Cellular immunotherapies have shown great promise in the treatment of various diseases. Chimeric engulfment receptor (CER)-engineered T cells were developed to utilize the extracellular T-cell immunoglobulin and mucin domain-containing 4 (TIM-4) domain and intracellular engulfment signaling domains to target and enhance phagocytosis and T-cell cytotoxic function. These processes are activated through TIM-4 binding with phosphatidylserine (PS), a pro-phagocytic "eat me" signal. HIV infection has been shown to induce extracellular PS exposure shortly after infection, and engineered CER T cells have been shown to kill CD4[+] T cells infected with simian immunodeficiency virus (SIV) in vitro. In this study, we infused two rhesus macaques (RMs) with CER-1236 T cells (the iteration of CER T cells currently moving forward in human clinical trials for cancer) and evaluated safety, the tissue distribution of the CER-1236 T cells, and antiviral activity against SIV (SIVmac239). Prior to infusions, RMs underwent SIV infection, antiretroviral therapy (ART), and ART cessation. The infusions were well tolerated. Neither of the macaques exhibited clinical evidence of illness nor changes in vital signs, serum chemistry, hematology, or other evaluated physiological parameters beyond what is typically observed with SIV infection. Post-infusion proliferation of CER T cells in PBMC was limited and seen with cells manufactured by the Prodigy system. Histologic and flow cytometry evaluation from post-infusion tissue biopsies and necropsy revealed tissue detection of CER T cells in bronchoalveolar lavage fluid with intermittent detection of infused cells in lymphoid tissue in concert with the limited expansion of T cells in PBMC. No laboratory or clinical evidence of hepatic, splenic, bone marrow, or CNS alterations was noted, and no evidence of in vivo suppression of SIVmac239 was observed as a result of the infusions. The CER-1236 T cell infusions were not associated with any discernable histopathological toxicity. This safety profile of CER-1236 T cells in nonhuman primates portends well for its potential for clinical development, especially for tumors with high expression of the tissue damage receptor PS. Optimization of in vivo functionality will be required for CER T cells to be effective against HIV infection.

Young people living with perinatally acquired HIV (YPLHIV) represent a unique population for HIV cure research, offering opportunities to assess interventions in a group for whom adherence to antiretroviral treatment (ART) is particularly challenging. Understanding their perspectives about participating in HIV cure research could inform the design of future YPLHIV-centered study protocols. In this cross-sectional study, we assessed awareness and willingness to engage in HIV cure research among YPLHIV in Cameroon from February to April 2025. A questionnaire was administered to 157 YPLHIV [50.7% male; median (interquartile range) age: 18(16-20) years]; 83.6% were attending secondary school, and 9.6% were living in rural settings with 145 (92.3%) full respondents. The majority (63.0%) were aware that HIV cure research is being conducted (3.3% of them from rural vs. 96.7% from urban settings, p = .093); with awareness higher among secondary-school students (94.6%; p = .029), and those having internet access (77.2% vs. 21.7% for others; p = .032). The understanding of HIV "cure" included: "no more treatment needed" (31.2%), "elimination of the virus" (16.0%), and "no longer having the disease" (7.6%). Almost 90% were apparently willing to participate in cure research across sex, educational level, adherence, and geographical settings, with 44/145 (30.3%) reporting at least one concern about participation, such as "collection of many samples" (10/145; 6.90%). The main motivation to participate was the "possibilities of finding a cure" (28.7%). While over 60% were aware of ongoing HIV cure research, efforts to improve awareness are needed in rural settings. Identifying challenges perceived by YPLHIV offers a guide for developing tailored communication and support. The high presumed willingness of YPLHIV to participate in HIV cure research offers promise for implementation in Cameroon and similar settings across Africa, where YPLHIV need alternatives to daily ART. However, further research into informed willingness and actual real-world clinical trial participation will be essential to determine overall feasibility and implementation success.

The continuous HIV-1 recombination forms circulating in China poses a persistent challenge to epidemic control. And this study identifies two novel unique recombinant forms (URFs), BDNY017 and BDK025, from antiretroviral therapy (ART)-failing patients in Hebei Province. Near full-length genomic analysis revealed that BDNY017 is a triple mosaic of CRF08_BC, CRF07_BC, and subtype B, whereas BDK025 is a dual recombinant of CRF07_BC and CRF08_BC. Genotypic resistance testing further uncovered M184V, A98G, and E138K mutations in BDNY017, while BDK025 carried no major pol-region resistance mutations. Notably, the report of CRF08_BC-involved URFs in northern China, expanding the known geographic distribution of such recombinants beyond their traditional southwestern focus and underscoring the urgent need for enhanced molecular surveillance, particularly among ART-failing individuals, to track emerging recombinants and assess their potential impact on treatment outcomes and transmission dynamics.

Human immunodeficiency virus (HIV) persists in diverse body tissues, including the gut, lymph nodes (LNs), and lungs, requiring direct sampling to characterize heterogeneous reservoirs. HIV cure-related trials may include tissue sampling to evaluate intervention efficacy and mechanisms to eliminate viral reservoirs. Repeated invasive sampling carries risks that must be balanced against safety, acceptability, and scientific value. We assessed the experiences of young women undergoing serial excisional LN and gut biopsies during an HIV cure-related trial in South Africa. We conducted a qualitative secondary analysis of in-depth interviews (IDIs) with women enrolled in a Phase 2A HIV cure-related trial (NCT05281510) that included an analytical treatment interruption (ATI). We conducted IDIs at enrollment and pre-ATI at the Females Rising through Education, Support and Health research site in Durban, South Africa, in isiZulu. We audio-recorded, transcribed, translated, and deidentified the interviews and analyzed them using inductive conventional content analysis. We interviewed 19 participants. Each underwent LN excision 1-3 times (mean 2.6) and gut biopsy 0-3 times (mean 2.5). Motivations included scientific curiosity and contributing to future generations. LN excision was generally painless, although some reported itching and slow healing. Gut biopsies caused abdominal pressure and transient bloating. One adverse event occurred among 48 LN excisions. Initial apprehension was common, but clear communication, supportive staff, and recognition of contributions fostered trust and willingness to undergo repeat procedures. Serial tissue sampling was acceptable among young South African women despite some discomfort. Altruism was a primary motivator, while clear communication and participant-centered care were critical to supporting informed participation and repeat sampling.

In this study, the relationship between the allele and genotype frequencies of the rs7975232 (ApaI) and rs731236 (TaqI) polymorphisms of the vitamin D receptor (VDR) gene and country-based HIV/AIDS prevalence and mortality rates were examined using Spearman rank correlation analyses. These Spearman analyses were validated for significance using the False Discovery Rate (FDR) method, considering traditional criteria (Adjusted p-value <.05). The findings revealed that ApaI_CC and TaqI_TT genotype frequencies showed weak inverse correlations with HIV/AIDS prevalence and mortality rates (ρ ≈ -0.30 and -0.25); however, these correlations were not statistically significant after FDR correction (p_adj > 0.05). These results suggest that VDR polymorphisms showed no statistically significant association with HIV/AIDS epidemiology in this ecological analysis; at most, these findings generate a population-level hypothesis that vitamin D-mediated immune responses may warrant further study. These findings should be regarded as exploratory and hypothesis-generating, and may inform future individual-level genotype-phenotype and functional studies.

HIV infection remains a significant public health challenge. Although antiretroviral therapy has substantially improved survival, chronic complications such as renal impairment increase morbidity and mortality, making the estimated glomerular filtration rate (eGFR) crucial for early detection. This prospective, observational, and analytical cohort study aimed to identify the clinical, sociodemographic, and laboratory factors associated with short-term eGFR decline in people living with HIV (PLWH) over a 6-month follow-up at a second-level Mexican hospital. We included 166 PLWH aged > 18 years, collecting data on serum creatinine, eGFR, viral load, and CD4[+] T cell counts. Patients were stratified based on the magnitude of eGFR decline into four groups (<5, 5-9, 10-19, and ≥20 mL/min/1.73 m[2]). The median age was 35 years (91% male). Median eGFR was 101.81 mL/min/1.73 m[2] at baseline and 100.54 mL/min/1.73 m[2] at 6 months. Most patients achieved virological suppression, and only 2.4% developed chronic kidney disease. Group analysis revealed a significant association between a greater short-term eGFR decline and advanced age, unemployment, and opportunistic infections. In conclusion, short-term renal decline was primarily associated with older age and unemployment. Although chronic kidney disease incidence was low, evaluating short-term eGFR decline allowed for the identification of clinically relevant alterations, highlighting the importance of periodic renal monitoring, particularly in clinically and socially vulnerable patients.

Several forms of HIV pre-exposure prophylaxis (PrEP) are approved, prescribed off-label, or in development in the United States, including daily oral tablets, long-acting injectable cabotegravir (CAB-LA), removable implants, and rectal tenofovir products. To understand how health care providers prioritize among these options, 30 providers from the United States, Thailand, and South Africa completed online surveys, and 10 participated in in-depth interviews. Providers shared their perspectives on current and emerging PrEP products, key informational needs for gay and bisexual men, and preferred educational strategies. When asked to rank PrEP options if all were simultaneously available, providers most often prioritized removable implants (N = 3), daily oral PrEP (N = 3), CAB-LA (N = 1), and rectal douches/enemas (N = 1), while others (N = 2) emphasized patient preference. Overall, providers noted that each product has unique advantages and expressed support for digital shared decision-making tools to enhance patient-provider communication about PrEP selection.

Despite over 40 years having passed since the discovery of human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS), neither a cure nor a prophylactic vaccine is yet clinically available. Promoting preventive measures and raising awareness remain critical to controlling the epidemic, especially among key populations such as college students and men who have sex with men (MSM), particularly in light of the rapid rise in adolescent AIDS cases in China. In this study, we conducted an annual anonymous online cross-sectional survey from 2018 to 2022 to assess HIV/AIDS-related knowledge and willingness to adopt preventive measures among college students in Shenzhen, China. A total of 3,095 valid questionnaires were collected. The knowledge attainment rate increased significantly from 28.2% to 49.5% during this period and was correlated with gender, age, grade, and household registration status (p < .05). Male participants (odds ratio = 1.232, 95% confidence interval: 1.053-1.422, p < .01) demonstrated higher HIV/AIDS knowledge awareness than females and were more willing to use self-testing. Fingerstick blood-based self-test kits were the most commonly preferred option among participants. Most participants preferred to access self-test kits in medical rooms, dormitories, and bathrooms. Although MSM individuals showed greater willingness to adopt preventive measures, their knowledge awareness rate was not significantly different from that of the general student population. These findings suggest that implementing peer-community health programs combined with edutainment approaches may improve HIV/AIDS knowledge and promote preventive behaviors and service utilization among college students.

Hospitalized people with advanced AIDS require potent, safe antiretroviral therapy (ART) with minimal drug interactions. This real-world retrospective cohort study aims to evaluate the efficacy and safety of albuvirtide (ABT) plus dolutegravir (DTG), with or without lamivudine (3TC), in this vulnerable population. We retrospectively analyzed clinical data from treatment-naïve (TN) and treatment-experienced (TE) hospitalized people with AIDS who received an ABT-based regimen for at least 24 weeks at the Chengdu Public Health Clinical Medical Center between July 2021 and July 2023. The primary outcome was the virological suppression rate (HIV-1 RNA <50 copies/mL) at week 24. A total of 174 patients (112 TN, 62 TE) were included, with 90.23% presenting with opportunistic infections. At week 24, the overall virological suppression rate was 79.89% (139/174). The suppression rate was 75.89% in TN patients and 87.10% in TE patients. From baseline, the median CD4 count increased by 115.50 cells/μL in the TN group and 89.00 cells/μL in the TE group (both p < .05). Treatment-related adverse events (AEs) occurred in only 5.17% of patients, all were mild-to-moderate, and no injection-site reactions were reported. No significant differences in efficacy or safety were found between the ABT + DTG and ABT + DTG/3TC regimens. In a real-world setting, ABT-based regimens containing DTG (with or without 3TC) demonstrated high efficacy and excellent safety in hospitalized people with advanced AIDS, supporting its use in this difficult-to-treat population.

Recombination events are a key driver of human immunodeficiency virus type 1 (HIV-1) genetic diversity. In this study, HIV-1 samples were collected from two male patients in Shenzhen, China. Two novel recombinant forms (Ls6449 and Ls16801) derived from CRF01_AE and CRF07_BC were identified, and their near full-length genomes were obtained. Analysis of these two forms suggested that the recombination between CRF01_AE and CRF07_BC continued to occur in Shenzhen, potentially contributing to the increasing genetic complexity of the local HIV-1 epidemic. These findings highlight the need for enhanced molecular surveillance and genotyping targeting key routes, specifically sexual transmission and mobility-associated spread. It is expected to generate precise epidemiological evidence and inform local HIV prevention and control strategies.

The COVID-19 pandemic was an event involving an actual threat of death, serious injury, or harm to the integrity of self or others, which could have served as a precipitant for unmasking symptoms of post-traumatic stress disorder (PTSD). Persons living with HIV and those with hepatitis C (HCV) coinfection could be at increased risk of PTSD symptoms after a traumatic event, given their lifetime experiences of trauma, stigma, poverty, mental health conditions, and substance use. We measured PTSD symptoms at three time points during the COVID-19 pandemic using a 17-item questionnaire in two established cohorts of persons living with HIV in Canada-those with HCV coinfection and those aging with HIV-groups at risk for having symptoms. We found that twice as many persons in the HCV coinfection cohort had moderate to severe PTSD symptoms at baseline relative to the aging cohort (49% vs. 25%) and that these percentages remained high in the coinfection cohort but declined in the aging cohort with time. Notably, those who self-reported depression had increased rates of PTSD symptoms over time. Our data points to the potential long-lasting impact that the COVID-19 pandemic or other traumatic events could have on the mental health of persons living with HIV and those with coinfection, especially among those with underlying depression. We stress the need for increased awareness and management strategies of vulnerable groups during times of trauma.

The long-term co-circulation of various HIV-1 subtypes and circulating recombinant forms (CRFs) in China has created an environment conducive to viral recombination. This study identified a novel HIV-1 CRF resulting from the recombination of CRF07_BC and CRF55_01B in Xishuangbanna Prefecture, Yunnan Province. Nearly full-length HIV-1 genome sequences were obtained from three individuals with no epidemiological link, including two men who have sex with men and one individual with heterosexual contact. These individuals were reported in 2023. These sequences form a monophyletic clade that is distinct from all known subtypes and CRFs. Recombination and phylogenetic analyses revealed that this recombinant strain exhibited a consistent mosaic genomic structure, with the CRF55_01B backbone incorporating two CRF07_BC segments. Bayesian phylogenetic analyses indicated that this recombinant form originated around 2019. In accordance with standard nomenclature, it has been designated CRF200_0755. In addition, this recombinant strain carries the V179E resistance mutation from CRF55_01B. The discovery of this novel CRF highlights the ongoing evolution of HIV-1 amid the co-circulation of prevalent strains and population mobility. It also emphasizes the importance of continuous molecular surveillance in guiding public health strategies, given the potential presence of preexisting resistance mutations.

This prospective cohort study compared the efficacy of bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) and tenofovir/lamivudine/efavirenz (TLE) regimens in 88 treatment-naïve persons living with HIV. The BIC regimen achieved faster HIV-1 RNA suppression at week 12, with comparable suppression thereafter. Regarding HIV-1 DNA, the TLE group exhibited a more rapid decline, largely attributable to its higher baseline levels, while both groups converged to comparable levels at week 48; this difference was no longer significant after adjusting for baseline HIV-1 DNA levels. Notably, the BIC group had significantly lower baseline CD4[+] counts, reflecting the real-world inclusion of individuals with more advanced disease. Cluster analysis within the BIC group revealed three distinct DNA decay trajectories. A subset of individuals with the lowest baseline CD4[+] counts (Cluster 1, n = 16) showed stable HIV-1 DNA through week 48 followed by significant decline only after 72 weeks, with CD4/CD8 ratio recovery preceding the decline. The early DNA plateau may reflect the interplay between immune reconstitution and viral reservoir dynamics. These findings suggest that baseline immune status influences early viral reservoir dynamics and that the timing of reservoir reduction may be linked to immune restoration, highlighting the heterogeneity of integrase inhibitor responses and the potential value of baseline immune assessment in guiding individualized management.

Yunnan Province is recognized as a hotspot for the emergence of HIV-1 recombinant forms due to its complex epidemiological history. This study identified a novel circulating recombinant form (CRF) of HIV-1 in the region, designated as CRF203_cpx. Near-full-length genome sequences were obtained from three individuals infected through heterosexual contact in Wenshan Prefecture, an area located near the border with Vietnam. These sequences formed a distinct monophyletic clade with strong bootstrap support, separate from all known subtypes and CRFs. The genome of this strain can be divided into 14 subregions: S1, S4, S7, and S8 were derived from CRF55_01B; S2, S11, and S13 from CRF07_BC; and S3, S5, S6, and S12 from CRF01_AE. S9, S10 and S14 were likely derived from recombination between CRF01_AE and CRF55_01B. Bayesian Markov chain Monte Carlo analysis indicated that CRF203_cpx emerged between 2018 and 2021. To the best of our knowledge, this is the first time that a complex CRF comprising three CRFs (CRF01_AE, CRF07_BC, and CRF55_01B) has been definitively identified in China. This reveals the dynamic process by which circulating strains accumulate evolutionary changes through multilevel recombination, raising new considerations for current surveillance and control strategies.

The cocirculation of CRF01_AE and CRF07_BC among men who have sex with men (MSM) in China may facilitate the emergence of genetically complex HIV-1 recombinants. Here, we identified and characterized a novel second-generation HIV-1 CRF01_AE/CRF07_BC recombinant, designated GY0192, from a 25-year-old MSM individual in Guiyang, Guizhou Province, southwest China, using near full-length genome (NFLG) analysis. Recombination analyses identified four breakpoints at HXB2 positions 3,125, 5,687, 6,375, and 9,176, generating a distinct five-segment mosaic genome. Subregion phylogenetic analyses showed that the two CRF01_AE-derived fragments clustered with the CRF01_AE cluster 5 lineage, while all three CRF07_BC-derived fragments grouped with CRF07_BC lineages frequently circulating among MSM in China, indicating that both parental components of GY0192 were phylogenetically related to lineages frequently reported among MSM populations in China. The virus was also predicted to be CCR5-tropic, adding epidemiological relevance because CCR5-tropic viruses are commonly involved in transmission and early infection. Together, these findings identify GY0192 as a distinct CRF01_AE/CRF07_BC mosaic and suggest that cocirculating MSM-associated HIV-1 lineages may provide opportunities for interlineage recombination. This case expands the known spectrum of CRF01_AE/CRF07_BC recombinants in Guizhou and underscores the value of NFLG-based surveillance for detecting underrecognized HIV-1 genetic complexity in southwest China.