2023
| 7th December | Congratulations to Katharina Kusejko and Luisa Salazar-Vizcaya |  |
We wish Luisa Salazar-Vizcaya and Katharina Kusejko all the best for their projects! | ||
| 6th December | Baumann et al., Long-term trends in HCV prevalence, treatment uptake and liver-related events in the SHCS |  |
Baumann et al. assessed trends in the prevalence of replicating hepatitis C virus (HCV) infection, the uptake of HCV treatment, and its impact on liver-related morbidity and mortality among people with HIV (PWH) and HCV in the Swiss HIV Cohort Study (SHCS). The study included all participants with follow-up after January 2002, when HCV-PCR became broadly available in clinical routine. Replicating HCV infection was defined as at least one HCV-RNA measurement >50 IU/mL, and HCV treatments included interferon (with or without ribavirin), first-generation direct acting antivirals (DAA; telaprevir, boceprevir, and faldaprevir), and second-generation DAAs (sofosbuvir, daclatasvir, velpatasvir, glecaprevir/pibrentasvir, and others). The study included 14’652 participants, of which 2’294 individuals had at least one detectable HCV-RNA measurement. Compared to individuals with HIV mono-infection, those with HIV/HCV coinfection were younger, more likely to be Caucasian, and more likely to have acquired HIV through injection drug use. The yearly prevalence of replicating HCV infection among all SHCS participants was highest in 2004 (16.5%), and declined to 1.3% in 2021. HCV treatment uptake rapidly increased with the availability of second-generation DAAs: In 2014, 6.7% of individuals with replicating infection received treatment, compared to 32.6% of people with active HIV/HCV coinfection in 2016. Among the 2’294 persons with replicating HCV infection, overall mortality declined from a maximum of 3.3 per 100 patient-years (PY) to 1.1 per 100 PY, and incidence of liver-related events decreased from 1.4/100 PY to 0.2/100 PY. In summary, the study showed that the widespread adoption of second-generation DAAs led to a substantial decline in HCV infections among PWH in Switzerland, with prevalence estimates now approaching that from the general population. The reduction in HCV burden was followed by lower rates of mortality and liver-related events, highlighting the considerable success of therapeutic interventions towards eliminating HCV among PWH. | ||
| 22nd November | Begré et al., QHBsAg trajectories in persons with HIV on TDF-containing ART | |
Begré et al. aimed to evaluate long-term trajectories of quantitative hepatitis B surface antigen (qHBsAg) and HBV (hepatitis B virus) DNA levels in persons with HIV/HBV with and without HBsAg loss during tenofovir-containing antiretroviral therapy (ART) in the SHCS. The authors included 29 participants with and 29 without HBsAg loss, defined as qHBsAg <0.05 IU/mL. They assessed qHBsAg decline during therapy in both groups and used agglomerative hierarchical clustering to identify different qHBsAg trajectory profiles in persons with HBsAg loss. The median follow-up time was 11.9 years (IQR 8.4–14.1), and the median time to HBsAg loss was 48 months (IQR 12–96). Among participants with HBsAg loss, 79% had a qHBsAg decline≥1log10IU/mL 2 years after starting tenofovir. The trajectories in qHBsAg levels during tenofovir therapy were heterogeneous, characterized by five distinct profiles. Among participants without HBsAg loss, only 7% had a qHBsAg decline≥1log10IU/ml after 2 years. In conclusion, the study shows that the majority of persons with HIV/HBV experiencing HBsAg loss have aqHBsAg decline of at least 1 log10IU/mL within 2 years of tenofovir therapy. These data suggest that early qHBsAg level changes precede HBsAg loss during tenofovir-containing ART. However, long-term qHBsAg trajectories among persons who experience HBsAg loss during tenofovir-containing ART were diverse, and HBsAg clearance also occurred more than 5 years after starting tenofovir therapy. | ||
| 16th November | Loosli et al., HIV-1 drug resistance in people on dolutegravir-based ART | |
Loosli et al. assessed risk factors for dolutegravir (DTG) resistance and patterns of drug resistance mutations (DRM) among people with HIV (PWH) and replicating HIV infection on DTG-containing antiretroviral therapy (ART). For this international collaboration, the authors combined data from the ART Cohort Collaboration (ART-CC) and the International epidemiology Databases to Evaluate AIDS (IeDEA), thereby including PWH from Europe, North America and South Africa. Participants who underwent genotypic resistance testing while receiving DTG-based ART were included in the study. The authors calculated adjusted odds ratios (aOR) with multivariable logistic regression to identify risk factors for DTG resistance according to the Stanford HIV Database algorithm. The study included 599 individuals with available drug resistance testing. The majority of individuals were male (69%), the median age was 44 years (interquartile range [IQR] 36-52), and the median CD4 cell count at resistance testing was 412 cells/μL (IQR 213-674). Most individuals (68%) did not have prior exposure to first-generation integrase inhibitors (e.g. raltegravir, elvitegravir). Drug resistance mutations against integrase inhibitors were present in 86 (14%) of all individuals, and 36 individuals (6%) had DRMs affecting DTG: 13 individuals acquired low-level DTG resistance, 17 had intermediate DTG resistance, and 6 showed high-level DTG resistance. Dolutegravir resistance was more likely to occur among individuals who received DTG monotherapy (aOR 34.1, 95% CI 9.9 - 117.0), among persons on dual therapy (DTG/lamivudine: aOR 9.2, 2.2 - 38.6), and among PWH and NRTI resistance mutations (low-level: aOR 5.2, 1.3 - 20.7; intermediate/high: aOR 13.4, 4.6 - 39.7). In summary, individuals on DTG monotherapy or DTG/lamivudine dual therapy, and individuals with NRTI resistance are at increased risk to develop DTG resistance in the event of a virological failure. Although still rare, the present study highlights that DTG resistance does occur. Improved access to drug resistance testing for all PWH will be critical to monitor DTG resistance rates after its global roll-out. | ||
| 10th November | Hentzien et al., Validation of the Dat'AIDS score in the SHCS | |
Hentzien et al. aimed to externally validate the Dat'AIDS score's capacity to predict 5-yearoverall mortality in people with HIV (PWH) aged 60 or older, using data from the Swiss HIV Cohort Study (SHCS). The Dat'AIDS score comprises the following predictors: age, CD4 cell count, non-HIV related cancer, cardiovascular disease, estimated glomerular filtration rate (eGFR), cirrhosis, low body mass index (BMI) and anaemia. The Dat'AIDS score ranges from 0 to a maximal value of 73. During derivation, the range was divided into four risk groups: low-risk (0–3 points); moderate risk (4–13 points); high-risk (14–19 points); and very high-risk (≥ 20 points). The authors calculated the Dat'AIDS score in PWH at their first visit between 1 January 2015 and 1 January 2020. The primary endpoint was all-cause mortality. They included 2’205 participants (82% male) of median [interquartilerange (IQR)] age 62.0 (60.3–67.0) years, mostly with viraemia <50 copies/mL(92.7%). Median follow-up time was 15.9 years and median (IQR) CD4 cell count at enrolment was 586 (420–782) cells/μL. In all, 152 deaths were recorded during a total follow-up period of 7147 patient-years. The median (IQR) observed Dat'AIDS score was 3 (0–8). Discriminative capacities were good as the C-statistic was 0.73 (95% CI: 0.69–0.77) and consistent across all subgroups. Comparison of observed and expected survival probabilities showed good calibration. In conclusion, this study demonstrates the external validity of the Dat'AIDS score in patients included in the SHCS aged 60 years or more in the late cART era. The score showed a good discrimination capacity as well as good calibration. It may be a useful tool for research, as well as for risk assessment by clinicians, especially as the population of aged PWH is becoming increasingly. | ||
| 1st November | Jörimann et al., No evolution on dolutegravir monotherapy | |
Jörimann et al. evaluated the impact of dolutegravir (DTG) monotherapy on the dynamics and the evolution of the viral reservoir among people with acute HIV infection. Specifically, the authors tested the hypothesis of ongoing low-level HIV replication as a mechanism for HIV-1 reservoir maintenance, which may lead to an increase in genetic distance, viral diversity or the occurrence of drug resistance mutations (DRM) in HIV-1 proviruses. The study included participants from the Early Simplified Study (ESS), in which people with acute HIV infection who received standard antiretroviral therapy (ART) for at least one year were randomized to either receiving DTG monotherapy or continuing standard ART. For the present work, peripheral blood mononuclear cells (PBMCs) or co-culture virus from ESS participants were collected at multiple time points, and near full-length HIV-1 PCR with next-generation sequencing (NGS) was performed to assess the viral diversity, genetic distance and to detect DRMs. Sequences were obtained from 210/297 samples (71%), and 163 NGS sequences were selected from 43 ESS participants with longitudinal data (25 on DTG monotherapy, 18 on standard ART). After filtering for APOBEC-induced hypermutations (which occur frequently but do not indicate proviral evolution), the median pairwise genetic distance over the study period was 0.50% (IQR 0.06-1.50), and did not differ between the two groups (p = 0.56). Similarly, average pairwise viral diversity assessed for the 3 genomic regions pol, gag, and env were similar in both groups, and did not change over time. Finally, after filtering for APOBEC signature mutations, one single proviral DRM emerged in an individual after receiving 48 weeks of DTG monotherapy. Importantly, this individual did not develop viral failure during a total of four years of DTG monotherapy. Taken together, the study shows that DTG monotherapy among individuals who entered HIV care during primary HIV infection did not lead to an increase in genetic distance, viral diversity or accumulation of DRMs. These findings argue against ongoing low-level HIV replication in those individuals, and highlight that a better understanding of HIV-1 reservoir dynamics is important to inform future ART simplification strategies. | ||
| 24th October | Labarile et al. Quantifying HIV-1 transmission dynamics | |
Labarile et al. aimed to analyze cluster growth dynamics in the Swiss HIV epidemic in the context of the Swiss HIV Cohort Study (SHCS) as well as the predictive capabilities that can be achieved in this framework. To reach this goal the authors adapted a distance-based clustering mechanism implemented in HIV-Transmission Cluster Engine (HIV-TRACE) using evolutionary distances between viral sequences from the SHCS and combined it with statistical learning approaches. They found that only a minority of clusters and patients acquired links to new infections between 2007 and 2020. While the growth of clusters and the probability of individual patients acquiring new links in the transmission network was associated with epidemiological, behavioral, and virological predictors, the strength of these associations decreased substantially when adjusting for network characteristics. Thus, these network characteristics were able to capture major heterogeneities beyond classical epidemiological parameters. When modeling the probability of a newly diagnosed patient being linked with future infections, they found that the best predictive performance (median area under the curve receiver operating characteristic AUCROC=0.77) was achieved by models including characteristics of the network as predictors and that models excluding them performed substantially worse (median AUCROC=0.54). In conclusion, the study shows that in the timespan from 2007 to 2020 only a minority of the HIV clusters in Switzerland were growing. Similarly, only a small fraction of patients enrolled up to the year 2007 have formed any new links, which would be an indication of onward transmission of HIV. The study presents new insights into the long-term dynamics of HIV cluster growth including the value of using cluster-based variables in predicting future growth both on the level of clusters and individual patients in the Swiss HIV epidemic. | ||
| 11th October | Trickey et al., Life expectancy of adults with HIV on long-term ART | |
Trickey et al. estimated the life expectancy of people with HIV (PWH) who received suppressive antiretroviral therapy (ART) after 2015, when treatment guidelines started to recommend ART for all PWH irrespective of CD4 cell count. The study used data from the Antiretroviral Therapy Cohort Collaboration (ART-CC) and the UK Collaborative HIV Cohort Study (UK CHIC). Cohort participants on ART between 1996 and 2019 who survived for at least 1 year after ART start were considered. Information about mortality was gathered through vital statistics agencies, hospitals, physician reports and clinical follow-up of patients. The authors applied Poisson regression models to estimate mortality rate ratios, and to evaluate the impact of age, CD4 cell count, other demographics, HIV and non-HIV related covariates on mortality. Based on the models, life expectancy from age 40 was calculated. The study included 206’891 PWH, and 5’780 deaths occurred during 619’356 person-years of follow-up. Mortality rates were lower in women compared to men (adjusted mortality rate ratio 0.85, 95% CI 0.80 - 0.91), and in individuals who started ART after 2015 compared with individuals who started before 2000 (0.58, 95% CI 0.52 - 0.66). Individuals who acquired HIV through injecting drug use (mortality rate ratio 3.93, 95% CI 3.65-4.24) and individuals with HIV/HCV coinfection (1.97, 95% CI 1.76-2.20) had the highest risk of dying during follow-up. At the age of 40 years, women who started ART after 2015 had a standardized estimated 39.0 years (95% CI 38.5-39.5) of life left. The estimated life years left for men at the same age was 37.0 years (95% CI 36.5-37.6). Compared to the general population, life expectancy in PWH was 3.8 years (women) and 1.5 years (men) shorter. In summary, the study highlights the advances in HIV care within the last decade, which translates into a life expectancy of PWH in North America and Europe that is only a few years lower than that of people without HIV. Although these findings are reassuring for many individuals, they also reveal disparities. Further efforts are needed to reduce the mortality of key populations such as intravenous drug users or individuals with HIV/HCV coinfection, who still remain at increased risk of death. | ||
| 4th October | Berton et al., Exposure and response of antiretrovirals in obese PWH | |
Berton et al. aimed to perform virtual trials using physiologically based pharmacokinetic (PBPK) modelling combined with therapeutic drug monitoring (TDM) data and the corresponding viral load data obtained from people with HIV (PWH) enrolled in the Swiss HIV Cohort Study (SHCS) to determine the exposure and response to antiretrovirals (ARVs) in obese and non-obese PWH and provide dosing guidance. Each trial included a cohort of virtual adults with a body mass index (BMI) between 18.5 and 60 kg/m2. Therapeutic drug-monitoring data from the Swiss HIV Cohort Study (SHCS) were used to verify the predictive performance of the model. Subsequently, the model was applied to predict the pharmacokinetics of ARVs for different obesity classes. The association between ARV plasma concentrations and virological response was investigated in obese and non-obese individuals. The PBPK model predicted an average reduction in ARV exposure of ∼20% and trough concentrations of ∼6% in obese (BMI ≥30 kg/m2) compared with non-obese (BMI: 18.5–25 kg/m2) individuals, consistent with observed clinical data. Etravirine and rilpivirine were the most impacted, especially in individuals with BMI >40 kg/m2 whose trough concentrations were below the clinical target threshold. Obese PWH in the SHCS did not have a higher rate of unsuppressed viral load than non-obese PWH. In conclusion, this study shows that obesity lowers the exposure of ARVs; nevertheless, the minimal concentrations of all evaluated ARVs were maintained above the target threshold, except for etravirine and rilpivirine in morbidly obese individuals in whom TDM is advised. When considering the data of the SHCS, the proportion of individuals with viral loads above 50 copies/mL was not higher in obese compared with non-obese PWH. Thus, a dose adjustment of ARVs is a priori not required in obese PWH. This data provide reassurance that substantial weight gain observed in some individuals on treatment with integrase inhibitors and/or the switch from tenofovir disoproxil fumarate to tenofovir alafenamide is unlikely to result in suboptimal drug exposure and response. | ||
| 28th September | Jaha and Schenkel et al., Prevalence of HIV-1 drug resistance mutations in proviral DNA | |
Jaha and Schenkel et al. developed a protocol to perform proviral DNA genotypic resistance testing and evaluated the prevalence of drug resistance mutations (DRM) among people with HIV in the Swiss HIV Cohort Study. As standard genotypic resistance testing can only be performed among individuals with replicating HIV infection, resistance testing in proviral DNA has been proposed for individuals with low or undetectable HIV viral loads. In this study, cohort participants with available PBMC samples from Lausanne and Geneva were included. Near full-length HIV-1 DNA amplification was performed and sequenced using next-generation sequencing (NGS). DRMs were systematically assessed using the Los Alamos and the Stanford HIV Drug Resistance Database. As certain mutations induced by the APOBEC enzymes could result in defective non-replicable viruses, a sensitivity analysis without those mutations was performed. The study included PBMC samples from 962 individuals (mean age 40 years, 33% women, median CD4+ 495 cells/μL). Amplification and NGS was successful in 71%, with samples from individuals with a low CD4 cell count, and samples with a high DNA concentration being more likely to be successfully amplified. At least one DRM was detected in 55% of patients, with DRMs against NRTI being most frequently detected, followed by NNRTI, protease and integrase inhibitors. After excluding mutations potentially induced by APOBEC, 43.8% had at least one DRM. Taken together, the authors presented a reliable method to perform genotypic resistance testing from HIV proviral DNA in a diverse population of people with HIV. More studies are needed to evaluate the clinical implication of these DRMs and to guide treatment decisions among people with low or undetectable HIV viral loads. | ||
| 20th September | Greenberg et al., Trends in cancer incidence in different ART-eras amongst PWH | |
Greenberg et al. on behalf of the RESPOND and D:A:D Study Groups aimed to assess changes in the incidence of both overall cancer and different types of cancer, including AIDS-defining cancers (ADCs), non-ADCs (NADCs), infection-related cancers, body mass index (BMI)-related cancers, and smoking-related cancers, from 2006 to 2021 in the D:A:D and the RESPOND international cohort collaborations. Amongst 64’937 individuals (31% ART-naïve at baseline) and 490’376 total person years of follow-up (PYFU), there were 3’763 incident cancers (IR 7.7/1000 PYFU [95% CI 7.4, 7.9]): 950 ADCs, 2’813 non-ADCs, 1’677 infection-related cancers, 1’372 smoking related cancers, and 719 BMI-related cancers (groups were not mutually exclusive). Age-standardised IRs for overall cancer remained fairly constant over time (8.22/1000 PYFU [7.52, 8.97] in 2006–2007, 7.54 [6.59, 8.59] in 2020–2021). The incidence of ADCs (3.23 [2.79, 3.72], 0.99 [0.67, 1.42]) and infection-related cancers (4.83 [4.2, 5.41], 2.43 [1.90, 3.05]) decreased over time, whilst the incidence of non-ADCs (4.99 [4.44, 5.58], 6.55 [5.67, 7.53]), smoking-related cancers (2.38 [2.01, 2.79], 3.25 [2.63–3.96]), and BMI related cancers (1.07 [0.83, 1.37], 1.88 [1.42, 2.44]) increased. Trends were similar after adjusting for demographics, comorbidities, HIV-related factors, and ART use. In conclusion, the study found that the age-standardised incidence of cancer overall has remained fairly constant over time from 2006 to 2021. ADCs and infection-related cancers have significantly decreased over time, whilst NADCs, smoking-related cancers, and BMI-related cancers have increased slightly. These results show the need for better prevention strategies to reduce the incidence of smoking- and BMI-related cancers, in particular. These data also suggest that initiatives to reduce the incidence of several infection-related cancers and ADCs, such as earlier HIV diagnosis and provision of ART, have been somewhat effective. Further research into individual cancer trends is needed to better understand the causes of the cancer trends presented in the presented study. | ||
| 14th September | Balakrishna et al., Comparison of HIV drug resistance mutation detection methods | |
Balakrishna et al. aimed to compare the HIV drug resistance mutations (DRMs) detected by Sanger sequencing (SS) and next-generation sequencing (NGS) at different thresholds and explored the dependency of the frequency and spectrum of low-abundance HIV-DRMs on the variant-calling thresholds. SS can detect HIV-DRMs that appear in more than 15%–25% of variants, whereas NGS detect low-abundance mutations. To compare the HIV-DRMs detected by SS and NGS, the authors included participants enrolled in the Swiss HIV Cohort Study (SHCS) with SS and NGS sequences available with sample collection dates ≤7 days apart. They tested for the presence of HIV-DRMs and compared the agreement between SS and NGS at different variant-calling thresholds. The authors included 594 pairs of SS and NGS from 527 SHCS participants. Males accounted for 80.5% of the participants, 76.3% were ART naive at sample collection and 78.1% of the sequences were subtype B. Overall, the study observed a good agreement (Cohen’s kappa >0.80) for HIV-DRMs for variant-calling thresholds ≥5%. The authors observed an increase in low-abundance HIV-DRMs detected at lower thresholds [28/417 (6.7%) at 10%–25% to 293/812 (36.1%) at 1%–2% threshold]. However, such low-abundance HIV-DRMs were overrepresented in ART-naive participants and were in most cases not detected in previously sampled sequences suggesting high sequencing error for thresholds <3%. In conclusion, the study observed, for different variant-calling thresholds above 5%, a good concordance (Cohen’s kappa and Light’s kappa >0.8) between SS and NGS in detecting HIV-DRMs as well as for the resulting resistance levels to ARV drugs. The authors observed a substantial number of low-abundance HIV-DRMs detected only by NGS at lower variant-calling thresholds. These findings suggest that a substantial fraction of the low-abundance HIV-DRMs detected at thresholds <3% may represent sequencing errors and hence should not be over interpreted in clinical practice. | ||
| 7th September | Ingle et al., Treating HIV in cryptococcal meningitis | |
Ingle et al. aimed to investigate the impact of antiretroviral therapy (ART) timing on mortality rates associated with cryptococcal meningitis (CM) among people in high-income settings. The authors used data from ART-naive people with HIV (PWH) with CM diagnosed from 1994 to 2012 from Europe/North America pooled from the COHERE, NA-ACCORD, and CNICS HIV cohort collaborations. The used marginal structural models to mimic a randomize controlled trial (RCT) comparing the effects of early (within 14 days of CM) and late (14–56 days after CM) ART on all-cause mortality, adjusting for potential confounders. Of 190 participants identified, 33 (17%) died within 6 months. At CM diagnosis, their median age (interquartile range) was 38 (33–44) years; the median CD4+ T-cell count, 19/μL (10–56/μL); and median HIV viral load, 5.3 (4.9–5.6) log10 copies/mL. Most participants (n = 157 [83%]) were male, and 145 (76%) started ART. Mimicking an RCT, with 190 people in each group, there were 13 deaths among participants with an early ART regimen and 20 deaths among those with a late ART regimen. The crude and adjusted hazard ratios comparing late with early ART were 1.28 (95% confidence interval, .64–2.56) and 1.40 (.66–2.95), respectively. In conclusion, the study found little evidence that early ART after CM was associated with higher mortality rates than late ART in ART-naive PWH living in high-income settings. Importantly, the present study used a selected sample of the total population, only representative of PWH in care in high-income settings, whereas current guidelines are based on low-income settings. | ||
| 23rd August | Mugglin and Hamusonde et al., MSM with HIV in times of COVID-19 | |
Mugglin and Hamusonde et al. evaluated changes in sexual behavior, satisfaction and incidence of sexually transmitted infections among men who have sex with men (MSM) related to restrictions due to the COVID-19 pandemic. All MSM from the Swiss HIV Cohort Study who reported sex with occasional partners were asked to complete an online questionnaire regarding their sexual behavior. Questions assessed aspects such as the number of sexual partners, attendance of sex parties, frequency of chemsex, traveling for sex, and overall satisfaction with their sexual life. In addition, the authors evaluated trends of STIs incidences between January 2018 and June 2022. The questionnaire was completed by 205 participants. Their median age was 49 years, 90% were White, and 96% had a suppressed HIV viral load. Compared to the area prior to the COVID-19 pandemic, 63% reported having less occasional partners, 22% reported no change, and 14% had more occasional partners during the pandemic. The proportion of individuals who attended sex parties declined from 33% to 5%, and the proportion of individuals who traveled abroad for sex at least once per month decreased from 26% before to 9% during the pandemic. Whereas 73% of individuals reported being satisfied with their sexual life prior to the COVID-19 related restrictions, this proportion decreased to 57% during the pandemic. In contrast, attending private sex parties, traveling for sex within Switzerland and practicing chemsex remained unchanged. Similarly, incidences of chlamydia, gonorrhea and syphilis infections remained stable throughout the study period. In summary, the study shows that although sexual activity somewhat decreased during COVID-19 related restrictions, people responded very differently to those measures. This heterogeneity is nicely illustrated by the substantial proportion of individuals who reported an increase in the number of non-steady partners, which might explain why STI incidence did not decrease during the studied period. These findings highlight that a better understanding of the drivers of sexual behavior among PWH is needed to tailor STI prevention programs. | ||
| 16th August | Filippidis et al., CSF HIV-1 escape in cognitive symptoms | |
Filippidis et al. for the NAMACO study group aimed to evaluate the prevalence of cerebrospinal fluid (CSF) HIV-1 escape among people living with HIV (PLWH) in Switzerland and to identify potential predictive factors and clinical characteristics associated with this phenomenon. The study group pooled data from the Neurocognitive Assessment in the Metabolic and Aging Cohort study and the neuro-HIV platform participants who underwent lumbar puncture between 2011 and 2019. Both patient groups had neurocognitive symptoms. Cerebrospinal fluid HIV-1 escape was defined as the presence of quantifiable CSF HIV-1 RNA when plasma HIV-1 RNA was suppressed or CSF HIV-1 RNA greater than plasma HIV-1 RNA when the latter was detectable. Of 1’166 PLWH assessed, 288 underwent lumbar puncture. Cerebrospinal fluid HIV-1 escape was observed in 25 PLWH (8.7%) of whom 19 (76%) had suppressed plasma HIV-1 RNA. Characteristics of PLWH were comparable whether they had CSF HIV-1 escape or not, including comorbidities, time since HIV diagnosis (15 vs 16 years, P = 0.9), median CD4 nadir (158.5/mm3 vs 171/mm3, P = 0.6), antiretroviral CSF penetration-effectiveness score (7 vs 7 points, P = 0.8), and neurocognitive diagnosis based on Frascati criteria and radiological findings. In conclusion, this study observed CSF HIV-1 escape in 8.7% of patients with suspected or confirmed neurocognitive impairment (NCI) in a large case series. Importantly, three-quarters of the patients with CSF HIV-1 escape had undetectable plasma viral loads. With the exception of detectable plasma HIV-1 RNA, the study found no reliable demographic, clinical, immunological, neurocognitive, or radiological predictive factor for CSF HIV-1 escape. Hence, the authors conclude that lumbar puncture is the only means to detect CSF HIV-1 escape, and should be considered in all patients presenting NCI, especially in the absence of other factors not directly linked to HIV, because the identification of CSF HIV-1 escape through LP may prompt ART modification. | ||
| 9th August | Damas et al., Neuro-HIV multidisciplinary platform for PLWH | |
Damas et al. describe the implementation of a multidisciplinary neuro-HIV platform, which aims at providing a comprehensive neurocognitive assessment. In the Lausanne University Hospital (CHUV), specialists from the departments of infectious diseases (ID), neurology, neuropsychology, and psychiatry collaborate closely when evaluating the neurocognitive function of people with HIV, and provide a multidisciplinary assessment and recommendations within 8 hours. Neuropsychological assessments are performed using tests that best reflect the patients’ complaints, and are focused on instrumental functions (e.g. language), memory, executive function and attention. A psychiatric evaluation is performed to estimate the extent to which cognitive problems could be attributed to psychopathology (e.g. depression). Examinations include an MRI to assess for alternative neurological disease, and a lumbar puncture to detect HIV central nervous system viral escape and to measure drug concentrations in the cerebrospinal fluid. Between March 2011 and April 2019, 185 individuals were evaluated within the framework of the neuro-HIV platform (median age 54 yeast, 58.9% were men). HIV-associated neurocognitive impairment was diagnosed in 37 individuals, of whom 24 (65%) had asymptomatic neurocognitive impairment, 11 (30%) had mild neurocognitive disorder, and 2 (5%) had HIV-associated dementia. HIV viral escape was present in 16 of 143 individuals who underwent a lumbar puncture (median HIV-RNA 49 cp/mL, IQR 35-190). Depression was the most important non-HIV cause, which accounted for 79.5% of individuals with non-HIV related neurocognitive impairment. In summary, the present work nicely illustrates the feasibility and benefits of addressing neurocognitive symptoms in a timely and comprehensive manner, as recommended in the European AIDS Clinical Society guidelines. The high prevalence of non-HIV related causes for neurocognitive impairment such as depression further underlines the importance of a multidisciplinary approach. | ||
| 2nd August | Chalouni et al., Impact of hepatitis C cure in PWH | |
Chalouni et al. for the Antiretroviral Therapy Cohort Collaboration (ART-CC) aimed to assess the risks of overall mortality, AIDS-defining events, and non-AIDS-defining nonliver-related (NANL) cancers between hepatitis C virus (HCV-) co-infected people with HIV (PWH) who reached sustained virological response (SVR) and matched mono-infected PWH with similar time since first starting antiretroviral therapy (ART). Among 62’495 PWH, 2’756 acquired HCV, of whom 649 reached SVR. For 582 of these, at least one mono-infected PWH could be matched, producing a total of 5’062 mono-infected PWH. The estimated hazard ratios comparing HCV-co-infected PWH who reached SVR with mono-infected PWH were 0.29 [95% confidence interval (CI) 0.12–0.73] for mortality, 0.85 [0.42–1.74] for AIDS-defining events, and 1.21 [0.86– 1.72] for NANL cancer. In conclusion, when compared with mono-infected PWH, PWH with HCV co-infection for a short time and who reached SVR, whatever the treatment generation, were at lower risk of overall mortality. Nevertheless, participants who reached SVR after a direct acting agents (DAA-) based treatment still exhibited a higher risk of NANL cancer after SVR, despite an important incertitude in the estimate with a large confidence interval. Treatment guidelines and the limited efficacy of pre-DAA HCV treatments could have resulted in a selection of the SVR population and, therefore, artificially decreased the risk of events in the SVR population. A study comparing HIV mono-infected participants and HCV-cured participants following highly effective DAA treatment could overcome this issue. | ||
| 26th July | Zeeb et al., HIV and tuberculosis in Switzerland | |
Zeeb et al. conducted a comprehensive study to evaluate trends of incident tuberculosis (TB) and its association with HIV viral suppression among people with HIV (PWH) in the Swiss HIV Cohort Study (SHCS). In addition, the study assessed the performance of screening and treating latent tuberculosis infection (LTBI) for TB prevention. Tuberculosis was defined as detection of Mycobacterium tuberculosis in a clinical specimen associated with signs and symptoms with the disease. Incident TB cases were defined as TB diagnosis after 6 months of HIV diagnosis or SHCS registration, and LTBI was defined as a positive interferon-gamma release assay or tuberculin skin test. Among participants in the SHCS, the TB incidence reached its peak in 1989, with 90.8 cases per 1000 person-years, and declined to 0.1 cases per 1000 person-years in 2021. This reduction was largely attributed to higher CD4 cell counts (relative indirect effect -77%) and HIV viral suppression (relative indirect effect -49%). Concurrently, LTBI prevalence dropped from a peak of 15.1% in 2001 to 4.6% in 2021. Of 1233 PWH who were tested positive for LTBI, 44% received preventive treatment. After 16 years of follow-up, 9 individuals who received preventive therapy developed TB, compared to 20 non-treated individuals. This represents an absolute risk reduction of 0.9%(95% CI 1.2% to 2.9%), or a number needed to prevent one TB case of 118. Among 277 PWH who developed incident TB, 60.1% were not tested for LTBI. Among those tested for LTBI, 73.4% had a negative test result before being diagnosed with active TB. In conclusion, the study highlights that effective HIV treatment played a crucial role in the decline of TB cases among PWH in Switzerland. However, the low percentage (less than 50%) of individuals with positive LTBI tests receiving preventive therapy underscores the need to enhance both patient and physician acceptance of preventive TB treatment. Finally, the fact that over 70% of individuals with TB had previously tested negative for LTBI emphasizes the need for better tools to assess the TB risk of PWH. | ||
| 20th July | Álvarez et al., Determinants of HIV virological outcomes | |
Álvarez et al. for the RESPOND (International Cohort Consortium of Infectious Diseases) Study Group aimed to examine baseline factors associated with virological nonsuppression outcomes (blips, low-level viremia [LLV], residual viremia [RV], and virological failure [VF]) in treatment-naive persons with HIV (PWH) who started a 3-drug antiretroviral therapy (ART) regimen in the integrase strand transfer inhibitor (INSTI) era in 2014–2020. Viral suppression (VS) was defined as HIV-1 RNA levels <50 copies/mL; LLV, as the first of ≥ 2 consecutive plasma HIV-1 RNA measurements of 50–199 copies/mL, following VS; viral blip, as an isolated plasma HIV-1 RNA level of 50–199 copies/mL with previous and subsequent HIV-1 RNA levels <50 copies/mL, following VS; RV, as any detectable and quantifiable plasma HIV-1 RNA between 20 and 49 copies/mL, among participants with a HIV-1 RNA measurement with a limit of detection of 20 copies/mL, following VS; and VF, as the first of 2 consecutive plasma HIV-1 RNA measurements ≥50 copies/mL, with 1 measurement ≥200 copies/mL, following VS. Of 4’310 eligible participants, 72% started INSTI-based regimens. At 48 and 96 weeks, 91.0% and 93.3% achieved virological suppression (VS), respectively. At 48 weeks, Kaplan-Meier estimates of rates were 9.6% for viral blips, 2.1% for LLV, 22.2% for RV, and 2.1% for VF. Baseline HIV-1 RNA levels >100 000 copies/mL and CD4+ T-cell counts ≤200/µL were negatively associated with VS at weeks 48 (adjusted odds ratio, 0.51 [95% confidence interval, .39–.68] and .40 [.27–.58], respectively) and 96 and with significantly higher rates of blips, LLV, and RV. CD4+ T-cell counts ≤200/µL were associated with higher risk of VF (adjusted hazard ratio, 3.12 [95% confidence interval, 2.02–4.83]). Results were consistent in those starting INSTIs versus other regimens and those starting dolutegravir versus other INSTIs. In conclusion, baseline plasma HIV-1 RNA levels >100 000 copies/mL and CD4+ T-cell counts ≤350/µL were associated with lower rates of VS at 48 and 96 weeks, and higher rates of viral blips, RV, and LLV. CD4+ T-cell counts ≤200/µL were associated with a higher risk of VF. Importantly, the association between HIV-1 RNA levels or CD4+ T-cell count and these virological outcomes persisted in participants initiating INSTI-based and specifically dolutegravir-based regimens. These data suggest that baseline HIV-1 RNA levels and CD4+ T-cell counts are determinants associated with virological nonsuppression outcomes regardless of the antiretroviral regimen initiated and point to underlying mechanisms established before ART initiation, likely focused on the HIV reservoir size. Further research is warranted to explore the impact of bictegravir-emtricitabine-TAF, doravirine, and INSTI-based 2-drug regimens on long-term virological non[1]suppression outcomes. | ||
| 12th July | Surial et al., INST and CVD events after starting ART | |
Surial et al. performed a target trial emulation to examine the effect of starting integrase inhibitor (INSTI) based antiretroviral therapy (ART) compared to other ART combinations on cardiovascular disease (CVD) events among treatment-naïve participants in the Swiss HIV Cohort Study (SHCS). The target trial framework is a method for designing an observational data analysis that specifies treatment eligibility, the intervention, patient follow-up and clinical outcomes similar to a randomized trial. This approach provides a clear alignment of time-zero, and reduces the potential for selection and immortal time bias. The authors included all SHCS participants who were HIV treatment-naïve after the first INSTI became available in Switzerland (May 2008) and subsequently initiated ART. Individuals were classified as INSTI starters if they received any INSTI-containing ART as their first treatment, and as other ART starters if they received other ART combinations. Time zero was defined as the date of first ART start, and the outcome of interest was the first CVD event, which included myocardial infarction, stroke, and invasive cardiovascular procedure. Between May 2008 and September 2022, 1’837 (34.3%) individuals started INSTI-based ART, and 3’525 (65.7%) started other ART combinations. Compared to people with HIV who started other ART combinations, those who started INSTI were less likely to be women, less likely to be of African origin, more likely to have an eGFR <60 mL at start, and to receive abacavir and tenofovir alafenamide. Within a median follow-up of 4.9 years, 116 CVD events occurred. Adjusted risk differences for CVD events between individuals who initiated INSTI and those who initiated other ART were as follows: -0.08% (95% CI, −0.20 to 0.19) at 6 months, -0.17% (−0.37 to 0.19) at 1 year, -0.61% (−0.72 to 0.09) at 2 years, and -0.71% (−2.16 to 0.94) at 8 years. In summary, this study found no difference in the risk of developing CVD events between individuals who started INSTI-based ART and those who started other ART combinations. These findings contrast with the results from a large study from the RESPOND cohort collaboration, which reported a markedly increased risk for CVD events within the first two years of exposure. The accompanying editorial from the French epidemiologist Dr. Dominique Costagliola provides an excellent discussion of the methodological differences between the two studies. Further target trial emulations including treatment-experienced individuals are needed to evaluate the impact of switching to INSTI-based ART on CVD events. | ||
| 5th July | Thoueille et al., Tenofovir population pharmacokinetics | |
Thoueille et al. aimed to describe tenofovir pharmacokinetics (PK) and its variability in people living with HIV (PLWH) under tenofovir alafenamide in a real-life setting. The authors conducted a population PK analysis (NONMEM®) on 877 tenofovir and 100 tenofovir alafenamide concentrations measured in 569 PLWH. Model-based simulations allowed prediction of tenofovir trough concentrations (Cmin) in patients having various levels of renal function. Tenofovir PK was best described using a one-compartment model with linear absorption and elimination. Creatinine clearance (CLCR, estimated according to Cockcroft and Gault), age, ethnicity and potent P-glycoprotein inhibitors were statistically significantly associated with tenofovir clearance. However, only CLCR appeared clinically relevant. Model-based simulations revealed 294% and 515% increases of median tenofovir Cmin in patients with CLCR of 15–29 mL/min (CKD stage 3), and less than 15 mL/min (stage 4), respectively, compared with normal renal function (CLCR = 90–149 mL/min). Conversely, patients with augmented renal function (CLCR > 149 mL/min) had a 36% decrease of median tenofovir Cmin. In conclusion, this study demonstrates that CLCR is the main factor affecting circulating tenofovir exposure after tenofovir alafenamide administration. The proposed model reveals that patients with stage 3 and stage 4 CKD reach plasma tenofovir exposure of the same order as patients with normal kidney function receiving tenofovir disoproxil fumarate. A dosage adaptation to one-half and one-third of the standard tenofovir alafenamide regimen seems reasonable in patients with stage 3 and 4 CKD, respectively. A prospective validation of these suggestions regarding tenofovir alafenamide dosing intervals as a function of CKD remains warranted. | ||
| 28th June | Griessbach et al., Antibody response after third vaccination with mRNA-1273 or BNT162b2 | |
In this randomized trial, nested within the Swiss HIV Cohort (SHCS) and the Swiss Transplant Cohort Study (STCS), Griessbach et al. compared the antibody responses after receiving the third dose of one of the two mRNA vaccines against COVID-19 (Moderna mRNA-1273 vs. Pfizer-BioNTech BNT162b2) in people with HIV (PWH) or solid organ transplant (SOT) recipients. The study extends the previous comparison of immune response after receiving two mRNA vaccine doses (COVERALL-1). Between December 2021 and March 2022, cohort participants who were previously randomized in COVERALL-1 and received a third mRNA vaccine dose were included in the study. The primary outcome was the proportion of individuals with a positive antibody response 8 weeks after the third dose, defined as SARS-CoV-2 spike S1 antibody titer of ≥100 units/mL (Elecsys S). The prespecified non-inferiority margin was -10%. Of the 430 individuals randomized in COVERALL-1, 312 (72.6%) were included in the present study. The median age was 54 years (IQR 44-60), 25% were women, 90.7% were PWH, and 9.3% were SOT recipients. Of PWH, 84% had CD4 cell counts >350 cells/µL, and 95% had an undetectable HIV viral load. Eight weeks after receiving the third dose of Moderna mRNA-1273, 95.3% (95% CI 91.9–98.7) had a positive vaccine response, compared to 98.1% (95.9–100) who received Pfizer-BioNTech BNT162b (difference -2.8 percentage points, 95% CI -6.8 to 1.3). Whereas 276 of the 277 PWH (99.6%, 95% CI 98.9–100.9) showed an adequate immune response, this was the case in only 17 of the 26 SOT recipients (65.4%, 47.1–83.7). In conclusion, the study showed that the antibody response after a third dose of Moderna mRNA-1273 was non-inferior to a third dose of Pfizer-BioNTech BNT162b2 among PWH and SOT recipients. | ||
| 16th June | Paioni et al., Viral suppression and retention in HIV care during the postpartum period among WLWH | |
Paioni et al. assessed the postnatal retention in care, viral suppression and infant follow-up among pregnant women living with HIV (WLWH) in the Swiss Mother and Child HIV Cohort Study (MoCHiV). For the study, the authors included all pregnant WLWH in the “optimal scenario” (being under regular clinical care during pregnancy, and having stable HIV suppression, confirmed within the last four weeks prior to delivery) between January 2000 and December 2018. Women were assumed to be engaged in postpartum care if they had ≥1 HIV RNA measurement within the first 90 days, and to be retained in care if they had ≥1 HIV RNA measurement within 180 days of the postpartum period. Rates of viral suppression were assessed at 90 and 180 days after delivery. Correct infant follow-up was defined as having at least 1 HIV RNA measurement within the first 6 months, and a negative antibody serology test at 18-24 months. The study included 737 deliveries in 586 mothers who were in the optimal scenario (median age at delivery 33 years, 56.4% were of African origin, median CD4 cell count 512 cells/μL). The rate of HIV care engagement was 81.8% (603/737), and 94.2% (694/737) were retained in care within 180 days, with start of antiretroviral therapy during the third trimester being the most important risk factor for failure of retention in care (OR 3.9, 95% CI 1.5-10.2). HIV suppression rates were 98% both at 90 and 180 days postpartum, and 26 women experienced viral failure, with illicit drug use being the most important risk factor (HR 13.2, 95% CI 2.3-73.6). Among the 553 infants with complete follow-up, 97% had an HIV-RNA performed within the first 6 months, and 69% had definitive exclusion of transmission with a serologic test no later than 24 months after delivery. Infants from mothers who delivered prior to 2005, and from mothers who experienced depression in the postpartum period were less likely to have a correct infant follow-up. In summary, the present study shows high rates of retention in care and maternal HIV viral suppression among WLWH in the postpartum period. However, the authors identified clear risk factors for peri- and postpartal outcomes, including late start of antiretroviral therapy, illicit drug use and depression. These modifiable aspects should be addressed in the clinical care of pregnant WLWH, and considered when discussing the possibility of breastfeeding the newborn child. | ||
| 17th May | Schöpf et al., Epigenetic ageing in people with HIV | |
Accelerated epigenetic ageing can occur in untreated HIV infection and is partially reversible with effective antiretroviral therapy (ART). Previously, the authors showed in a longitudinal study over 17 years in 107 people with HIV serving as their own controls a significant telomere length shortening during untreated HIV infection and no evidence of any telomere length change during suppressive ART. In this work, Schöpf et al. aimed to investigate epigenetic ageing dynamics in the same people with HIV with longitudinal samples available during more than 8 years of untreated HIV infection and during almost 10 years of suppressive ART. They applied 5 established epigenetic age estimators (epigenetic clocks) in peripheral blood mononuclear cells (PBMCs) in Swiss HIV Cohort Study participants before or during suppressive ART. All participants had a longitudinal set of PBMC samples available at four timepoint. The authors assessed epigenetic age acceleration (EAA) and a novel rate of epigenetic ageing. Between March 13, 1990, and Jan 18, 2018, the authors recruited 81 people with HIV from the Swiss HIV Cohort Study. 52 (65%) of 80 patients were men, 76 (95%) were white, and the median patient age was 43 (IQR 37·5–47) years. Per year of untreated HIV infection (median observation 8·08 years, IQR 4·83–11·09), mean EAA was 0·47 years (95% CI 0·37 to 0·57) for Horvath’s clock, 0·43 years (0·3 to 0·57) for Hannum’s clock, 0·36 years (0·27 to 0·44) for SkinBlood clock, and 0·69 years (0·51 to 0·86) for PhenoAge. Per year of suppressive ART (median observation 9·8 years, IQR 7·2–11), mean EAA was –0·35 years (95% CI –0·44 to –0·27) for Horvath’s clock, –0·39 years (–0·50 to –0·27) for Hannum’s clock, –0·26 years (–0·33 to –0·18) for SkinBlood clock, and –0·49 years (–0·64 to –0·35) for PhenoAge. These findings indicated that people with HIV epigenetically aged by a mean of 1·47 years for Horvath’s clock, 1·43 years for Hannum’s clock, 1·36 years for SkinBlood clock, and 1·69 years for PhenoAge per year of untreated HIV infection; and 0·65 years for Horvath’s clock, 0·61 years for Hannum’s clock, 0·74 years for SkinBlood clock, and 0·51 years for PhenoAge, per year of suppressive ART. GrimAge showed some change in the mean EAA during untreated HIV infection (0·10 years, 0·02 to 0·19) and suppressive ART (–0·05 years, –0·12 to 0·02). The authors obtained very similar results using the rate of epigenetic ageing. Contribution of multiple HIV-related, antiretroviral, and immunological variables, and of a DNA methylation-associated polygenic risk score to EAA was small. In conclusion, this study shows that EAA is significantly increased during 8 years of untreated HIV infection. By contrast, ART appears to initiate a reversal of EAA that is sustained for almost 10 years of viral suppression. The effects of untreated HIV infection and of ART on epigenetic ageing appear to be clinically relevant due to their large effect compared with the smaller effects of selected clinical, immunological, and HIV-related variables and host genetics. Thus, ART appears to have a key beneficial effect on epigenetic ageing, and thereby could powerfully contribute to healthy ageing and mitigate concerns about accelerated ageing in people with HIV. | ||
| 10th May | Crisinel et la., Successful implementation of new Swiss recommendations on breastfeeding of infants born to WLWH | |
In the Swiss Mother and Child HIV Cohort Study (MoCHiV), Crisinel et al. investigated the motivational factors for breastfeeding among women with HIV in Switzerland. They also evaluated the transmission risk to infants after the 2018 Swiss recommendation that allowed breastfeeding for women in the "optimal scenario." From January 2019 to February 2021, 41 women gave birth, and 25 of them (61%) decided to breastfeed their infants. The median age of these 25 women was 34.8 years (IQR 31.1 - 38.2), with 68% of African origin. The median CD4 cell count at delivery was 649 cells/mcL, and the median gestational age at birth was 39.5 weeks (IQR 39-41). No HIV transmission occurred despite no infant receiving prophylactic ART. Mothers reported that the most important reasons for breastfeeding were to be in closer contact with their child and because of perceived health benefits for both the child and herself. Notably, 95% of mothers emphasized the importance of interdisciplinary discussions in making their decision. Taken together, this study shows that breastfeeding is a priority for women with HIV. The findings support the 2018 Swiss recommendation, in which physicians are encouraged to engage in interdisciplinary discussions with pregnant women with HIV to weigh the potential harms and benefits of breastfeeding. | ||
| 4th May | Blondet et al., Scores to predict type 2 diabetes in HIV | |
Blondet et al. aimed to assess the capacity of five diabetes risk scores (the Kraege score, the FINDRISC versions 1 and 2, the Swiss Diabetes Association (SDA) score [15], and the Balkau clinical risk score in predicting incident type 2 diabetes (T2D) in people living with HIV (PWH). The scores are composed of different variables, including age, sex, body mass index, weight, waist, hypertension, positive family history, history of hyperglycemia, physical activity and smoking. Overall, 3’853 T2D-free PWH (78.5% men, 39.9 ± 11.3 years) were included. After a median follow-up of 4.8 years (interquartile range 2.2–7.8), 62 participants (1.6%) developed T2D, corresponding to an incidence rate of 3.18 per 1’000 person-years (95% confidence interval = 2.47–4.08). Participants who developed T2D were older (48.7 ± 12.4 vs. 39.8 ±11.2 years), more likely to be obese (22.6% vs. 7.4%), abdominally obese (9.7% vs. 1.5%), and to have a family history of diabetes (32.3% vs. 19.1%) than those without T2D. The area under the curve (AUC) for incident T2D ranged between 0.72 (Kraege 16) and 0.81 (SDA, FINDRISC2 and Balkau). Sensitivity ranged between 3.2% (Balkau) and 67.7% (FINDRISC1) and specificity between 80.9% (FINDRISC1) and 98.3% (Balkau). Positive predictive values of all scores were below 20%, while negative predictive values were above 98% In conclusion, the study shows that the performance of conventional diabetes risk scores in PWH is promising, especially for Balkau and FINDRISC2, which showed good discriminatory power. These scores may help identify patients at a low risk of T2D in whom careful assessment of modifiable T2D risk factors can be spared. | ||
| 25th April | Hachfeld and Atkinson et al., Does menopause transition influence viral suppression and adherence in women with HIV? | |
Hachfeld and Atkinson et al. evaluated the occurrence of depression, the need for psychiatric care, and intravenous drug use in women with HIV who transition through menopause in the Swiss HIV Cohort Study. In addition, trends in treatment adherence, viral blips, low-level viremia, and viral failure during menopause were assessed. All women who experienced menopause between January 2010 and December 2018 were included. Menopause onset was determined as amenorrhea, as first reported by the cohort physician. Trends were assessed within 8 years prior and 8 years after menopause onset. The authors used interrupted time series logistic regression models comparing trends before and after menopause onset. The study included 1’130 women (25% of African origin), with a median age of menopause onset of 50 years (IQR 32-55). In the 8 years prior to menopause onset, there was an increase in the proportion of individuals with depression (odds ratio 1.04 per year, 95% CI 1.00-1.08) and of individuals receiving psychiatric care (OR 1.02 per year, 0.99-1.05). After menopause onset, the proportion of individuals in psychiatric care decreased, whereas trends in the prevalence of depression remained unchanged. Intravenous drug use at menopause onset was rare and declined further thereafter. Similar to the declining trend in women reporting low treatment adherence, the rate of viral blips, low-level viremia, and viral failures declined significantly in both 8-year periods before and after menopause onset. In summary, the present study highlights that among women with HIV in perimenopause, HIV treatment outcomes continued to improve, whereas the prevalence of depression and psychiatric care utilization increased over time. These findings suggestthat addressing mental health should be a priority in the clinical care of perimenopausal women with HIV. | ||
| 19th April | Avery and Kleynhans et al., Leukocyte count and CAD events in PWHIV | |
Avery and Kleynhans et al. assessed the association between blood leukocyte count and coronary artery disease (CAD) events among people with HIV (PWH) in the Swiss HIV Cohort Study (SHCS). In this nested case-control study, the authors applied incidence density sampling to select individuals who experienced a CAD event and CAD event-free controls, matched on sex, age, and date of SHCS registration. CAD events included myocardial infarction, coronary angioplasty/stenting, and coronary artery bypass grafting. Associations were evaluated using multivariable conditional logistic regression models, with the latest leukocyte count prior to the event included as exposure. The study included 2’000 individuals (536 cases and 1’464 CAD event-free individuals). The median age at CAD event was 56 years (IQR 49-63), 87% were male, 30% were heterosexual individuals, 50% were men who have sex with men, and 17% were people who inject drugs. Overall, 536 CAD events occurred: 274 myocardial infarctions, 211 coronary angioplasty/stentings, 39 coronary artery bypass grafting, and 12 fatal CAD cases. Compared to individuals without CAD events, those who experienced a CVD event had a higher median leukocyte count (6’495/μL vs. 5’900/μL), although leukocytosis (>11’000/μL) was infrequent in both groups (4.3% vs. 2.1%). After adjusting for confounders, individuals with a high-normal leukocyte count (in the fifth percentile) had a higher risk of developing a CAD event (adjusted odds ratio 1.59, 95% CI 1.09-2.30) compared to other individuals. This association was partly attenuated when smoking was included in the model. In summary, the present study shows an independent association between leukocyte count and the risk of CAD events among PWH even when leukocytes were within the normal range, underlining the importance of inflammation in the process of CAD development. The authors conclude that leukocyte counts may identify PWH with an increased risk for CAD events. | ||
| 28th March | Béguelin et al., Hepatitis delta infection among PWHIV in Europe | |
Béguelin et al. described the prevalence and clinical consequences of hepatitis delta (HDV) infection among individuals with HIV and hepatitis B virus (HBV) coinfection in Europe using data from the Swiss HIV Cohort Study and EuroSIDA. All individuals with a positive HBsAg between 01/1988 and 12/2019 were considered, and if not already available from clinical specimens, HDV serology and HDV RNA were measured using stored samples. For prevalence estimates, HDV infection was defined as positive serology, and prevalence was calculated separately for the European regions (North-western Europe, Southern Europe, and Eastern Europe). Overall mortality, liver-related mortality, and incidence of hepatocellular carcinoma (HCC) were compared between individuals with HIV/HBV/HDV coinfection and those with HIV/HBV without HDV infection using multivariable Cox regression models. Of 2’793 individuals with a positive HBs-Ag, 1’556 (56%) had results for HDV serology available. The prevalence of HDV coinfection overall was 15.2% (95% CI 13.5-17.1), and was similar across European regions. The highest prevalence was found among individuals who inject drugs, 50.5% being seropositive for HDV (95% CI 45.3-55.7). Compared to individuals with HIV/HBV coinfection, those with additional HDV coinfection were more likely to die from any cause (adjusted hazard ratio [aHR] 1.8, 95% CI 1.3-2.5) and from liver-related causes (aHR 3.1, 1.7-5.7), and were at higher risk for developing HCC (aHR 6.3, 2.5-16.0). In summary, this large cohort collaboration found an overall prevalence of 15% of HDV infection among individuals with HIV/HBV coinfection, and of 50% among individuals who inject drugs. As individuals with additional HDV infection are at increased risk for morbidity and mortality, the present study underlines the importance of a systematic HDV screening of all individuals with HIV/HBV coinfection to provide HCC close clinical follow-up including screening for HCC. | ||
| 22nd March | Herderschee et al., High-dimensional immune phenotyping of blood cells by mass cytometry in patients infected with HCV | |
Herderschee et al. aimed to assess whether elimination of hepatitis C (HCV) with direct-acting antivirals (DAA) leads to a restoration of the immune system affected by HCV. To answer this research question, the authors analyzed before and 12 weeks after sustained virological response (SVR12) to DAA therapy 22 cell populations by mass cytometry in blood collected from ten healthy control individuals and 20 HCV-infected patients with or without human immunodeficiency virus (HIV) infection. They found that HCV infection altered the frequency of 14/22 (64%) blood cell populations. At baseline, the frequencies of intermediate monocytes, non-classical monocytes, conventional dendritic cells type 2 and CD56dim natural killer cells were reduced by 35% to 65%, particularly in HCV/HIV co-infected patients. In contrast, activated double-negative T cells activated CD4 T cells and activated CD8 T cells 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. In conclusion, high-dimensional immune profiling of blood cells provided a broad and in-depth picture of the systemic immune dysregulation induced by chronic HCV. A salient finding was the observation of a profound derangement of the homeostasis of the immune system triggered by HCV, characterized by a pro-inflammatory innate immune signature extending well beyond the clearance of HCV, especially in HCV/HIV-infected patients. This inflammatory phenotype may contribute to the pathogenesis of systemic complications of chronic HCV infection. | ||
| 9th March | Surial et al., PAGE-B score for HCC risk prediction in HIV/HBV coinfection | |
Surial et al. assessed the usefulness of PAGE-B to determine the risk of developing hepatocellular carcinoma (HCC) among people with HIV and hepatitis B virus (HBV) coinfection from four large European cohorts of people with HIV. PAGE-B is an easy-to-calculate score (range: 0-25) based on the covariates age, sex, and platelet count, and is widely used to determine the need for HCC screening in individuals with HBV mono-infection. The study included all individuals with HIV/HBV coinfection who received tenofovir-containing antiretroviral therapy from the ATHENA cohort (Netherlands), the Aquitaine cohort (France), EuroSIDA, and the Swiss HIV Cohort Study (SHCS). Hepatocellular carcinoma cases were identified using standardized case report forms in all cohorts. The prediction model was evaluated by calculating the c-index (with 1.0 indicating the highest and 0.5 indicating the lowest possible accuracy of the predictions) and negative predictive values. The study included 2’963 individuals with HIV/HBV coinfection; the median age at tenofovir start was 41 years, 16% were female, and 18% were of African origin. PAGE-B was <10 in 26.5%, 10–17 in 57.7%, and ≥18 in 15.7% of patients. Within a median follow-up of 9.6 years, 68 HCCs occurred. The c-index was 0.77 (range 0.73-0.80 across multiple imputations), close to the one found in the original derivation study (c-index 0.80). A PAGE-B cut-off of <10 had a negative predictive value for developing an HCC within 5 years of 99.4% and would spare unnecessary HCC screening in 27% of individuals. Taken together, the present study shows that the PAGE-B score performs well in individuals with HIV/HBV coinfection. In addition, the high negative predictive value of 99.4% in this population indicates that the PAGE-B score is useful to determine the need for HCC screening. | ||
| 1st March | Zhao et al., Phylogenetic estimation of the viral fitness landscape of HIV-1 set-point viral load | |
Set-point viral load (SPVL), a common measure of human immunodeficiency virus (HIV)-1 virulence, is partially determined by viral genotype. Epidemiological evidence suggests that this viral property has been under stabilising selection, with a typical optimum for the virus between 104 and 105 copies of viral RNA per ml. In the current study, Zhao et al. aimed to detect transmission fitness differences between viruses from individuals with different SPVLs directly from phylogenetic trees inferred from whole-genome sequences. They used the local branching index (LBI) as a proxy for transmission fitness. The authors found that LBI is more sensitive to differences in infectiousness than to differences in the duration of the infectious state. By analysing subtype-B samples from the Bridging the Evolution and Epidemiology of HIV in Europe project, they inferred a significant positive relationship between SPVL and LBI up to approximately 105 copies/ml, with some evidence for a peak around this value of SPVL. In sum, the study results suggest that there is evidence of selection against low values of SPVL in HIV-1 subtype-B strains, likely related to lower infectiousness, and perhaps a peak in the transmission fitness in the expected range of SPVL. The less prominent signatures of selection against higher SPVL could be explained by an inherent limit of the method or the deployment of antiretroviral therapy. The authors propose, that the application of this phylogeny-based method should also be expanded to other viruses and other phenotypes as well, not limited to SPVL. | ||
| 15th February | Bosetti and Mugglin et al., Risk factors and incidence of sexually transmitted infections in the SHCS | |
Bosetti and Mugglin et al. assessed the incidence and related risk factors of sexually transmitted infections (STI) among people living with HIV in the Swiss HIV Cohort Study (SHCS). The authors considered all sexually active cohort participants with follow-up between April 2017 and November 2019. All individuals were screened for syphilis every two years or yearly if they were men who have sex with men (MSM). Testing for chlamydia and gonorrhea was performed at the discretion of cohort physicians and included asymptomatic screening as well as targeted testing of symptomatic individuals. Risk factors for STIs were evaluated using multivariable Poisson regression. The study included 7’667 sexually active individuals (median age 51 years, 27.2% were women, 46.7% were MSM). During 17’766 person-years (PY) of follow-up, 1’634 STIs were reported (incidence rate 91.9 per 1000 PY), with 41.1% of STIs being asymptomatic. Of those, syphilis was diagnosed in 573 episodes (35.1%), followed by gonorrhea in 497 episodes (30.4%), and 418 (25.6%) episodes were chlamydia infections. The most important risk factors for any STI were male sex (adjusted incidence rate ratio [aIRR] 2.03, 95% CI 1.36–3.02), being MSM (aIRR 3.62, 2.99–4.55), age 18-34 years (aIRR 1.78, 1.51–2.10), having occasional sexual partners (aIRR 6.87, 5.40–8.73) and injecting drug use (aIRR 2.48, 1.91–3.23). In summary, the present study shows a high incidence of STIs in the SHCS. Together with the high proportion of asymptomatic infections, these findings underline the importance of performing regular screening of sexually active individuals with risk factors for STIs. | ||
| 9th February | Hamusonde et al., Triggers of change in sexual behavior among people with HIV | |
Hamusonde et al. aimed to investigate the impact of 2 external factors (termed “triggers” herein) which might influence sexual behavior: (1) the Swiss U = U statement (“trigger of relief”), and (2) the COVID-19 social distancing (“trigger of restriction”). For this purpose, they investigated over 20 years of long-term trajectories in condom use and occasional partnership among people with HIV in the Swiss HIV Cohort Study (SHCS). Trajectories of condom use were assessed among 2’212 men who have sex with men (MSM) and 2’417 heterosexuals (HET). Trajectories of occasional partnership were assessed among 5’617 MSM and 6’356 HET. Since the publication of the Swiss Statement in 2008, consistent condom use with an HIV-negative stable partner declined from over 90% to around 30% in 2021. Consistent condom use with an HIV-positive stable partner declined from over 50% to around 10%. The long-term trajectories in condom use were remarkably similar between MSM and HET. Consistent condom use with occasional partners declined following the Swiss Statement with a more pronounced decrease among MSM. Occasional partnership frequencies were consistently higher among MSM than HET with stable levels until the COVID-19 pandemic. Shortly after the onset of the COVID-19 pandemic, there was a marked decline in the frequency of occasional partnership among MSM. In sum, this study shows that overall external triggers of relief and restriction had a marked impact on sexual behavior among people with HIV. | ||
| 1st February | Jaschinski et al., Recent abacavir use and incident CVD in contemporary treated people living with HIV | |
Jaschinski et al. analyzed the relationship between abacavir (ABC) use and the development of cardiovascular disease (CVD) events among participants of RESPOND, a large collaboration of HIV cohorts from Europe and Australia. All individuals with follow-up after 2012 were included. CVD events included a composite of myocardial infarction, stroke, or invasive cardiovascular procedures. The association between recent ABC use (within the last 6 months) and CVD events were evaluated using negative binomial regression models, adjusted for clinical and HIV-specific confounders. The study included 29’340 individuals, of whom 74% were men, 43% were of Western European origin, 45% were MSM, and the median age was 44 years (interquartile range 36-51). Within 6.2 years of follow-up (3.9-7.5), 748 CVD events occurred: 299 myocardial infarctions, 228 strokes, and 221 invasive cardiovascular procedures. After adjusting for confounders, the incidence rate ratio (IRR) for developing CVD events was higher for individuals with recent ABC use compared to those who did not receive ABC (adjusted IRR 1.40, 95% CI 1.20-1.64). In summary, the present study found a 40% CVD risk increase for individuals who receive ABC as part of their antiretroviral therapy. These results confirm previous findings from the D:A:D cohort, and add to the body of evidence of CVD-related adverse effects of ABC. | ||
| 25th January | Chaudron et al., HIV-1 superinfection screen in the SHCS | |
Chaudron et al. aimed to study immunodeficiency virus type 1 (HIV-1) superinfection in the Swiss HIV Cohort Study (SHCS). Superinfection is the acquisition of another HIV-1 strain among individuals with an already established HIV-1 infection. The authors used a phylogeny built from 22’243 HIV-1 partial polymerase sequences to identify potential superinfections among 4’575 SHCS participants with longitudinal sequences. A subset of potential superinfections was tested by near-full-length viral genome sequencing (NFVGS) of biobanked plasma samples. Based on phylogenetic and distance criteria, 325 potential HIV-1 superinfections were identified and categorized by their likelihood of being detected as superinfections due to sample misidentification. NFVGS was performed for 128 potential superinfections; of these, 52 were confirmed by NFVGS, 15 were not confirmed, and for 61 sampling did not allow confirming or rejecting superinfection because the sequenced samples did not include the relevant time points causing the superinfection signal in the original screen. Thus, NFVGS could support 52 of 67 adequately sampled potential superinfections. In conclusion, the study confirms that superinfections are rare but not negligible events, with an estimated prevalence of 1% to 7%, most likely an underestimation since detection is challenging. Nevertheless, this work paves the way for follow-up studies to benefit from the sample size and the NGS data generated to molecularly characterize HIV-1 superinfection and investigate other risk factors associated. Better molecular characterization and risk factors understanding could provide further insights into HIV transmission and pathogenesis, benefit HIV vaccine research, and enable preventive measures to raise awareness on HIV-1 superinfection in the community. | ||
| 19th January | Hofmann et al., HBV replication during tenofovir therapy | |
Hofmann et al. analyzed rates of hepatitis B virus (HBV) suppression with tenofovir-containing antiretroviral therapy (ART), and assessed determinants for ongoing HBV replication despite treatment among people living with HIV and HBV in the Swiss HIV Cohort Study (SHCS). The present study included all cohort participants with chronic HBV infection. The authors evaluated HBV replication at 2 years and at the latest available follow-up (categorized as suppression if HBV DNA was <20 IU/mL, low-level viremia if HBV DNA was 20-2000 IU/mL, and high-level viremia if HBV DNA was >2000 IU/mL). Risk factors for persistent viral replication (HBV DNA >20 IU/mL) were assessed using multivariable logistic regression. The study population consisted of 222 individuals with HIV/HBV coinfection on tenofovir-containing ART. The median age was 41 years (IQR 36-47), 19% were female, 21% were of African origin, and 59% had been previously treated with lamivudine- or emtricitabine-containing ART. After 2 years of tenofovir, 61/222 (27%) had persistent HBV replication. Persistent HBV replication was more common among individuals with high HBV-DNA at tenofovir start (adjusted odds ratio [aOR] 1.38, 95% CI 1.20-1.57), and less likely among patients with a CD4 cell count >350cells/μL (aOR 0.41, 0.19-0.90), among people with hepatitis D coinfection (aOR 0.07, 0.01-0.59) and those with good self-reported ART adherence (aOR 0.04, 0.01-0.33). Of the 61 individuals with a replicating HBV infection at 2 years, 14 (23%) had persistent replication at the latest follow-up visit (median 8.4 years after starting tenofovir). In summary, this work shows that ongoing HBV replication is frequent after 2 years of tenofovir-containing ART, especially in individuals with a high HBV viral load at tenofovir start and suboptimal ART adherence. In contrast, HDV coinfection was associated with higher rates of HBV suppression. As 77% of individuals eventually achieved HBV viral suppression during follow-up, replication after 2 years does not necessarily imply treatment failure. As ongoing viral replication contributes to liver fibrosis and to the development of hepatocellular carcinoma, these findings highlight the importance of continued follow-up of individuals with HIV/HBV coinfection. | ||
| 11th January | Isfordink et al., DAAs in people with HIV/HCV from sub-Saharan Africa or Southeastern Asia | |
Isfordink et al. for EuroSIDA, the Swiss HIV Cohort Study, and the ATHENA Observational Cohort aimed to investigate the real-world efficacy of direct-acting antivirals (DAA) treatment in individuals with HIV/hepatitis C virus (HCV) originating from low- and middle-income countries (LMICs), namely for sub-Saharan Africa (SSA) and Southeastern Asia (SEA) in multiple European cohorts of people with HIV (PWH). The author group retrospectively analyzed data from the above-mentioned cohorts of PWH. The primary outcome was HCV cure defined as sustained virological response at least 12 weeks after the end of treatment (SVR12). Of the 3’293 individuals with HIV/HCV treated with DAA and with available SVR12 data, 142 were from SSA (n=64) and SEA (n=78). SVR12 was achieved by 60 (94% [95% confidence interval {CI}, 86%–98%]) individuals from SSA and 76 (97% [95% CI, 92%–99%]) from SEA. The genotypes of the 6 individuals failing DAA treatment were 2, 3a, 3h, 4a, 4c, and 6j. For 2 of the 4 unsuccessfully treated individuals with available sequence data at treatment failure, NS5A resistance-associated substitutions were present (30R/93S in an individual with genotype 4c and 31M in an individual with genotype 6j). In conclusion, the study shows that DAA efficacy in people with HIV/HCV originating from SSA or SEA and living in Europe is high. Although the limited number of participants with genotypes of concern and the lack of data on location of HCV acquisition limit conclusions on DAA efficacy for individuals with HIV/HCV residing in SSA or SEA, it seems unlikely that suboptimal response to DAAs specific to these individuals could become a complicating factor for overall HCV elimination in Europe in the near future. | ||