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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 articleSaini R, Fidler S, Boffito M, et al., 2026,
Prior PrEP use and discontinuation in individuals newly diagnosed with HIV.
, HIV MedBACKGROUND: 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 articleSconza R, Taylor GP, Ene L, et al., 2026,
Dosing of ritonavir-boosted darunavir for treatment of HIV in pregnancy.
, AIDS, Vol: 40, Pages: 831-839OBJECTIVE: To assess the effectiveness of once- and twice-daily ritonavir-boosted darunavir (DRV/r)-containing regimens for treating HIV in pregnancy to inform the 2025 World Health Organization antiretroviral treatment guidelines update. DESIGN: Analysis of pooled data from two observational study networks with sites in Romania, Switzerland, and the United Kingdom. METHODS: Pregnancies resulting in a live birth or stillbirth in women receiving 800/100 mg DRV/r once-daily or 600/100 mg twice-daily during pregnancy were included. The primary outcome was viral suppression (<50 copies/ml) near delivery (from 28 days prior to 7 days after delivery). RESULTS: Among 162 women on once-daily DRV/r, 95% were virally suppressed near delivery, with no difference between those on DRV/r from conception (95%, 113/119) and those who started on or switched to DRV/r during pregnancy (95%, 41/43). Among 27 women on twice-daily DRV/r, 78% were virally suppressed near delivery. Most women remained on the same DRV/r regimen until delivery, and there were no vertical transmissions. Darunavir drug concentrations for the limited number of pregnancies with data available fell within the expected ranges. CONCLUSIONS: This analysis provides some reassurance that once-daily DRV/r can be used successfully in pregnancy. However, given the possibility of reduced drug levels in pregnancy with once-daily dosing, viral load monitoring during pregnancy remains essential. Surveillance of pregnancies in women receiving once-daily DRV/r is needed to further support the use of this dosing during pregnancy.
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Journal articleGnan G, Vosper J, Foster C, et al., 2026,
"If there was no stigma around it, I would tell people": perspectives of UK youth living with perinatally acquired HIV, their social networks and healthcare professionals on HIV status sharing.
, AIDS Care, Vol: 38, Pages: 1268-1281Sharing one's HIV status with others is complex for youth with perinatally acquired HIV (PAH). However, the support from sharing one's HIV status may assist with HIV-related challenges. This study explored barriers and facilitators of HIV status sharing among UK-based youth living with PAH. Drawing on semi-structured interviews with ten youth with PAH, ten members of their social networks and five HIV professionals, this study examined the complex relational nature of disclosure. The data were examined using thematic analysis. While many youths expressed a desire to be open, sharing was shaped by stigma, cultural silence, familial secrecy, fear of rejection and lack of HIV education. Facilitators included emotional readiness, peer support, increased knowledge and positive prior experiences of disclosure. Social network participants often saw themselves as supportive, although professionals tended to focus on potential emotional risks. This study underscores disclosure as a process requiring ongoing support and suggests that empowering youth with education, skills and confidence is key. It identifies the need for better professional guidance and disclosure interventions co-designed with youth to support health and well-being. The findings have implications for stigma reduction, education and psychosocial support, contributing to improving the quality of life for youth with PAH.
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Journal articleKarakosta A, Nicholls EJ, Coukan F, et al., 2026,
Missed opportunities to prevent HIV acquisition with pre-exposure prophylaxis: A mixed methods study of people with recently acquired HIV in the United Kingdom.
, HIV Med, Vol: 27, Pages: 979-990OBJECTIVES: To explore missed opportunities for PrEP use among people with recently acquired HIV in the United Kingdom. METHODS: Data were derived from CASCADE, an international, longitudinal, mixed-methods study of adults (≥16 years) with recently acquired HIV (≤12 months). Individuals were recruited from nine UK clinics (08/2022-09/2024) to self-complete a questionnaire; a subset participated in semi-structured interviews (SSIs). RESULTS: 46 questionnaires were completed (39 cisgender men and 7 women, including 2 transgender women) and 11 SSIs (1 cisgender woman). Among men, 22 perceived HIV risk before diagnosis; 21 had ≥5 sexual partners and 17 reported group sex in the 3 months before diagnosis. Thirty (29 men and 1 woman) reported sexualized drug use. Twenty men had ever used PrEP; seven of them had not used it in the 6 months prior to diagnosis. No women had ever used PrEP. Most gay, bisexual and other men who have sex with men (GBMSM) were aware of PrEP; however, risk perception, social meanings of PrEP and concerns about side effects hindered utilization. Among five men using event-based dosing (EBD), three described difficulty predicting sexual activity that led to missed or mistimed pre-/post-sex doses - while others were reluctant to take daily PrEP. For women, the biggest barrier was lack of awareness. CONCLUSIONS: PrEP barriers vary by population. For GBMSM, addressing barriers to uptake/adherence (e.g., EBD challenges) are key, highlighting the potential benefit of long-acting injectables. However, awareness of PrEP remains a key challenge for women to achieve equity in prevention.
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Journal articleLee MJ, Cherrill L-R, Zacharopoulou P, et al., 2026,
Time to HIV rebound after infusion of long-acting broadly neutralising antibodies 3BNC117-LS and 10-1074-LS and analytical treatment interruption (the RIO trial): a double-blind, randomised, placebo-controlled trial
, The Lancet HIV, ISSN: 2352-3018BackgroundHIV-specific broadly neutralising antibodies (bNAbs) can maintain viral control after interrupting antiretroviral therapy (ART). We investigated the duration and efficacy of Fc-engineered long-acting bNAbs (LS-bNAbs) in maintaining ART-free HIV control compared with placebo.MethodsRIO is a double-blind, randomised, placebo-controlled trial. Eligibile participants were adults age 18–60 years, initiated on ART in early-stage HIV infection, virally suppressed on ART, and had no evidence of viral insensitivity to 10-1074. Participants were randomly assigned (1:1) to receive two LS-bNAbs (3BNC117-LS and 10-1074-LS) in arm A or saline placebo in arm B; participants and study staff were masked to assignment. Eligible participants interrupted ART after receiving blinded intravenous infusions of either bNAbs or placebo. A second optional infusion was offered after 20 weeks for participants who remained virally suppressed without ART. The primary outcome was time to viral rebound 20 weeks after ART interruption, defined as either the first of six consecutive plasma HIV RNA measurements greater than 1000 copies per mL, or two measurements greater than 100 000 copies per mL. All randomly assigned participants were included in the analyses. This study is registered with ClinicalTrials.gov, NCT04319367.Findings68 participants were randomly assigned, 34 to each arm. By week 20, viral rebound had occurred in eight participants in arm A and 30 in arm B; 75% (95% CI 61–92) of participants in arm A did not have viral rebound, compared with 11% (4–29) of participants in arm B. Participants in arm A were 91% less likely to rebound than were those in arm B (hazard ratio 0·09; 95% CI 0·04–0·21, p<0·0001). There were 326 adverse events in arm A and 260 in arm B, including 19 treatment-related or procedure-related adverse events in arm A and 41 in arm B. Of nine serious adverse events, none were treatment-related. The most com
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Journal articleTurner H, Ahmed S, Nguyen HA, et al., 2026,
Economic evaluation of alternative hepatitis C treatment options: a post hoc analysis of the VIETNARMS trial
, EClinicalMedicine, ISSN: 2589-5370BackgroundHepatitis C remains a leading cause of liver disease worldwide, and access to Direct-Acting Antiviral (DAA) treatment remains limited in many settings. Alternative treatment strategies that require fewer tablets and clinical visits could help improve equitable access, and new approaches have recently been found to be non-inferior in producing sustained viral suppression. MethodsWe did a cost-minimization analysis of alternative treatment options for non-cirrhotic patients evaluated in the VIETNARMS trial (ISRCTN61522291), conducted between 19/06/2020 and 10/05/2023 in Vietnam. These were: (i) ‘response guided’ (which adjusts treatment duration based on 1-week viral load); (ii) ‘induction maintenance’ (which reduces the dosing frequency in later weeks of treatment); and (iii) ‘Peg-IFN+DAA’ (4 weeks of DAAs combined with four weekly doses of PEGylated interferon (Peg-IFN). The primary outcome was the cost per cure. A disaggregated societal perspective was adopted, including stratification for the healthcare provider and patient costs. FindingsThe three alternative treatment strategies were projected to have lower costs per cure than standard 12-week DAA treatment in the base-case scenario: US$202 (15%) less for ‘response guided’, US$234 (18%) less for ‘induction maintenance’, and US$163 (12%) less for ‘Peg-IFN+DAA’. However, the potential for cost savings, and which strategy had the lowest cost per cure, depended on the assumed cost of DAA drugs: the strategy with the lowest cost per cure was generally ‘induction maintenance’ when DAA drug costs for a standard treatment course were under US$1,000, but Peg-IFN+DAA when DAA costs exceeded US$1,500. In some scenarios, lower costs per cure were achieved through reduced health system expenditures, despite increased costs to patients.InterpretationAlternative strategies for Hepatitis C treatment could reduce costs for providers an
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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.
, AIDSOBJECTIVE: Non-AIDS-related morbidity and mortality in people with HIV are associated with adverse metabolic health, influenced by both traditional- 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: 85 youth enrolled in the "Bone Density in Youth living with PHIV" (BONDY) underwent assessment of metabolic health including fasting biochemistry, body mass index (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 count 623 cells/μL at enrolment with 82% viral load <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 articleWeterings DA, Chiou Yee LL, Watber P, et al., 2026,
Loss of HTLV-1–specific CD8⁺ T-cell immunity in virus-carriers predisposed to adult T-cell leukemia/lymphoma
, Blood Neoplasia, ISSN: 2950-3280Adult T-cell Leukemia/Lymphoma (ATL) is caused by chronic infection with Human T-lymphotropic virus type-1 (HTLV-1). HTLV-1 contains highly immunogenic CD8+ T-cell epitopes which elicit high frequencies of virus-specific CD8+ T-cells in most virus-carriers. Despite the virus being present in the tumour, HTLV-1-specific CD8+ cells are often undetectable in ATL. To characterise HTLV-1-specific CD8+ T-cells during ATL development, we studied a sub-group of people living with asymptomatic HTLV-1 infection at very high risk of developing ATL. These so- called ‘high-risk’ carriers have suspected premalignant lesions: expanded, HTLV-1-infected ‘ATL-like’ clones circulating in their peripheral blood. Compared to viral antigen-burden matched controls, high-risk carriers had significantly fewer Tax-specific IFN-γ+CD8+ cells in peripheral blood. Furthermore, ex vivo CD8+ T-cells from high-risk carriers did not efficiently kill autologous HTLV-1-infected T-cells, including premalignant ATL-like clones. We stained Tax11–19/HLA-A*0201 pentamer+CD8+ T-cells to test whether the low frequencies of functional CD8+ T-cells resulted from the phenotype or absolute frequency of HTLV-1-specific CD8+ T-cells. Again, high-risk carriers had significantly lower frequencies of Tax11–19/HLA-A*0201 pentamer+CD8+ T-cells than controls, but we observed no difference in effector function, memory phenotype or expression of checkpoint control molecules (PD-1, TIGIT, TIM-3, LAG-3, CTLA-4). In contrast, there was no difference in the frequency of CD8+ T-cells specific for other viruses (CMV, EBV, Flu) between high-risk carriers and controls. This is the first report of HTLV-1-specific immune dysregulation in the premalignant stage of ATL. Low frequencies of HTLV-1-specific CD8+ T-cells may contribute to ATL development, and may be a novel therapeutic target for ATL prevention.
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