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PubMed2026

Solutions for engaging priority populations in HIV cure research: a hybrid Delphi consensus-building process.

BACKGROUND: To achieve consensus on barriers and strategies to improve the engagement of three priority populations - Black and Latino/a/x individuals, cisgender women, and transgender women in HIV cure research. METHODS: We assembled a panel of 54 experts assigned to six groups in a hybrid Delphi process: (1) HIV community members, (2) biomedical researchers, (3) medical providers, (4) funders and private industry members, (5) bioethicists and regulators, and (6) social scientists. Over 18 months, we conducted four iterative survey rounds and three group discussions to identify barriers and strategies to arrive at a consensus on how to engage these priority populations in HIV cure research. RESULTS: For Black and Latino/a/x populations, the panellists identified inadequate outreach and a lack of accessible educational information as primary barriers and emphasised community-driven engagement and partnerships with trusted leaders as key strategies. For cisgender women, logistical hurdles, caregiving responsibilities and time constraints were identified as major barriers, with flexible trial designs and equitable compensation proposed as solutions. For transgender women, the lack of transgender-focused research design, including misrepresentation and exclusion, was identified as a key barrier, while centring transgender-specific needs in study design achieved consensus as the most effective strategy. CONCLUSION: Among all four priority populations, investment in outreach, engagement along the research process, better integration of health needs with research, and enhanced incentives are not novel ideas, but remain obviously ignored in a way that has led to underrepresentation of people in HIV cure research, who carry the greatest burden of HIV in the U.S. SUMMARY: This paper uses a hybrid Delphi process to identify and reach consensus on key barriers and strategies to engage underrepresented groups: Black and Latino/a/x individuals, cisgender women, and transgender women in HIV cure research across the United States.

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PubMed2026

Efficacy of NAs in combination with Peg-IFN for functional cure in patients with CHB: a meta-analysis of RCTs.

BACKGROUND: The goal of treating chronic hepatitis B (CHB) is to achieve functional cure. We aimed to evaluate the efficacy of the combination of nucleoside (acid) analogues (NAs) and pegylated interferon (Peg-IFN) on the functional cure of CHB patients at the EOT and at the EOF. METHOD: PubMed, Embase, and Web of Science were searched systematically up to March 15, 2025. Sixteen RCTs on CHB patients receiving combination or monotherapy were included. RESULT: Compared with NAs treatment, the NAs combined with Peg-IFN treatment group significantly improved HBsAg clearance rate (RR: 14.05, 95% CI 6.13-32.20) and HBsAg seroconversion rate (RR: 12.82, 95% CI 5.08-32.33) at the EOT. Moreover, compared with NAs treatment, the NAs combined with Peg-IFN treatment group significantly improved HBsAg clearance rate (RR: 7.70, 95% CI 4.24-13.98), HBsAg seroconversion rate (RR: 11.93, 95% CI 5.14-27.67) at the EOF. However, compared with Peg-IFN monotherapy, the combination therapy group did not show any improvement in HBsAg clearance rate, HBsAg seroconversion rate, and the rate of qHBsAg decrease > 1 log10 IU/mL at the EOT and the EOF. Moreover, in terms of safety, the Peg-IFN monotherapy group showed more ALT flares (ALT > 5 × ULN) during the treatment process. CONCLUSION: Compared with NAs therapy, Peg-IFN combined with NAs therapy significantly improves functional cure rate. However, combination therapy shows no additional advantage over Peg-IFN monotherapy in achieving functional cure. The Peg-IFN monotherapy group has a higher incidence of ALT flares than the combination therapy group.

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PubMed2026

A systematic review of qualitative research on HIV and food insecurity in high-income countries.

OBJECTIVES: Food insecurity leads to adverse health outcomes in people living with HIV, including obesity, poor mental health and viral non-suppression. Qualitative studies in low- and middle-income countries have described the impact of food insecurity on medication adherence. However, limited qualitative research exists on the lived experiences of food insecurity among people living with HIV in high-income countries (HICs). We aimed to synthesize qualitative literature on food insecurity among people living with HIV in HICs. DESIGN: Systematic review and textual narrative synthesis. METHODS: We searched MEDLINE, CINAHL, Scopus, Embase, and PsycINFO, extracting data from included articles on a standardized form in Covidence. We synthesized literature using a textual narrative approach. We conducted quality appraisal (Critical Appraisal Skills Programme Qualitative Studies Checklist) and graded certainty of findings (GRADE-CERQual). RESULTS: We reviewed 2772 articles, reduced to 940 after deduplication, with 12 articles included after full text screening. Included articles reported on studies conducted in the United States ( n  = 7), and Canada ( n  = 5). We identified three key themes, each with their own sub-themes: the role of structural inequalities in shaping and navigating food insecurity; the impacts of food insecurity on health and wellbeing; and the labour of acquiring of food. CONCLUSIONS: Our review highlights the syndemic nature of food insecurity and HIV; intersecting experiences of multiple structural hardships constellate and interact synergistically to amplify poor health outcomes. Interventions should address the multiple and reinforcing social and structural conditions that shape food insecurity among people living with HIV.

Humans↗

PubMed2026

Pathways of onward HIV disclosure in relationships among young people living with vertically acquired HIV receiving antiretroviral therapy: A qualitative analysis from the BREATHER Plus trial, South Africa.

For young people living with HIV (YPLHIV) navigating their status since birth, managing onward disclosure of a potentially stigmatising condition in relationships is challenging, and may or may not lead to social support, with implications for wellbeing. In a clinical trial setting in KwaZulu-Natal, South Africa, we investigate how young people living with vertically acquired HIV navigate onward disclosure. Data were from the qualitative component of the BREATHER Plus randomised controlled trial evaluating the efficacy, safety and acceptability of short-cycle dolutegravir/tenofovir-based triple antiretroviral therapy (ART) in young people aged 12-19 years. We analyse data on 35 participants receiving ART engaged in clinical trials at the research site: 29 in longitudinal in-depth interviews (IDIs) and 12 across three focus group discussions (FGDs), including 6 in IDIs and FGDs. The Disclosure Processes Model was applied in the thematic analysis. Pre-disclosure was characterised by social assessments of potential confidants. During disclosure, reciprocal vulnerability and partial information-sharing were employed. Post-disclosure processes entailed linear and non-linear feedback trajectories, impacting future disclosures. The findings show that the study cohort of young people receiving ART navigated many bidirectional disclosure pathways to maintain social connections in relationships, and counselling guidelines need to be responsive to this.

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PubMed2026

Hypertension in a Randomized Trial of Dolutegravir- Versus Efavirenz-Based Antiretroviral Therapy in Pregnant and Postpartum Women with HIV.

INTRODUCTION: We performed an analysis of incident hypertension in a randomized trial comparing dolutegravir (DTG) + emtricitabine (F)/tenofovir alafenamide (TAF) versus DTG + F/tenofovir disoproxil fumarate (TDF) versus efavirenz (EFV)/F/TDF in pregnant and postpartum women with HIV. METHODS: Women were randomized at 14-28 weeks gestational age (GA) to start DTG + F/TAF, DTG + F/TDF, or EFV/F/TDF and followed through 50 weeks postpartum. The composite incident hypertension outcome was defined as initiation of antihypertensive medication or ≥2 elevated blood pressures categorized as elevated (130-139 and/or 80-89 mmHg), mild (140-159 and/or 90-99 mmHg), moderate (≥160-179 and/or ≥100-109 mmHg), and severe (≥180 and/or ≥110 mmHg). Incident gestational hypertension was defined by initiation of antihypertensive medication or ≥2 blood pressures ≥ 140 and/or ≥90 mmHg at ≥20 weeks GA with resolution by 12 weeks postpartum. Cox proportional hazard models were used for by-arm comparisons of the composite outcome and to look for the effect of weight change within arm. RESULTS: Of 626 women without baseline hypertension (median age 26.6 years), the composite incident outcome occurred in 49% (n = 308), predominantly due to the incident elevated category of elevated blood pressure, with no significant differences by arm, although hypertension was numerically more likely in the DTG arms. Each additional 5 kg of weight was associated with an 8%-17% higher hazard of the composite hypertension outcome. Twenty-seven participants (4.3%) had gestational hypertension with no apparent differences between arms. CONCLUSIONS: Our data contribute information regarding the safety of DTG-based ART and TAF in pregnant and postpartum women and highlight the importance of monitoring weight and performing hypertension screening as part of maternal health care for young women with HIV.

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PubMed2026

Safety and Tolerability of Oral Islatravir Once Monthly as Pre-exposure Prophylaxis in Cisgender Men and Transgender Women Who Have an Elevated Likelihood of HIV-1 Exposure: Results From the IMPOWER-24 Randomized Phase 3 Study.

BACKGROUND: Islatravir once monthly (qm), a nucleoside reverse transcriptase translocation inhibitor with a long half-life, was evaluated for safety and tolerability in cisgender men and transgender women who have sex with men and are at increased likelihood of HIV-1 (HIV) exposure. METHODS: IMPOWER-24 (NCT04652700) was a double-blind, Phase 3 study. Participants were randomized 2:1 to islatravir 60 mg oral qm or emtricitabine (FTC; 200 mg) coformulated with either tenofovir disoproxil (245 mg) or tenofovir alafenamide (TAF; 25 mg) once daily (qd). After ∼9 months, blinded islatravir was discontinued due to lymphocyte reductions; participants were offered open-label comparator for 20 months. RESULTS: In total, 494 participants were enrolled (328 islatravir; 166 comparator): 91.5% were cisgender men, 41.7% were White, and median age was 27 years. Mean blinded dosing duration was 4.7 months (islatravir) versus 4.3 months (comparator). Overall, 211 participants (64.3%) in the islatravir group and 128 (77.1%) in the comparator group had ≥1 adverse event (AE). Most AEs were mild or moderate, with 1 AE leading to product discontinuation (islatravir; gastroesophageal reflux). Serious AEs occurred in <2%; none were related to study product. Change in total lymphocytes in the islatravir group at Month 3 was -7.4%; a trend toward recovery was observed after islatravir was stopped. Mean total lymphocytes remained within normal range. No HIV infections occurred in either group during the double-blind phase. CONCLUSIONS: Islatravir qm was generally well tolerated; decreases in total lymphocytes were observed with islatravir. Original primary efficacy objectives were not assessed due to early study stoppage.

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PubMed2026

Ten years on, still out of reach: barriers to PrEP access and retention in France according to frontline actors (QualiPrEP Study).

Pre-exposure prophylaxis (PrEP) for HIV has been available in France since 2014, and reimbursed since 2016, with general practitioners allowed to prescribe it since 2021. Despite these policy advances, uptake remains low among some of the most affected populations. This community-based qualitative study explored barriers to PrEP access and retention ten years into its implementation.Interviews were conducted with 28 PrEP frontline actors (healthcare professionals and community-based workers involved in promoting, prescribing, or supporting PrEP). The sample included one group discussion (n = 5), two triads (n = 6), two dyads (n = 4), and nine individual interviews (n = 13). Thematic analysis was inductive, with barriers classified across four main domains.Participants were mostly cisgender men, median age 48, born in France and abroad, and employed by NGOs in Paris. Thirteen barriers and four major themes emerged: (1) Internal psychosocial barriers: lack of knowledge, negative health-related reactions; HIV stigma; STI risk perception, taboos; (2) Internal pragmatic barriers: perceived limits of protection, usage and follow-up constraints; (3) External psychosocial barriers: limited physician knowledge and reluctance; (4) External pragmatic barriers: communication failures; structural constraints, lack of human and financial resources.Findings call for more targeted messaging, simplified care models and provider training. They highlight the need to address social and symbolic dimensions of PrEP, with insights from those supporting users to ensure more equitable implementation.

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PubMed2026

Therapeutic approaches for the treatment of bovine metritis: a systematic review of clinical, reproductive and productive outcomes.

Bovine metritis is a complex multifactorial disease associated with substantial clinical and economic impact due to reduced milk production, subfertility, and increased culling rates. Considerable uncertainty remains regarding the comparative efficacy of the many therapeutic strategies used to manage it. This systematic review aimed to summarize and critically evaluate the available evidence on therapeutic approaches for bovine metritis, with respect to clinical cure, reproductive performance, productive performance, and culling. A literature search conducted in PubMed, Web of Science and CABI Digital Library (2010-2025) identified 18 randomized controlled clinical trials eligible for inclusion. Risk of bias was assessed independently by two reviewers using the Cochrane RoB 2 tool. Given substantial clinical and methodological heterogeneity across studies, findings were synthesized narratively by outcome, without meta-analytic pooling, and the certainty of evidence was assessed using GRADE for the comparisons supported by more than one study. Overall, systemic antimicrobial therapies consistently improved short-term clinical cure rates, although their effects on long-term reproductive and productive performance remained inconsistent. In selected cases, nonsteroidal anti-inflammatory drugs (NSAIDs) showed clinical outcomes comparable to antimicrobial treatments, allowing reductions in antimicrobial use ranging from 50% to 92%. Alternative approaches, such as intrauterine flavonoid, chitosan or dextrose-based therapies, produced inconsistent results that appeared to correlate with disease severity and treatment protocol. The evidence base is limited by substantial heterogeneity in disease definitions, postpartum timing of diagnosis, and cure criteria across studies, and by the near-universal absence of allocation concealment in the primary literature; these limitations restrict the certainty of most conclusions to low or moderate. Therefore, effective metritis control should move beyond symptom resolution and incorporate integrated and preventive strategies targeting inflammatory and metabolic dysregulation during the transition period.

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PubMed2026

Predictors of Treatment Failure in Children With HIV Starting First-line Antiretroviral Therapy in the ODYSSEY Trial.

BACKGROUND: Data on predictors of treatment failure in children starting antiretroviral therapy (ART) are limited, particularly on dolutegravir-based regimens (DTG). METHODS: ODYSSEY demonstrated superior efficacy of DTG versus standard-of-care (SOC). We assessed predictors at ART initiation of treatment failure by 96 weeks. RESULTS: Three hundred and eighty-one children started first-line ART (82% African). At ART-initiation, median age was 10.5 years (IQR: 6.5, 14.0, 67 < 3 years), CD4% 20% (IQR: 12, 28), BMI-for-age Z-score -.58 (IQR:-1.48, +.25). One hundred and eighty-nine children started DTG, 192 started SOC (91% ≥3 years started efavirenz; 79% <3 years started lopinavir). Seventy-five children experienced treatment failure (24 DTG, 51 SOC). Failure risk was lower on DTG than SOC (hazard ratio [HR] = 0.47, 95% CI: 0.29-0.77, P = .002). Lower BMI-for-age Z-score (HR = 0.82 for each unit gain, 95% CI: 0.70-0.96, P = .01) and being at an African site (HR = 2.09, 95% CI: 0.82-5.31, P = .09) were associated with higher failure risk. Risk was also higher at younger ages with the steepest increase in the youngest children and increased at lower CD4%, with a stronger CD4% effect at younger ages. At CD4% = 20, HRs relative to age 10 years were 2.40 (95% CI: 1.58-3.65) at age 1 year, 1.30 (95% CI: 1.15-1.48) at age 5 years, and 0.80 (95% CI: 0.72-0.89) at age 18 years. At age 1 year, HRs relative to CD4% = 20 were 1.39 (95% CI: 1.16-1.66) at CD4% = 15, and 0.52 (95% CI: 0.36-0.75) at CD4% = 30; at age 10, corresponding estimates were 1.07 (95% CI: 0.94-1.20) at CD4% = 15, and 0.88 (95% CI: 0.69-1.13) at CD4% = 30. CONCLUSIONS: Young age, low BMI-for-age, and low CD4% at ART initiation predicted higher risk of treatment failure and can guide targeted support.

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PubMed2026

"Everybody thinks that it won't happen to them": A mixed-methods study of HIV prevention strategies among people experiencing homelessness who use drugs.

BACKGROUND: HIV disproportionately affects people experiencing homelessness, particularly those who use drugs. Although effective prevention strategies exist, uptake remains suboptimal in high-risk populations. Limited research has examined how this population engages with HIV prevention strategies and the contextual factors shaping behaviors. METHODS: We conducted a mixed-methods study of adults (≥18 years) experiencing homelessness with recent drug use, recruited from three Boston sites (Feb 2024-Jan 2025). Participants completed a survey assessing HIV prevention strategy uptake. A subsample completed in-depth interviews on factors influencing behavior. Guided by the Theoretical Domains Framework, we coded qualitative data and identified themes to help contextualize uptake. RESULTS: Among 196 participants, mean age was 48; 61% identified as male and 44% as non-Hispanic White. Forty-two percent reported condomless sex, and among those who had ever injected drugs (n = 123), 24% reported syringe sharing in the prior three months. Only 9% reported current PrEP use, and 12% had ever used HIV self-tests. Qualitative findings highlighted perceived control as a key facilitator, while low perceived HIV risk hindered uptake across strategies. Additional barriers varied by strategy and included partner dynamics and substance use affecting condom use, structural constraints affecting syringe use, and knowledge, stigma, and cost concerns affecting PrEP and self-testing. CONCLUSION: In this cohort of people experiencing homelessness who use drugs, HIV prevention strategy uptake was suboptimal, with particularly low PrEP and HIV self-testing use. Qualitative findings suggest that interventions to promote HIV prevention strategy uptake in this population should leverage perceived control, address perceived risk, and target strategy-specific interpersonal and structural barriers.

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PubMed2026

Willingness to switch to long-acting regimens among people with HIV: a systematic review and meta-analysis.

OBJECTIVES: Long-acting regimens (LARs) offer promising alternatives for people with HIV, enhancing autonomy and convenience. Understanding preferences for LAR is essential to guide policy and implementation. DESIGN: This systematic review and meta-analysis examined willingness among adults with HIV to switch from daily oral antiretroviral therapy (ART) to LAR. METHODS: Following PRISMA guidelines, we included studies of adults with HIV using daily oral ART reporting willingness to switch to existing or hypothetical LAR. The primary outcome was the proportion willing to switch. Articles were searched in PubMed and Embase up to October 2024. Risk of bias was assessed using the RoB-PrevMH tool. A random-effects meta-analysis with a generalized linear mixed model synthesized willingness for LAR. Subgroup analyses explored heterogeneity. Alternative LAR were summarized descriptively. RESULTS: Searches identified 2038 records, of which 22 studies were included. Most studies were conducted in Europe or North America (96%). Willingness to switch to any LAR was 70% [95% confidence interval (95% CI): 59-79; I2  = 97.9%]. Furthermore, two-monthly intramuscular injections were the most frequently investigated LAR, with a pooled willingness of 60% (95%CI: 42-76; I2  = 97.5%). No study-level characteristics explained heterogeneity. Limited studies investigated willingness for alternative LAR. CONCLUSION: The majority of people with HIV expressed willingness to switch to LAR, with two-monthly intramuscular injections being the most commonly investigated formulation. Substantial heterogeneity persisted, suggesting that LAR preferences are highly context dependent. Evidence on alternative LAR, including tablets, implants and intravenous infusions, is limited. Low and middle-income countries were underrepresented, highlighting the need for geographically diverse research to better understand context-specific preferences and thereby inform treatment policy.

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PubMed2026

Whole-exome characterization of host genetic variation in HIV-associated genes across the high-prevalence Mizo population, Northeast India.

BACKGROUND: The Mizoram state of Northeast India has one of the highest HIV prevalence rates in Asia, yet the host genetic factors influencing HIV susceptibility in this Tibeto-Burman population remain uncharacterised. METHODS: We performed whole-exome sequencing using Illumina NovaSeq 6000, mean coverage 100X on 76 HIV-negative Mizo individuals. Variants were called using GATK HaplotypeCaller v4.3 against GRCh38p14, annotated with ANNOVAR, and filtered using hard-quality thresholds (QD ≥ 2, SOR ≤ 3, MQ ≥ 40, DP ≥ 10, GQ ≥ 20). The allele frequencies were compared against gnomAD v2.1.1 population databases. Hardy-Weinberg equilibrium was assessed using the Wigginton exact test with Bonferroni correction. RESULTS: Post-quality filtering resulted in 12,011 sample-variants across 2,821 unique positions from 36 HIV-associated loci (33 protein-coding genes, 2 chemokine ligands, and 3 lncRNA targets). Of these, 784 observations (51 unique positions) were high-impact nonsynonymous or loss-of-function variants. ADAR rs2229857 (p.K384R, NM_015840) was the most frequently observed variant (Mizo carrier frequency = 0.895; 95% CI: 0.806-0.946). CXCR1 rs16858808 (p.R335C) showed the greatest population enrichment (Mizo carrier frequency = 0.197; 95% CI: 0.123-0.300; 7.65-fold carrier-frequency enrichment versus gnomAD South Asian; CADD = 15.60). Sixteen of 20 tested variants deviated from Hardy-Weinberg equilibrium after Bonferroni correction (p < 0.0025), predominantly showing excess homozygosity consistent with the endogamous Mizo population. The protective variant CCR5-Δ32 was absent in all the 76 individuals tested. CONCLUSION: This first whole-exome characterization of HIV host genes in the Mizo population identifies CXCR1 rs16858808 as the most population-enriched functional variant and reveals a pervasive endogamy signature. These findings provide a population-specific genetic framework for future HIV susceptibility studies and ART pharmacogenomics research.

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PubMed2026

The association of 25-hydroxyvitamin D deficiency with neuroinflammation and prognosis in HIV-negative cryptococcal meningitis.

BACKGROUND: Cryptococcal meningitis (CM) in HIV-negative individuals is increasing, yet the role of vitamin D remains unclear. This study investigates serum 25-hydroxyvitamin D [25(OH)D] levels and their clinical implications in HIV-negative CM patients. METHODS: We conducted a retrospective case-control study of 93 HIV-negative CM patients and 191 healthy controls (HCs). Serum 25(OH)D levels, cerebrospinal fluid (CSF) fungal burden, cytokine profiles, the incidence of postinfectious inflammatory response syndrome (PIIRS), and one-year mortality were assessed. Bivariate logistic regression models identified predictors of mortality. RESULTS: CM patients had significantly lower serum 25(OH)D levels than HCs (18.33 vs. 23.69 ng/mL, p < 0.001), with a higher rate of deficiency (<20 ng/mL) in the CM group (59.14% vs. 34.03%, p < 0.001). Lower 25(OH)D levels were associated with elevated CSF levels of IL-6 and IL-8 (p < 0.05). Deficiency was linked to increased PIIRS incidence (43.64% vs. 21.05%, p = 0.028). Bivariate logistic regression showed a protective trend for 25(OH)D levels (OR 0.939, 95% CI 0.877-1.006, p = 0.075), although deficiency was not associated with higher mortality. CONCLUSIONS: Serum 25(OH)D deficiency is prevalent in HIV-negative CM patients and linked to neuroinflammation and increased risk of PIIRS. Serum 25(OH)D levels may serve as a useful prognostic marker, although further research is needed.

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PubMed2026

A randomized trial of viral vector and adjuvanted protein HBV therapeutic vaccine in people with chronic hepatitis B on nucleos(t)ide analogs.

BACKGROUND: This study assessed the safety, efficacy, and immunogenicity of a therapeutic immunization strategy aimed at reaching a functional cure for chronic hepatitis B (CHB), relying on a heterologous prime-boost with viral vectors ChAd155-hIi-HBV and MVA-HBV, combined with sequential or concomitant administration of adjuvanted recombinant HBV proteins (HBc-HBs/AS01B). METHODS: This single-blind, randomized, controlled, first-in-human, phase 1/2 trial enrolled adults aged 18-65 years with HBeAg-negative CHB, virally suppressed on nucleos(t)ide analogs (NAs), with HBsAg >50 IU/mL. Participants received NAs and the following regimens of 4 doses (8-week intervals): sequential administration of ChAd155-hIi-HBV, MVA-HBV, and 2 HBc-HBs/AS01B doses; co-administration of ChAd155-hIi-HBV+HBc-HBs/AS01B, followed by 3 co-administered MVA-HBV+HBc-HBs/AS01B doses; 4 HBc-HBs/AS01B doses; 2 placebo doses followed by ChAd155-hIi-HBV and MVA-HBV administered alone or with HBc-HBs/AS01B; or 4 placebo doses. Safety, efficacy (≥1-log decrease in quantitative (q)HBsAg or HBsAg loss 24 weeks post-dose 4 [day (D)337]), antibody, and T-cell responses were evaluated. RESULTS: In all, 134 participants were vaccinated. Grade 3 solicited adverse events (AEs) (median duration: 2-3 days) were more frequent after co-administration (systemic: 59.3%; administration-site: 33.3%) than sequential administration (systemic: 10.3%; administration-site: 12.8%) of high-dose viral vectors and proteins. No vaccine-related or fatal serious AEs were reported. After 4 doses, no participant had HBsAg loss or ≥1-log decrease in qHBsAg (D337 vs. D1). Co-administration induced the strongest anti-HBs response (73.7% achieved anti-HBs ≥10 mIU/mL 2 weeks post-dose 4 vs. 40.0% after sequential administration). Both sequential and co-administration induced HBc-specific CD4+ and CD8+ T-cell responses, with a prime-boost effect of the viral vectors. CONCLUSIONS: Heterologous prime-boost with ChAd155-hIi-HBV and MVA-HBV, combined with sequential or co-administration of HBc-HBs/AS01B, had an acceptable safety profile, were moderately immunogenic, but no participants showed the expected efficacy outcome.

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PubMed2026

Characterisation of HIV-1 Gag Cytotoxic T-Lymphocyte Epitopes in the Southern African Region-A Systematic Review.

During early HIV-1 infection, robust Cytotoxic T-lymphocyte (CTL) responses are mostly targeted at immunodominant Gag p24 epitopes to reduce HIV-1 viraemia to a set-point. The aim of this study was to review the current body of knowledge on HIV-1 Gag CTL epitopes in the southern African region where subtype C is prevalent. Peer-reviewed records were obtained from three databases: PubMed Central, Web of Science Core Collection, and Scopus, using the following search terms: HIV subtype C Gag epitopes, and HIV clade C Gag epitopes. The search results were restricted to countries within the southern African region, and only data published in English and between the years 2000-2025 were considered for this review. The search from the three databases produced a total of 2103 peer-reviewed records, and 49 records were included in the review. The majority of studies (58.44%) were conducted in South Africa, followed by Botswana (15.58%), Zambia (10.39%), Malawi (7.79%), Zimbabwe (6.49%) and Angola (1.30%). There were no studies identified from other southern African countries. A total of 60 Gag CTL epitopes were identified, of which 17 (28.33%) were located within the matrix protein (p17), 33 (55.00%) within the capsid protein (p24), and 4 (6.67%) within the Gag polyprotein (p2p7p1p6). The commonly detected immunodominant epitopes were mostly located within the Gag p24 protein; and included TPQDLNTML (TL9, Gag p24 48-56) and TSTLQEQIGW (TW10, Gag p24 108-117) present at 16.00% and 13.3%, respectively. The proportion of HLA-A, B and C allotypes in this systematic review were 18%, 78%, and 4%, respectively. The more common HLA-B allotypes that restrict immunodominant Gag epitopes and facilitate better control of HIV-1 were HLA-B*57, -B*58:01, -B*42:01 and -B*81:01. This systematic review has provided important insights into the description of immunodominant Gag epitopes and HLA-I alleles that contribute to the control of HIV-1 viraemia in the southern African region. It has also exposed that some CTL epitopes identified in the southern African studies are not reported on the Los Alamos HIV database (LANL HIV database). This highlights a need to have this database updated with this information as it is used as a reference for epitopes. This review could provide insights into the design of an epitope-based HIV-1 vaccine that would also be effective in the southern African region.

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PubMed2026

Safety, Pharmacokinetics, and Pharmacodynamics of Single-Dose Programmed Cell Death Protein 1 Inhibitor, Budigalimab, in People With HIV-1 With Antiretroviral Therapy-Suppressed Viral Load.

BACKGROUND: Blockade of inhibitory immune checkpoint receptor programmed cell death protein 1 (PD-1) on target immune cells is associated with improved HIV-specific immune function and activation of latent HIV. This randomized, placebo-controlled, Phase 1b study assessed low doses of investigational anti-PD-1 monoclonal antibody, budigalimab, for safety, tolerability, pharmacokinetics, and pharmacodynamics in people with HIV (PWH) on antiretroviral therapy. METHODS: Participants received single doses of budigalimab 10 mg subcutaneous (SC), 20 mg SC, 10 mg intravenous (IV), or placebo (n = 8 per arm) and were followed for 24 weeks. RESULTS: Of 32 randomized participants, 22 reported adverse event(s) (AE); most (n = 19) were grade ≤2 and no grade ≥4 AE or treatment-related serious AE. Two participants reported a non-treatment-related grade 3 AE (placebo, n = 1 pneumonia; 10 mg IV, n = 1 elevated aspartate aminotransferase). One reversible immune-related AE (grade 2 lichenoid keratosis) was reported (20 mg SC). Geometric mean maximum serum concentrations were 0.37, 1.57, and 3.2 µg/mL with 10 mg SC, 20 mg SC, and 10 mg IV, respectively. Drug exposure with 20 versus 10 mg SC dosing was more than dose proportional and less variable. Subcutaneous bioavailability was approximately 53%-62%. The PD-1 receptor saturation was ≥95% in most participants (median duration: 20 mg SC, 42 days; 10 mg SC, 14 days; 10 mg IV, 35 days). CONCLUSIONS: Findings suggest an acceptable safety profile for single-dose budigalimab in PWH, with a favorable pharmacokinetic profile for 20 mg SC and 10 mg IV. Further evaluation as a potential component of an HIV treatment is underway.

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PubMed2026

Comparing Clinical and Cytokine Profiling of Genital Inflammation as Predictors of HIV Acquisition in Women.

BACKGROUND: Inflammation in the female genital tract is a key risk factor for HIV acquisition, but it remains unclear whether clinical or immunological measures best predict risk. We aimed to compare HIV acquisition among women with clinically and/or immunologically defined inflammation. SETTING: HIV-uninfected women enrolled in the CAPRISA 004 tenofovir gel randomized controlled trial in South Africa were followed for up to 34 months. METHODS: We analyzed data from 889 women, with cytokine measurements available for 774 participants. Clinical genital abnormalities were assessed at scheduled visits, and 9 cytokines were measured in cervicovaginal lavage samples. HIV incidence was compared across categories of clinical and immunological inflammation using time varying Cox proportional hazards models, adjusting for relevant covariates. RESULTS: Immunological inflammation, defined as ≥9 elevated cytokines, was present in 18% (140/774) of women. Among specific clinical signs, abnormal genital discharge (adjusted hazard ratio: 2.67, 95% confidence interval [CI]: 1.14 to 6.23, P = 0.024) and cervicitis (adjusted hazard ratio: 10.34, 95% CI: 2.46 to 43.65, P = 0.001) were significantly associated with increased HIV acquisition. Women with both clinical and immunological inflammation had the highest risk of HIV acquisition, with adjusted hazard ratios of 2.08 (95% CI: 1.10 to 3.91, P = 0.022) and 2.46 (95% CI: 1.21 to 5.03, P = 0.013), respectively. CONCLUSIONS: Clinical and immunological definitions of inflammation were each independently associated with increased HIV acquisition risk and combined, they reflected greater susceptibility. These findings highlight the important role of genital inflammation in women's HIV susceptibility, suggesting that clinical signs may provide practical early indicators of risk even as cytokine profiles provide more sensitive measures of underlying inflammation.

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PubMed2026

Safety and Immunogenicity of Varicella Vaccination in Children and Adolescents Living With HIV: A Systematic Review.

INTRODUCTION: Preventing varicella-zoster virus infection is important in the management of human immunodeficiency virus (HIV)-positive persons. Varicella remains endemic worldwide, and HIV-positive persons can experience greater morbidity than the general population. We summarized the global literature on the safety and immunogenicity of the varicella vaccine in HIV-positive children. METHODS: Systematic review of original reports on varicella vaccination of HIV-positive children, published through December 31, 2024, including assessment of safety, immunologic responses and effectiveness after vaccination. RESULTS: Eighteen articles were analyzed. Local reactions were the most common adverse events, albeit infrequent (<21% and <10% of vaccinees after dose 1 and 2, respectively). Systemic reactions were also infrequent, consisting mostly of low-grade fever. A vaccine-related rash, reported in <5% of vaccinees, had fewer lesions and a shorter duration than typical varicella. Serious adverse events were reported only when the vaccine was inadvertently administered to children with severe HIV immunosuppression. Varicella vaccination had no clinically significant impact on plasma HIV RNA or CD4+ T-cell count after either dose. An antibody response was reported in 60%-79% of HIV-positive vaccinees after dose 2 and often declined more rapidly than in uninfected children. Cell-mediated immunity was detected in 67%-83% after dose 2. No significant differences in adverse events or short-term immune response after vaccination correlated with past or current CD4+ T-cell status. CONCLUSIONS: The varicella vaccine had a favorable safety profile and induced specific immune responses in most nonseverely immunocompromised HIV-positive children. The vaccine remains contraindicated for persons with severe HIV infection. Robust data on the durability of immune response and long-term effectiveness are needed.

Humans↗