2024
| 10th April | Caraballo Cortés et al., T-cell exhaustion in HIV-1/hepatitis C virus coinfection |  |
Caraballo Cortés et al. Caraballo Cortés et al. investigated immune exhaustion markers in individuals with HIV and hepatitis C virus (HCV) coinfection before and after HCV treatment, comparing these to markers in individuals with HCV monoinfection. The study involved 31 participants with HIV/HCV coinfection from the Swiss HIV Cohort Study, all undergoing antiretroviral therapy, and 45 individuals with HCV monoinfection from the Warsaw Hospital for Infectious Diseases. Key markers analyzed included PD-1, Tim-3, and IL-10, measured in plasma and peripheral blood mononuclear cell (PBMC) samples prior to and approximately one year after PEG-interferon based HCV treatment. The results showed that before HCV treatment, individuals with coinfection had higher levels of soluble PD-1 and IL-10 compared to those with HCV alone, and these levels decreased after successful HCV treatment. Soluble Tim-3 levels were similar between both groups and also decreased post-treatment. In PBMCs, individuals with coinfection had lower PD-1 mRNA levels and higher IL-10 mRNA levels compared to the group with HCV monoinfection, with no significant change post-treatment except for a decrease in Tim-3 mRNA levels. In summary, the findings indicate a greater immune exhaustion in individuals with HIV/HCV coinfection, evidenced by higher sPD-1 and IL-10 levels in plasma, and higher IL-10 mRNA in PBMCs. The study also highlights the beneficial effect of HCV treatment in reducing immune exhaustion markers, underlining the importance of eliminating HCV antigen load. Further studies are needed to evaluate the changes in immune exhaustion after the contemporary HCV treatments using direct-acting antivirals. | ||
| 27th March | Schwenke et al., Association of polygenic risk score and osteoporosis in people living with HIV | |
Schwenke et al. aimed to investigate whether a low bone mineral density (BMD; i.e., osteopenia and osteoporosis)-associated polygenic risk score (PRS) is independently associated with osteoporosis in people living with HIV (PLWH) in Switzerland. Of note, BMD has a strong genetic component, with a heritability in the range of 50% to 90% [7–9]. Genome-wide association studies (GWASs) have identified >500 single-nucleotide polymorphisms (SNPs) that are reliably associated with BMD in the general population. By combining the effect of the SNPs in these GWASs, it is possible to obtain a single measurement of the genetic risk conferred for the predicted outcome in the form of a PRS. Swiss HIV Cohort Study participants of self-reported European descent underwent ≥2 per-protocol dual x-ray absorptiometry (DXA) measurements ≥2 years apart (2011–2020). Univariable and multivariable odds ratios (ORs) for DXA- defined osteoporosis were based on traditional and HIV-related risk factors and a genome-wide PRS built from 9'413 SNP’s associated with low BMD in the general population. Controls were free from osteoporosis/osteopenia on all DXA measurements. The study included 438 participants: 149 with osteoporosis and 289 controls (median age, 53 years; 82% male, 95% with suppressed HIV RNA). Participants with unfavorable osteoporosis PRS (top vs bottom quintile) had univariable and multivariable-adjusted osteoporosis ORs of 4.76 (95% CI, 2.34–9.67) and 4.13 (1.86–9.18), respectively. For comparison, hepatitis C seropositivity, 5-year tenofovir disoproxil fumarate exposure, and parent history of hip fracture yielded univariable osteoporosis ORs of 2.26 (1.37–3.74), 1.84 (1.40–2.43), and 1.54 (0.82–2.9). In conclusion, this study shows that osteoporosis is of considerable concern in PLWH - for whom osteoporosis risk factors and the cumulative effects of certain ART agents may be prevalent and aging may be accentuated or even accelerated. In this study of PLWH in Switzerland, an unfavorable genetic background, as captured by an individual PRS, independently increased osteoporosis risk 4-fold when adjusted for multiple clinical risk factors, including antiretroviral therapy. | ||
| 13th March | Rein et al., INSTI use and cardiovascular events in adults with HIV | |
Rein et al. on behalf of the Antiretroviral Therapy Cohort Collaboration and the HIV-CAUSAL Collaboration aimed to examine the effect of initiation of integrase strand-transfer inhibitors (INSTI) regimens on the risk of cardiovascular events by emulating target trials separately in individuals who had never previously used antiretroviral therapy (ART) (ART-naive) and in individuals with previous use of non-INSTI-based ART (ART experienced). They used routinely recorded clinical data from 12 cohorts that collected information on cardiovascular events, BMI, and blood pressure from two international consortia of cohorts of people with HIV from Europe and North America. The study estimated the standardised 4-year risks of cardiovascular events (myocardial infarction, stroke, or invasive cardiovascular procedure) via pooled logistic regression models adjusting for time and baseline covariates. The analysis in ART-naive individuals included 10’767 INSTI initiators and 8’292 non-initiators of INSTI. There were 43 cardiovascular events in INSTI initiators (median follow-up of 29 months; IQR 15–45) and 52 in non-initiators (39 months; 18–47): standardised 4-year risks were 0·76% (95% CI 0·51 to 1·04) in INSTI initiators and 0·75% (0·54 to 0·98) in non-INSTI initiators; risk ratio 1·01 (0·57 to 1·57); risk difference 0·0089% (–0·43 to 0·36). The analysis in ART-experienced individuals included 7’875 INSTI initiators and 373’965 non-initiators. There were 56 events in INSTI initiators (median follow-up 18 months; IQR 9–29) and 3103 events (808 unique) in non-INSTI initiators (26 months; 15–37) in non-initiators: standardised 4-year risks 1·41% (95% CI 0·88 to 2·03) in INSTI initiators and 1·48% (1·28 to 1·71) in non-initiators; risk ratio 0·95 (0·60 to 1·36); risk difference –0·068% (–0·60 to 0·52). In conclusion the study suggest that initiation of INSTI does not substantially increase cardiovascular risk across 4 years with 4-year risk ratios centred around 1 and risk differences centred around 0 in both ART-naive and ART-experienced individuals. The upper limit of the 95% CI for the risk difference corresponds to an absolute increase in 4-year risk in INSTI initiators of only 0·36% in ART-naive individuals and 0·52% in ART-experienced individuals, which is unlikely to be a clinically meaningful difference. Overall, the risk of cardiovascular events was higher in ART-experienced compared with ART-naive individuals, which would be expected due to the ART-experienced population being older and havening higher prevalence of cardiovascular risk factors. | ||
| 29th February | Griessbach et al., Third SARS-CoV-2 Vaccine in patients who are immunocompromised | |
Griessbach et al. aimed to assess the benefit and potential harm of a third SARS-CoV-2 vaccine for patients who were immunocompromised among those recruited from the Swiss HIV Cohort Study (SHCS) and the Swiss Transplant Cohort Study (STCS). This observational study entitled COVERALL-2 allowed for the inclusion of additional patients beyond the original randomized trial population in the COVERALL-1 study. The study team collected blood samples before and 8 weeks after the third SARS-CoV-2 vaccination with either mRNA-1273 (Moderna) or BNT162b2 (Pfizer- BioNTech). The primary outcome was the proportion of participants showing an antibody response (Elecsys Anti-SARS-CoV-2 S test; threshold ≥100 U/mL) 8 weeks after the third SARS-CoV-2 vaccination. They also compared the proportion of patients who reached the primary outcome from basic immunization (the first and second vaccines) to the third vaccination. Nearly all participants (97.2% [95% CI, 95.9%–98.6%], 564/580) had an antibody response. This response was comparable between mRNA-1273 (96.1% [95% CI, 93.7%–98.6%], 245/255) and BNT162b2 (98.2% [95% CI, 96.7%–99.6%], 319/325). Stratification by cohort showed that 99.8% (502/503) of people living with HIV and 80.5% (62/77) of recipients of solid organ transplants (SOT) achieved the primary endpoint. The proportion of patients with an antibody response in SOT recipients improved from the second vaccination (22.7%, 15/66) to the third (80.5%, 62/77). In conclusion, this study shows a high proportion of patients who were immunocompromised had an antibody response after the third SARS-CoV-2 vaccination, and relatively few vaccine-related adverse events were reported. SOT recipients profited substantially in terms of an increased antibody response between the second and third doses. For patients with low humoral response, alternatives have to be explored. The new bivalent SARS-CoV-2 mRNA vaccines may represent a promising approach. | ||
| 22nd February | Trickey et al., Alcohol use in HIV/hepatitis C virus co-infection | |
Trickey et al. compared the impact of alcohol on mortality between people with HIV (PWH) with and without HCV coinfection within the Antiretroviral Therapy Cohort Collaboration (ART-CC), including participants from cohorts of PWH in Europe and North America. For the present study, the authors included PWH who started antiretroviral therapy (ART) between 2001 and 2017. Alcohol consumption at ART start was categorized into 0 grams per day (no alcohol use), 0.1-20 grams per day, and >20 grams per day. HCV coinfection at ART start was defined as having detectable HCV-RNA. For individuals without available HCV-RNA measurement, HCV seropositivity was used to indicate co-infection. Multivariable Cox regression was used to estimate adjusted hazard ratios (aHR) between alcohol use and all-cause mortality. The associations were stratified by HCV infection status using interaction terms. The study included 58’769 PWH (median age 40 years, 79% male, 4% individuals who inject drugs) of which 4799 (8%) had HIV/HCV coinfection. During a median follow-up of 7.8 years, 3599 deaths occurred. The mortality rate was 22.4 per 1000 person-years in people with HIV/HCV coinfection, compared to 6.2 per 1000 person-years in those without HCV. For PWH without HCV coinfection, authors observed a J-shaped association between alcohol use and mortality: Compared with individuals who consumed 0.1-20 grams of alcohol per day (reference group), aHR for mortality was 1.17 (95% CI 1.09-1.27) for individuals who consumed no alcohol, and 1.88 (95% CI 1.68-2.09) for those who consumed >20 grams of alcohol per day. Among individuals with HIV/HCV coinfection, the aHR was 1.00 (0.86-1.17) for individuals with no alcohol consumption, and 1.64 (1.33-2.02) for those who consumed >20 grams of alcohol per day. In summary, the authors observed differing associations of alcohol use and mortality between PWH with and without HCV coinfection. Among PWH without HCV, there was a J-shaped pattern of higher mortality in those reporting no drinking and heavy drinking, while among PWH with HCV, there was higher mortality only among those reporting heavy drinking. Given that individuals with HIV/HCV coinfection have a higher mortality rate compared to other PWH, the excess mortality risk associated with heavy alcohol use is worrying, and therefore interventions to reduce alcohol consumption are warranted in this population. | ||
| 7th February | Congratulations to Alexandra Trkola |  |
The grant will fund vaccine studies in well-studied groups of people living with HIV in Switzerland and South Africa to guide the design of a preventative HIV vaccine. We wish Alexandra Trkola and her team all the best for their project! | ||
| 1st February | Chammartin et al., Immune dysfunction and risk of malignancy in HIV | |
Chammartin et al. for the RESPOND Study Group aimed to assess whether CD4:CD8 ratio and CD8 cell counts may be useful biomarkers for the risk of non-AIDS defining malignancies (NADM), AIDS-defining malignancies (ADM) and specific cancers, after accounting for known risk factors of cancers and sociodemographic participant characteristics. The authors found found that CD4:CD8 ratios below 0.5, compared to above 1.0, were independently associated with a 12-month time-lagged higher risk of ADM and infection-related malignancies (adjusted hazard ratio 2.61 [95% confidence interval {CI}1.10–6.19] and 2.03 [95% CI 1.24–3.33], respectively). CD4 cell counts below 350 cells/μL were associated with an increased risk of NADMs and ADMs, as did infection, smoking, and body mass index-related malignancies. In conclusion, in this large cohort study with pooled data on people with HIV across Europe and Australia, a CD4 cell count of<350 cells/µL was associated with an increased risk of any studied malignancy. The study provides additional evidence that a low CD4:CD8 ratio carries an additional risk for ADM and infection-related malignancies. Therefore, regular monitoring of CD4 cells and CD4: CD8 ratios may provide benefit if it leads to enhanced cancer screening strategies for individuals who initiate ART late and do not achieve immune restoration above 350 cells/µL and >1.0, respectively. The study findings illustrate the importance of early HIV diagnosis and ART initiation with lifelong HIV suppression to reduce, in addition to other relevant clinical events, the risk of ADM and NADM. Whether people with HIV with insufficiently restored immune function profit on top of smoking cessation counselling from enhanced cancer screening programs should be further investigated. | ||
| 25th January | Thoueille et al., Concentrations and effectiveness of long-acting cabotegravir and rilpivirine | |
Thoueille et al. analyzed the drug levels of participants from the Swiss HIV Cohort Study (SHCS) who received long-acting cabotegravir (CAB) and rilpivirine (RPV) after the approval in March 2022 in Switzerland. Drug concentrations were measured by multiplex high-performance liquid chromatography coupled with tandem mass spectrometry. The authors assessed the relationship between the observed drug trough levels with the following previously proposed thresholds: the protein-adjusted concentrations required for 90% inhibition of viral replication (PAIC90), the clinical threshold set at four times the PAIC90 (4xPAIC90), and the 25th percentile of the trough levels observed in the registrational ATLAS-2M trial (Q1trough). In addition, the influence of sex, body mass index (BMI), and albumin on the observed variability of drug concentrations was evaluated using multivariable mixed-effect models. Between March 2022 and March 2023, 186 people with HIV (PWH) were included: 82% were male, 57% were white, the median age was 45 years (range 20-79), and 172 (92%) received an oral lead-in. In total, 725 samples were obtained, of which 569 were collected during the injection phase. For RPV, 273 measurements (48%) were below 4xPAIC90, 108 (18%) were below Q1trough, and 3 (<1%) were below PAIC90. For CAB, 201 drug levels (37%) were below Q1trough, 83 (15%) were below 4xPAIC90, and 8 (1%) were below PAIC90. CAB levels were 35% lower (95% CI -47 to -20) in males compared to females, whereas there was no variation according to BMI or albumin. Neither sex, BMI, nor albumin did impact RPV concentrations. Three individuals (1.6%) experienced virologic failure (defined as an HIV viral load >200 copie/mL), of whom two had suboptimal drug levels. Three additional individuals had CAB/RPV discontinued due to persistently low drug levels. In summary, whereas RPV levels were similar to previous results from randomized trials, CAB levels were substantially lower in the present real-world analysis compared with previous analyses. Sex differences appear to explain some of the observed interindividual variability, which may be due to differences in the distribution of fat and muscle mass. Nevertheless, the proportion of individuals experiencing virologic failure was similar to what was observed in registrational trials, which is reassuring for implementing long-acting CAB/RPV in clinical care. Further studies are ongoing to improve the characterization of the pharmacokinetic profile of these new drugs. | ||
| 18th January | Alberto et al., Evaluation of a specific intrathecal anti-Treponema pallidum IgG index as a diagnostic biomarker of neurosyphilis | |
Alberto et al. aimed to evaluate the diagnostic performance of measuring an antibody index (AI) for the intrathecal synthesis of specific anti-Treponema pallidum (T. pallidum) IgG for the diagnosis of neurosyphilis (NS). Specific anti-T. pallidum IgG were measured simultaneously in paired cerebrospinal fluid (CSF)–serum samples collected retrospectively and prospectively between 2007 and 2022, from patients suspected of NS, in Switzerland. An AI was calculated to account for blood-brain barrier integrity. Area under the receiver operating characteristic curve, sensitivity/specificity and positive/negative predictive values of AI test were estimated. Two NS definitions were used: NS1 included patients with NS suspicion presenting with neurological symptoms and/or acute neurosensory signs, and positive T. Pallidum Hemagglutinations Assay (TPHA)/T. pallidum particle agglutination assay (TPPA) serology and CSF- TPHA/TPPA ≥320, and either CSF- leucocytes >5 cells/ mm3 and/or CSF- protein >0.45 g/L and/or a reactive CSF- venereal disease research laboratory (VDRL)/rapid plasma reagin (RPR) test. NS2 included patients with suspected NS presenting with acute ocular and/or otologic symptoms, and positive TPHA/TPPA serology, and a favourable response to NS treatment. Controls were patients diagnosed with any other central nervous system (CNS) pathologies and with positive TPHA/TPPA serology. The study included 71 NS (43 NS1 and 28 NS2) and 110 controls. With a threshold of ≥1.7, sensitivity and specificity of the specific AI test were 90.7% (CI 77.7 to 97.4) and 100% (CI 96.7 to 100.0), respectively, for NS1 and 14.3% (CI 4 to 32.7) and 100% (CI 96.7 to 100.0) for NS2. In patients suspected of NS with a CNS involvement (NS1 group), NS could be confirmed by the positivity of this specific AI. In conclusion, the proposed AI test of specific anti-T. pallidum IgG appears to be useful to confirm or exclude NS diagnosis in the presence of an inflammatory CSF profile and seems to show better sensitivity and specificity than other published diagnostic tools such as CSF-TPPA. This test has the potential to be an accurate tool in a disease that remains complex if the findings of the study are confirmed by larger clinical evaluations. In ocular or otic syphilis with few or no CNS inflammation, the AI test is helpful to confirm but not to exclude the diagnosis as only 14.3% (4/28) of NS2 had a positive AI, illustrating well the compartment phenomena of the infection. | ||
| 11th January | McLaren et al., Africa-specific human genetic variation near CHD1L associates with HIV-1 load | |
McLaren et al. assessed genetic factors that determine HIV-1 viral replication capacity among individuals of African descent. The authors performed a genome-wide association study including more than 3’800 individuals from the International Collaboration for the Genomics of HIV. This collaboration included individuals from 11 cohorts, with the majority being African American, and a minority of individuals being from Kenya. The authors assessed around 10 million common genetic variants for association with the set-point HIV viral load, an established correlate for disease progression and transmission potential. In addition, in-vitro experiments were performed to evaluate the biological plausibility of their findings. In addition to a region on the HLA-B gene which was previously identified to be associated with HIV control, the authors identified a new locus on chromosome 1 (CHD1L), which seems to be specific for individuals of African ancestry. The presence of the genetic variant conferred a reduction in the set-point viral load of 0.17-0.57 log10-transformed RNA copies per mL. The observed reduction is of similar magnitude to the one conferred by the CCR5Δ32 allele, which slows disease progression in heterozygote individuals and leads to HIV-resistance in homozygote individuals of European ancestries. CHD1L encodes for a protein involved in DNA repair, and interacts with an enzyme implicated in HIV-1 integration and transcription. Knock-out of CHD1L in in-vitro HIV-1 infection models led to increased viral replication, confirming that CHD1L is implicated in HIV replication. Taken together, the present study provides strong evidence that variants in the CHD1L gene limit HIV-1 viral replication. These variants seem to be specific to individuals of African descent, highlighting the need for dedicated studies in this often under-represented patient population. Future studies aimed at understanding the mechanisms behind the observed association may inform new treatment options for people with HIV worldwide. | ||
| 6th January | Thank you letter 2023 / 2024 | |
Dear ladies and gentlemen, The Swiss HIV Cohort Study (SHCS) is celebrating its 35th anniversary this year and we would like to take this opportunity to express our sincere thanks to you. Thank you for your active participation in the SHCS and for helping us to continuously expand our knowledge about HIV and to use this knowledge for the treatment of people with HIV. With your help, we have already achieved a great deal over the last few decades and HIV infection has changed from a fatal disease to a well-treatable chronic disease. SHCS research has produced many important new findings and improved the quality of treatment for people with HIV in Switzerland. Above all, this includes the message that people with HIV cannot infect other people if they receive successful antiretroviral therapy. This is why we are also seeing a decline in new diagnoses thanks to the widespread use of antiretroviral therapy. We have always promoted the involvement of people with HIV in research. In the last two years, we have intensified these efforts. You as a person with all your needs and challenges in connection with HIV are at the centre of our science. Our main goal has always been and will always be to bring all the knowledge we gain back to you so that we can continuously improve the lives of people living with HIV. We would like to thank you, but also encourage you to let us know what we can do better in the future or where you personally see the biggest challenges with HIV. We would also like to take this opportunity to draw your attention to our community newsletter in German, French and Italian, through which you can regularly receive the latest findings from SHCS research in non-technical language: https://www.shcs.ch/community/de We wish you and your loved ones all the best and good health for the time ahead. The team of the Swiss HIV Cohort Study https://www.shcs.ch | ||