2025年 · 第05卷第04期

Dyslipidemia is a common comorbidity in people with human immunodeficiency virus (HIV) (PWH), driven by both viral persistence and antiretroviral therapy (ART), and it plays a pivotal role in cardiovascular disease (CVD) development through complex inflammatory and metabolic pathways. HIV infection is associated with dyslipidemia, with a reported prevalence of 53% among PWH, and dyslipidemia has been observed in both ART-naïve and ART-experienced individuals.^[1]The typical lipid profile in untreated HIV infection features reduced levels of high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C), along with a progressive increase in triglyceride (TG) levels as the disease advances.^[2]The advent of ART over the past three decades has transformed HIV into a manageable chronic condition; however, its long-term use introduces heterogeneous effects on lipid homeostasis. Among these, protease inhibitors (PIs) cause the most pronounced and enduring disruptions, and these disruptions often exceed the lipid disturbances attributable to HIV infection itself. Yet, in the evaluation of dyslipidemia profiles across different ART agents, most available evidence comes from switch therapy studies, where 48 weeks or 96 weeks serve as key time points. Analyses are conducted by comparing patients’ lipid changes before and after switching from conventional ART regimens to newer-generation ones, and in such studies, integrase strand transfer inhibitors (INSTIs), whose "lipid-friendly" effects are widely recognized, are often designated as the reference group for assessing lipid changes (Table 1).^[3,4,5]Notably, in treatment-naïve patients, clinical observations show that the use of INSTI may cause a slight increase in lipids within 48 weeks. However, this change is generally considered statistically insignificant and is mostly interpreted as a restorative manifestation of patients’ metabolic function.^[3]

Decades of hard work and solidarity have reduced the annual numbers of people acquiring HIV and people dying from AIDS-related causes to their lowest levels in more than 30 years. At the end of 2024, the declines in numbers were not sufficient to end AIDS as a public health threat by 2030—but the means and the momentum for doing so existed. Examples of country successes were multiplying, and national governments were assuming greater responsibility for their HIV responses. New scientific breakthroughs continued to be made, including long-acting injectable antiretroviral medicines.

Acquired drug resistance (ADR) in people living with HIV (PLWH) reduces treatment efficacy, restricts drug options, and increases the risk of human immunodeficiency virus (HIV) transmission. The resistance characteristics and associated risk factors of PLWH suffering from virological failure (VF) in Guangdong remain unclear, thus highlighting the need for further research in this area. This retrospective study examines the prevalence, resistance characteristics, and contributing factors of ADR among PLWH who experienced VF in Guangzhou, China, between 2018 and 2023.

Blood samples, epidemiological and demographic data were collected from PLWH with VF at Guangzhou Eight People’s Hospital in Guangzhou, China, between January 1, 2018 and December 1, 2023. ADR was analyzed through HIV pol sequences, with drug resistance mutations (DRMs) identified using the Stanford University HIV Drug Resistance Database. A 1:1 matched group of virologically suppressed (VS) patients was randomly selected using the "sample" function in R from those who maintained VS during the same study period to facilitate the study’s analysis of ADR-associated factors, which were chosen based on clinical relevance, previous studies, and data availability, and identified through logistic regression models.

A total of 1592 patients experienced VF during the study period, with 959 having protease/reverse transcriptase sequences and 479 having integrase sequences. DRMs were identified in 60.2% (577/959) of the patients, with an overall ADR prevalence of 46.1% (442/959). The resistance rates for specific drug classes were as follows: nucleotide reverse transcriptase inhibitors (NRTIs) at 33.3% (319/959), non-nucleoside reverse transcriptase inhibitors (NNRTIs) at 36.8% (353/959), protease inhibitors at 3.3% (32/959), and integrase strand transfer inhibitors (INSTIs) at 1.5% (7/479). The multivariable logistic regression analysis revealed several factors linked to a higher risk of ADR, including World Health Organization clinical stages III and IV, baseline CD4⁺ T cell counts <200 cells/mm³, and relatively more antiretroviral therapy regimen changes. Conversely, patients who were on 2NRTI+INSTI regimens and experienced heterosexual transmission were at relatively lower risk of ADR.

The prevalence of ADR in Guangzhou was primarily driven by NNRTI resistance. The choice and use of treatment regimens are closely linked to ADR occurrence, and minimizing unnecessary regimen changes may help significantly lower ADR risk.

Integrase Strand Transfer Inhibitors (INSTIs) have emerged as the preferred first-line antiretroviral therapy (ART) regimen globally, primarily due to their superior efficacy and favorable safety profile. However, in China, the high cost of INSTIs and their later market introduction have resulted in relatively limited reporting on INSTI-based regimens. Specifically, there is a lack of comprehensive data regarding side effects, immunological outcomes, and virological responses among the Chinese population living with human immunodeficiency virus (HIV). Against this backdrop, this cohort study aims to evaluate the changes in T-cells, laboratory parameters, viral decay, and CD8⁺ T-cell functional capacity after switching from non-INSTI-based regimens to INSTI-based regimens in virologically suppressed individuals living with HIV.

From December 2022 to May 2023, 59 adults (aged 18—60 years), all of whom had received more than three years of ART and achieved sustained virological suppression (plasma HIV RNA <200 copies/mL for ≥6 months), were enrolled in this study at the Fifth Medical Center of Chinese PLA General Hospital. The participants were divided into two groups according to whether they received elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (EVG/c/FTC/TAF)—that is, whether they switched to EVG/c/FTC/TAF (the INSTI group, n = 23) or maintained a non-nucleoside reverse transcriptase inhibitor (NNRTI)-or protease inhibitor (PI)-based regimen (the n-INSTI group, n = 36). Clinical and laboratory evaluations (including the CD4⁺ T-cell count, CD8⁺ T-cell count, CD4:CD8 ratio, and plasma HIV RNA) were performed at both baseline and week 24. Changes in participants’ HIV DNA, cell-associated (CA) HIV RNA, and CD8⁺ T-cell functional capacity (CD107a, perforin, granzyme-B, TNF-α, and IFN-γ) were assessed at baseline and weeks 2, 4, 8, 12, and 24.

At week 24, the INSTI group showed a significant increase in the CD4⁺ T-cell count from 497.30 ± 38.20 cells/µL to 594.92 ± 51.95 cells/µL (P<0.001) and in the CD4:CD8 ratio from 0.76 (0.53, 1.01) to 0.85 (0.57, 1.27) (P = 0.006), while the CD8⁺ T-cell count remained stable. The laboratory values showed improved liver function (alanine transaminase, aspartate aminotransferase) and decreased renal function (estimated Glomerular Filtration Rate, serum creatinine, blood urea nitrogen, uric acid) in the INSTI group. The CD8⁺ T-cell functional capacity, including the expression of CD107a, perforin, and granzyme-B on CD8⁺ T-cells, was significantly enhanced in the INSTI group. The HIV DNA and CA HIV RNA levels significantly decreased in the INSTI group, suggesting a reduction in the HIV reservoir in these participants.

The EVG/c/FTC/TAF regimen significantly improves immune recovery, enhances the CD8⁺ T-cell functional capacity, and reduces the HIV DNA and CA HIV RNA levels in virologically suppressed individuals.

HIV (human immunodeficiency virus)/HBV (hepatitis B virus) coinfection remains a significant public health challenge. HIV infection affects the natural course of chronic HBV infection, with HIV/HBV coinfected patients experiencing higher liver-related morbidity, hospitalization rates, and mortality than those with HBV monoinfection. Surprisingly, an increasing number of studies have shown that hepatitis B surface antigen (HBsAg) clearance rates in HIV/HBV coinfection can reach over 10%, which is significantly higher than in HBV monoinfection. In this review, we summarize the predictive factors for HBsAg clearance observed in HIV/HBV coinfection, including baseline HBsAg levels, baseline HBV DNA levels, baseline CD4+T cell-counts, and immune reconstitution inflammatory syndrome-related hepatic flare. Based on current evidence, we further discuss a potential mechanism for HBsAg clearance: HIV-induced immunodeficiency, particularly the depletion of CD4+ T cells, may unexpectedly disrupt preexisting HBV-specific tolerance. After antiretroviral therapy (ART) in HIV/HBV coinfected individuals, partial immune system reconstitution occurs, and the reconstituted immune system, no longer tolerized by HBV, effectively clears HBV-infected hepatocytes, triggering transient hepatitis and ultimately achieving a functional cure through HBsAg clearance. Additionally, emerging data suggest that the underlying immunological mechanisms of HBsAg clearance in HIV/HBV coinfection may primarily involve: PD-1/PD-L1 pathway inhibition, cytokine induction promoting immune cell recruitment and an inflammatory environment, and natural killer (NK) cell functional remodeling. These collective observations highlight the important role of immune modulation in HBV clearance, providing insights that can facilitate the development of a functional HBV cure. Identifying the mechanisms involved in HBsAg loss in HIV/HBV patients may facilitate the development of drugs that mimic these anti-HBV responses.

Long coronavirus disease (COVID) is defined as the continuation or development of new symptoms three months after the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, and that last for at least two months, with no other explanation for their cause. This disease includes various clinical manifestations that affect multiple organ systems, such as complications in respiratory, cardiovascular, neurological, and musculoskeletal systems. The most commonly reported symptoms include fatigue, cognitive dysfunction, dyspnea, and chest pain; however, the prevalence and severity of these symptoms vary greatly among individuals. The underlying mechanisms of long COVID are complex and multifaceted, encompassing viral persistence, immune system dysfunction, mitochondrial abnormalities, endothelial impairment, and alterations in the microbiome. Further, long COVID has imposed a significant burden on individuals, healthcare systems, and the economy by impairing an individual’s quality of life and functional capacity, thereby increasing costs and demand for care and rehabilitation services. This review summarizes the definition, phenotypes, mechanisms, and current treatment advancements of long COVID and highlights specific research directions for future investigation.

Although the coronavirus disease 2019 (COVID-19) pandemic has ended, the enduring health impacts of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection continue to garner global attention, as approximately 10% of patients develop long COVID (post COVID-19 condition). The epidemiological characteristics and symptoms of long COVID have been reported, and various pathogenic hypotheses have been proposed. Recent evidence suggests that SARS-CoV-2 nucleic acids or fragments persist in some patients post-infection and that these are correlated with long COVID symptoms. This review focuses on clinical studies linking SARS-CoV-2 persistence to long COVID symptoms, and explores the relationship between viral persistence and other etiological hypotheses, such as immune dysregulation, vascular issues, coagulation dysfunction, microbiome dysbiosis, brainstem/vagus nerve signaling dysfunction, and latent virus reactivation. Futhermore, treatment strategies for long COVID are proposed based on current clinical trials of antiviral and immune modulation therapies. Understanding the role of viral persistence in long COVID pathogenesis is critical for developing targeted therapies and improving clinical management of this debilitating condition.

The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has significantly burdened global public health. However, the tropism of SARS-CoV-2 within the human body remains not fully understood. In this review, we overview the literature on SARS-CoV-2 infection across various human organs and tissues. We summarize the relevant specimen types, techniques for examining SARS-CoV-2 tropism, and findings at both organ/tissue and cellular levels. To systematically evaluate the evidence supporting SARS-CoV-2 tissue tropism, we establish a hierarchical classification system based on two key criteria: (1) specimen origin and (2) detection methodology. Clinical specimens obtained directly from COVID-19 patients provide the most definitive evidence, whereas organoid-derived specimens and animal models indicate potential infectivity under artificial conditions. In terms of detection methods, we prioritize viral particle identification over viral protein or RNA detection, as the latter requires further confirmation to establish productive infection. Our findings indicate that SARS-CoV-2 potentially targets multiple human organ systems, including the respiratory tract, lungs, kidneys, heart, blood vessels, pancreas, small intestine, liver, and salivary glands. By contrast, viral tropism for the central nervous system and the reproductive system remains uncertain and requires further validation. At the cellular level, we identify specific target cell types vulnerable to infection, including ciliated epithelial cells, alveolar type II pneumocytes, enterocytes, cardiomyocytes, vascular endothelial cells, renal tubular epithelial cells, and pancreatic acinar cells. Furthermore, we analyze the correlation between angiotensin-converting enzyme 2 receptor distribution patterns and viral tropism, as well as potential variations in tissue specificity among different viral variants. We expect this review to provide a comprehensive landscape of SARS-CoV-2 tropism and enhance our understanding of the life cycle and consequences of SARS-CoV-2 infection within the human body.

Immune reconstitution inflammatory syndrome (IRIS) is a collection of inflammatory disorders characterized by the paradoxical worsening of preexisting infections processes following the initiation of antiretroviral therapy in human immunodeficiency virus (HIV)-infected individuals. Diagnosing IRIS accurately and promptly remains challenging in areas with limited medical resources. Herpes simplex virus-2 (HSV-2) is highly endemic in sub-Saharan Africa and is one of the primary opportunistic pathogens underlying IRIS, manifesting as mucocutaneous lesions. Here, we report a case of HSV-2-associated IRIS presenting as a genital ulcer, confirmed through nanopore high-throughput sequencing and successfully treated with acyclovir antiviral therapy. This study emphasizes the importance of clinicians maintaining proficiency in recognizing IRIS manifestations and being aware of region-specific opportunistic pathogens, both essential for timely diagnosis and etiology-directed therapy.

To the Editor: