2024
| 31st October | Berton et al., Exposure and response of antiretrovirals in obese PWH |  |
Several physiological changes impact drug exposure in individuals with obesity. Increased liver blood flow or higher glomerular filtration rate can accelerate metabolic clearance, and drugs accumulated in the tissue may redistribute to the blood, impacting drug trough concentrations. How these changes can lead to ineffective antiretroviral (ARV) drug levels in obese individuals remains unclear. In this article published in Clinical Infectious Diseases, Berton et al. performed virtual trials to assess the impact of obesity on current ARV drug exposure among people with HIV from the Swiss HIV Cohort Study (SHCS). During these virtual trials, predictions from physiologically based pharmacokinetic (PBPK) modeling were validated with available drug plasma levels from the SHCS database. The validated models were then used to extrapolate pharmacokinetics across obesity classes (up to a BMI of 60 kg/m2). Compared to individuals without obesity, individuals with a BMI ≥30 kg/m2 had an average reduction in ARV exposure of 20%, and a decrease in trough concentrations of 6%. Trough concentrations were above the efficacy threshold for most drugs, except for etravirine and rilpivirine, in which approximately 40% of individuals with a BMI >40 kg/m2 did not reach the target. However, these lower trough levels were not accompanied by increased rates of detectable HIV viral loads in the cohort. In summary, the present study provides evidence that the efficacy of current antiretroviral drugs are unlikely to be affected by obesity. This is reassuring particularly given the increasing rates of obesity among people with HIV worldwide. Nevertheless, therapeutic drug monitoring should be considered among obese individuals who receive drugs such as etravirine and rilpivirine to prevent suboptimal drug exposure. | ||
| 24th October | Abela et al., Gender disparities in statin prescriptions in people with HIV | |
Abela et al. aimed to explore whether gender and ethnicity influence statin prescriptions for cardiovascular disease (CVD) prevention in people with HIV in Switzerland, a high-income country with a high standard of care and more equitable access compared to countries such as the United States—where health insurance significantly impacts medication prescriptions. The authors computed the CVD risk at each follow-up visit using SCORE2 for participants between ages 40 and 70 years, and SCORE2-OP for participants aged >70 years of age, as recommended by the most recent EACS guidelines. They included d in the analysis participants who were not receiving a statin and whose first CVD risk score in a given category (low/moderate, high, or very high) occurred after 2015, when the systematic collection of co-medications started in the SHCS. Statins were not commonly prescribed in the low/moderate and high-risk categories, with respectively 7.9% and 13.7% of SHCS participants receiving a statin prescription at some point following the risk assessment. Statin prescriptions were higher in people at very high CVD risks versus those at low/moderate and high risk, with 29.4% of them receiving a statins prescription at some point after the risk assessment. They found no significant differences in statin prescription between people of White and Black ethnicity across all CVD risk categories. Importantly, among people with a low/moderate and high CVD risk, cisgender women were less likely to be prescribed a statin compared to cisgender men, with adjusted hazard ratio of 0.47 (0.31-0.72) and 0.53 (0.37-0.75), respectively. However, in the very high CVD risk category, there were no significant gender-related prescription differences. In conclusion, the study findings provide opportunities to address inequalities in CVD management across gender in people with HIV and ensure equal access to adequate treatments. Given the REPRIEVE results, the ideal strategy for prescribing statins in primary prevention needs to be defined in clinical care. Efforts are needed to ensure a good communication between clinicians and people with HIV to ensure that people at risk initiate therapy. Finally, further research is needed to understand the gender gap in statin prescription and to develop methods to address it. | ||
| 18th October | Funding of the SHCS by the SNSF from 2025 to 2028 - thanks to all |  |
We would like to thank first
We also thank all of you who are working tirelessly for the SHCS
Thanks again for all your continuous support of the SHCS. We are looking forward very much to our further collaboration. | ||
| 2nd October | Begré et al., HIV/HBV coinfection and HBsAg loss during tenofovir therapy | |
Novel hepatitis B virus (HBV) serum markers have improved our understanding of the HBV replication cycle. Among these markers, hepatitis B core-related antigen (HBcrAg) serves as a surrogate for measuring the molecular reservoir of covalently closed circular DNA (cccDNA) within hepatocytes, while circulating HBV RNA indicates ongoing cccDNA transcriptional activity during antiviral therapy. In a new study, Begré et al. explored the trajectories and potential roles of these markers in individuals with HBV and HIV coinfection who achieved hepatitis B surface antigen (HBsAg) loss, a marker of functional cure. The study measured HBcrAg and HBV RNA levels in participants from the Swiss HIV Cohort Study who were receiving tenofovir-based antiretroviral therapy, and compared their trajectories between 29 individuals who achieved functional cure, and 29 matched individuals who remained HBsAg positive. Over a median follow-up of 12 years, HBsAg loss occurred after a median of 4 years (interquartile range 1-8). All participants who achieved HBsAg loss reached undetectable HBV RNA levels during tenofovir-based therapy, with undetectable HBV RNA levels observed prior to HBsAg loss. In contrast, among those who did not achieve HBsAg loss, only 79% reached undetectable HBV RNA levels while on tenofovir-based therapy. Persistent HBcrAg levels were observed in 34% of individuals who achieved HBsAg loss and in 48% of those who did not. The study highlights that undetectable HBV RNA consistently preceded HBsAg loss in individuals who achieved a functional cure, while those who did not achieve HBsAg loss were less likely to reach undetectable HBV RNA levels. Additionally, persistent HBcrAg levels were more common in individuals without HBsAg loss, suggesting ongoing low-level cccDNA translation despite tenofovir-based therapy. The clinical significance of this ongoing transcriptional activity, including its potential role in liver-related outcomes such as hepatocellular carcinoma, remains to be determined. | ||
| 25th September | Zeeb et al., Genetic diversity from proviral DNA as a proxy for time since HIV-1 infection | |
HIV-1 RNA genetic diversity predicts time since infection, which is important for clinical care and research. It is unclear, however, whether proviral DNA genetic diversity sampled under suppressive antiretroviral therapy can be used for this purpose. In this study, the authors tested whether proviral genetic diversity from next-generation sequencing predicts time since infection and recency in 221 people with HIV-1 with known infection time. Proviral diversity was significantly associated with time since infection (P < 5×10−7, R 2 up to 25%) and predictive of treatment initiation during recent infection (area under the curve-receiver operating characteristic up to 0.85). Predictive accuracy was lower than that of viral diversity derived from plasma HIV-1 RNA, in particular when partial sequences were included. When restricting the analysis to full-length sequences and hypermutation filtering, predictive performances were in the range of what is achieved with treatment-naive plasma RNA for pol/env (AUC of 0.84/0.85 for proviral DNA compared to ≥0.95 for viral RNA). In summary, this work shows the utility of average pairwise diversity scores derived from proviral sequences as a proxy for the time since infection and for prediction of infection recency. This may be useful for people with HIV without a baseline drug resistance test to decide on treatment simplification strategies in clinical practice or to determine infection recency in HIV research, for example, to retrospectively estimate HIV-1 incidence. | ||
| 19th September | Trickey et al., Mortality in spectrum among adults with HIV | |
Trickey et al. aimed to review AIDS-related and non–AIDS related mortality rates over time using data from a collaboration of cohorts of people living with HIV (PLHIV) on antiretroviral therapy (ART) in Europe and compare the estimated mortality rates for 2016–2020 with the estimates produced by Spectrum. The AIDS Impact Module in Spectrum is a compartmental HIV epidemic model coupled with a demographic population projection model. The authors used national Spectrum projections developed for the 2022 HIV estimates round to calculate mortality rates among PLHIV on ART, adjusting to the age/country distribution of PLHIV starting ART from 1996 to 2020 in the Antiretroviral Therapy Cohort Collaboration (ART-CC)’s European cohorts. In the ART-CC, 11,504 of 162,835 PLHIV died. Between 1996–1999 and 2016–2020, AIDS-related mortality in the ART-CC decreased from 8.8 (95% CI: 7.6 to 10.1) to 1.0 (0.9–1.2) and from 5.9 (4.4–8.1) to 1.1 (0.9–1.4) deaths per 1000 person-years among men and women, respectively. Non–AIDS-related mortality decreased from 9.1 (7.9–10.5) to 6.1 (5.8–6.5) and from 7.0 (5.2–9.3) to 4.8 (4.3–5.2) deaths per 1000 person-years among men and women, respectively. Adjusted all-cause mortality rates in Spectrum among men were near ART-CC estimates for 2016–2020 (Spectrum: 7.02–7.47 deaths per 1000 person-years) but approximately 20% lower in women (Spectrum: 4.66–4.70). Adjusted excess mortality rates in Spectrum were 2.5-fold higher in women and 3.1–3.4-fold higher in men. In sum, this study found that Spectrum produces estimates of all-cause mortality among PLHIV that are consistent with mortality observed in ART-CC after controlling for age and country. The authors found that a substantial proportion of excess mortality among PLHIV on ART in Europe is from non-AIDS causes and that excess mortality rates among PLHIV on ART in Spectrum are 2.5–3.4-fold higher than AIDS-related death rates in the ART-CC. This suggests that 60%–70% of excess deaths among PLHIV on ART in Spectrum are from non AIDS causes. Thus, misinterpreting excess deaths as AIDS-related deaths risks overstating the numbers of deaths that might be prevented through ART, although ART should also reduce some deaths that are currently classified as non-AIDS mortality. | ||
| 12th September | Lubreras Areta et al., Trends in preterm birth in women living with HIV in Switzerland | |
Previous studies have shown that preterm birth is more common among pregnant women with HIV than among those without HIV. Several HIV-specific treatments may explain this: antiretroviral therapy can lead to early labor induction, past policies favored cesarean sections, increasing emergency interventions, and proactive delivery was advised for premature rupture of membranes. However, most studies were conducted over ten years ago, and recommendations for the treatment of pregnant women with HIV have since changed. In the present study, Lumbreras Areta et al. assessed the rates of preterm birth among pregnant women with HIV in Switzerland between 1986 and 2020, compared them with the general population, and tried to identify factors and interventions associated with changes over time. Of 1’238 singleton pregnancies born to 948 mothers, the rate of preterm birth was 20.4% prior to 2010, and progressively declined to 11.3% thereafter. However, these rates remain more than twice as high as in the general population. In multivariable analyses, higher CD4 cell counts and vaginal mode of delivery were associated with lower rates of preterm birth. The study did not find an association between antiretroviral drugs and preterm births. In summary, although the rate of preterm birth decreased, pregnant women with HIV in Switzerland remain twice as likely to deliver preterm compared to women without HIV. The authors conclude that, given their findings, limiting cesarean sections to obstetric reasons and maintaining effective HIV control are necessary to close this gap. | ||
| 4th September | Thoueille et al., Population pharmacokinetics of cabotegravir in real-world people with HIV | |
Thoueille et al. aimed to characterize the concentration-time profile of long-acting cabotegravir and its associated variability among people with HIV (PWH) in the SHCS and therefore to build real-world reference percentile curves of cabotegravir concentrations that can be used to support the interpretation of therapeutic drug monitoring (TDM) results in PWH receiving this treatment. Adults (>18 years old) receiving long-acting cabotegravir/rilpivirine enrolled in the SHCS were included. Blood sampling and last administration times, dosage, individual body weight (BW), height, and BMI were recorded Overall, 238 PWH contributed to 1’038 cabotegravir levels (186 during the initial oral administration phase and 852 after intramuscular injection). The model showed almost 40% faster absorption and 30% higher clearance than previously reported, resulting in a time to steady- state of 8 months and an elimination half-life of 4.6 weeks for long-acting cabotegravir. Sex and body mass index significantly influenced absorption, and body weight affected clearance. Model-based simulations showed that cabotegravir trough concentrations in females were 25% lower 4 weeks after the intramuscular loading dose, but 42% higher during the late maintenance phase. Finally, simulations indicated that in females, despite significantly higher cabotegravir concentrations, longer intervals between injections may not consistently ensure levels above the 4-fold protein-adjusted 90% inhibitory target concentration. In conclusion, the proposed population pharmacokinetic model shows a faster absorption rate constant and elimination than previously described, resulting in lower trough concentrations of cabotegravir. Sex was found to have a strong effect on the long-acting cabotegravir absorption rate. The analysis highlights discrepancies in pharmacokinetic between clinical trial participants and people with HIV followed in a routine clinical setting, and provides the basis for further studies on their implications for clinical care. In addition, simulations show that 3-monthly injections of cabotegravir might not consistently provide exposure levels ensuring effectiveness. | ||
| 29th August | Pasin et al., Impact of hormonal therapy on HIV-1 immune markers in cis women and gender minorities | |
Sex hormones play a crucial role in modulating the immune response. However, the effects of exogenous sex hormones - administered for contraception, menopause-related symptom management, or gender-affirming therapy - on HIV-related immune markers in people living with HIV are not well understood. In this study, Pasin et al. investigated the impact of these hormones on CD4, CD8, and lymphocyte counts in cis women, trans women, and non-binary individuals within the Swiss HIV Cohort Study. The study analyzed 3’175 participants (median age 53 years), including 83 trans women and non-binary individuals (3%). The use of sex hormones varied significantly, reflecting diverse treatment indications: most cis women under 40 years were on systemic progestogen alone or combined with estrogen, while those over 60 primarily used local estrogens. Trans women and non-binary participants predominantly used systemic estrogens, either alone or combined with antiandrogens. The findings revealed that among trans women and non-binary individuals, exogenous sex hormones were associated with increased CD4-cell counts, CD4:CD8 ratios, and total lymphocyte counts compared to those not receiving hormone therapy. Cis women using sex hormones also showed higher CD4-cell counts than those not taking hormones, but no significant impact was observed in older cis women. In conclusion, the diverse hormonal therapies used underscore the complexity of understanding their effects on the immune system. This study highlights a potential impact of hormonal therapy on immune function, particularly in its influence on CD4 cell counts in people living with HIV. These results emphasize the nuanced effects of hormone therapy on immune markers, varying by both the type of therapy and the population receiving it. | ||
| 21st August | Byonanebye et al., Associations between change in BMI and the risk of hypertension and dyslipidaemia in people receiving INSTI’s and TAF | |
Byonanebye et al. on behalf of the RESPOND consortium aimed to compare the risk of new-onset hypertension or dyslipidaemia in people receiving integrase strand-transfer inhibitors (INSTIs), tenofovir alafenamide, or both versus regimens without INSTIs and tenofovir alafenamide, and established whether increases in BMI could explain any associations between antiretroviral therapy (ART) regimens and hypertension or dyslipidaemia. Participants were eligible if receiving INSTI-containing ART regimens or a contemporary non-INSTI, did not have hypertension or dyslipidaemia at baseline, and had baseline and at least two follow-up BMI, lipid, and blood pressure measurements. Participants receiving non-ART medications associated with weight changes, including antipsychotics and mood stabilisers, corticosteroids, insulin, and insulin secretagogues were excluded. Of the 35 941 RESPOND participants, 9'704 (7'327 [75·5 %] male and 2'377 [24·5%] female) were included in the hypertension analysis and 5'231 (3'796 [72·6%] male and 1'435 [27·4%] female) were included in the dyslipidaemia analysis. In the univariable model, hypertension was more common in individuals receiving an INSTI with tenofovir alafenamide (IRR 1·70, 95% CI 1·54–1·88) or an INSTI without tenofovir alafenamide (1·41, 1·30–1·53) compared with those receiving neither INSTIs nor tenofovir alafenamide. Adjustment for time-updated BMI and confounders attenuated risk in participants receiving an INSTI with (IRR 1·48, 1·31–1·68) or without (1·25, 1·13–1·39) tenofovir alafenamide. Similarly, dyslipidaemia was more common in participants using tenofovir alafenamide with an INSTI (IRR 1·24, 1·10–1·40) and tenofovir alafenamide alone (1·22, 1·03–1·44) than in participants using neither INSTI nor tenofovir alafenamide. Adjustment for BMI and confounders attenuated the risk in participants receiving tenofovir alafenamide with an INSTI (adjusted IRR 1·21, 1·07–1·37), whereas the risk in those receiving tenofovir alafenamide alone became non-significant (1·15, 0·96–1·38). The associations between increasing BMI and risk of hypertension and dyslipidaemia did not differ between participants receiving different ART regimens (pinteraction = 0∙46 for hypertension; pinteraction = 0∙31 for dyslipidaemia). In conclusion, the study reports an association between weight gain, the concurrent or separate use of INSTIs or tenofovir alafenamide, and hypertension and dyslipidaemia. The association between INSTIs and hypertension appears to be partly mediated by weight gain. Furthermore, the association between weight gain and hypertension or dyslipidaemia was not different in regimens with INSTIs or tenofovir alafenamide than in other contemporary antiretroviral regimens. Interpreted with results that have linked INSTIs with increased cardiovascular risk, further research is warranted to fully understand the associations between the use of INSTIs and tenofovir alafenamide, weight gain, and cardiovascular risk. | ||
| 7th August | Fursa et al., SARS-CoV-2 testing, positivity, and factors associated with COVID-19 among PLWH | |
Fursa et al. on behalf of the EuroSIDA cohort investigated SARS-CoV-2 testing positivity and hospital admissions in a large prospective cohort of people with HIV in Europe between 1 January 2020 and 31 December 2021 and looked at inter-regional differences in SARS-CoV-2 testing. Of 9’012 participants, 2’270 (25.2%, 95% confidence interval [CI] 24.3–26.1) had a SARS-CoV-2 polymerase chain reaction test during the study period (range: 38.3% in Northern to 14.6% in Central-Eastern Europe). People from Northern Europe, women, those aged <40 years, those with CD4 cell count<350 cells/mm3, and those with previous cardiovascular disease or malignancy were significantly more likely to have been tested, as were people with HIV in 2021 compared with those in 2020. Overall, 390 people with HIV (4.3%, 95% CI3.9–4.8) tested positive (range: 2.6% in Northern to 7.1% in Southern Europe), and the odds of testing positive were higher in all regions than in Northern Europe and in 2021 than in 2020. In total, 64 people with HIV (0.7%, 95% CI0.6–0.9) were hospitalized, of whom 12 died. Compared with 2020, the odds of positive testing decreased in all regions in 2021, and the associations with cardiovascular disease, malignancy, and use of tenofovir disoproxil fumarate disappeared in 2021. Among study participants, 58.9% received a COVID-19 vaccine (range: 72.0% in Southern to 14.8% in Eastern Europe). In conclusion, the study demonstrated a high variability in SARS-CoV-2 testing and positive test results in people with HIV across regions of Europe, whereas the proportion of severe COVID-19 was consistent across regions and the proportion of deaths was lower than that in the general population. The EuroSIDA region was the strongest factor associated with SARS-CoV-2 testing, suggesting the need to address the large inter-regional disparity in testing in a population that remains vulnerable to COVID-19. Female sex, younger age, and prior CVD and malignancy were associated with a higher likelihood of being tested, whereas TDF use was negatively associated with testing positive in 2020 but not in 2021. The changes in the associations in 2021, along with the decline in the proportion of admissions due to COVID-19 in the regions with better vaccine coverage, highlight the importance of SARS-CoV-2 vaccine provision to protect people eat risk. | ||
| 31st July | Damas et al., Weight changes after discontinuing TAF | |
Managing obesity and cardiovascular disease has become an important aspect of clinical care in people with HIV (PWH). Concerns over antiretroviral therapy (ART) related weight gain, particularly with tenofovir alafenamide (TAF), prompted Damas et al. to investigate the reversibility of weight and metabolic changes after stopping TAF-based therapy among participants from the Swiss HIV Cohort Study. The study included 6’555 participants who received TAF-based ART for at least six months between January 2016 and March 2023. Participants who discontinued TAF switched to either tenofovir disoproxil fumarate (TDF)-containing ART, dolutegravir/lamivudine (DTG/3TC), long-acting cabotegravir/rilpivirine, or other TAF-free ART. The study found that stopping TAF led to significant weight decreases only in individuals who switched to TDF-containing ART (adjusted mean weight change of -1.89 kg after 12 months, 95% CI -2.76 to -1.01), whereas no substantial weight changes occurred after switching to DTG/3TC (-0.17 kg, -0.82 to 0.84), CAP/RPV (-0.64 kg,-2.16 to 0.89 ), or other ART regimens (0.16 kg, -0.71 to 1.02). Additionally, stopping TAF resulted in decreased total cholesterol, triglycerides, and total cholesterol-HDL ratio, primarily driven by switches to TDF or DTG/3TC regimens. In conclusion, replacing TAF with TDF in PWH leads to weight loss and improved lipid profiles, offering a potential strategy for managing ART-induced obesity. However, these benefits must be balanced against the improved safety profile of TAF compared to TDF, which includes improvements in renal function and lower rates of bone demineralization. | ||
| 17th July | Weber et al., Death causes shift in the SHCS | |
In their January 2024 article published in Clinical Infectious Diseases, Weber et al. analyzed the evolving causes of death among people living with HIV in the Swiss HIV Cohort Study over the past 17 years. The authors of the study formed a narrative of the events leading to each reported death between 2005 and 2022, leveraging all available information from the cohort’s comprehensive data source. The study included 1630 deaths, of which 23.7% occurred in women. The demographic profile at the time of death showed significant shifts: The median age at death rose from 45 years in 2005-2007 to 61 years in 2020-2022, and the proportion of people who inject drugs decreased from 46.4% to 22.5% of the deaths reported over the same period. Over the study period, there was a notable decline in HIV/AIDS-related deaths, dropping from 18.5% of total deaths in 2005-2007 to just 3.7% in 2020-2022. Similarly, liver-related deaths decreased significantly from 15.2% to 2.2% during the same timeframe. These declines underscore the efficacy of antiretroviral therapy and advancements in managing hepatitis C coinfection. Cardiovascular-related deaths remained stable over time, accounting for approximately 11% of total deaths throughout the study period. Conversely, non-AIDS and non-hepatic (NANH) cancers have emerged as a growing concern, increasing from 14.9% of deaths in 2005-2007 to 31.1% of deaths in 2020-2022, with lung cancer being the predominant cause in this category. In conclusion, the findings underscore the success of current HIV treatment and care, along with effective interventions targeting HCV coinfection, which have significantly reduced HIV/AIDS and liver-related mortality in recent decades. Future efforts should focus on prevention, early detection and enhanced treatments for NANH cancers and cardiovascular conditions. | ||
| 23rd May | Riebensahm et al., Physical activity and liver steatosis | |
Riebensahm et al. explored the relationship between physical activity and liver steatosis in people with HIV (PWH) at a single site within the Swiss HIV Cohort Study (SHCS). This investigation included 466 participants screened for liver steatosis using vibration-controlled transient elastography from November 2019 to March 2023 at the University Hospital of Bern. Liver steatosis was defined as a controlled attenuation parameter of ≥248 dB/m. Physical activity levels were assessed using the International Physical Activity Questionnaire. The researchers employed multivariable logistic regression models to examine the link between physical activity and liver steatosis. The study group had a median age of 52 years, with 27.3% being female, and 52.4% classified as overweight. Liver steatosis was detected in 50.4% of participants. The multivariable analysis revealed that physical activity levels below the European Association for the Study of the Liver (EASL) recommendations (≥200 minutes of moderate or ≥75 minutes of vigorous activity per week, with an adjusted odds ratio [aOR] of 2.34 and a 95% confidence interval [CI] of 1.44 to 3.85) and increased sitting time (aOR of 1.16, 98% CI of 1.07 to 1.26 for each additional hour of sitting) were significantly associated with a higher likelihood of liver steatosis. These associations remained significant irrespective of body mass index (BMI). In summary, the findings indicate that insufficient physical activity and extended periods of sitting are linked to an increased risk of liver steatosis in PWH, independent of BMI. This underscores the critical need for promoting regular physical activity to prevent liver steatosis in this population. | ||
| 2nd May | Mocroft et al., Heavy antiretroviral exposure and exhausted/limited antiretroviral options | |
Mocroft et al. assessed determinants of developing an HIV treatment status with limited antiretroviral treatment options among people with HIV (PWH) in the International Cohort Consortium of Infectious Diseases (RESPOND). Authors included RESPOND cohort participants with at least 5 years of antiretroviral therapy. Limited and exhausted treatment options were defined as receiving (1) at least two anchor agents together with a third drug from any class, (2) exactly two anchor agents (excluding dual therapies recommended by HIV treatment guidelines such as cabotegravir and rilpivirine), (3) any regimen that included enfuvirtide, or (4) at least three nucleotide reverse transcriptase inhibitors (NRTI). Predictors were assessed using multivariable Poisson regression. The study included 23’827 PWH, of which 26% were female. The median age was 46 years (IQR 39-53), and the median nadir CD4 cell count was 230 cells/μL (IQR 119-348). Within a median follow-up of 5.5 years, 2'164 persons (9.1%) developed a status of limited or exhausted treatment options. Individuals with follow-up in 2018–2021 had a lower probability of having limited treatment options than those with follow-up in 2015–2017. In addition, individuals with high CD4 cell counts and suppressed HIV viral loads were less likely to have limited treatment options compared with those with ongoing HIV replication. In contrast, individuals who had HIV for more than 15 years were most likely to have limited treatment options. In summary, the present study shows that PWH are less likely to have limited or exhausted antiretroviral treatment options in recent years. Effective suppression of HIV viral load and successful immune recovery with current medications likely contributed to this improvement. | ||
| 17th April | Real et al., Metagenome-wide association study of HIV disease progression in HIV controllers | |
Some HIV controllers experience immunologic progression with CD4+ T cell decline. In this study, Real et al. aimed to identify genetic factors associated with CD4+ T cell lost in HIV controllers. Non-long-term non-progressor HIV phenotype was defined as CD4+ T-cells A total of 561 HIV controllers were included, 442 and 119 from the International HIV controllers Study Cohort and the Swiss HIV Cohort Study, respectively. No single nucleotide polymorphism (SNP) or gene was associated with the long-term non-progressor HIV spontaneous control phenotype in the individual Genome-wide association studies (GWAS) or in the meta-analysis. However, SNPs previously associated with natural HIV control linked to HLA-B (rs2395029 [p = 0.005; OR = 1.70], rs59440261 [p = 0.003; OR = 1.78]),nMICA (rs112243036 [p = 0.011; OR = 1.45]), and PSORS1C1 loci (rs3815087 [p =0.017; OR=1.39]) showed nominal association with this phenotype. In conclusion, this study performed the first meta-GWAS focusing in the long-term maintenance of CD4+ T cells in HIV controllers. These results suggest that genetic factors previously associated with the overall HIV controller phenotype, mainly those linked to PSORS1C1, HLAB, and MICA loci, seem to have a role in this complex trait. The results of the present study could help to refine the best definition for HIV controllers. Consequently, these HIV controllers should be considered as the best model of functional cure. The study of this specific phenotype could help to design new strategies for preventing HIV progression, not necessarily associated with antiretroviral treatment, in those subjects who show CD4+ T cell loss. | ||
| 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 | ||