Current HIV Research - Online First
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Comparative Effectiveness of Daily Oral and Long-acting Injectable Prep: A Critical Review of Clinical Evidence and Public Health Implications
Available online: 23 January 2026More LessThe Human Immunodeficiency Virus (HIV) is the cause of Acquired Immunodeficiency Syndrome (AIDS). Preexposure Prophylaxis (PrEP) antiretroviral drugs to prevent HIV-1 infection are currently available in many countries. In Brazil, the recommended and approved regimen for PrEP is a daily Fixed-Dose Combination (FDC) tablet of Tenofovir Disoproxil Fumarate (TDF) with Emtricitabine (FTC) (300/200 mg), marketed as Truvada®. However, adherence to daily oral pill regimens remains one of the greatest challenges for the successful use of PrEP. Therefore, a Long-Acting Injectable (LAI) PrEP regimen, such as Cabotegravir (CAB), could significantly improve adherence to prophylaxis. The aim of this study was to compare the use of PrEP with TDF+FTC and the long-acting injectable cabotegravir, as well as to examine the mechanisms of action of the drugs involved in PrEP. In fact, the results confirmed the safety and efficacy of the use of CAB as an LAI PrEP. In June 2025, the FDA approved the use of LEN for PrEP, and it is expected that other regulatory agencies will follow suit by the end of the year. Emerging strategies under development include annual LEN formulations, the use of broadly Neutralizing Antibodies (bNAbs), and the Dapivirine Vaginal Ring (DPV), which has demonstrated greater convenience and improved adherence among pregnant women compared to oral PrEP. Additionally, digital monitoring tools are being explored, although their effectiveness relies on the implementation of equitable health policies. Thus, integrated prevention models that combine biomedical innovations with community-based interventions emerge as essential to expanding the reach and impact of PrEP.
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The Changing Face of HIV-Associated Malignancies: Is this the Same in Turkey As Well?
Authors: Yıldız Olçar, Alper Gündüz, Dilek Yıldız Sevgi and İlyas DökmetaşAvailable online: 22 January 2026More LessIntroductionCancers remain a major cause of mortality among individuals with HIV infection. This study aimed to determine the incidence, prevalence, and mortality of AIDS-defining cancers (ADCs) and non-AIDS-defining cancers (NADCs) in people living with HIV (PLWH).
MethodsThis retrospective, cross-sectional study was conducted in Istanbul. Among patients diagnosed with HIV/AIDS between January 2011 and December 2019, those who developed cancer were analyzed. To assess changes in cancer types over time, the study period was divided into three-year intervals.
ResultsCancer was diagnosed in 57 (3.9%) of the 1,438 patients. The mean CD4 count was 272.3/mm3. Patients in the cancer group had significantly higher mean age at HIV diagnosis, higher HIV RNA levels, and lower CD4+ T lymphocyte counts. A notably high rate (72%) of simultaneous diagnosis of cancer and HIV was observed in the ADCs group. Kaposi sarcoma was identified in 23 (71.8%) patients, and non-Hodgkin lymphoma (NHL) in 9 patients. Hodgkin lymphoma and lung cancer were the most common cancers in the NADCs group.
DiscussionPeople living with HIV are experiencing longer life expectancy due to ART; however, this also increases cancer risk, emphasizing the need for national screening guidelines that consider age, gender, and immune status. A multidisciplinary approach is essential for effective prevention and treatment strategies. Since cancer risk is multifactorial, larger prospective and multicenter studies are needed to strengthen and expand these findings.
ConclusionsThese findings highlight that AIDS-defining cancers continue to be a significant clinical concern in Turkey. Cancer screening should be integrated both at the time of HIV diagnosis and during routine follow-up of PLWH.
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Transverse Comparison of Clinical Characteristics and Prognostic Factors in HIV-Infected Patients with Cytomegalovirus Encephalitis in Guangdong, China
Authors: Yu Meng, Yueping Li, Yuping Ning, Weiying Lin, Heping Zhao, Mingyue Ren, Jialong Guan and Linghua LiAvailable online: 22 January 2026More LessIntroductionCytomegalovirus encephalitis (CME) is one of the serious opportunistic complications in human immunodeficiency virus (HIV)-infected patients, characterized by rapid onset, poor prognosis, and high mortality. Until now, there has been limited comprehensive research on the clinical and prognostic characteristics of HIV/CME patients reported in China.
MethodsWe conducted a retrospective study of 43 patients diagnosed with CME among individuals infected with HIV from 2015 to 2023 at Guangzhou Eighth People’s Hospital. Among them, 27 patients had a favorable prognosis, while 16 patients had an unfavorable prognosis (which includes death, treatment ineffectiveness, or aggravated condition), as determined by clinical diagnosis. The clinical symptoms and laboratory examination data for the two groups were analyzed. Multivariate analysis and a nomogram were developed using statistical variables.
ResultsHIV/CME patients with an unfavorable prognosis exhibited more consciousness disorders and nuchal rigidity than those with a favorable prognosis. There were no significant differences between the two groups in terms of clinical characteristics, such as hemiparalysis, meningeal irritation, cerebrospinal fluid (CSF) pressure, and other relevant factors. In the CSF, the chloride (Cl) level was significantly higher in HIV/CME patients with a favorable prognosis, whereas the Cytomegalovirus (CMV)-DNA levels showed the opposite trend. A multivariate analysis of fever, nuchal rigidity, consciousness disorder, and CSF CMV-DNA can be used to predict prognosis in HIV/CME patients, with a C-index of 0.83 (95% CI: 0.64–1.00). The log CSF CMV-DNA copies/mL emerged as an independent risk factor for prognosis. High CSF CMV-DNA (≥300,000 copies/mL) indicated an unfavorable prognosis. This study is the first to propose a prognostic threshold for CSF CMV-DNA (≥300,000 copies/mL) and develop a nomogram that integrates clinical and laboratory features for risk prediction in HIV/CME patients in China.
DiscussionThe findings highlight that CSF CMV-DNA ≥ 300,000 copies/mL, along with neurological symptoms such as consciousness disorder and nuchal rigidity, are significant predictors of unfavorable prognosis in HIV/ CME patients. The constructed nomogram offers a clinically useful tool for early risk stratification, which may aid in timely therapeutic decision-making.
ConclusionHIV/CME patients with an unfavorable prognosis showed more obvious signs and symptoms of central nervous system infection, lower CSF Cl levels, and higher CSF CMV-DNA compared to patients with a favorable prognosis. Recognizing these indicators early and administering timely antiviral therapy before the disease progresses to CME are of great value in improving the survival rate of patients. Our findings extend beyond existing international studies by providing novel prognostic evidence in a Chinese cohort and offering a practical predictive tool for clinical risk stratification.
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Correlation of BDNF and CD4 with Cognitive Function in Patients with HIV Infection
Available online: 22 January 2026More LessIntroductionHuman Immunodeficiency Virus (HIV) remains a global epidemic and is frequently associated with neurocognitive impairment, known as HIV-Associated Neurocognitive Disorder (HAND). Brain-Derived Neurotrophic Factor (BDNF), which regulates neuroplasticity, learning, and memory, may play a key role in this process. This study aimed to investigate the correlation between BDNF, CD4 levels, and cognitive function in patients with HIV.
MethodsWe conducted a cross-sectional study at Adam Malik General Hospital, Medan, Indonesia, from July 2024 to January 2025. Fifty-eight HIV-positive patients aged 18–60 years with CD4 ≥200 cells/mm3 and on antiretroviral therapy for at least 4 months were included. Blood samples were analyzed for serum BDNF (ELISA) and CD4 counts. Cognitive function was assessed using the Stroop Test, and correlations were examined with Spearman’s test.
ResultParticipants had a mean age of 38.77 ± 9.28 years; 79.3% were male. The mean BDNF level was 1.08 ± 0.59 ng/mL, the mean CD4 count was 512.60 ± 331.08 cells/mm3, and the mean Stroop Test score was 68.75 ± 24.60 seconds. A significant negative correlation was observed between BDNF and Stroop performance (r = -0.288, p = 0.028), indicating that higher BDNF was associated with better cognitive function. No significant correlation was found between CD4 and cognitive function (p = 0.336)
DiscussionThese findings suggest that reduced BDNF may contribute to cognitive impairment in HIV, whereas CD4 levels may not directly reflect neurocognitive status, particularly in patients with CD4 ≥200.
ConclusionBDNF levels are significantly correlated with cognitive function in HIV-positive patients, underscoring its potential role as a biomarker for HAND.
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Managing Drug Interactions between Antiretrovirals and Opportunistic Infections in People with HIV
Authors: Emily Ott, Kubwayo Kayihura Mike, Karissa Grey, Camaron R Hole and Theodore James CoryAvailable online: 22 January 2026More LessIntroductionWhile care for people with HIV has significantly improved, opportunistic infections remain a risk for patients. Antiretrovirals can interact with the drugs used to treat opportunistic infections, and care must be taken to minimize these interactions.
MethodologyWe completed a narrative review of medications to treat opportunistic infections in people with HIV and antiretrovirals.
ResultsHere we review the risks of opportunistic infections, most notably hepatitis B, hepatitis C, tuberculosis, cryptococcal meningitis, and pneumocystis pneumonia, in people with HIV, including known and potential interactions between antiretrovirals and the treatments for opportunistic infections, and the mechanisms of these interactions. We also discuss immune reconstitution inflammatory syndrome, an inflammatory response due to immune rebound, which can occur in people treated with antiretrovirals, particularly in patients who have active opportunistic infections.
DiscussionWhile the risk of IRIS has decreased for many opportunistic infections, it can still occur, particularly in patients who are infected with Cryptococcus neoformans. Treating opportunistic infections in people with HIV requires considerable care and expertise.
ConclusionWhile advancements in care have simplified treatment for these patients, there is still a considerable risk of interactions between antiretrovirals and opportunistic infections, as well as the drugs used to treat them. Future strategies, including newer agents, regimen simplification, and comprehensive management strategies, can further decrease the risk of interactions between antiretrovirals and opportunistic infection agents, as well as further decrease the risk of IRIS.
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Impact of Counselling on the Uptake of STI-Preventive Vaccines Among MSM Using PrEP: A Retrospective Cohort Study in Policlinico Umberto 1, Italy
Available online: 15 January 2026More LessIntroductionThe introduction of pre-exposure prophylaxis (PrEP) has significantly improved HIV prevention among men who have sex with men (MSM). Vaccination against hepatitis A (HAV), hepatitis B (HBV), human papillomavirus (HPV), and monkeypox (Mpox) is strongly advised for MSM, yet coverage remains suboptimal. Recent studies suggest moderate effectiveness against gonorrhoea infection from the 4-component MenB vaccine (4CMenB). This study evaluates the impact of targeted counselling strategies on the uptake of STI-preventive vaccines in a cohort of MSM on PrEP at Policlinico Umberto I, Rome.
MethodsThis retrospective observational cohort study analysed 511 MSM receiving PrEP between January 2021 and December 2024. Participants were assessed for baseline vaccination status and uptake over an 18-month period. The primary outcome was vaccination coverage at follow-up, while the secondary outcome was STI incidence. Statistical analyses included chi-square tests and t-tests to compare vaccination rates across time points and age groups.
ResultsAt baseline, vaccination coverage was low for HAV (9.8%), HPV (17.6%), 4CMenB (5.9%), HBV (52.6%), and Mpox (48.9%). After 18 months, significant increases were observed (HAV: 56.4%, HPV: 63.6%, 4CMenB: 20.3%, HBV: 86.1%, and Mpox: 65.6%, p<0.05 for all). STI incidence remained high, with syphilis (11.35/100 person-years of follow-up) and Neisseria gonorrhoeae/Chlamydia trachomatis (NG/CT) urethritis (9.35/100 person-years of follow-up) being the most frequent infections.
DiscussionTargeted vaccination counselling integrated with PrEP care significantly increased vaccine uptake among MSM. Structured interventions led to substantial improvements across all age groups. Persistent high STI incidence highlights the need for combined pharmacological and non-pharmacological strategies to optimize STI prevention in this population.
ConclusionsThe integration of structured vaccine counselling within PrEP care significantly increased vaccination uptake in MSM.
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Brain Abscess Caused by Nocardia sp. in an HIV Patient: A Case Report Highlighting Challenges and Treatment Success
Available online: 23 October 2025More LessBackgroundNocardia brain abscess is a rare opportunistic infection in people living with HIV at an advanced stage. Immunosuppression, especially with very low CD4 counts and non-adherence to treatment, increases the risk. These infections are diagnostically challenging due to their nonspecific presentation and the limited sensitivity of routine molecular panels in detecting Nocardia.
Case presentationWe present a 57-year-old HIV-positive female who developed a brain abscess after discontinuing antiretroviral therapy (ART) in 2019. She presented in 2023 with progressive headaches, fever, and vomiting. MRI revealed a ring-enhancing lesion, suggesting a brain tumor or severe infection. Craniotomy with pus aspiration confirmed Nocardia sp. The patient was treated with trimethoprim/sulfamethoxazole (TMP-SMX) and imipenem-cilastatin, showing significant improvement after two weeks of intravenous therapy. The patient was then discharged on oral TMP-SMX.
ConclusionThis case highlights the diagnostic challenges of nocardial brain abscesses in patients with HIV and highlights the importance of diagnosis, early neurosurgical intervention, and targeted antimicrobial therapy in improving outcomes.
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The Rising Impact of HPV Infection in the Antiretroviral Therapy (ART) Era
Available online: 14 October 2025More LessIntroductionSince the introduction of antiretroviral therapy (ART), non-AIDS malignancies—particularly anal cancer—have increased in people living with HIV (PLHIV). However, associated risk factors and disease progression remain poorly defined.
Material and MethodsThis retrospective observational study analysed PLHIV who developed anal cancer between 2000 and 2021 at a third-level university hospital. Epidemiological, immunological, and microbiological factors, as well as disease management and outcomes, were assessed.
ResultsA total of 38 patients were included, 95% of whom were men, with an incidence rate of 105 cases per 100,000 person-years. The median CD4 nadir was 169 cells/μl, with 60% of patients having a CD4 nadir <200 cells/μl, and 93.3% had a CD4/CD8 ratio <0.4. HPV infection was documented in 100% of tested patients (35/38), and 50% presented with advanced tumor stages. At 2 years post-diagnosis, 66% achieved complete remission, while 13.2% had a recurrence. Long-term tumor-related mortality was 15%, with an overall survival of 66%.
DiscussionA significant number of patients presented with advanced-stage anal cancer and ongoing immunosuppression, emphasising the need for earlier detection and better follow-up. Despite guidelines, screening participation remains low, highlighting the importance of multidisciplinary care and targeted prevention strategies in high-risk PLHIV populations. However, as a retrospective single-centre study with a limited sample size, our findings may be affected by information and selection bias, restricting broader applicability.
ConclusionCo-infection with HIV and HPV and low CD4 nadir were common features in these patients. HPV prevention and anal dysplasia screening are crucial to reducing this emerging condition.
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A Randomized Controlled Trial Evaluating Virologic and Renal Outcomes After Switching from TDF+FTC or 3TC+EFV to TDF/3TC/DTG (TLD) Versus DTG+3TC in Virologically Suppressed Thai PWH – A Pilot Study
Authors: Sathaporn Kanogtorn, Opass Putcharoen and Samadhi PatamatamkulAvailable online: 29 September 2025More LessIntroductionTenofovir disoproxil fumarate (TDF)/lamivudine (3TC)/dolutegravir (DTG) (TLD) is the preferred first-line therapy for all people living with HIV (PWH) per WHO 2019 and Thai HIV guidelines. This has prompted switches from TDF+FTC or 3TC+EFV to TLD in Thailand.
MethodsWe conducted a randomized trial among virologically suppressed PWH aged ≥18 years on TDF+FTC or 3TC+EFV who were switched to either TLD or DTG+3TC. The primary outcome was the change in estimated glomerular filtration rate (eGFR) calculated by cystatin C at 24 weeks.
ResultsSixteen participants (eight per group), 69% male with a mean age of 41 years and a median duration of HIV diagnosis of 7.1 years, were enrolled. A greater, though not statistically significant, decline in eGFR was observed in the TLD group. The mean differences were 5.15mL/ min/1.73m2 (95% CI: -12.06 to 22.35; p=0.532) for cystatin C and 4.01mL/min/1.73m2 (95% CI: -3.58 to 11.59; p=0.277) for creatinine. All participants maintained virological suppression. No significant differences were observed in BMI, LDL, or CD4 counts.
DiscussionAlthough not statistically significant, TLD was associated with a trend toward greater eGFR decline. This finding warrants attention, particularly in patients at risk for renal dysfunction.
ConclusionDual therapy with DTG+3TC may be a preferable switch option over TLD for virologically suppressed PWH with renal safety concerns.
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Impact of HIV-1 Tat on FDFT1 Suppression, Changes in Cholesterol Level, and KSHV Replication in BCBL1 Cells
Authors: Qiaozhen Liu, Xiaoying Chen, Dewen Liu, Yuting Zou, Weiling Yang, Ziyi Cao, Yao Ding, Weihang Ji, Na Xiao, Huaying Tang, Yan Jiang, Liandeng Wei and Yi ZengAvailable online: 11 September 2025More LessIntroductionThe present study investigated the molecular mechanism by which the transactivator of transcription (Tat) protein of Human Immunodeficiency Virus 1 (HIV-1) activates the replication cycle of Kaposi’s Sarcoma-associated Herpesvirus (KSHV).
MethodsBCBL-1 cells were initially infected with lentivirus overexpressing HIV-1 Tat. The relative mRNA expression of Farnesyl Diphosphate Farnesyltransferase 1 (FDFT1), HIV-1 Tat, KSHV Open Reading Frame 73 (ORF73), and KSHV Open Reading Frame 50 (ORF50) was quantified by real-time fluorescent quantitative Polymerase Chain Reaction (RT-qPCR). The cellular cholesterol levels were determined using a total cholesterol assay kit. BCBL-1 cells treated with 12-O-tetradecanoylphorbol-13-acetate (TPA) served as a positive control for the lytic replication of KSHV. The relative mRNA expression levels of HIV-1 Tat, FDFT1, KSHV ORF73, and KSHV ORF50 were subsequently evaluated in BCBL-1 cells following infection with lentiviruses for FDFT1 overexpression or FDFT1-RNAi knockdown, and the cellular cholesterol content was quantified.
ResultsThe findings revealed that HIV-1 Tat downregulated FDFT1 and upregulated the expression of KSHV ORF50 in BCBL-1 cells. FDFT1 overexpression upregulated the expression of the latency-associated gene, ORF73, of KSHV in BCBL-1 cells, while knockdown of FDFT1 upregulated the expression of genes associated with the lytic reactivation of KSHV. Infection with the HIV-1 lentivirus, which overexpresses Tat, as well as manipulation of FDFT1, significantly altered the cholesterol content in BCBL-1 cells.
ConclusionThe downregulation of FDFT1 by HIV-1 Tat modulates cellular cholesterol levels and is associated with KSHV replication in BCBL-1 cells.
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Characterization of Early Viral Populations in Infants Acquiring HIV Through Perinatal and Breastmilk Transmission: A Review of what is Currently Known and the Gaps that Need to be Addressed to Guide Passive HIV Immunization of Breastfeeding Infants
Available online: 04 September 2025More LessNewborns represent only 1% of the population. Yet, HIV vertical transmissions represent 10% of all new infections globally, even though antiretroviral therapy (ART) has been shown to reduce the risk of vertical transmission to less than 2%. While vaccines still represent the most efficient and cost-effective intervention to eradicate new infections, HIV immunogens that can effectively elicit broad-spectrum protection are still at least a decade away. In contrast, passive immunization with broadly neutralizing antibody (bnAb) combinations has the potential to provide a more immediate pathway to HIV prophylaxis. Early-phase infant trials are underway to establish the safety and pharmacokinetics of bnAb combinations selected for their potency against viruses acquired via adult transmissions. However, the specific characteristics and phenotypic differences of vertically transmitted viruses in infants compared to those in adults remain uncertain, including their susceptibility to known broadly neutralizing antibodies (bnAbs). We review the current knowledge of vertically transmitted HIV viruses, including their genetics and phenotypic features. Differences in immunity between adults and infants lead us to hypothesize that distinct selection and evolutionary pressures act on the virus at the time of transmission and during the early phases of infection, and these may in turn affect the choice of bnAb combinations needed for protection against vertical transmission of HIV.
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HIV-Associated Lymphomas: Updates from Pathogenesis to Treatment Strategies
Available online: 04 September 2025More LessHIV-associated lymphoma (HAL) is an aggressive malignancy directly linked to HIV infection and accounts for more than 30% of cancer-related deaths in people living with HIV (PLWH). HAL subtypes, including diffuse large B-cell lymphoma (DLBCL), Burkitt lymphoma (BL), primary effusion lymphoma (PEL), and plasmablastic lymphoma (PBL), exhibit five to ten times higher incidence rates and distinct molecular profiles compared to HIV-negative lymphomas. Pathogenesis involves HIV-driven CD4+ T-cell depletion, chronic B-cell activation, and oncogenic viral coinfection. First-line therapy combines antiretroviral therapy (ART) with chemotherapy, achieving complete remission rates of 60-70% for DLBCL using R-EPOCH and 50-60% for BL with CODOX-M/IVAC. Relapsed/refractory cases show durable responses to CD19-CAR-T therapy; however, only 10% of HAL patients are enrolled in pivotal immunotherapy trials. Severe immunosuppression necessitates PET-CT-guided de-escalation and nanoparticle-based drug delivery systems to minimize toxicity. Emerging strategies include PD-1 inhibitors and broad-spectrum antivirals targeting HIV reservoirs, underscoring the need for precision medicine that integrates tumor genomics and viral dynamics.
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Advancing HIV Treatment Through Nanoparticles: A Precision Medicine Approach
Authors: Akmal Zubair, Muhammad Jawad, Laveeza Khan, Zeeshan Hidayat and Muhammad AliAvailable online: 27 August 2025More LessThe poor solubility and bioavailability of antiretroviral drugs complicate the management of Human Immunodeficiency virus. The efficacy of these medications is diminished due to restricted absorption in the gastrointestinal tract. Patients often exhibit a wide range of reactions attributable to fluctuations in blood drug concentrations. Achieving the target plasma concentrations is challenging and often necessitates higher dosages, which increases the risk of adverse effects. The formulation of pharmaceuticals with poor solubility is a complex and costly process that hinders overall drug development. Given the limitations of traditional formulation strategies to address these issues, it is essential to explore alternative methods. The innovative method of nano-crystallization enhances the solubility and dissolution rates of pharmaceuticals by reducing their particle sizes to the nanoscale. The increased surface area improves the medication's solubility and bioavailability. Nanomedicine antiretroviral medications offer several advantages over their water-insoluble counterparts, including enhanced efficacy and safety, a higher drug load, and a more rapid onset of action. For this study, various databases, including Scopus, PubMed, Google Scholar, ScienceDirect, and Web of Science, were utilized to retrieve relevant literature on nanoparticles for HIV treatment. We examine the challenges associated with current treatment methods for HIV/AIDS and highlight the remarkable potential of nanotechnology to improve both the treatment and prevention of the disease through the development of antiretroviral therapy, gene therapy, immunotherapy, vaccinology, and microbicides. This review article focuses on various nanomedicine approaches used to target HIV in different sites, including the spleen, liver, kidneys, gastrointestinal tract, lungs, and brain.
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The Characteristics of Peripheral Blood Lymphocyte Subsets in HIV-related Diffuse Large B-cell Lymphoma Patients and Their Impact on Treatment Efficacy
Authors: Huiyu Xiang, Can Lin, Shuang Chen, Yu Peng, Tingting Jiang, Changhai Lin, Qing Xiao, Xiaomei Zhang, Tingting Liu, Nanjun Li, Xinyi Tang, Yakun Zhang, Junxi Liu and Zailin YangAvailable online: 26 August 2025More LessIntroductionPeripheral blood lymphocyte subsets have been shown to influence prognosis in HIV-associated Diffuse Large B-Cell Lymphoma (HIV-DLBCL), a rare and highly aggressive form of non-Hodgkin's lymphoma linked to immunosuppression and abnormal B-cell proliferation. To lay the foundation for individualized therapy based on factors such as CD4+/CD8+ ratio and Treg/NK cell characteristics, this retrospective study was conducted to explore the variations in lymphocyte subset levels.
MethodsOverall, 51 HIV-DLBCL patients, 50 DLBCL patients, and 42 Healthy Donors (HD) were enrolled in the study. Data were extracted from outpatient records and the Hospital Information Management System. SPSS 27.0 software was used for statistical analysis of the data.
ResultsSignificant differences in lymphocyte subsets were observed between groups. HIV-DLBCL patients showed decreased CD4+ T cell and regulatory T cell (Treg) counts/percentages compared to DLBCL patients and HD, but increased CD8+ T cell counts and percentages, as well as Treg percentages. Age-stratified analysis revealed that older HIV-DLBCL patients had lower CD8+ T cell counts, reduced CD3+ T cell percentages, and elevated CD56+CD16+ NK cell proportions compared to their younger counterparts.
DiscussionThis study revealed a distinct pattern of immune dysregulation in HIV-DLBCL patients, characterized by CD4+ T cell depletion and CD8+ T cell expansion, which is consistent with previous studies. Age-related immunosenescence may exacerbate the increased proportion of NK cells and the decline in T-cell function, suggesting a poorer prognosis in elderly patients. However, the lack of association between lymphocyte subsets and chemotherapy efficacy may reflect the broad impact of standard regimens on immune reconstitution. Limitations include the small sample size, absence of functional experiments, and failure to assess the influence of co-infections. Future studies should expand the cohort and integrate multi-omics data to validate these findings.
ConclusionPatients with HIV-DLBCL have distinctive alterations in peripheral blood lymphocyte subsets, such as a decreased absolute count and percentage of CD4+ T cells, in comparison to individuals with DLBCL. These alterations appear age-related and showed no significant association with prior antiretroviral therapy. The therapeutic effect of chemotherapy for HIV-DLBCL, however, might not be impacted by the low absolute count and percentage of CD4+ T-cells in peripheral blood, as well as whether or not they had previously received antiretroviral therapy.
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Epidemiology of Kidney Disease in People Living with HIV in Türkiye; Comorbidities and Drug Toxicities are Emerging Problems
Available online: 25 August 2025More LessIntroduction/ObjectiveTo reveal the epidemiology of kidney disease (KD) in people living with HIV (PLWH) and to report the antiretroviral treatment (ART) management in case of kidney disease.
MethodsThis multicenter, retrospective observational study identified KD under four categories: acute kidney disease (AKD), chronic kidney disease (CKD), accelerated decline of glomerular filtration rate (GFR > 60 mL/min), and asymptomatic kidney disease indicated by markers of kidney damage. Clinical characteristics and etiological causes of KD in patients were evaluated.
ResultsAmong 2092 PLWH screened, 131 patients (6.26%) had at least one form of KD. All patients with KD were Caucasian; 112 (84.5%) were male, with a median age of 51 9range 21–80) years. The most common comorbidities were hyperlipidemia (43.5%), diabetes mellitus (33.6%), and hypertension (26.9%). AKD developed in 20 patients (0.95%), CKD in 35 patients (1.67%), accelerated GFR decline in 69 patients (3.29%), and asymptomatic KD in 7 patients (0.33%). Regarding the etiological causes, 39.7% of KD cases were attributed to ART-related nephrotoxicity, 21.4% to HIV-related nephropathy, 19.8% to comorbidity-associated KD, and 6.9% to non-ART drug nephrotoxicity. ART regimen modification was performed in 39 patients (29.6%) with ART-related nephropathy. Lamivudine-based ART required fewer treatment changes (9.5%) than tenofovir disoproxil fumarate (38.1%) or tenofovir alafenamide (36.4%) (P = 0.04).
DiscussionART-related nephrotoxicity and comorbidity-associated kidney diseases are emerging challenges in the epidemiology of KD among PLWH.
ConclusionLamivudine-based ART regimens appear to be favorable in cases of KD development, showing a greater likelihood of preserving the initial treatment regimen.
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HIV-1 bNAb Vaccinal Effect – An Underachieving Goal?
Authors: Hannah King, Mario Roederer and Diane L. BoltonAvailable online: 19 August 2025More LessReports of HIV-1-specific broadly neutralizing monoclonal antibodies (bNAbs) mediating a potential ‘vaccinal effect’ implicate passively transferred bNAbs in promoting endogenous anti-HIV-1 immune responses. To date, three clinical trials have reported either increased anti-HIV-1 neutralizing antibodies or T cell responses following bNAb administration to people living with HIV. Despite strong enthusiasm for this hypothesis, motivated in large part by its potential application to HIV-1 therapeutic strategies, the mechanism(s) underlying a vaccinal effect remain unclear. Moreover, vaccinal effects on antibody and T cell responses are not consistently replicated. Partly, this inconsistency may be due to numerous difficulties in sensitively measuring a vaccinal effect in the context of human clinical trials. The magnitude of immune response increase following bNAb administration is generally modest, even when it is observed; a far greater enhancement of neutralization or T cell responses is likely required for a biologically meaningful impact. We review clinical and pre-clinical nonhuman primate studies that evaluated HIV-1/SIV monoclonal antibodies for vaccinal effects, with an emphasis on the strengths and limitations of these studies. Considerations for future studies investigating vaccinal effects are discussed, including appropriate comparators and specificity controls. Lastly, immune response characteristics of elite controller cohorts are outlined as potential vaccinal effect endpoints more likely to mediate HIV-1 suppression. As bNAb therapeutic interventions increasingly turn to combination approaches, including incorporation of immunomodulatory agents, attention to study design incorporating appropriate control groups, and relevant immunogenicity assays will enable more conclusive interpretation of vaccinal effects likely to mediate durable control of HIV. In any case, to date, the elicitation of vaccinal effects has been disappointing.
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Integration of Preclinical and Clinical Vaccine Safety and Immunogenicity Testing for Development of a Pediatric HIV Vaccine to Achieve Protective HIV Immunity Prior to Adolescence
Available online: 08 August 2025More LessAn optimal HIV vaccine should provide protective immunity before sexual debut to prevent infection in adolescents and young adults, including acute infections in women of childbearing age. Such a vaccine will likely require multiple sequential immunization doses and would therefore be ideally initiated in childhood. Many of the world’s most successful vaccines are initiated in childhood for the induction of lifelong immunity and/or immunity that can be boosted later in life as part of the WHO Expanded Program on Immunization (EPI). Thus, the EPI vaccine framework provides an infrastructure that could be leveraged for the implementation of a multidose HIV immunization regimen. Early childhood also provides a window of time in which there is minimal HIV exposure risk, and the plasticity of the early life immune landscape may present advantages for the elicitation of broadly neutralizing Antibodies (bnAbs), a primary target for HIV vaccination. Sequential vaccination with adjuvanted immunogens targeting specific bnAb lineages is a promising HIV vaccine strategy, and several vaccine candidates are currently being tested in adult clinical trials. It will be critical to evaluate the most promising immunogens and adjuvants in pediatric settings. Preclinical studies, including in vitro and in silico modelling as well as studies in animal models, will be essential to guide the design of future pediatric vaccine trials. This review summarizes current advances in bnAb germline targeting immunization. It provides the rationale for a better integration of preclinical and clinical vaccine studies to facilitate the development of a vaccine that achieves protective immunity in preadolescence.
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Accelerating Innovation: Advancing Opportunities in HIV Vaccine Development
Authors: Carlos A. Diazgranados, Thandi Onami and Pervin AnklesariaAvailable online: 28 July 2025More LessThis review outlines the Gates Foundation’s investments in support of global efforts dedicated to the research and development of a safe, highly effective, prophylactic HIV vaccine. Our current Collaboration for AIDS Vaccine Discovery (CAVD) portfolio encompasses a wide range of initiatives, including projects aimed at eliciting broadly neutralizing antibodies, enhancing CD8 T cell responses, and, through central service facilities, developing innovative analytical tools and animal models to assess immune responses. One central service facility also offers product development services to translate preclinical findings into clinical trials. Additionally, we are investing in platforms designed for the controlled release of HIV immunogens, simplifying complex vaccine regimens. Our ultimate objective is to develop a highly efficacious, safe, and durable vaccine that ensures broad access, uptake, and affordability. Furthermore, we emphasize the critical importance of fostering global partnerships, with a focus on supporting research capacity in low- and middle-income countries. By making intentional investments, we aim to stimulate sustainable research and development in the regions most affected by the HIV epidemic.
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Unveiling an Immunological Mystery: Deciphering the Durability Divide in Vaccine-Elicited Antibody Responses
Authors: George K. Lewis, Stanca Ciupe and Mohammad SajadiAvailable online: 23 July 2025More LessAchieving durable antibody-mediated protection remains critical in vaccine development, particularly for viral diseases like COVID-19 and HIV. We discuss factors influencing antibody durability, highlighting the role of long-lived plasma cells (LLPCs) in the bone marrow, which are essential for sustained antibody production over many years. The frequencies and properties of bone marrow LLPC are critical determinants of the broad spectrum of antibody durability for different vaccines. Vaccines for diseases like measles and mumps elicit long-lasting antibodies; those for COVID-19 and HIV do not. High epitope densities in the vaccine are known to favor antibody durability, but we discuss three underappreciated variables that also play a role in long-lived antibody responses. First, in addition to high epitope densities, we discuss the importance of CD21 as a critical determinant of antibody durability. CD21 is a B cell antigen receptor (BCR) complex component. It significantly affects BCR signaling strength in a way essential for generating LLPC in the bone marrow. Second, all antibody-secreting cells (ASC) are not created equal. There is a four-log range of antibody secretion rates, and we propose epigenetic imprinting of different rates on ASC, including LLPC, as a factor in antibody durability. Third, antibody durability afforded by bone marrow LLPC is independent of continuous antigenic stimulation. By contrast, tissue-resident T-bet+CD21low ASC also persists in secondary lymphoid tissues and continuously produces antibodies depending on persisting antigen and the tissue microenvironment. We discuss these variables in the context of making an HIV vaccine that elicits broadly neutralizing antibodies against HIV that persist at protective levels without continuous vaccination over many years.
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Toxoplasma gondii Coinfection in HIV-Positive Patients at a Tertiary Care Hospital
Available online: 14 July 2025More LessIntroductionToxoplasma gondii (T. gondii) can cause serious complications in both immunocompetent and immunosuppressed individuals. This study aims to assess the seroprevalence of T. gondii among HIV-positive individuals and to investigate its association with age, sex, CD4+ T cell count, HIV RNA levels, and hematological parameters.
MethodsThis study included 247 HIV-positive individuals followed up at a tertiary care hospital between November 1, 2022, and November 30, 2024. We analyzed serum samples for T. gondii IgG antibodies using electrochemiluminescent microparticle immunoassay.
ResultsThe prevalence of T. gondii IgG seropositivity was found to be 32.8% (n=81; 95% CI: 26.9-39). The median age of seropositive individuals was 52 years (IQR: 42-61), which was significantly higher compared to seronegative individuals (p<0.001). The highest IgG seropositivity rate (66.7%) was observed in the 61-80 age group. Hemoglobin levels were significantly lower in IgG seropositive individuals (p=0.040). Logistic regression analysis indicated an increased risk of T. gondii infection with advancing age. The odds ratio for the 41-60 age group was 13.3 (95% CI: 1.6-106, p=0.02), while for the 61-80 age group, it was 28 (95% CI: 3.3-240, p=0.002).
DiscussionThe seroprevalence of T. gondii in HIV-positive individuals was lower than both global and regional averages. Age was identified as an independent risk factor for T. gondii seropositivity. Additionally, hematological alterations associated with anemia were observed in seropositive individuals. Further large-scale, multi-center, and regionally representative studies are required to optimize T. gondii infection management and screening strategies in people living with HIV.
ConclusionThese findings suggest that T. gondii infection in HIV-positive individuals increases with age and may be associated with anemia, highlighting the need for age-focused screening and management strategies.
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