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Journal articleCassar O, Djuicy DD, Begliomini G, et al., 2026,
HTLV-1 genetic diversity of 52 complete sequences from 14 African countries reveals novel variants and a lack of typical P12/P8 and P30 accessory proteins in HTLV-1b, d, and f genotypes
, Emerging Microbes and Infections, Vol: 15, ISSN: 2222-1751Central Africa is the largest region of human T-cell Leukaemia virus (HTLV-1) endemicity with several million people estimated to be infected. Based on the study of the LTR region, it is also the region with the highest HTLV-1 diversity, with the presence of genotypes a-b and d-g. However, complete genomic sequences are still lacking for Central African genotypes. Here, we report the first large collection of complete HTLV-1 sequences for genotypes b, d and f from Central Africa and neighbouring countries. We identified substantial diversity within the HTLV-1b genotype, including a newly defined clade that we designated HTLV-1b-del. It mainly comprises strains from the Democratic Republic of the Congo (COD) and neighbouring countries and is characterized by a distinctive 12-bp-long deletion. We also generated the complete sequence of the STLV-1 strain from Allenopithecus nigroviridis from the COD. This strain belongs to the PTLV-1b genotype and carries a 12-bp duplication in the pX region. Lastly, we found that, except for HTLV-1a strains, HTLV-1 genomes generally lack open reading frames encoding the canonical accessory protein P12; instead, they encode either shorter versions of the protein or an ORF lacking a start ATG codon. This work substantially expands the genomic landscape of HTLV-1 in Central Africa and provides a critical resource for understanding viral diversity.
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Journal articleEvangeli M, Gnan G, Musiime V, et al., 2026,
The process of developing an HIV disclosure intervention for youth with perinatally acquired HIV: The HIV Empowering Adults' Decisions to Share - UK/Uganda Project (Heads-Up).
, Glob Public Health, Vol: 21Sharing one's HIV status with others (onward HIV disclosure) for youth with perinatally acquired HIV (PAH) is often difficult but may assist with challenges associated with living with HIV. We describe the development of an intervention to help HIV-sharing decision-making for UK and Ugandan youth with PAH. The methods included : (1) semi-structured interviews with 50 participants (20 with PAH patients aged 18-25 years, 20 friends, family or partners and 10 professionals), (2) a survey of 57 UK participants with PAH patients aged ≥17, (3) the development of an intervention conceptual model, (4) intervention development, including obtaining intervention feedback from 13 youth with PAH. The survey showed that group (23/57; 40%) and mixed individual and group formats (21/57; 37%), mixed gender groups (52/57; 91%) and peer worker involvement (54/57; 95%) were preferred. The interviews highlighted the importance of overcoming feelings of shame and accepting one's status before sharing, having support to feel confident to share, personal values playing a part in sharing decisions and friends and partners explaining that they had not been educated about HIV until someone had shared their status with them. We describe the finalised intervention, and strengths and limitations of the intervention development process are outlined.Trial registration: ISRCTN Registry, ISRCTN31852047, Registered on 21 January 2019.
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Journal articleFoster C, Blenkinsop A, Henderson M, et al., 2026,
Risk factors associated with adverse metabolic health in youth with perinatally acquired HIV living in the United Kingdom.
, AIDS, Vol: 40, Pages: 1459-1466OBJECTIVE: Non-AIDS-related morbidity and mortality in people with HIV are associated with adverse metabolic health, influenced by both traditional-related and HIV-related risk factors. There is a paucity of data for youth with perinatal HIV (PHIV). We explored the relationship between markers of metabolic health and antiretroviral therapy (ART) in youth with PHIV. DESIGN: Longitudinal observational cohort study; 26 months. METHODS: Eighty-five youth enrolled in the 'Bone Density in Youth living with PHIV' (BONDY) underwent assessment of metabolic health including fasting biochemistry, BMI, total body dual energy x-ray absorptiometry scan and hepatic transient elastography. RESULTS: Of 85 participants with PHIV, mean age 21.7 years, 58% were female and 82% black African. Median ART exposure was 15 years, median CD4 + cell count 623 cells/μl at enrolment with 82% viral load less than 200 copies/ml. Median weight gain over 26 months was 3 kg, with BMI category overweight/obese increasing from 37 to 50% with 48% having dyslipidaemia. Metabolic syndrome criteria were fulfilled in 7%, with 13% having hypertension, 18% hepatic steatosis, and 7% fibrosis on transient elastography. Bayesian regression analyses demonstrated no association of integrase strand transfer inhibitor (INSTI) and/or tenofovir alafenamide (TAF) use, and sex at birth or prior CDC-C diagnoses or current HIV viraemia on metabolic outcomes. CONCLUSION: While adverse metabolic outcomes are common in this youth cohort with PHIV, no association was observed with INSTI and/or TAF use. Given the relatively young age of this cohort, preventative interventions targeting traditional metabolic risk factors are required to avoid comorbidities in later life.
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Journal articleAli MW, Nightingale S, Kellermann T, et al., 2026,
Population Pharmacokinetics of Dolutegravir in Plasma and Cerebrospinal Fluid in Adults Living With HIV.
, CPT Pharmacometrics Syst Pharmacol, Vol: 15Characterizing dolutegravir penetration into the central nervous system is important for optimizing human immunodeficiency virus treatment outcomes, yet population-specific pharmacokinetic data describing cerebrospinal fluid disposition and equilibration kinetics remain lacking. This study characterizes dolutegravir pharmacokinetics in plasma and cerebrospinal fluid to describe the plasma-to-cerebrospinal fluid equilibration rate constant and cerebrospinal fluid-to-plasma pseudo-partition coefficient. Sparse pharmacokinetics samples were collected from 121 antiretroviral therapy-experienced adults who are predominantly overweight or obese (body mass index: 32.2 ± 8.7 kg/m2) receiving daily dolutegravir (50 mg)-based therapy. The model was developed using nonlinear mixed-effects modeling in NONMEM. Plasma dolutegravir pharmacokinetics were best described by a one-compartment model with first-order absorption and elimination. The population estimate for apparent oral clearance was 1.38 L/h/70 kg. Cerebrospinal fluid data were modeled using a sequential approach with a hypothetical effect compartment linked to plasma to estimate equilibration kinetics and relative cerebrospinal fluid exposure at steady-state. Key cerebrospinal fluid penetration parameters included a plasma-to-cerebrospinal fluid equilibration rate constant of 0.38 h-1, corresponding to an equilibration half-life of 1.82 h, and a cerebrospinal fluid-to-plasma pseudo-partition coefficient of 0.0015, indicating 0.15% cerebrospinal fluid penetration relative to plasma. Post hoc estimated area under the concentration-time curve (0-24) demonstrated a moderate inverse correlation with body mass index (r = -0.34), indicating that dolutegravir exposure decreases with increasing body mass index. The model revealed rapid plasma-to-cerebrospinal fluid equilibration kinetics with low steady-state cerebrospinal fluid penetration in this pre
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Journal articleFumagalli MJ, Kaczynska A, Allombert M, et al., 2026,
Broadly neutralizing antibodies in adult males living with HIV undergoing analytical treatment interruption: secondary and exploratory outcomes of the phase II randomized controlled RIO trial.
, Nat MedRIO is an ongoing phase 2 double-blind randomized placebo-controlled human trial. Sixty-eight adult men living with human immunodeficiency virus (HIV), who were predominantly white and initiated antiretroviral therapy (ART) during primary or early-stage infection, underwent treatment interruption and were randomly assigned to a group receiving one or two doses of two long-acting broadly neutralizing antibodies (bNAbs) 3BNC117-LS and 10-1074-LS (arm A, n = 34) or saline (arm B, n = 34). The primary clinical study met its primary endpoint and was published elsewhere, demonstrating significantly delayed viral rebound and prolonged ART-free control in participants receiving bNAbs compared with placebo. The infusions were generally safe and well tolerated, with no study-related serious adverse events reported. The most common reported treatment-related adverse events were fatigue, lethargy and somnolence. Here we report on prespecified secondary analyses examining viral rebound, antibody sensitivity and reservoir dynamics, as well as prespecified exploratory analyses of rebound virus evolution and autologous antibody activity. Preinfusion reservoir measurements showed low levels of intact proviral HIV-1 DNA in circulating CD4+ T cells in both arms. The rebounding viruses in participants who received the antibodies showed significant selection for resistance to 10-1074-LS but not to 3BNC117-LS. Notably, there was a significant correlation between greater initial reservoir sensitivity to autologous antibodies and 10-1074 and time to rebound. Finally, comparison of preinfusion and prerebound HIV-1 proviral reservoir showed a decrease in intact but not defective proviruses in arm A but not in arm B. Together, these findings suggest that baseline humoral immunity and prolonged exposure to LS-bNAbs jointly shape post-treatment viral rebound dynamics in individuals who initiate ART during primary infection. ClinicalTrials.gov identifier: NCT04319367 .
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Journal articleMughal S, Tosswill J, Rosadas C, et al., 2026,
A systematic review of Human T-cell Lymphotropic Virus type-1 (HTLV-1) seroprevalence worldwide and an update on HTLV-1 diagnoses and associated diseases in England and Wales.
, Int J STD AIDSBackgroundHuman T-cell lymphotropic virus type-1 (HTLV-1) is a retrovirus, mainly transmitted sexually, which causes adult T-cell leukaemia/lymphoma (ATLL) and HTLV-1 associated myelopathy (HAM). We aimed to update global HTLV-1 seroprevalence estimates, estimate the number of people living with HTLV-1 (PLHTLV) in England and Wales (E&W), and present E&W HTLV-1 surveillance data.MethodWe systematically reviewed countries with new HTLV-1 prevalence data since the 2015 European Centres for Disease Control report, including studies of adults in the general population, pregnant women and blood donors (Ovid MEDLINE, 01/09/2014-17/02/2023). Global seroprevalence and UK census data were used to estimate the number of PLHTLV in E&W for 1991 and 2021. Reference laboratory and hospital data were combined to describe patterns in new HTLV-1 diagnoses, and associated diseases, in 2013-2022, in E&W. Diagnoses in 2013-2022 were compared with 1993-1997 using Incidence Rate Ratios (IRR).ResultsNew seroprevalence data were found for Pakistan (0.19%, blood donors), Malawi (0.96%, healthy mothers), Jordan (0.00%, blood donors), Vietnam (0.00%, blood donors) and New Caledonia (0.60%, general population); 4/5 studies had a high risk of bias. Among 749 newly-diagnosed PLHTLV in E&W (2013-2022), most were women (58%, 434/749) and tested in London (64%, 480/749). Where recorded, Black Caribbean ethnicity predominated (61%, 228/373); 51% (396/619) were symptomatic, most commonly with ATLL (47%, 187/396). Comparing 1993-1997 with 2013-2022, the IRR was 1.26 (95%CI 1.09-1.46) overall, 1.60 (95%CI 1.17-2.23) for ATLL and 0.35 (95%CI 0.23-0.51) for HAM. Assuming all cases were due to migration from endemic countries, the estimated number of PLHTLV in E&W increased from 11,654 (range 3,804-19,504) in 1991 to 28,846 (range 10,365-47,328) in 2021.ConclusionsIn E&W, rising annual ATLL diagnoses are consistent with an increase in the estimate of the number of PLHTLV, neces
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Journal articleDi Gravio C, Guzmàn V, Wu S, et al., 2026,
Long COVID symptom profiles, workforce participation, and working hours among adults in England: a population-based cohort study
, The Lancet Regional Health. Europe, Vol: 68, ISSN: 2666-7762Background. Long COVID, marked by ongoing multi-systemic symptoms following COVID-19 infection, can impair ability to maintain employment. However, its relationship to workforce retention and working hours remains unclear. Methods. Long COVID was defined as symptoms lasting >12 weeks post-infection. We analysed data from a late-2022 follow-up survey involving 45,864 participants of the Real-time Assessment of Community Transmission (REACT) Study in England (median follow-up: 23 months). Hierarchical clustering identified symptom groups. Multivariable regressions examined associations between Long COVID, being in paid work, and changes in working hours. Findings. Of 45,864 participants employed at recruitment, 86% (N = 39,341) remained in paid work at follow-up and 11% (N = 4,877) changed work hours. Approximately 4% (N = 1,967/45,864) had unresolved Long COVID. Compared with participants with no/short (<4 weeks) symptoms, those with unresolved Long COVID had lower odds of being in paid work at follow-up (adjusted odds ratio [aOR]: 0·62, 95% confidence interval [CI]: 0·55,0·70), and higher odds of changing work hours (aOR: 4·34, 95%CI: 3·88,4·85). Three clusters were identified: multisystem severe, fatigue-predominant and anosmia-predominant Long COVID. Compared with the fatigue-predominant cluster, participants with multisystem severe Long COVID had lower odds of paid work (aOR: 0·63, 95%CI: 0·47,0·84) and higher odds of changing work hours (aOR 2·76, 95%CI 2·21,3·46).Interpretations. Unresolved Long COVID was associated with worse employment outcomes. Symptom clusters highlighted the importance of considering heterogeneity in Long COVID when assessing workforce impacts and designing public health responses.Fundings. National Institute for Health and Care Research, UK Research and Innovation.
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Journal articleSaini R, Fidler S, Boffito M, et al., 2026,
Prior PrEP use and discontinuation in individuals newly diagnosed with HIV.
, HIV Med, Vol: 27, Pages: 1434-1442BACKGROUND: In settings with high uptake of HIV pre-exposure prophylaxis (PrEP), an increasing proportion of individuals newly diagnosed with HIV report prior PrEP exposure. Understanding patterns of PrEP use, discontinuation and adherence in such settings is essential to inform future HIV prevention strategies. METHODS: We conducted a retrospective case-note review of individuals newly diagnosed with HIV at 56 Dean Street, London, UK, between 1 January 2017 and 31 December 2024. Data collected included demographics, prior PrEP use, adherence and reasons for discontinuation and baseline blood results. Individuals with prior PrEP use were compared with those who had never used PrEP. RESULTS: Among 1080 individuals newly diagnosed with HIV, 210 (19.4%) reported prior PrEP use. The annual proportion with prior PrEP use increased from 4.3% in 2017 to 60.5% in 2024. Compared with never-PrEP users, those with prior PrEP use were more likely to have recently acquired HIV (85.7% vs. 58.2%, p < 0.00001), to have previously attended the clinic (70.0% vs. 37.7%, p < 0.00001) and to have undergone more frequent HIV testing. Among prior PrEP users, 36.2% reported PrEP discontinuation, and in those who had not discontinued PrEP at diagnosis, 73.5% reported poor adherence. The most common reasons for discontinuation were lack of PrEP supply, monogamy and gastrointestinal side effects. The only major resistance mutation that showed a significant difference between the two groups was M184I/V: 27 (19.6%) in PrEP-exposed versus 7 (0.8%) in not-PrEP-exposed. CONCLUSIONS: In this high-PrEP-uptake setting, a growing proportion of individuals newly diagnosed with HIV report prior PrEP use, most commonly characterized by discontinuation or suboptimal adherence. These findings highlight an ongoing unmet need for interventions that support PrEP persistence and continuity, including improved access pathways and alternative PrEP formulations.
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Journal articlede Oliveira ACP, Assone T, Haziot ME, et al., 2026,
Asymptomatic is not silent: proposal of HTLV-1-associated multiple inflammatory disorder as an early neuroinflammatory state.
, Expert Rev Anti Infect Ther, Vol: 24, Pages: 891-898BACKGROUND: Human T-lymphotropic virus type 1 (HTLV-1) infection is classically categorized as either asymptomatic or associated with HTLV-1-associated myelopathy (HAM). However, accumulating clinical evidence suggests that a proportion of individuals labeled as asymptomatic present early inflammatory and neurological manifestations that do not fulfill HAM diagnostic criteria. RESEARCH DESIGN AND METHODS: We conducted an observational study within a large, long-standing Brazilian HTLV-1 cohort. Between January 2015 and December 2025, adults previously classified as asymptomatic were systematically evaluated during follow-up at an outpatient clinic. Standardized clinical and neurological examinations were newly performed by clinicians not previously involved in their care and assessment. These findings were then integrated with neuropsychological, radiological and laboratory assessments. RESULTS: Among individuals previously considered asymptomatic, 24% fulfilled predefined criteria for an intermediate condition termed HTLV-1-associated multiple inflammatory disorder (HAMID). HAMID was associated with older age, female sex, higher proviral load, markers of chronic immune activation, subtle spinal cord abnormalities, and cognitive impairment, particularly affecting episodic memory. CONCLUSIONS: HTLV-1 infection encompasses an early, biologically active inflammatory disease stage distinct from both asymptomatic infection and overt HAM. Recognition of HAMID refines the clinical spectrum of HTLV-1 infection and provides a framework for earlier diagnosis, improved risk stratification, and clinical surveillance.
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Journal articlePenner J, Poletti de Chaurand V, Seery P, et al., 2026,
Timing of Loss of Transplacental Antibodies in Infants Born to Mothers Living With Human T-cell Lymphotropic Virus Type 1.
, Pediatr Infect Dis JBACKGROUND: To date, evidence suggesting the optimal timing of antibody testing in human T-cell lymphotropic virus type 1 (HTLV-1)-exposed infants is lacking. Testing HTLV-1-exposed infants must balance the need for repeat testing if done too early while minimizing loss to follow-up with protracted follow-up intervals. METHODS: Single-center, retrospective cohort analysis of HTLV-1 serologic testing and breastfeeding practices in infants born to HTLV-1 seropositive pregnant individuals between 01/01/2016 and 10/03/2026. RESULTS: Nineteen children were identified, of whom 5 had positive serological tests for HTLV-1 when first tested, and 14 were seronegative on the first sample, with a median age at first negative test of 18.4 months (95% confidence interval: 6.9). None have been confirmed infected. Six children were known to have breast/chest-fed for an average of 4.5 months. CONCLUSIONS: Serologic testing of HTLV-1-exposed infants can be done at 18 months, minimizing persistent transplacental positives and follow-up attrition.
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