Per-protocol analysis showed similar results, with viral suppression in 96.5% of patients in both arms (risk difference 0.0%; 95% CI -5.6% to 5.5%). There was no relevant interaction between the type of treatment and monitoring (interaction ratio 0.98; 95% CI 0.85 to 1.13; p = 0.81). Using the FDA snapshot algorithm, 84/93 (90.3%) participants in the DTG + FTC arm had an HIV-1 RNA viral load of <50 copies/ml compared to 86/94 (91.5%) participants on standard cART (risk difference -1.1%; 95% CI -9.3% to 7.1%; p = 0.791). The overall proportion of patients with adverse events and discontinuations did not differ by randomization arm. The proportion of patients with serious adverse events was higher in the cART arm (16%) compared to the DTG + FTC arm (6.5%) (p = 0.041), but none was considered to be related to the study medication. Quality of life improved more between baseline and week 48 in the DTG + FTC compared to the cART arm (adjusted difference +2.6; 95% CI +0.4 to +4.7). The study's main limitations included a rather small proportion of women included, the open label design, and its short duration.

Conclusions: In this study, DTG + FTC as maintenance therapy was non-inferior to cART in terms of efficacy, with a similar safety profile and a greater improvement in quality of life, thus expanding the offer of 2-drug simplification options among virologically suppressed individuals.

Trial Registration: ClinicalTrials.gov NCT03160105.
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http://dx.doi.org/10.1371/journal.pmed.1003421DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7654764PMC
November 2020

HCV Genetic Diversity Can Be Used to Infer Infection Recency and Time since Infection.

Viruses 2020 10 31;12(11). Epub 2020 Oct 31.

Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, CH-8091 Zurich, Switzerland.

HIV-1 genetic diversity can be used to infer time since infection (TSI) and infection recency. We adapted this approach for HCV and identified genomic regions with informative diversity. We included 72 HCV/HIV-1 coinfected participants of the Swiss HIV Cohort Study, for whom reliable estimates of infection date and viral sequences were available. Average pairwise diversity (APD) was calculated over each codon position for the entire open reading frame of HCV. Utilizing cross validation, we evaluated the correlation of APD with TSI, and its ability to infer TSI via a linear model. We additionally studied the ability of diversity to classify infections as recent (infected for <1 year) or chronic, using receiver-operator-characteristic area under the curve (ROC-AUC) in 50 patients whose infection could be unambiguously classified as either recent or chronic. Measuring HCV diversity over third or all codon positions gave similar performances, and notable improvement over first or second codon positions. APD calculated over the entire genome enabled classification of infection recency (ROC-AUC = 0.76). Additionally, APD correlated with TSI (R = 0.33) and could predict TSI (mean absolute error = 1.67 years). Restricting the region over which APD was calculated to - further improved accuracy (ROC-AUC = 0.85, R = 0.54, mean absolute error = 1.38 years) Genetic diversity in HCV correlates with TSI and is a proxy for infection recency and TSI, even several years post-infection.
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http://dx.doi.org/10.3390/v12111241DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7692400PMC
October 2020
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