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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.En pratique clinique, la transplantation de microbiote fécal (TMF) s’est établie comme une thérapie sans équivalent à ce jour pour les infections à

BackgroundWomen 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.MethodsThe 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”.ResultsA 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.ConclusionGiven 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.

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.

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 Z 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.

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 randomised 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 male (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 value = 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 due to an adverse event (7 [15.9%] vs 2 [5·0%], p = 0.011). CONCLUSIONS In PLHIV statins prescribed at a lower threshold than guidelines did not lead to improvements in CIMT but was associated with significant adverse events.

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.

IntroductionSmoking tobacco and unhealthy alcohol use may negatively influence HIV care continuum outcomes but have not been examined in combination.MethodsParticipants 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 (ResultsThe 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).ConclusionsIn 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.

BackgroundOver the last decade, syphilis diagnoses among men-who-have-sex-with-men (MSM) have strongly increased in Europe. Understanding the drivers of the ongoing epidemic may aid to curb transmissions.Methods and FindingsWe set up an epidemiological model to assess the drivers of syphilis in MSM in Switzerland between 2006 and 2017. We stratified the model by syphilis stage, HIV-diagnosis, and behavioral factors to account for syphilis infectiousness and risk for transmission. In the main model, we used ‘reported non-steady partners’ (nsP) as the main proxy for sexual risk. We parameterized the model using data from the Swiss HIV Cohort Study, Swiss Voluntary Counselling and Testing center, cross-sectional surveys among the Swiss MSM population, and published syphilis notifications from the Federal Office of Public Health.The main model reproduced the increase in syphilis diagnoses from 168 cases in 2006 to 418 cases in 2017. It estimated that between 2006 and 2017, MSM with HIV diagnosis had 45.9 times the median syphilis incidence of MSM without HIV diagnosis. Defining risk as condomless anal intercourse with nsP decreased model accuracy (sum of squared weighted residuals, 378.8 vs 148.3). Counterfactual scenarios suggested that increasing screening of MSM without HIV diagnosis and with nsP from once every two-years to twice per year may reduce syphilis incidence (at most 12.8% reduction by 2017). Whereas, increasing screening among MSM with HIV diagnosis and with nsP from once per year to twice per year may substantially reduce syphilis incidence over time (at least 63.5% reduction by 2017).ConclusionsThe model suggests that reporting nsP regardless of condom use is suitable for risk stratification when modelling syphilis transmission. More frequent screening of MSM with HIV diagnosis, particularly those with nsP may aid to curb syphilis transmission.

Die HIV-Diagnostik hat in den letzten zwei Jahren verschiedene Neuerungen erfahren. Was muss man 2021 uber verkurzte Testintervalle, Selbsttests und die HIV-PCR wissen? Welche Bedeutung haben sie fur die praktische Arbeit?

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.La pandémie de Covid-19 est le sujet d’actualité mondial tant par son ampleur que par ses immenses conséquences. Du point de vue médical, plusieurs facteurs de risque de développer une maladie sévère ont été établis dans la littérature, et l’immunosuppression en fait partie. Concernant les personnes vivant avec le VIH, plusieurs questions se sont posées : sont-elles plus vulnérables à l’acquisition de SARS-CoV-2, ou à une maladie Covid-19 sévère ? Ou au contraire sont-elles protégées par les antirétroviraux ? Cet article aborde ces deux pandémies et recherche des similitudes et des différences en termes de traitement, de guérison, de prévention et de recherche clinique. Nous décrivons brièvement quelques-uns des traitements antirétroviraux les plus innovants.

Background: Coronary artery disease (CAD) is in part genetically determined. Aging is accentuated in people with human immunodeficiency virus (HIV) (PLWH). It is unknown whether genetic CAD event prediction in PLWH is improved by applying individual polygenic risk scores (PRSs) and by considering genetic variants associated with successful aging and longevity., Methods: In the Swiss HIV Cohort Study participants of self-reported European descent, we determined univariable and multivariable odds ratios (ORs) for CAD events, based on traditional CAD risk factors, adverse antiretroviral exposures, and different validated genome-wide PRSs. PRSs were built from CAD-associated single-nucleotide polymorphisms (SNPs), longevity-associated SNPs, or both., Results: We included 269 patients with CAD events between 2000 and 2017 (median age, 54 years; 87% male; 82% with suppressed HIV RNA) and 567 event-free controls. Clinical (ie, traditional and HIV-related) risk factors and PRSs, built from CAD-associated SNPs, longevity-associated SNPs, or both, each contributed independently to CAD events (P < .001). Participants with the most unfavorable clinical risk factor profile (top quintile) had an adjusted CAD-OR of 17.82 (95% confidence interval [CI], 8.19-38.76), compared with participants in the bottom quintile. Participants with the most unfavorable CAD-PRSs (top quintile) had an adjusted CAD-OR of 3.17 (95% CI, 1.74-5.79), compared with the bottom quintile. After adding longevity-associated SNPs to the CAD-PRS, participants with the most unfavorable genetic background (top quintile) had an adjusted CAD-OR of 3.67 (95% CI, 2.00-6.73), compared with 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.

Le diagnostic du VIH a connu différentes nouveautés au cours des deux dernières années. Que faut-il savoir en 2021 sur les délais de test raccourcis, les autotests et la PCR VIH? Quelles sont leurs implications pour la pratique? Die HIV-Diagnostik hat in letzten zwei Jahren verschiedene Neuerungen erfahren. Was muss man 2021 über verkürzte Testintervalle, Selbsttests und die HIV-PCR ­wissen? Welche Bedeutung haben sie für die praktische Arbeit?

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 3 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.

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 3 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.

The HIV-1 reservoir is the major hurdle to curing HIV-1. However, the impact of the viral genome on the HIV-1 reservoir, i.e. its heritability, remains unknown. We investigate the heritability of the HIV-1 reservoir size and its long-term decay by analyzing the distribution of those traits on viral phylogenies from both partial-pol and viral near full-length genome sequences. We use a unique nationwide cohort of 610 well-characterized HIV-1 subtype-B infected individuals on suppressive ART for a median of 5.4 years. We find that a moderate but significant fraction of the HIV-1 reservoir size 1.5 years after the initiation of ART is explained by genetic factors. At the same time, we find more tentative evidence for the heritability of the long-term HIV-1 reservoir decay. Our findings indicate that viral genetic factors contribute to the HIV-1 reservoir size and hence the infecting HIV-1 strain may affect individual patients’ hurdle towards a cure., The HIV reservoir is a major hurdle for a cure of HIV, but the factors determining its size and dynamics remain unclear. Here the authors show in a large cohort of 610 HIV-1 infected individuals, who are on suppressive ART for a median of 5.4 years, that viral genetic factors contribute substantially to the HIV-1 reservoir size.

Background Rosuvastatin is a lipid-lowering agent widely prescribed in people living with HIV, which is actively transported into the liver, making it a potential victim of drug–drug interactions with antiretroviral agents. Objectives The aims of this study were to characterise the pharmacokinetic profile of rosuvastatin and to describe the relationship between rosuvastatin concentrations and non-high-density lipoprotein (HDL)-cholesterol levels in people living with HIV. Methods A population pharmacokinetic model (NONMEM) was developed to quantify the influence of demographics, clinical characteristics and comedications on rosuvastatin pharmacokinetics. This model was combined with an indirect effect model to describe non-HDL-cholesterol measurements. Results A two-compartment model with sequential zero- and first-order absorption best fitted the 154 rosuvastatin concentrations provided by 65 people living with HIV. None of the tested covariates significantly influenced rosuvastatin pharmacokinetics. A total of 403 non-HDL cholesterol values were available for pharmacokinetic-pharmacodynamic modelling. Baseline non-HDL cholesterol decreased by 14% and increased by 12% with etravirine and antiretroviral drugs with a known impact on the lipid profile (i.e. protease inhibitors, efavirenz, cobicistat), respectively. The baseline value was surprisingly 43% lower in people living with HIV aged 80 years compared with those aged 40 years. Simulations based on the covariate-free model predicted that, under standard rosuvastatin dosages of 5 mg and 20 mg once daily, 31% and 64% of people living with HIV would achieve non-HDL-cholesterol targets, respectively. Conclusions The high between-subject variability that characterises both rosuvastatin pharmacokinetic and pharmacodynamic profiles remained unexplained after the inclusion of usual covariates. Considering its limited potential for drug–drug interactions with antiretroviral agents and its potent lipid-lowering effect, rosuvastatin prescription appears safe and effective in people living with HIV with hypercholesterolaemia. Clinical Trial Registration No. NCT03515772. Electronic supplementary material The online version of this article (10.1007/s40262-020-00946-3) contains supplementary material, which is available to authorized users.

Background Prevalence of potential drug–drug interactions (PDDIs) between antiretroviral drugs (ARVs) and co-medications was high in 2008 in a Swiss HIV Cohort Study (SHCS) survey. We reassessed the prevalence of PDDIs in the era of human immunodeficiency virus (HIV) integrase inhibitors (INIs), characterized by more favorable interaction profiles. Methods The prevalence of PDDIs in treated HIV-positive individuals was assessed for the period 01–12/2018 by linkage of the Liverpool HIV drug interactions and SHCS databases. PDDIs were categorized as harmful (red flagged), of potential clinical relevance (amber flagged), or of weak clinical significance (yellow flagged). Results In 9298 included individuals, median age was 51 years (IQR, 43–58), and 72% were males. Individuals received unboosted INIs (40%), boosted ARVs (30%), and nonnucleoside reverse transcriptase inhibitor (NNRTIs) (32%)–based regimens. In the entire cohort, 68% received ≥1 co-medication, 14% had polypharmacy (≥5 co-medications) and 29% had ≥1 PDDI. Among individuals with co-medication, the prevalence of combined amber and yellow PDDIs was 43% (33% amber—mostly with cardiovascular drugs—and 20% yellow-flagged PDDIs) compared to 59% in 2008. Two percent had red-flagged PDDIs (mostly with corticosteroids), the same as in the 2008 survey. Compared with 2008, fewer individuals received boosted ARVs (−24%) and NNRTIs (−13%) but the use of co-medications was higher. Conclusions Prevalence of PDDIs was lower with more widespread use of INIs in 2018 than in 2008. Continued use of boosted regimens and increasing needs for co-medications in this aging population impeded lower rates of PDDIs.

Medical advances in the treatment of HIV over the last 35 years mean that people living with HIV (PLHIV) now have a life expectancy close to that of the general population. Further, when successfully treated, PLHIV cannot transmit the virus. Despite this, HIV-related stigma remains widespread, including within healthcare settings. Stigma is not a vague sociological notion but represents a real threat to public health, with repercussions for both PLHIV and HIV-negative individuals. Stigma has been shown to have a negative impact on HIV prevention, testing, access to health services, and on the healthcare management of PLHIV. Taking stigma into consideration is essential, both in meeting the medical and psycho-social needs of PLHIV and in order to effectively combat HIV/AIDS.Les progrès des 35 dernières années dans la prise en charge médicale du VIH ont permis aux personnes vivant avec ce virus (PVVIH) d’avoir une espérance de vie similaire à celle de la population générale. Avec un traitement efficace, les PVVIH ne peuvent plus transmettre le virus. Cependant, la stigmatisation associée au VIH reste considérable, y compris dans les milieux de soins. La stigmatisation n’est pas une vague notion sociologique, mais un véritable enjeu de santé publique pouvant avoir un impact tant chez les personnes séronégatives que chez les PVVIH. Elle a un impact néfaste sur la prévention de l’infection, le dépistage, l’accès aux soins, et sur la gestion de la santé des PVVIH. Une prise en considération de la stigmatisation est essentielle pour garantir aux PVVIH un accompagnement médical et psychosocial optimal, ainsi que pour lutter contre l’épidémie du VIH/sida.

The majority of cells with latent human immunodeficiency virus 1 infection are located in lymphoid tissues that are difficult to access. In the current study, we used single-genome near-full-length proviral sequencing to evaluate intact and defective proviruses in blood and lymph node CD4 T cells enriched for specific functional polarizations. We observed minor variations between the frequencies of proviral sequences within individual CD4 T-cell subsets and across tissue compartments. However, we noted multiple clonal clusters of identical intact or defective proviral sequences from distinct compartments and CD4 T-cell subpopulations, suggesting frequent interchanges between viral reservoir cells in blood and tissues.

The risk of drug-drug interactions (DDIs) is elevated in aging people living with HIV (PLWH) because of highly prevalent age-related comorbidities leading to more comedications. To investigate the impact of aging on DDI magnitudes between comedications (amlodipine, atorvastatin, rosuvastatin) and boosted darunavir, we conducted a clinical trial in aging PLWH aged at least 55 years. DDI magnitudes were comparable with those reported in young individuals supporting that the clinical management of DDIs in aging PLWH can be similar.

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 CD56dim 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.

Background: Kaposi's sarcoma, the most common AIDS-related cancer, represents a major public concern in resource-limited countries. Single nucleotide polymorphisms within the Interferon lambda 3/4 region (IFNL3/4) determine the expression, function of IFNL4, and influence the clinical course of an increasing number of viral infections., Objectives: To analyze whether IFNL3/4 variants are associated with susceptibility to AIDS-related Kaposi's sarcoma among MSM enrolled in the Swiss HIV Cohort Study (SHCS)., Methods: The risk of developing Kaposi's sarcoma according to the carriage of IFNL3/4 SNPs rs8099917 and rs12980275 and their haplotypic combinations was assessed by using cumulative incidence curves and Cox regression models, accounting for relevant covariables., Results: Kaposi's sarcoma was diagnosed in 221 of 2558 MSM Caucasian SHCS participants. Both rs12980275 and rs8099917 were associated with an increased risk of Kaposi's sarcoma (cumulative incidence 15 versus 10%, P=0.01 and 16 versus 10%, P=0.009, respectively). Diplotypes predicted to produce the active P70 form (cumulative incidence 16 versus 10%, P=0.01) but not the less active S70 (cumulative incidence 11 versus 10%, P=0.7) form of IFNL4 were associated with an increased risk of Kaposi's sarcoma, compared with those predicted not to produce IFNL4. The associations remained significant in a multivariate Cox regression model after adjustment for age at infection, combination anti retrovi ral therapy, median CD4(+) T-cel I count nadir and CD4(+) slopes (hazard ratio 1.42, 95% confidence interval 1.06-1.89, P=0.02 for IFLN P70 versus no IFNL4)., Conclusion: This study reports for the first time an association between IFNL3/4 polymorphisms and susceptibility to AIDS-related Kaposi's sarcoma. Copyright (C) 2018 Wolters Kluwer Health, Inc. All rights reserved.

Understanding the determinants of broadly neutralizing antibody (bNAb) evolution is crucial for the development of bNAb-based HIV vaccines. Despite emerging information on cofactors that promote bNAb evolution in natural HIV-1 infections, in which the induction of bNAbs is genuinely rare, information on the impact of the infecting virus strain on determining the breadth and specificity of the antibody responses to HIV-1 is lacking. Here we analyse the influence of viral antigens in shaping antibody responses in humans. We call the ability of a virus strain to induce similar antibody responses across different hosts its antibody-imprinting capacity, which from an evolutionary biology perspective corresponds to the viral heritability of the antibody responses. Analysis of 53 measured parameters of HIV-1-binding and neutralizing antibody responses in a cohort of 303 HIV-1 transmission pairs (individuals who harboured highly related HIV-1 strains and were putative direct transmission partners or members of an HIV-1 transmission chain) revealed that the effect of the infecting virus on the outcome of the bNAb response is moderate in magnitude but highly significant. We introduce the concept of bNAb-imprinting viruses and provide evidence for the existence of such viruses in a systematic screening of our cohort. The bNAb-imprinting capacity can be substantial, as indicated by a transmission pair with highly similar HIV-1 antibody responses and strong bNAb activity. Identification of viruses that have bNAb-imprinting capacities and their characterization may thus provide the potential to develop lead immunogens.

Nucleoside reverse transcriptase inhibitors (NRTIs) have been the first class of antiretroviral drugs used against HIV infection. Despite NRTI-free regimens have been eagerly sought over the years in an effort for treatment simplification, NRTIs remain in most antiretroviral combination treatment. There has been generally a limited interest for their therapeutic drug monitoring, arguably because NRTIs levels measured in plasma poorly predict the concentration of pharmacologically active metabolites in cells. Plasma concentrations do impact cellular levels, while large differences between NRTIs have been found with regard to their ability to distribute into the cerebrospinal fluid (CSF) compartment. The renewed interest for the measurements of NRTIs concentrations in plasma and CSF was raised by ongoing efforts to understand some instances of toxicity or for determining their actual implication in the development of HIV-associated neurological disorders. In this context, a 5-min multiplex ultra-high-pressure chromatography tandem mass spectrometry (UHPLC-MS/MS) analysis in human plasma and CSF was developed for NRTIs used in clinical practice: abacavir, emtricitabine, lamivudine, tenofovir and zidovudine along with zidovudine glucuronide (Gln-ZDV). The 200-fold dilution of blank human plasma was shown to be a reliable surrogate matrix for quantification of NRTIs and Gln-ZDV in CSF. Both methodologies were fully validated over the clinically relevant concentrations, and satisfactorily fulfilled all parameters for bioanalytical methods validation. This sensitive, rapid, and robust UHPLC-MS/MS assay offers a methodology for increasing our understanding of the ability of NRTIs to cross the blood-brain barrier and their potential implication in neuropsychological disorders observed in HIV-infected patients.

OBJECTIVE: The extent to which controlled and uncontrolled HIV interact with ageing, European region of care and calendar year of follow-up is largely unknown.METHOD: EuroSIDA participants were followed after 1 January 2001 and grouped according to current HIV progression risk; high risk (CD4 cell count ≤350/μl, viral load ≥10 000 copies/ml), low risk (CD4 cell count ≥500 cells/μl, viral load RESULTS: A total of 16 839 persons were included with 136 688 person-years of follow-up. In persons aged 30 years or less, those at high risk had a six-fold increased incidence of non-AIDS compared with those at low risk, compared with a two-to-three-fold increase in older persons (P = 0.0004, interaction). In Eastern Europe, those at highest risk of non-AIDS had a 12-fold increased incidence compared with a two-to-four-fold difference in all other regions (P = 0.0029, interaction). Those at high risk of non-AIDS during 2001-2004 had a two-fold increased incidence compared with those at low risk, increasing to a five-fold increase between 2013 and 2016 (P CONCLUSION: Factors other than optimal control of HIV become increasingly important with ageing for predicting non-AIDS, whereas differences across Europe reflect differences in patient management as well as underlying socioeconomic circumstances. The differences between those at high, intermediate and low risk of non-AIDS between 2013 and 2016 likely reflects better quality of care.

Pathogen strains may differ in virulence because they attain different loads in their hosts, or because they induce different disease-causing mechanisms independent of their load. In evolutionary ecology, the latter is referred to as “per-parasite pathogenicity”. Using viral load and CD4+ T cell measures from 2014 HIV-1 subtype B infected individuals enrolled in the Swiss HIV Cohort Study, we investigated if virulence — measured as the rate of decline of CD4+ T cells — and per-parasite pathogenicity are heritable from donor to recipient. We estimated heritability by donor-recipient regressions applied to 196 previously identified transmission pairs, and by phylogenetic mixed models applied to a phylogenetic tree inferred from HIV pol sequences. Regressing the CD4+ T cell declines and per-parasite pathogenicities of the transmission pairs did not yield heritability estimates significantly different from zero. With the phylogenetic mixed model, however, our best estimate for the heritability of the CD4+ T cell decline is 17% (5%–30%), and that of the per-parasite pathogenicity is 17% (4%–29%). Further, we confirm that the set-point viral load is heritable, and estimate a heritability of 29% (12%–46%). Interestingly, the pattern of evolution of all these traits differs significantly from neutrality, and is most consistent with stabilizing selection for the set-point viral load, and with directional selection for the CD4+ T cell decline and the per-parasite pathogenicity. Our analysis shows that the viral genetype affects virulence mainly by modulating the per-parasite pathogenicity, while the indirect effect via the set-point viral load is minor.

Rapid HIV testing may circumvent the practical barriers to HIV testing in several settings. User preference of the testing kits available has been relatively underexplored. We examined healthcare provider (HCP) ratings of two validated rapid testing kits in clinical practice. From 1 July to 1 December 2012 we prospectively recruited HCPs (clinic nurses) from three outpatient clinics linked to Lausanne University Hospital, Lausanne, Switzerland. The HCPs had experience in taking blood samples but varying experience in rapid HIV testing. Participating HCPs performed rapid HIV testing using Determine™ Combo (DETE) or INSTI™ (INSTI), according to a predefined randomization sequence, and rated practical aspects of each test using a Likert scale. Seventeen HCPs of 23 approached (74%) were eligible and agreed to participate, performing a total of 336 HIV tests. Globally, the testing procedure was rated as easy or very easy by 97% (DETE) to 99% (INSTI) of tests performed. Among experienced HCPs, DETE was rated easier than INSTI for kit storage (p

We analyzed changes in hepatitis B virus and hepatitis delta virus (HDV) viral loads (VL) during tenofovir-containing antiretroviral therapy among patients with a replicating HDV infection in the Swiss HIV Cohort Study. Only 28.6% experienced a ≥2.0 log reduction in HDV RNA, and 14.3% had undetectable HDV VL within 5 years.