We report a rare case of malignant solitary fibrous tumor (MSFT) in the cervical region presenting with aggressive bone destruction and lung metastasis in a 54-year-old HIV-infected male. The patient, who was on long-term antiretroviral therapy (EFV + 3TC+TDF), presented with a 5-month history of a progressively enlarging mass in the posterior neck (approx. 10.0 cm x 8.0 cm x 4.0 cm) accompanied by radiating pain in the right upper limb. Initial imaging revealed an osteolytic, destructive lesion involving the C3-C5 vertebrae and multiple solid pulmonary nodules, suspicious for malignancy. Preliminary biopsy and immunohistochemistry initially suggested a mesenchymal malignant tumor, possibly a BCOR-altered sarcoma. Following a multidisciplinary team (MDT) consultation and according to the 2024 CSCO guidelines for bone and soft tissue tumors, the patient received two cycles of neoadjuvant chemotherapy (Epirubicin 30mg D1-D3 and Ifosfamide 2g D1-D5). Subsequent surgical resection was performed, and definitive histopathological and immunohistochemical analysis of the postoperative specimen confirmed MSFT (STAT6+, CD34+, P53 mutant type ~85%, and Ki-67 ~60%). This case emphasizes the diagnostic challenge of differentiating rare spindle cell sarcomas in HIV-infected patients; high-grade MSFT can mimic other aggressive sarcomas, and comprehensive postoperative pathological evaluation, especially STAT6 staining, is essential for definitive diagnosis and tailoring oncological management.

The World Health Organization (WHO) recommends human immunodeficiency virus (HIV) drug resistance testing (DRT), but current tests are too complex and expensive for routine use. Genotypic DRT is challenging to interpret because of the growing list of mutations responsible for HIV drug resistance. Although phenotypic DRT is simpler to interpret, it requires slow and labor-intensive viral culture. Phenotypic tests that measure the activity of isolated HIV enzymes are faster and less labor-intensive, but none have yet met the 2023 WHO Target Product Profile (TPP) for HIV DRT. Here, we present an optimized product-enhanced reverse transcriptase (PERT) assay for sensitive and quantitative detection of HIV viral load and drug resistance. PERT combines complementary DNA (cDNA) synthesis by HIV-reverse transcriptase (HIV-RT) with cDNA amplification and detection by quantitative PCR (qPCR). We established sensitive detection down to 10 HIV-RT molecules in a 25 µL sample corresponding to a viral load of ~10 HIV RNA copies/mL. We demonstrated the assay's feasibility for phenotypic DRT using lamivudine-5'-triphosphate (3TC-TP)-to which the M184V mutation confers high-level resistance-and quantified 3TC-TP inhibition using the difference in cDNA produced between drug and no-drug conditions. We surpassed WHO minimal analytical sensitivity requirements (20% low-abundance variant detection) by differentiating 10% M184V HIV-RT fractions in heterogeneous mixtures (1,000 total HIV-RT, viral load ~2,500 copies RNA/mL). Finally, we showed that PERT could detect resistance to existing and emerging RT inhibitors, including tenofovir-diphosphate (TFV-DP), doravirine (DOR), and islatravir (ISL)-TP.IMPORTANCEAlthough antiretroviral therapy can effectively treat and prevent HIV infection, treatment efficacy and global control of the HIV epidemic are threatened by rising rates of HIV drug resistance. Inexpensive and decentralized HIV drug resistance testing (DRT) could facilitate surveillance efforts to understand the prevalence of HIV drug resistance in local and global contexts. This need is especially timely and pressing considering anticipated increased rates of HIV acquisition and drug resistance due to the reductions in global HIV services driven by recent funding cuts. Our optimized product-enhanced reverse transcriptase (PERT) assay for simultaneous viral load and phenotypic drug resistance quantification is fast (~2 h), sensitive, and accurate. We can also leverage existing RT-qPCR instruments used for viral load measurement to significantly improve access to HIV drug resistance monitoring and tailored regimen selection.

SIRT1, a sirtuin family member, has been extensively documented to be closely linked to aging and aging-related disease. Cellular senescence is a state of irreversible cell cycle arrest that functions as a key driver of aging. During cellular senescence, LINE-1 (L1) retrotransposable elements become transcriptionally activated and stimulate a type-I interferon (IFN-I) response. L1 activity has been strongly linked to aging and a variety of age-related disorders. However, whether SIRT1 influences cellular senescence through the transposable element L1 remains unknown. In this study, we discovered that SIRT1 significantly suppresses L1 retrotransposition. Under quiescent conditions, SIRT1 exhibits increased enrichment at the L1 5'-UTR region. This recruitment enhances its interaction with the heterochromatin-regulatory factors Lamin B1 and KAP1, subsequently elevating H3K9me3 levels. This repressive chromatin mark inhibits L1 transcription, thereby maintaining genomic stability and delaying cellular senescence. Consistent with these observations, SIRT1-deficient cell lines exhibited a marked reduction of the interaction of Lamin B1 and KAP1 and a reduced presence of these factors at the L1 5'-UTR. Consequently, the elevated L1 transcription resulting from SIRT1 deficiency activated the cGAS-STING pathway and ultimately triggered cellular senescence, an effect that was rescued by treatment with 3TC (a nucleoside reverse transcriptase inhibitor). In summary, our findings demonstrate that SIRT1 suppresses L1 retrotransposition by recruiting heterochromatin factors, thereby delaying cellular senescence and providing new insights with implications for delaying aging and mitigating age-related pathologies.

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.

Although hepatitis C virus (HCV) infection is typically diagnosed by anti-HCV antibody testing, rare cases of seronegative HCV infection, defined by detectable HCV ribonucleic acid (RNA) in the absence of antibodies, have been reported in a small number of human immunodeficiency virus (HIV)-positive patients. We describe the case of an HIV-positive patient with persistently elevated alanine aminotransferase levels who was found to have a high HCV RNA viral load (1,140,000 IU/mL) despite a negative HCV antibody screening. The patient had been receiving combination antiretroviral therapy (cART) initially with efavirenz, TAF and 3TC, and was later switched to bictegravir/TAF/3TC. Following hepatological evaluation and initiation of sofosbuvir/velpatasvir therapy, plasma HCV RNA became undetectable. Remarkably, this patient, who maintained a stable immunological profile, also exhibited spontaneous HIV seroreversion, characterized by the loss of detectable HIV-specific antibodies. These observations illustrate the importance of a molecular-based diagnostic approach to complement serological testing in individuals at risk for HIV-related infections.