2025
| 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. | ||