2025
| 26th March | Neuner-Jehle et al., Genome-wide screen for HIV-1 variants under HLA-dependent selection |  |
HIV constantly evolves to escape the human immune system, particularly through interactions with the human leukocyte antigen (HLA) system, which helps the body recognize and fight infections. Neuner-Jehle et al. developed a new method to systematically identify HIV mutations influenced by HLA pressure over time. Using 4’464 HIV genome sequences and 1’044 HLA genotypes from the SHCS, they analyzed how the virus mutates in response to immune selection and how these mutations affect viral load. The study revealed key insights into HIV adaptation and immune escape:
These findings highlight the importance of understanding how human genetics shape HIV evolution, with potential implications for:
In conclusion, this study provides a powerful new approach to tracking HIV’s evolution and immune escape strategies, offering valuable insights for treatment and vaccine development. | ||
| 19th March | Zhang et al., New findings on HIV reservoirs highlight importance of early treatment | |
Individuals living with HIV carry persistent virus reservoirs that can remain hidden even during effective antiretroviral therapy (ART). These reservoirs can potentially reactivate, leading to renewed infection. In a recent study published in PLOS Pathogens, Zhang et al. explored the genetic diversity and dynamics of HIV reservoirs in different immune cell subsets among individuals who began ART shortly after their HIV diagnosis. Using advanced sequencing methods, the researchers analyzed how virus variants evolve within these reservoirs over time. The study revealed two main reservoir patterns: Furthermore, the researchers found that replication-competent viruses predominantly persisted in less differentiated T-cell subsets, such as naïve and central memory T-cells. In contrast, more differentiated subsets (transitional and effector memory T-cells) mainly harbored genetically diverse but mostly defective viral variants. Despite being defective, these variants could potentially recombine or reactivate, posing future health risks. In conclusion, these findings by Zhang et al. highlight the significant advantage of initiating ART early after HIV infection. Early therapy not only preserves immune function but also limits the formation of genetically diverse and potentially harmful viral reservoirs. By restricting the complexity and size of these reservoirs, early intervention may reduce the risk of future HIV reactivation, thus improving long-term clinical outcomes. These insights emphasize the need for continued efforts to promote early diagnosis and timely initiation of ART to effectively manage HIV infection. | ||
| 12th March | Hutchinson et al., Clinical characteristics of women with HIV in the RESPOND cohort | |
Women with HIV remain underrepresented in clinical research, yet understanding sex and gender differences is crucial to addressing their unique needs, particularly as the population ages and comorbidities become more prevalent. In a study published in HIV Medicine, Hutchinson et al. provide a comprehensive analysis of the clinical characteristics of women in the RESPOND cohort, a multi-cohort collaboration including over 34,000 people with HIV across Europe and Australia. The study compared demographics, treatment and health outcomes between women and men with HIV. Women accounted for 26% of the cohort (n=9,019), with a median age of 42 years. The majority (75.8%) acquired HIV through heterosexual contacts, and 30.3% were of African origin. At enrollment in RESPOND, women with HIV had a median CD4 count of 523 cells/μL, and 73.6% achieved HIV viral suppression at some time during the follow-up. Compared to men who have sex with men, women were more likely to have a nadir CD4 count below 200 cells/μL (9.8% vs. 6.5%). Treatment patterns also differed significantly: women with HIV were more likely to receive protease inhibitors (30.6% vs. 21.1%) and less likely to receive integrase inhibitors (34.6% vs. 45.6%) compared to men who have sex with men. In addition, women with HIV were more likely to be free of comorbidities compared to men (26.9% vs. 20.8%), but had higher rates of chronic kidney disease and non-AIDS-defining malignancies, particularly breast cancer. These findings highlight key disparities between women with HIV and men with HIV. The lower CD4 nadir among women with HIV may reflect delayed access to care, while the underuse of integrase inhibitors -despite their improved safety and efficacy - suggests a need for interventions to ensure equitable access to optimal treatments. | ||
| 6th March | Tepekule et al., Transcriptional profile of MTB infection in PWH | |
Tepekule et al. investigated whether changes in the immune system induced by Mycobacterium tuberculosis (MTB), as predicted from epidemiological observations, can be detected in peripheral blood in people with HIV (PWH). The authors hypothesized that exposure to MTB does not only induce an antigen specific T-cell response but also impacts the activation state of the innate immune system analogous to the trained immunity phenotype described after BCG vaccination. To investigate the impact of MTB infection on the transcriptome of PWH, the authors conducted a detailed analysis using peripheral blood mononuclear cells (PBMC). 78% of samples coinciding with the TB testing date. Total follow up was median 78.5 months after MTB testing (range 9.7–244.5 months). They focused PWH with a suppressed viral load to adjust for the potential effects of a replicating HIV-1 infection on the transcriptome. The algorithm matched 22 PWH in pairs based on their CD4 cell count, ethnicity, and sex to minimize further confounding variables. The analysis of PBMC transcriptomic profiles in PWH revealed distinct clustering in MTB-infected individuals. Functional annotation identified alterations in IL-6, TNF, and KRAS pathways. Notably, MTB related genes displayed an inverse correlation with HIV-1 viremia, at both individual and signature score levels. In conclusion, this study shows that MTB-specific T cell responses correlate with systemic transcriptional changes in PWH, independently of HIV-1 viral load. These MTB-associated transcriptional changes were inversely correlated with HIV-1 viremia, suggesting a potential causal link between MTB infection and improved control of HIV-1 replication. The consistent upregulation of TNF alpha signalling via NF-kB and the IL6-JAK-STAT3 pathway in MTB infection irrespective of HIV-1 viremia indicates a sustained inflammatory response. These data seamlessly align with the evolving idea of MTB infection as a spectrum of diseases, wherein stages of MTB infection differently influence the innate immune system. | ||
| 26th February | Marinosci et al., Simplified monitoring in HIV-suppressed patients switching to dual therapy | |
Personalized strategies are crucial to accommodating the diverse needs of people with HIV. These strategies are not limited to antiretroviral treatments (ART) but also include aspects related to consultations. In this study published in Swiss Medical Weekly, Marinosci et al. assessed the impact of simplifying the monitoring of people with HIV on costs and treatment satisfaction within the Swiss HIV Cohort Study. SIMPL’HIV is a randomized trial with a factorial design, in which participants were randomized 1:1 to standard ART or dual treatment with dolutegravir and emtricitabine, and 1:1 to standard vs. simplified monitoring. In addition to HIV RNA measurements taken at baseline, weeks 6, and 3-monthly thereafter in all participants, individuals in the simplified monitoring arm had CD4 cell counts and other lab tests (e.g. full blood count) at baseline and week 48 only. In addition, these participants were given the possibility to (1) complete some of the visits with a phone call, (2) have their drugs delivered to a specific address, and (3) perform blood tests at the location of their choice (e.g. their general practitioner). The results confirming the efficacy and safety of dolutegravir and emtricitabine have been published previously. The study included 188 individuals: 95 were randomized into the simplified and 92 into the standard monitoring arm. Overall, 83% were male, the mean age was 48 years, and the majority received an integrase inhibitor-based ART before randomization. Of the individuals in the simplified monitoring arm, 80% chose phone calls as a simplification option, followed by mail drug supply (50%), and laboratory tests at alternative locations (17%). In the 48 months, total healthcare-related costs, including ART, were similar in the patient-centered and the standard monitoring arm (median difference 50$, 95% confidence interval -1021 to 1059). No difference in treatment satisfaction was observed, but the satisfaction was very high in both groups at the end of the study (96.2 and 94 of 100 on a visual analog scale). When comparing ART-related costs, dual therapy with dolutegravir and emtricitabine was substantially cheaper than other guideline-recommended ART (-4643$, 95% CI -5128 to 3160). In summary, simplified monitoring did not decrease healthcare costs but was associated with a very high level of treatment satisfaction. The present study nicely illustrates that ART remains the main driver of healthcare costs for people with HIV, and simplifying treatments may be the most effective way to decrease treatment-related costs. | ||
| 20th February | Trickey et al., Care interruptions and mortality among adults in Europe and North America | |
For people with HIV, continuous antiretroviral therapy (ART) has dramatically reduced HIV-related illness and death. However, interruptions in HIV care and treatment remain a significant challenge. In a comprehensive study published in AIDS, Trickey et al. examined how breaks in care affect survival among people with HIV in Europe and North America. The researchers analyzed data from 89'197 individuals across 18 cohorts in the Antiretroviral Therapy Cohort Collaboration (ART-CC). The study included people who started ART between 2004 and 2019, defining care interruptions as gaps in clinical contact of one year or longer, followed by a return to care. Several key factors increased the likelihood of care disruptions: younger age (16–24 years), having a history of injection drug use, and acquiring HIV through heterosexual contact. The consequences of these interruptions proved substantial. When people resumed ART after a break in care, their risk of death increased by 72% compared to those starting ART for the first time (adjusted hazard ratio 1.72, 95% CI 1.57-1.88), resulting in 24 deaths per 1000 person-years. More concerning still, this risk grew with repeated interruptions, more than doubling after a second break in care. The study revealed that these deaths weren't limited to AIDS-related causes like opportunistic infections, but also included non-AIDS conditions such as cardiovascular disease and non-hepatitis cancers, highlighting how care interruptions affect overall health. These findings underscore the critical importance of maintaining continuous HIV care, particularly for vulnerable groups such as young people with HIV and those who inject drugs. This research, conducted within the ART-CC framework, provides compelling evidence to inform public health strategies and policies aimed at keeping people engaged in life-saving HIV care. | ||
| 12th February | Zeeb et al., Self-reported neurocognitive complaints in the SHCS | |
People with HIV (PWH) may experience neurocognitive complaints which can significantly impact their quality of life. While these complaints are often multifactorial, the role of the HIV genome in their development has remained unclear. In a study published in Brain Communications, Zeeb et al. conducted the first viral genome-wide association study to explore the genetic basis of self-reported neurocognitive complaints in PWH. The study analyzed data from 8’547 participants in the Swiss HIV Cohort Study who reported neurocognitive problems such as memory loss, concentration difficulties, or cognitive slowing between 2014 and 2020. Using partial pol sequences and near full-length HIV genomes, the researchers estimated the heritability and identified specific viral genetic variants associated with these complaints. Overall, 56% of participants reported at least one neurocognitive complaint during the study period, with memory loss being the most common one. The study found that self-reported neurocognitive symptoms are partially heritable through the HIV genome, with heritability estimates ranging from 1% to 22%, depending on the phylogenetic distance threshold and HIV subtype. In addition, a mutation in the HIV envelope protein (Env L641E) was significantly associated with increased memory loss complaints. While only one variant reached statistical significance, several other mutations showed nominal associations with SRNCs, highlighting the complex, polygenic nature of these complaints. In summary, this research advances our understanding of the pathogenesis of neurocognitive disorders in people with HIV. It provides strong evidence for viral genetic contributions to the variability in neurocognitive complaints, offering new insights into the complex interplay between viral genetics and cognitive health in PWH. | ||
| 5th February | Trickey et al., Causes of death among adults with HIV on ART | |
Trickey et al. aimed to investigate longitudinal trends in rates of cause-specific mortality among adult people with HIV who started ART in Europe and North America between 1996 and 2020. The authors used data from 17 European and North American HIV cohorts contributing data to the Antiretroviral Therapy Cohort Collaboration. They included data for people with HIV who started ART between 1996 and 2020. Causes of death were classified into a single cause by both a clinician and using a specific algorithm, or independently by two clinicians. Disagreements were resolved through panel discussion. The analysis was adjusted for time-updated age, CD4 count, and whether the individual was ART-naive at the start of each period. Among 189’301 people with HIV included in this study, 16’832 (8·9%) deaths were recorded during 1’519’200 person-years of follow-up. 13’180 (78·3%) deaths were classified by cause: the most common causes were AIDS (4203 deaths; 25·0%), non-AIDS non-hepatitis malignancy (2311; 13·7%), and cardiovascular or heart-related (1403; 8·3%) mortality. The proportion of deaths due to AIDS declined from 49% during 1996–99 to 16% during 2016–20. Rates of all-cause mortality per 1000 person-years decreased from 16·8 deaths (95% CI 15·4–18·4) during 1996–99 to 7·9 deaths (7·6–8·2) during 2016–20. Rates of all-cause mortality declined with time: the average adjusted mortality rate ratio per calendar period was 0·85 (95% CI 0·84–0·86). Rates of cause-specific mortality also declined: the most pronounced reduction was for AIDS-related mortality (0·81; 0·79–0·83). There were also reductions in rates of cardiovascular-related (0·83, 0·79–0·87), liver-related (0·88, 0·84–0·93), non-AIDS infection related (0·91, 0·86–0·96), non-AIDS-non-hepatocellular carcinoma malignancy-related (0·94, 0·90–0·97), and suicide or accident-related mortality (0·89, 0·82–0·95). Mortality rates among people who acquired HIV through injecting drug use increased in women (1·07, 1·00–1·14) and decreased slightly in men (0·96, 0·93–0·99). In conclusion, this study shows that rates of most categories of cause-specific mortality declined between 1996 and 2020: the largest reductions were in rates of AIDS-related and cardiovascular or heart-related mortality. Rates of all-cause mortality declined over calendar time for men who have sex with men and for both men and women who acquired HIV through heterosexual sex, but they did not decline in women who acquired HIV through injection drug use. In this group, rates of mortality related to substance use, suicide or accident, and respiratory disease increased over time. | ||
| 30th January | Lanz et al., HIV low-level viremia predicts viral failure | |
Lanz et al. aimed to investigate the impact and clinical significance of low-level viremia (LLV), accounting for its dynamic nature on the highly granular longitudinal data set from the SHCS spanning >2 decades, enabling a detailed and dynamic assessment of LLV without relying on aggregated or cumulative data. The authors analysed participants in the Swiss HIV Cohort Study, starting ART between July 1999 and April 2023, with HIV RNA values <200 copies/mL 6 months after ART initiation. Using longitudinally collected data, they applied a time-updated Cox proportional hazards model to determine the association of LLV with the risk of subsequent viral failure, defined as ≥200 copies/mL. LLV was quantified by the time-updated area under the curve (AUC) of HIV RNA values, categorized as undetectable or, based on AUC tertiles, low, intermediate, or high. They included 8’132 participants with a total of 49’579 person-years of follow-up. The median follow-up time was 4.7 years, and the median number of HIV RNA measurements was 16. Participants had a median age of 38 years, 75.9% were male, 74.4% were white, and 45.9% had HIV-1 subtype B. In total, 625 participants (7.7%) experienced viral failure during the observation period. LLV was associated with an increased risk of subsequent viral failure, with the highest LLV category showing the strongest association (hazard ratio, 3.3 [for comparison with undetectable viral load]) among all included variables, including race/ethnicity, age, and ART. Treatment modifications were common; 3’134 (participants 38.5%) had no modification, 2’202 (27.1%) had 1, and 2796 (34.4%) >1 (median number of modifications, 2 [IQR, [1–3]). Among participants with LLV, most (1873 of 2341 [80.0%]) achieved subsequent undetectable viral loads regardless of ART modification (7.9% with modification, 92.1% without modification. Starting the observation period in 2008 or 2014 led to stronger effects for high LLV (aHR [95% CI], 5.3 [3.0–9.4] for 2008 and 10.9 [5.0–23.8] for 2014), in line with the observation of a decreasing proportion of LLV in those without viral failure. To summarize, this study demonstrates that LLV is a strong predictor for subsequent viral failure. Although the incidence of LLV has declined over time, its association with subsequent viral failure—particularly for high levels—has become progressively stronger, highlighting its clinical relevance in the INSTI era. Further research is needed to elucidate the mechanisms linking LLV and viral failure and identify clinically relevant patient subgroups for whom LLV is most concerning. In conclusion, individuals experiencing LLV, especially those with prolonged episodes of LLV, are at increased risk of viral failure. While current guidelines state that viral loads <200 copies/mL do not necessitate treatment changes, these findings suggest that LLV warrants close monitoring, with treatment adjustments considered in clinical practice. | ||
| 8th January | Roen et al., cLEE and use of contemporary ARVs among PWH | |
Roen et al. on behalf of the RESPOND consortium aimed to identify risk factors associated with chronic liver enzyme (transaminase) elevation (cLEE), focusing on commonly prescribed antiretrovirals (ARVs) in RESPOND, namely INSTIs (dolutegravir [DTG], raltegravir [RAL], cobicistat boosted elvitegravir [EVG/c], and bictegravir [BIC]), protease inhibitors (PIs; boosted darunavir [DRV/b] and atazanavir [ATV/b]), non-nucleoside reverse transcriptase inhibitors (NNRTIs; rilpivirine [RPV] and efavirenz [EFV]), and backbone nucleoside reverse transcriptase inhibitors (NRTIs) that have been associated with liver impairment (tenofovir disoproxil fumarate [TDF]) and ALT normalization (tenofovir alafenamide [TAF]). People with HIV enrolled in the RESPOND cohort who started an ARV after January 1, 2012 were included (baseline). Incidence rates (IRs; events/1000 person-years) were calculated for each ARV overall and by ARV exposure (6-12 months, 1-2 years, and 2+ years). Of 17’106 individuals included contributing 87’924 person-years of follow-up, 1’932 (11.3%) experienced cLEE (incidence rate [IR], 22.0; 95% CI, 21.0–23.0). There was no evidence of a cumulative ARV effect on cLEE incidence, (6-12 months: IR, 45.8; 95% CI, 41.4-50.19; 1-2 years: IR, 34.3; 95% CI, 31.5-37.4; and 2+ years: IR, 18.5; 95% CI, 17.4-19.7). Any use (vs no prior use) of non-nucleoside reverse transcriptase inhibitors (NNRTIs) as a class and tenofovir disoproxil fumarate (TDF) was independently associated with an increased IRR of cLEE, and any use of darunavir (DRV) was associated with a decreased risk of cLEE. In conclusion, the author team analyzed a large observational study and systematically examined the relationship between commonly used ARVs and chronic liver injury, assessed using liver enzymes, and found no short-term safety concerns with the use of INSTIs. The study found an elevated risk of cLEE with use of NNRTIs (driven by EFV, RPV) and TDF, a decreased risk of cLEE with DRV/b use, and a nonsignificant trend toward decreased risk of cLEE with TAF. Further research is needed to monitor longer-term associations with cLEE, particularly for INSTIs, associations with other liver end points including markers of fibrosis, and the impact of cLEE on mortality for newer ARVs in different settings. | ||