2022

19th May Friedrich et al., Conformations of the HIV-1 V3 loop crown are targetable for broad neutralization


Distinct conformations of the HIV-1 V3 loop crown are targetable for broad neutralization.    Nature Communications

The V3 loop of the HIV-1 envelope (Env) protein elicits a vigorous, but largely non-neutralizing antibody response directed to the V3-crown, whereas rare broadly neutralizing antibodies (bnAbs) target the V3-base.

In this work, Friedrich et al. used the Designed Ankyrin Repeat Proteins (DARPin) technology in order to define conformational states of the V3-crown that are targetable for broad neutralization.

While most bnAbs target prefusion Env, V3-crown bnDs binded open Env conformations triggered by CD4 engagement. BnDs achieved breadth by focusing on highly conserved residues that are accessible in two distinct V3 conformations, one of which resembles CCR5-bound V3.

The authors showed that these V3-crown conformations can, in principle, be attacked by antibodies. Supporting this conclusion, analysis of antibody binding activity in the Swiss 4.5 K HIV-1 cohort (n = 4,281) revealed a co-evolution of V3-crown reactivities and neutralization breadth.

In sum, these findings strongly suggest that directing antibody responses to distinct V3-crown conformations accessible after CD4 attachment should be feasible, thus opening roads for developing vaccine strategies to elicit bnD-like V3-crown bnAbs.

Exploiting this knowledge will likely require the design of appropriate epitope scaffolds to be used as immunogens in order to channel the polyclonal V3-crown response to the desired specificity. These responses will likely not be potent, but due to their high breadth and capacity to recognize an entry state in which bnAbs targeting prefusion Env have less activity, may add important functionality to multivalent vaccines.

PubMed

12th May Salazar-Vizcaya et al., Interaction between behavioral and transmission clusters


An approach to quantifying the interaction between behavioral and transmission clusters.   Viruses

Groups of individuals with similar sexual risk behavior have been identified previously in people living with HIV and incident hepatitis C virus (HCV) infection. In addition, phylogenetic analyses have confirmed the presence of HCV transmission networks. However, little is known about the interplay of sexual risk behavior and the conformation of transmission networks.

In this proof-of-concept study, Salazar-Vizcaya et al. aimed to quantify the relationship between behavioral and transmission clusters in people living with HIV and incident HCV infection in the Swiss HIV Cohort Study. The authors used hierarchical clustering algorithms to identify individuals with similar condom use for anal intercourse with unsteady partners (behavioral cluster), and used maximum-likelihood phylogenetic trees of the HCV virus to identify transmission networks (transmission cluster). Membership of behavioral and transmission clusters for were then combined for each patient, and Monte Carlo simulation was used to quantify the strength of the interaction between them.

The study included 36 men who have sex with men and were part of an HCV transmission cluster. Five distinct behavioral clusters were identified and subsequently combined with the information on the HCV transmission cluster. The authors identified interactions between behavioral and transmission groups that were non-random, suggesting some influence of risk behavior on the conformation of transmission clusters. However, the study was not powered to confirm statistical significance.

In summary, the present study outlines a useful approach to characterize associations between clusters of behavior and clusters of transmission. Such analyses could be applied to other infections including HIV or COVID-19 with large transmission networks and increased power. Future studies using this approach may prove useful to complement and guide public health interventions to limit transmission.

PubMed

4th May Seifert et al., Detecting selection in the HIV-1 genome during sexual transmission events


Detecting selection in the HIV-1 genome during sexual transmission events.   Viruses

Little is known about whether and how variation in the HIV-1 genome affects its transmissibility. Assessing which genomic features of HIV-1 are under positive or negative selection during transmission is challenging, because very few virus particles are typically transmitted, and random genetic drift can dilute genetic signals in the recipient virus population

In the current work, Seifert et al. developed a new statistical test to detect selection during transmission, called Selection Test in Transmission (SeTesT), based on comparing the transmitter and recipient virus population and accounting for the transmission bottleneck. They analyzed 30 transmitter-recipient pairs from the Zurich Primary HIV Infection Study and the Swiss HIV Cohort Study using near full-length HIV-1 genomes.

The authors performed extensive simulations and found that sensitivity of detecting selection during transmission is limited by the strong population bottleneck of few transmitted virions. When pooling individual test results across patients, they found two candidate HIV-1 genomic features for affecting transmission, namely amino acid positions 3 and 18 of Vpu, which were significant before but not after correction for multiple testing.

In summary, SeTesT provides a general framework for detecting selection based on genomic sequencing data of transmitted viruses. The authors found new potential candidates for selection in Vpu. However, the results suggest that a higher number of transmitter–recipient pairs is required to improve sensitivity of detecting selection. Besides HIV transmission events, SeTesT could be used in other settings and for different viruses. For instance, it could also be used for estimating selection on the genome of the Hepatitis C virus, given that the genetic bottleneck for an intravenous transmission mode could be estimated.

PubMed

20th April Fursa et al., Hepatitis C virus cascade of care in Europe


The hepatitis C cascade of care in HIV/hepatitis C virus coinfected individuals in Europe: regional and intra-regional differences.   AIDS

Fursa et al. aimed to identify gaps in the care for individuals with HIV and hepatitis C virus (HCV) infection in the EuroSIDA cohort. Using the cascade of care method, the authors monitored the progress towards the WHO target of diagnosing 90% of all individuals with HCV coinfection, and treating 80% of those diagnosed.

The cascade of care described (1) the number of anti-HCV antibody positive individuals, (2) the proportion of individuals who ever had an HCV-RNA test, and (3) the proportion of individuals currently HCV-RNA positive. In addition, authors assessed the proportion of chronically infected individuals who ever started and completed anti-HCV treatment, respectively. The cascade of care was assessed separately for five European regions: South (e.g. Greece, Italy), Central-West (e.g. Switzerland, France), North (e.g. Denmark, Finland), Central-East (e.g. Poland, Romania), and East (e.g. Ukraine, Belarus).

Of 22’356 EuroSIDA participants, 20’437 (91.4%) ever had an anti-HCV antibody test, and 40.7% were anti-HCV positive. For this study, 4773 anti-HCV positive individuals under active follow-up were included (median age 42, IQR 38-46; 70% men; HIV transmission with injection drug use in 57% of cases). Of those, 4446 (93.1%) ever had HCV-RNA measured, of which 19% were HCV-RNA positive at the last visit closest to October 2019. HCV-RNA positivity ranged from 10% in Central-West to 33% in East Europe. Overall, 72.5% of all individuals estimated to have had chronic HCV infection ever started HCV treatment, with 98% of them having completed the treatment. The proportion of individuals who received treatment was highest in Central-Western Europe (85.1%), and lowest in Eastern Europe (46.7%). With a proportion of just below 80%, Switzerland had the lowest HCV treatment rate of the Central-Western region, thereby missing the WHO targets.

Taken together, the present study performed in the era of highly effective direct-acting antivirals revealed regional differences in the HCV cascade of care, with the largest gaps in HCV-RNA testing and treatment coverage detected in Eastern Europe. The detailed analysis in this pan-European cohort identified distinct regional and country level gaps, allowing stakeholders to take targeted actions to reach the WHO hepatitis C elimination targets.

PubMed

4th April Congratulation to Roger Kouyos !

It is with great pleasure that we inform you that the Swiss National Science Foundation (SNF) will support the following project of Roger Kouyos

The Evolutionary Epidemiology of HIV Elimination

The awarded amount is CHF 698’541 for a 4 years period starting May 2022 until April 2026.

partners: Andri Rauch, Huldrych Günthard, Mary-Ann Davies, Niko Beerenwinkel

We wish Roger Kouyos and his partners all the best for this project!

Kind regards,
Huldrych Günthard
President of the SHCS

1st April Tepekule et al., Impact of latent tuberculosis on diabetes


Impact of latent tuberculosis infection on the incidence of type 2 diabetes mellitus in HIV-infected participants in the Swiss HIV Cohort Study.   Journal of Infectious Diseases

Tepekule et al. assessed whether latent tuberculosis infection (LTBI) is a risk factor for diabetes among people living with HIV in the Swiss HIV Cohort Study.

The authors compared the risk of developing diabetes in patients with LTBI (defined as having a positive tuberculin skin test or interferon-γ release assay) and in those without LTBI. They used time-dependent Cox proportional hazards regression models adjusted for sex, ethnicity, and time-varying calendar year, age, BMI, ART treatment status, CD4 cell counts, and smoking status. The adjustment was performed using multivariable regression and inverse probability weighting, the latter allowing an estimation of the average causal effect

The study included 10’841 individuals with an LTBI test available (70% male, 14.2% of African origin, 37% were overweight or obese). Overall, 974 individuals had LTBI (69% by means of tuberculin skin testing, and 25% by interferon-γ release assay). Within the first 10 years after LTBI testing, 5.5% of patients with a positive test developed diabetes (60 cases), compared to 3.8% of individuals without LTBI (433 cases, log-rank test p = 0.006). The hazard ratios were 1.44 (95% CI 1.09-1.90) using multivariable Cox regression, and 1.47 (95% CI 1.06-2.03) after adjustment with inverse probability weighting, indicating a 47% risk increase for diabetes with LTBI. These findings were robust across several sensitivity analyses.

In summary, the study shows that LTBI may be a risk factor for diabetes mellitus. In people living with HIV, LTBI has previously been associated with lower HIV viral loads and a lower risk for opportunistic infections. However, the present findings indicate that this state of chronic low-grade inflammation may lead to increases in individuals' risk for metabolic diseases.

PubMed

24th March Wymant et al., A highly virulent variant of HIV-1 circulating in the NL


A highly virulent variant of HIV-1 circulating in the Netherlands.   Science

Wymant et al. on behalf of the ATHENA HIV Observational Cohort and the BEEHIVE Collaboration report on the discovery of a highly virulent variant of subtype-B HIV-1 in the Netherlands.

In this study, 109 individuals with this variant had a 0.54 to 0.74 log10 increase (i.e., a ~3.5-fold to 5.5-fold increase) in viral load compared with, and exhibited CD4 cell decline twice as fast as, 6’604 individuals with other subtype-B strains. Without treatment, advanced HIV-CD4 cell counts below 350 cells per cubic millimeter, with long-term clinical consequences—is expected to be reached, on average, 9 months after diagnosis for individuals in their thirties with this variant.

Age, sex, suspected mode of transmission, and place of birth for the aforementioned 109 individuals were typical for HIV-positive people in the Netherlands, which suggests that the increased virulence is attributable to the viral strain. Genetic sequence analysis suggests that this variant arose in the 1990s from de novo mutation, not recombination, with increased transmissibility and an unfamiliar molecular mechanism of virulence.

In conclusion, this study shows that widespread treatment is helpful to prevent new virulent variants, not harmful. The absolute fitness of viral variants must be considered in addition to their relative fitness, and treatment reduces the total onward transmission over the course of one infection, regardless of virulence. Early treatment also prevents CD4 cell decline from leading to later morbidity and mortality; thus clinical, epidemiological, and evolutionary considerations are aligned. The discovery of a highly virulent and transmissible viral variant therefore emphasizes the importance of access to frequent testing for at-risk individuals and of adherence to recommendations for immediate treatment initiation for every person living with HIV.

PubMed

16th March VITA Label for the SHCS Biobank


We are happy to announce that our SHCS Biobank has been awarded with the VITA Label by the Swiss Biobanking Platform (SBP).

This label demonstrates compliance with the applicable legal and ethical framework. This labelling approach is part of our long-term strategy to strengthen biobanking practices and provide high-quality samples to the research community.

https://www.biobanksqan.ch/#/biobanks/4346 

 

10th March Greenberg et al., INSTI use and cancer incidence


Integrase strand transfer inhibitor use and cancer incidence in a large cohort setting.   Open Forum Infectious Diseases

Greenberg et al. on behalf of the RESPOND Study Group aimed to assess whether there is an association between integrase strand transfer inhibitors (INSTI) use and the incidence of cancer, among people with HIV (PWH) in real-life settings in the International Cohort Consortium of Infectious Diseases (RESPOND).

Participants were followed from baseline (latest of local cohort enrollment or January 1, 2012) until the earliest of first cancer, final follow-up, or December 31, 2019.

Of 29’340 individuals, 74% were male, 24% were antiretroviral treatment (ART)-naive, and median baseline age was 44 years (interquartile range [IQR], 36–51). Overall, 13’950 (48%) individuals started an INSTI during follow-up. During 160’657 person-years of follow-up ([PYFU] median 6.2; IQR, 3.9–7.5), there were 1’078 cancers (incidence rate [IR] 6.7/1000 PYFU; 95% confidence interval [CI], 6.3–7.1). The commonest cancers were non-Hodgkin lymphoma (n = 113), lung cancer (112), Kaposi’s sarcoma (106), and anal cancer (103). After adjusting for potential confounders, there was no association between cancer risk and INSTI exposure (≤6 months vs no exposure IR ratio: 1.15 [95% CI, 0.89–1.49], >6–12 months; 0.97 [95% CI, 0.71–1.32], >12–24 months; 0.84 [95% CI, 0.64– 1.11], >24–36 months; 1.10 [95% CI, 0.82–1.47], >36 months; 0.90 [95% CI, 0.65–1.26] [P= .60]). In ART-naive participants, cancer incidence decreased with increasing INSTI exposure, mainly driven by a decreasing incidence of acquired immune deficiency syndrome cancers; however, there was no association between INSTI exposure and cancer for those ART-experienced (interaction P <.0001).

In conclusion, there was no association between the risk of cancer and cumulative exposure to INSTIs among ART-experienced PWH. The risk of cancer decreased with increasing exposure to INSTIs among ART-naive individuals, which was mainly driven by a decreasing incidence of AIDS-defining cancers.

PubMed

1st March Hachfeld and Atkinson et al., Women with HIV transitioning through menopause


Women with HIV transitioning through menopause: Insights from the Swiss HIV Cohort Study.   HIV Medicine

Hachfeld and Atkinson et al. determined the prevalence of menopause, the age of its onset, and risk factors for early menopause among women in the Swiss HIV Cohort Study (SHCS).

All women who reported menopause (defined as the absence of menstrual bleeding for at least 12 months) were included in the study. Onset before the age of 45 years was considered as early menopause, and before 40 years as premature ovarian insufficiency. The authors assessed the proportion of women in the SHCS with menopause over time and used multivariable logistic regression to explore risk factors for its early onset.

Reflecting the aging of the SHCS, the proportion of women in menopause rose from 11.5% in 2010 to 36% in 2018. For the present study, 1’130 women without menstrual bleeding for at least 12 months were included. Sixty-seven percent were Caucasian and 25% were of African origin, the median age at menopause was 50 years (range 32 - 55), 115 women (10%) were classified as having an early menopause, and 23 (2%) had premature ovarian insufficiency. Importantly, 27% of the study participants were diagnosed with depression or currently received psychiatric care. In multivariable analyses, women of African origin were most likely to have early menopause (adjusted odds ratio 4.2, 95% CI 2.5 - 7.2), whereas no other covariates (including HIV-associated factors such as CD4 cell count, viral suppression, or hepatitis coinfection) were significantly associated with the age of menopause onset. The authors also noted that within the 36 months after documentation of menopause, 11% of women received hormone replacement therapy, and 27% had a bone mineral density measurement to evaluate the risk for osteoporosis.

In summary, the present study highlights the importance of addressing menopause in the clinical care of people living with HIV. The high proportion of psychiatric conditions is concerning and warrants special attention in the care of menopausal women living with HIV. Although menopause onset occurred 2 years earlier in women living with HIV compared with HIV-negative women in Switzerland, these findings were mainly driven by the high proportion of women of African origin, whereas HIV-related factors seemed to play a lesser role. Finally, access to hormone replacement therapy and screening for osteoporosis should be improved for optimal treatment of women living with HIV.

PubMed

23rd February Delabays et al., CVR assessment in PLWH compared to the general population


Cardiovascular risk assessment in people living with HIV compared to the general population.   European Journal of Preventive Cardiology

Delabays et al. aimed to assess and to compare the accuracy of cardiovascular risk scores in people living with HIV (PLWH) and individuals from the general population using the CoLaus/PsyCoLaus cohort. The CoLaus/PsyCoLaus study is a Swiss population-based prospective cohort investigating clinical, psychological, genetic, and social determinants of cardiovascular diseases.

The authors used three validated prediction scores: i) the Data-Collection on Adverse Effects of Anti-HIV Drugs (D:A:D) risk score, ii) the Systematic COronary Risk Evaluation 2 score (SCORE2) and iii) the Pooled Cohort Equations (PCE) score. All scores were calculated in participants free from atherosclerotic cardiovascular disease (ASCVD) between 2003 and 2009. They tested discrimination and calibration, and the value of adding HIV-specific factors to scores using the net reclassification improvement (NRI).

In total, 6’373 [mean age, 40.6 years (SD, 9.9)] PLWH from the Swiss HIV Cohort Study (SHCS) and 5’403 [52.8 years (SD, 10.7)] individuals from the CoLaus/PsyCoLaus study were eligible for analysis. During mean follow-ups of 13.5 (SD, 4.1) in SHCS and 9.9 (SD, 2.3) years in CoLaus/PsyCoLaus study, 533 (8.4%) and 374 (6.9%) people developed an incident ASCVD, respectively. This translated into age-adjusted incidence rates of 12.9 and 7.5 per 1000 person-year, respectively. In SHCS, SCORE2, PCE, and D:A:D presented comparable discriminative capacities [area under the receiver operating characteristic curve of 0.745 (95% confidence interval, CI, 0.723–0.767), 0.757 (95% CI, 0.736–0.777), and 0.763 (95% CI, 0.743–0.783)]. Adding HIV-specific variables (CD4 nadir and abacavir exposure) to SCORE2 and PCE resulted in an NRI of -0.1% (95% CI, -1.24to 1, P = 0.83) and of 2.7% (95% CI, 0.3–5.1, P = 0.03), respectively.

In conclusion, the study shows that PLWH are still presenting a two-fold higher incidence rate of ASCVD compared to individuals from the general population, making the implementation and validation of prevention tools an urgent need. In people taking lipid-lowering treatments, PLWH less often reached LDL-C targets compared to individuals from the general population in the same category of risk. Using either SCORE2 or PCE in PLWH is valid to predict ASCVD, notably due to their set of variables that are easier to use compared to more complex scores integrating HIV-specific data. Adding HIV-specific factors to scores developed for the general population did not result in a clinically significant improvement.

PubMed

15th February Congratulations to Katharina Kusejko


Dear members and friends of the SHCS,

We are very pleased to announce that Katharina Kusejko has won the Pfizer prize in the field of infectiology with the publication

Diagnosis of latent tuberculosis infection is associated with reduced HIV viral load and lower risk for opportunistic infections in people living with HIV

Congratulations to Katharina Kusejko!

We wish her all the best for further research projects.

Kind regards,

Huldrych Günthard
President of the SHCS

 

9th February Schoepf et al., Telomere length and HIV


Telomere length declines in persons living with HIV before antiretroviral therapy start but not after viral suppression: A longitudinal study over >17 years.   Journal of Infectious Diseases

Telomere length (TL) shortens with age, and short TL is associated with coronary artery disease (CAD) and all-cause mortality in the general population. In people with HIV (PWH), associations of short TL with CAD events, metabolic syndrome, and neurocognitive impairment are reported. PWH have shorter TL and may have accelerated or accentuated aging and an increased risk of age-associated diseases compared with HIV-negative persons.

The aim of this study was to measure the rate of TL change during >3 years of untreated chronic HIV infection in participants of the Swiss HIV Cohort Study (SHCS) and to assess in these same PWH whether the rate of TL change continues to be affected during >3 years of suppressive ART.

The author team measured TL change in peripheral blood mononuclear cells by quantitative polymerase chain reaction in 107 Swiss HIV Cohort Study participants with longitudinal samples available both before and during suppressive ART. They obtained uni-/multivariable estimates for longitudinal TL dynamics including age, sex, and CD4/ CD8 ratio. Further, they assessed the effect of (1) individual antiretrovirals and (2) an individual TL-polygenic risk score (TL-PRS) based on 239 single-nucleotide polymorphisms on TL in 798 additional participants from our previous longitudinal studies.

During untreated HIV infection (median observation, 7.7; interquartile range [IQR], 4.7–11] years), TL declined significantly (median −2.12%/year; IQR, −3.48% to −0.76%/year; P = .002). During suppressive ART (median observation, 9.8; IQR, 7.1–11.1 years), there was no evidence of TL decline or increase (median+ 0.54%/year; IQR, −0.55% to + 1.63%/year; P = .329). The TL-PRS contributed to TL change (global P= .019) but particular antiretrovirals did not (all P > .15).

In conclusion, the study shows that TL declines significantly during almost 8 years of untreated HIV infection, with a significant association with an individual TL-PRS. Telomere length is stable during suppressive ART when measured longitudinally in the same participants, with no evidence of further TL decline or increase during almost 10 years after viral suppression. The effects of untreated HIV and suppressive ART on TL change appear large and thus clinically relevant. By contributing to TL preservation, suppressive ART may have a favorable effect on biological aging and the risk of aging-associated comorbidities in PWH.

PubMed

2nd February Rüeger et al., The influence of human genetic variation on Epstein-Barr virus sequence diversity


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

Rüeger, Hammer, and Loetscher et al. looked for associations between the human genome and genetic variants of Epstein-Barr virus (EBV) among individuals living with HIV in the Swiss HIV Cohort Study.

The authors hypothesized that EBV viremia is most prevalent in immunosuppressed individuals, and therefore identified treatment-naïve patients living with HIV with a CD4+ cell count below 200 cells/μL. Human genotyping, as well as EBV genome sequencing, was performed, and joint analyses for associations (so-called genome-to-genome analyses) were done using mixed models.

The study included 206 men and 62 women with a median age of 40 years (range 20-78). Of those, 57.1% of EBV sequences comprised predominantly EBNA T1, 5.7% predominantly EBNA T2, and 37.2% included multiple haplotypes. Genome-wide association studies (GWAS) were performed for 535 EBV amino acids and 52 EBV genes. Significant associations were identified between 25 human SNPs and viral variants mapping to 2 EBV genes and one EBV amino acid: the gene BALF5 which is involved in viral DNA replication, the gene BBRF1 which is involved in viral DNA translocation during packaging, and the amino acid BRLF1:p.Lys316Glu which plays a role in reactivation from latency and regulation of viral transcription. Strong associations were observed between the BALF5 gene and 17 SNPs in the human UNC5D gene, which is involved in the regulation of apoptosis.

To summarise, the present study is the first to identify genomic interactions between the human host and EBV. If confirmed in similar studies in HIV uninfected patients with EBV viremia, these findings may contribute to understanding the pathogenic processes and the very diverse clinical consequences of EBV infection.

PubMed

26th January Amele et al., HCV reinfection after HCV therapy among HIV/HCV-coinfected individuals in Europe


HCV reinfection after HCV therapy among HIV/HCV co-infected individuals in Europe.    HIV Medicine

Amele et al. on behalf of the EuroSIDA study group aimed to evaluate the 2-year prevalence of HCV reinfection after Interferon (IFN-) based or IFN-free direct acting agents (DAA) HCV therapy among HIV/HCV-coinfected individuals from the pan- European EuroSIDA cohort study.

The authors assessed factors associated with odds of reinfection by 2 years after sustained virological response (SVR) in EuroSIDA participants with one or more HCV- RNA test and 2 years follow-up.

Overall, 1’022 individuals were included. The median age was 50 (interquartile range: 43–54 years), and most were male (78%), injection drug users (52%), and received IFN-free DAAs (62%). By 24 months, 75 [7.3%, 95% confidence interval (CI): 5.7–8.9%] individuals were reinfected. Among individuals treated prior to 2014, 16.1% were reinfected compared with 4.2% and 8.3%, respectively, among those treated during or after 2014 with IFN-free and IFN-based therapy. After adjustment, individuals who had started treatment during or after 2014 with IFN-free or IFN-based therapy had significantly lower odds of reinfection (adjusted odds ratio = 0.21, 95% CI: 0.11–0.38; 0.43, 95% CI: 0.22–0.83) compared with those who had received therapy before 2014. There were no significant differences in odds of reinfection according to age, gender, European region, HIV transmission risk group or liver fibrosis.

In conclusion, this study of 1’022 HIV/HCV-coinfected people from all regions of Europe found that the HCV reinfection rate in the first 2 years after SVR was 7.3%, but with lower odds of reinfection among those treated in recent years or using IFN-free DAA therapy. Lower odds of reinfection among those treated in recent years can possibly be explained by a lower prevalence of HCV infection in the population due to the scale-up of DAA since 2014. The study found no differences in odds of reinfection when comparing IFN-treated (±DAAs) in 2014 or later with those who had received IFN-free DAA therapy in the same period. Hence, this data do not indicate that the ease of short, well-tolerated and effective DAA therapy compared with IFN-based therapy leads to increased risk of disinhibition and high rates of HCV reinfection after DAA therapy in this population.

PubMed

20th January Mocroft et al., Hepatitis B virus infection and nonliver malignancies


The association between hepatitis B virus infection and nonliver malignancies in persons living with HIV: results from the EuroSIDA study.    HIV Medicine

Mocroft and Miró et al. aimed to determine whether people living with HIV (PLWH) and hepatitis B virus (HBV) in the EuroSIDA study are at increased risk for nonliver cancer compared to PLWH without HBV.

All participants from the EuroSIDA study with known HBV status were included. HBV coinfection was defined as positive HBsAg, and the main outcome was the occurrence of any nonliver malignancy, including anal cancer, lung cancer, non-Hodgkin’s lymphoma and other cancers. Multivariable Poisson regression was used to compare incidence rates between individuals with and without HBV coinfection. The roles of HBV treatment and detectable HBV DNA were explored in additional models.

The study included 17’485 individuals, contributing 151’766 person-years of follow-up (PYFU). The median age was 41 years (IQR 35-49), median CD4 count 440 cells/μL (IQR 284-634), and 4’601 (26.3%) were women. HBV coinfection was present in 1’269 (7.2%) cohort participants. A total of 1’360 nonliver cancers occurred in 1’298 individuals (incidence rate [IR] 8.55 per 1’000 PYFU, 95% CI 8.09-9.92). The most common cancers were anal cancer (188 events), lung cancer (147 events) and non-Hodgkin’s lymphoma (131 events). In a multivariable analysis adjusted for age, CD4 cell count, HIV viral load, liver fibrosis and smoking status, individuals with HBV coinfection were at increased risk for the development of any nonliver malignancy compared to those without HBV (incidence rate ratio [IRR] 1.23, 1.00-1.51). The increased risk for HBV infected vs. HBV uninfected PLWH was most pronounced in individuals who did not receive tenofovir, emtricitabine or lamivudine during follow-up (IRR 1.45, 1.04-2.01), and in persons with detectable HBV DNA (IRR 1.37, 1.00-1.89 compared to HBV negative individuals).

In summary, the present study indicates that people living with HIV and HBV may be at increased risk for nonliver cancer. The association was strongest for individuals without HBV-active treatment and detectable HBV DNA, suggesting a role of HBV replication as a possible risk factor for the development of nonliver malignancies.

PubMed

12th January Balakrishna et al. Bacterial pneumonia in the SHCS


Decreasing incidence and determinants of bacterial pneumonia in people with HIV: The Swiss HIV Cohort Study.    Journal of Infectious Diseases

Balakrishna et al. aimed to estimate the incidence rate of bacterial pneumonia in the Swiss HIV Cohort Study (SHCS) and to assess the risk factors associated with incidence of bacterial pneumonia.

The authors included 12’927 people with HIV (PWH) with follow-ups between 2008 and 2018. These patients had 985 bacterial pneumonia events during a follow-up of 100’779 person-years. Bacterial pneumonia incidence significantly decreased from 13.2 cases/1000 person-years in 2008 to 6.8 cases/1000 person-years in 2018. Older age, lower education level, intravenous drug use, smoking, lower CD4-cell count, higher HIV load, and prior pneumonia were significantly associated with higher bacterial pneumonia incidence. Notably, CD4 cell counts 350–499 cells/μL were significantly associated with an increased risk compared to CD4 ≥ 500 cells/μL (adjusted hazard ratio, 1.39; 95% confidence interval, 1.01–1.89).

In conclusion, decreasing incidence over the last decade can be explained by increased CD4-cell counts and viral suppression and decreased smoking frequency. Hence, improvements in the cascade of care of HIV and decrease in smoking may have mediated a substantial decrease in bacterial pneumonia incidence.

PubMed

6th January Kowalska et al., Prevalence and outcomes of pregnancies in women with HIV


Prevalence and outcomes of pregnancies in women with HIV over a 20-year period.    AIDS

Kowalska et al. evaluated time trends and outcomes of pregnancies among European women with HIV between 1996 and 2015 in the EuroSIDA cohort.

Audits were performed annually to collect information on pregnancies in female cohort participants aged between 16 and 50 years. Outcomes were categorized as birth of a HIV negative child, HIV positive child or child with unknown HIV status, stillbirth, spontaneous abortion, medical abortion, still pregnant or unknown. Pregnancy trends were analysed in three distinct periods: 1996-2002, 2003-2009 and 2010-2015, and logistic regression with generalized estimating equations was performed to assess factors associated with pregnancy.

The study included 5’535 women of reproductive age, median age of 33 years (IQR 29-39 years), most were of white ethnicity, and 62% acquired HIV heterosexually. Of those women, 4’217 (76.2%) had pregnancy information available. Between 1996 and 2015, 912 women reported a total of 1’315 pregnancies. The proportion of women who reported at least one pregnancy was 15.3% between 1996 and 2002, 17.3% between 2003 and 2009, and 12.6% between 2010 and 2015. In multivariable analyses, younger women, women with previous pregnancies and participants from Western/Central and Northern Europe were most likely to report a pregnancy, whereas women from South, Central East and Eastern Europe and individuals with previous AIDS-defining illnesses were less likely to report a pregnancy. Out of 690 live births (69.1%), 23 children were HIV-positive (3.3%), 342 were HIV-negative (49.6%), and the HIV status was unknown in 325 (47.1%). Spontaneous abortions occurred in 103 pregnancies, and 199 women had medical abortions.

In summary, the present study shows that around 22% of women in the EuroSIDA cohort reported one or more pregnancies. The highest proportion of pregnancies occurred between 2003 and 2009, and declined in recent years - reflecting trends in the general population. Women reported a high rate of medical abortions, highlighting the importance of integrating family planning and ensuring access to sexual health counselling for women with HIV.

PubMed