CNS HIV Escape Presenting as VP Shunt Malfunction - A Rare Clinical Entity

CNS HIV Escape Presenting as VP Shunt Malfunction - A Rare Clinical Entity | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Case Report CNS HIV Escape Presenting as VP Shunt Malfunction - A Rare Clinical Entity Preeti Singh, Harsh Patel, Abhaya Kumar This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8125428/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background Ventriculoperitoneal (VP) shunt malfunction is a common neurosurgical problem. In contrast, central nervous system (CNS) HIV Escape is exceedingly rare and is almost never the initial presentation of HIV infection. This case highlights a unique neurosurgery–infectious disease intersection where CNS HIV Escape clinically mimicked shunt failure. Case Description: A 38-year-old male presented with severe headache, vomiting, and altered sensorium. MRI revealed obstructive hydrocephalus, for which a VP shunt was placed with subsequent clinical improvement. One year later, he developed confusion and visual blurring. MRI demonstrated diffuse periventricular hyperintensities with stable ventricular size and a functioning shunt. CSF analysis, including routine parameters, was unremarkable. However, markedly elevated CSF HIV RNA in the setting of undetectable plasma HIV RNA confirmed the diagnosis of CNS HIV Escape. The patient was started on antiretroviral therapy with high CNS penetration, resulting in significant clinical improvement. Conclusion CNS HIV Escape can closely simulate VP shunt malfunction and may rarely present as the first manifestation of HIV infection. Recognizing this uncommon entity can prevent unnecessary surgical intervention and underscores the importance of CSF viral studies in atypical neurological presentations. Neurosurgery CNS HIV Escape CSF HIV RNA MRI VP shunt Figures Figure 1 Figure 2 Figure 3 Introduction Ventriculoperitoneal (VP) shunting is a standard and widely performed procedure for managing hydrocephalus, yet postoperative evaluation can be clinically challenging. Shunt malfunction—whether due to mechanical obstruction, infection, or over-/under-drainage—is a frequent concern and typically prompts urgent imaging and, at times, surgical revision. However, a subset of patients present with symptoms that mimic shunt failure despite stable ventricular size and an intact shunt system. In such cases, identifying alternative neurological or systemic causes becomes essential to avoid unnecessary operative interventions. Among the wide spectrum of conditions that can simulate shunt dysfunction, central nervous system (CNS) HIV Escape is exceptionally rare. CNS HIV Escape is characterized by detectable or elevated cerebrospinal fluid (CSF) HIV RNA levels disproportionately higher than plasma HIV RNA levels, indicating compartmentalized viral replication within the CNS. Clinically, it manifests as cognitive decline, behavioral changes, encephalopathy, or focal deficits—features that can closely resemble shunt-related complications. The phenomenon has been largely documented in individuals with known HIV infection, particularly those on antiretroviral therapy (ART), where suboptimal CNS penetration of ART leads to isolated intrathecal viral replication. Importantly, CNS HIV Escape has never been reported as the initial clinical presentation of HIV infection . Its occurrence in an ART-naïve patient with a VP shunt creates a unique diagnostic dilemma. The resulting overlap of symptoms—headache, altered mental status, visual disturbances—may be misinterpreted as shunt obstruction or malfunction, especially when neuroimaging reveals nonspecific white-matter changes. This case is thus uniquely significant for three reasons: It represents a previously unreported scenario where CNS HIV Escape was the patient’s first manifestation of HIV infection. It clinically mimicked VP shunt malfunction , posing a substantial diagnostic pitfall. It highlights the crucial role of CSF virology in evaluating atypical neurological deterioration in shunted patients, especially when imaging and shunt assessment do not correlate with suspected mechanical failure. By presenting this rare neurosurgery–infectious disease crossover, we aim to broaden the differential diagnosis for shunted patients who exhibit unexplained neurological decline and emphasize the importance of considering compartmentalized viral processes before proceeding with invasive surgical management. Case Report A 38-year-old male, previously seronegative for HIV, presented with severe headache, vomiting, and altered sensorium secondary to obstructive hydrocephalus. He underwent ventriculoperitoneal (VP) shunt placement with satisfactory initial recovery. One year later, he developed subacute confusion, worsening headache, and visual blurring. Repeat MRI showed new diffuse periventricular white-matter changes, unchanged ventricular dimensions, and no evidence of mechanical shunt failure. CSF analysis, including cell counts, protein, and glucose, was normal, and CSF cultures were sterile, making shunt dysfunction unlikely. Repeat HIV serology, previously non-reactive at the time of his initial presentation, was now reactive, indicating recent seroconversion. CSF HIV RNA was markedly elevated at 1.2 × 10⁵ copies/mL, while plasma viral load remained < 50 copies/mL, confirming CNS HIV Escape. Given his immunocompetent status and new seroconversion, CNS HIV Escape as the first clinical manifestation of HIV infection was exceptionally unusual. A protective CCR5 mutation was excluded, and further testing identified a CXCR4-tropic viral strain, known for its high neurotropism. The patient was started on antiretroviral therapy with high CNS penetration, leading to rapid neurological improvement. Follow-up MRI showed regression of the periventricular white-matter abnormalities. Discussion CNS HIV Escape is a phenomenon characterized by compartmentalized viral replication in the central nervous system (CNS) —typically with elevated HIV RNA in cerebrospinal fluid (CSF) despite suppressed or undetectable plasma viremia. While most documented cases occur in patients on antiretroviral therapy (ART), particularly where the CNS penetration of the ART regimen is suboptimal ( 6 , 8 , 14 , 15 ), our patient was ART-naïve , making this presentation highly unusual and strongly suggestive of early neuroinvasion and autonomous CNS viral replication. Early CNS Seeding and Compartmentalization. Several studies have shown that HIV can enter the CNS very early during infection, even in ART-naïve individuals. In primary infection, compartmentalization between CSF and plasma has been documented ( 14 ), suggesting that the CNS may serve as a reservoir soon after systemic infection. Genetic and phenotypic analyses further support this notion: distinct viral populations in CSF can evolve independently, reflecting local replication in CNS-resident cells ( 3 , 11 , 14 ). Cellular Reservoirs in CNS. The CNS reservoir is believed to be largely composed of long-lived myeloid cells such as microglia and perivascular macrophages ( 17 , 12 , 13 ). Recent work has directly isolated replication-competent HIV from microglia in the brains of ART-suppressed individuals, demonstrating that microglia harbor intact proviruses ( 2 , 4 ). Macrophages/microglia harbor HIV DNA during suppressive therapy ( 12 ) and are a key challenge for eradication ( 5 ). Co-receptor Usage and Neurotropism. The ability of HIV to infect CNS cells is tightly linked to its co-receptor tropism. Classical neurotropic viruses are often macrophage-tropic (M-tropic), replicating in cells with low CD4 expression ( 4 ). Interestingly, brain-derived HIV variants do not always conform strictly to CCR5 (R5) usage: some use CXCR4, or even both CCR5 and CXCR4 ( 4 , 9 ). Our patient’s virus being CXCR4-tropic supports a model wherein neurotropic variants with high CNS affinity may seed early and replicate within the CNS compartment. Influence of VP Shunt on CSF Dynamics. The presence of a ventriculoperitoneal (VP) shunt may have significantly altered CSF flow dynamics, potentially creating microenvironments favoring localized viral replication or sequestration. While there are no direct precedents for shunt-related CSF escape, altered flow could theoretically reduce washout of infected cells or viral particles, facilitating compartmental persistence. Clinical Overlap with Shunt Malfunction. The clinical and radiological overlap between CNS HIV Escape and shunt malfunction can be striking. Both can present with headaches, cognitive decline, visual symptoms, periventricular white matter changes on MRI, but in our case, the stable ventricle size , intact shunt , and normal routine CSF parameters argued strongly against mechanical failure. Recognition of CNS HIV Escape prevented unnecessary surgical revision. Inflammation and Biomarkers. In neurosymptomatic CSF escape (NSE), CSF biomarkers correlate with viral diversity and inflammation, suggesting that ongoing replication drives immunopathology ( 9 , 11 ). Though our case did not show gross CSF abnormalities, the presence of high CSF HIV RNA implies that local inflammatory processes (perhaps subtle) could still contribute to neurological symptoms. Therapeutic Implications. Optimal ART selection in CNS escape is critical. Drugs with high CNS penetration should be prioritized, and resistance profiles from CSF should be considered ( 15 ). Following initiation of a CNS-penetrant ART regimen, our patient improved rapidly, echoing prior reports of neurological recovery after therapy optimization ( 5 , 8 ). Uniqueness and Significance. To our knowledge, this is among the first reported cases of CNS HIV Escape manifesting as the initial presentation of HIV infection in an ART-naïve patient with a VP shunt . This underscores an important diagnostic pitfall in neurosurgery: not all “shunt malfunctions” are mechanical; infectious and virological etiologies—including compartmentalized HIV—must be considered, especially when imaging and CSF studies are incongruent with shunt failure. Limitations and Future Directions. As this is an isolated case, causality (e.g., precise role of shunt in facilitating escape) is speculative. Longitudinal studies and more cases are needed to validate this mechanism. Future work should explore the dynamics of CSF flow post-shunt and its influence on viral compartmentalization, and also systematic screening for CSF HIV RNA in atypical post-shunt neurological presentations. Conclusion CNS HIV Escape can clinically and radiologically mimic ventriculoperitoneal shunt malfunction, making diagnosis particularly challenging in neurosurgical practice. This case is the first reported instance of CNS HIV Escape presenting as the initial manifestation of HIV infection in an ART-naïve individual with a functioning VP shunt. Stable ventricular size, normal CSF parameters, and atypical white-matter changes should prompt clinicians to consider CNS HIV Escape in the differential diagnosis, even when routine HIV serology is newly reactive or only weakly positive. Incorporating CSF HIV RNA quantification and plasma–CSF viral load comparison into the evaluation of such patients is crucial. Early identification allows prompt initiation of antiretroviral therapy with high CNS penetration, which can lead to rapid neurological recovery and prevents unnecessary surgical intervention. Declarations Acknowledgement The authors express their sincere gratitude to Dr. Abhaya Kumar for his guidance, exceptional neurosurgical expertise, and the opportunity to learn under his mentorship. His clinical insight and support were invaluable in the management of this case and in the preparation of this report. Consent Consent has been taken from the patient to publish the study References Edén A, Fuchs D, Hagberg L, Nilsson S, Spudich S, Svennerholm B et al (2010) HIV-1 viral escape in cerebrospinal fluid of subjects on suppressive antiretroviral treatment. J Infect Dis 202(12):1819–1825 Tang Y, Chaillon A, Gianella S, Wong LM, Li D, Margolis DM, Jiang G (2023) Brain microglia serve as a persistent HIV reservoir despite durable antiretroviral therapy. 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2","display":"","copyAsset":false,"role":"figure","size":189198,"visible":true,"origin":"","legend":"\u003cp\u003eMRI Brain showing new diffuse periventricular white-matter changes\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-8125428/v1/11eea7ea4157d39244c79624.png"},{"id":96162281,"identity":"79b5ee45-0222-4074-9808-b71d53397fc0","added_by":"auto","created_at":"2025-11-18 08:58:31","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":252163,"visible":true,"origin":"","legend":"\u003cp\u003eMRI Brain showing \u003cstrong\u003eregression of the periventricular white-matter abnormalities.\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-8125428/v1/4f5eaf5f55743b44cb7d9884.png"},{"id":96257111,"identity":"cbff3af1-69ff-4b2d-88db-63dc678a8730","added_by":"auto","created_at":"2025-11-19 07:51:33","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1684181,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8125428/v1/5773b2be-0898-4fa0-a283-46aef1f18f0e.pdf"}],"financialInterests":"The authors declare no competing interests.","formattedTitle":"\u003cp\u003eCNS HIV Escape Presenting as VP Shunt Malfunction - A Rare Clinical Entity\u003c/p\u003e","fulltext":[{"header":"Introduction","content":"\u003cp\u003eVentriculoperitoneal (VP) shunting is a standard and widely performed procedure for managing hydrocephalus, yet postoperative evaluation can be clinically challenging. Shunt malfunction\u0026mdash;whether due to mechanical obstruction, infection, or over-/under-drainage\u0026mdash;is a frequent concern and typically prompts urgent imaging and, at times, surgical revision. However, a subset of patients present with symptoms that mimic shunt failure despite stable ventricular size and an intact shunt system. In such cases, identifying alternative neurological or systemic causes becomes essential to avoid unnecessary operative interventions.\u003c/p\u003e\u003cp\u003eAmong the wide spectrum of conditions that can simulate shunt dysfunction, central nervous system (CNS) HIV Escape is exceptionally rare. CNS HIV Escape is characterized by detectable or elevated cerebrospinal fluid (CSF) HIV RNA levels disproportionately higher than plasma HIV RNA levels, indicating compartmentalized viral replication within the CNS. Clinically, it manifests as cognitive decline, behavioral changes, encephalopathy, or focal deficits\u0026mdash;features that can closely resemble shunt-related complications. The phenomenon has been largely documented in individuals with known HIV infection, particularly those on antiretroviral therapy (ART), where suboptimal CNS penetration of ART leads to isolated intrathecal viral replication.\u003c/p\u003e\u003cp\u003eImportantly, CNS HIV Escape has \u003cb\u003enever been reported as the initial clinical presentation of HIV infection\u003c/b\u003e. Its occurrence in an ART-na\u0026iuml;ve patient with a VP shunt creates a unique diagnostic dilemma. The resulting overlap of symptoms\u0026mdash;headache, altered mental status, visual disturbances\u0026mdash;may be misinterpreted as shunt obstruction or malfunction, especially when neuroimaging reveals nonspecific white-matter changes.\u003c/p\u003e\u003cp\u003eThis case is thus uniquely significant for three reasons:\u003c/p\u003e\u003cp\u003e\u003col\u003e\u003cspan\u003e\u003cli\u003e\u003cp\u003e\u003cb\u003eIt represents a previously unreported scenario\u003c/b\u003e where CNS HIV Escape was the patient\u0026rsquo;s first manifestation of HIV infection.\u003c/p\u003e\u003c/li\u003e\u003c/span\u003e\u003cspan\u003e\u003cli\u003e\u003cp\u003e\u003cb\u003eIt clinically mimicked VP shunt malfunction\u003c/b\u003e, posing a substantial diagnostic pitfall.\u003c/p\u003e\u003c/li\u003e\u003c/span\u003e\u003cspan\u003e\u003cli\u003e\u003cp\u003e\u003cb\u003eIt highlights the crucial role of CSF virology\u003c/b\u003e in evaluating atypical neurological deterioration in shunted patients, especially when imaging and shunt assessment do not correlate with suspected mechanical failure.\u003c/p\u003e\u003c/li\u003e\u003c/span\u003e\u003c/ol\u003e\u003c/p\u003e\u003cp\u003eBy presenting this rare neurosurgery\u0026ndash;infectious disease crossover, we aim to broaden the differential diagnosis for shunted patients who exhibit unexplained neurological decline and emphasize the importance of considering compartmentalized viral processes before proceeding with invasive surgical management.\u003c/p\u003e"},{"header":"Case Report","content":"\u003cp\u003eA 38-year-old male, previously seronegative for HIV, presented with severe headache, vomiting, and altered sensorium secondary to obstructive hydrocephalus. He underwent ventriculoperitoneal (VP) shunt placement with satisfactory initial recovery.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eOne year later, he developed subacute confusion, worsening headache, and visual blurring. Repeat MRI showed new diffuse periventricular white-matter changes, unchanged ventricular dimensions, and no evidence of mechanical shunt failure.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eCSF analysis, including cell counts, protein, and glucose, was normal, and CSF cultures were sterile, making shunt dysfunction unlikely. Repeat HIV serology, previously non-reactive at the time of his initial presentation, was now reactive, indicating recent seroconversion. CSF HIV RNA was markedly elevated at 1.2 \u0026times; 10⁵ copies/mL, while plasma viral load remained\u0026thinsp;\u0026lt;\u0026thinsp;50 copies/mL, confirming CNS HIV Escape. Given his immunocompetent status and new seroconversion, CNS HIV Escape as the \u003cem\u003efirst clinical manifestation\u003c/em\u003e of HIV infection was exceptionally unusual. A protective CCR5 mutation was excluded, and further testing identified a CXCR4-tropic viral strain, known for its high neurotropism. The patient was started on antiretroviral therapy with high CNS penetration, leading to rapid neurological improvement. Follow-up MRI showed regression of the periventricular white-matter abnormalities.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eCNS HIV Escape is a phenomenon characterized by \u003cb\u003ecompartmentalized viral replication in the central nervous system (CNS)\u003c/b\u003e\u0026mdash;typically with elevated HIV RNA in cerebrospinal fluid (CSF) despite suppressed or undetectable plasma viremia. While most documented cases occur in patients on antiretroviral therapy (ART), particularly where the CNS penetration of the ART regimen is suboptimal (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e), our patient was \u003cb\u003eART-na\u0026iuml;ve\u003c/b\u003e, making this presentation highly unusual and strongly suggestive of \u003cb\u003eearly neuroinvasion\u003c/b\u003e and autonomous CNS viral replication.\u003c/p\u003e\u003cp\u003e\u003cb\u003eEarly CNS Seeding and Compartmentalization.\u003c/b\u003e Several studies have shown that HIV can enter the CNS very early during infection, even in ART-na\u0026iuml;ve individuals. In primary infection, compartmentalization between CSF and plasma has been documented (\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e), suggesting that the CNS may serve as a reservoir soon after systemic infection. Genetic and phenotypic analyses further support this notion: distinct viral populations in CSF can evolve independently, reflecting local replication in CNS-resident cells (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003cb\u003eCellular Reservoirs in CNS.\u003c/b\u003e The CNS reservoir is believed to be largely composed of long-lived myeloid cells such as \u003cb\u003emicroglia\u003c/b\u003e and perivascular macrophages (\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e). Recent work has directly isolated replication-competent HIV from microglia in the brains of ART-suppressed individuals, demonstrating that microglia harbor intact proviruses (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e). Macrophages/microglia harbor HIV DNA during suppressive therapy (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e) and are a key challenge for eradication (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003cb\u003eCo-receptor Usage and Neurotropism.\u003c/b\u003e The ability of HIV to infect CNS cells is tightly linked to its co-receptor tropism. Classical neurotropic viruses are often macrophage-tropic (M-tropic), replicating in cells with low CD4 expression (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e). Interestingly, brain-derived HIV variants do not always conform strictly to CCR5 (R5) usage: some use CXCR4, or even both CCR5 and CXCR4 (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e). Our patient\u0026rsquo;s virus being \u003cb\u003eCXCR4-tropic\u003c/b\u003e supports a model wherein neurotropic variants with high CNS affinity may seed early and replicate within the CNS compartment.\u003c/p\u003e\u003cp\u003e\u003cb\u003eInfluence of VP Shunt on CSF Dynamics.\u003c/b\u003e The presence of a ventriculoperitoneal (VP) shunt may have significantly altered CSF flow dynamics, potentially creating microenvironments favoring \u003cb\u003elocalized viral replication\u003c/b\u003e or sequestration. While there are no direct precedents for shunt-related CSF escape, altered flow could theoretically reduce washout of infected cells or viral particles, facilitating compartmental persistence.\u003c/p\u003e\u003cp\u003e\u003cb\u003eClinical Overlap with Shunt Malfunction.\u003c/b\u003e The clinical and radiological overlap between CNS HIV Escape and shunt malfunction can be striking. Both can present with headaches, cognitive decline, visual symptoms, periventricular white matter changes on MRI, but in our case, the \u003cb\u003estable ventricle size\u003c/b\u003e, \u003cb\u003eintact shunt\u003c/b\u003e, and \u003cb\u003enormal routine CSF parameters\u003c/b\u003e argued strongly against mechanical failure. Recognition of CNS HIV Escape prevented unnecessary surgical revision.\u003c/p\u003e\u003cp\u003e\u003cb\u003eInflammation and Biomarkers.\u003c/b\u003e In neurosymptomatic CSF escape (NSE), CSF biomarkers correlate with viral diversity and inflammation, suggesting that ongoing replication drives immunopathology (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e). Though our case did not show gross CSF abnormalities, the presence of high CSF HIV RNA implies that local inflammatory processes (perhaps subtle) could still contribute to neurological symptoms.\u003c/p\u003e\u003cp\u003e\u003cb\u003eTherapeutic Implications.\u003c/b\u003e Optimal ART selection in CNS escape is critical. Drugs with \u003cb\u003ehigh CNS penetration\u003c/b\u003e should be prioritized, and resistance profiles from CSF should be considered (\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e). Following initiation of a CNS-penetrant ART regimen, our patient improved rapidly, echoing prior reports of neurological recovery after therapy optimization (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003cb\u003eUniqueness and Significance.\u003c/b\u003e To our knowledge, this is among the \u003cb\u003efirst reported cases of CNS HIV Escape manifesting as the initial presentation of HIV infection in an ART-na\u0026iuml;ve patient with a VP shunt\u003c/b\u003e. This underscores an important diagnostic pitfall in neurosurgery: not all \u0026ldquo;shunt malfunctions\u0026rdquo; are mechanical; infectious and virological etiologies\u0026mdash;including compartmentalized HIV\u0026mdash;must be considered, especially when imaging and CSF studies are incongruent with shunt failure.\u003c/p\u003e\u003cp\u003e\u003cb\u003eLimitations and Future Directions.\u003c/b\u003e As this is an isolated case, causality (e.g., precise role of shunt in facilitating escape) is speculative. Longitudinal studies and more cases are needed to validate this mechanism. Future work should explore the dynamics of CSF flow post-shunt and its influence on viral compartmentalization, and also systematic screening for CSF HIV RNA in atypical post-shunt neurological presentations.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eCNS HIV Escape can clinically and radiologically mimic ventriculoperitoneal shunt malfunction, making diagnosis particularly challenging in neurosurgical practice. This case is \u003cb\u003ethe first reported instance of CNS HIV Escape presenting as the initial manifestation of HIV infection\u003c/b\u003e in an ART-na\u0026iuml;ve individual with a functioning VP shunt. Stable ventricular size, normal CSF parameters, and atypical white-matter changes should prompt clinicians to consider CNS HIV Escape in the differential diagnosis, even when routine HIV serology is newly reactive or only weakly positive. Incorporating \u003cb\u003eCSF HIV RNA quantification and plasma\u0026ndash;CSF viral load comparison\u003c/b\u003e into the evaluation of such patients is crucial. Early identification allows prompt initiation of antiretroviral therapy with high CNS penetration, which can lead to rapid neurological recovery and prevents unnecessary surgical intervention.\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch2\u003eAcknowledgement\u003c/h2\u003e\u003cp\u003eThe authors express their sincere gratitude to \u003cb\u003eDr. Abhaya Kumar\u003c/b\u003e for his guidance, exceptional neurosurgical expertise, and the opportunity to learn under his mentorship. His clinical insight and support were invaluable in the management of this case and in the preparation of this report.\u003c/p\u003e\u003ch2\u003eConsent\u003c/h2\u003e\u003cp\u003eConsent has been taken from the patient to publish the study\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eEd\u0026eacute;n A, Fuchs D, Hagberg L, Nilsson S, Spudich S, Svennerholm B et al (2010) HIV-1 viral escape in cerebrospinal fluid of subjects on suppressive antiretroviral treatment. J Infect Dis 202(12):1819\u0026ndash;1825\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eTang Y, Chaillon A, Gianella S, Wong LM, Li D, Margolis DM, Jiang G (2023) Brain microglia serve as a persistent HIV reservoir despite durable antiretroviral therapy. 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(From J Med Virol) PubMed\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eRole of microglia turnover and longevity in HIV reservoir maintenance. \u003cem\u003eFront Cell Infect Microbiol.\u003c/em\u003e Frontiers\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eAstrocytes and their limited capacity as HIV reservoirs: review. OUP Academic\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eLatent reservoir challenges in CNS HIV cure strategies. PubMed\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eGenetic diversity and resistance in CSF escape populations. (JCI) JCI\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eViral compartmentalization during early infection and effect on long-term CNS reservoir. NATAP\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eEntry phenotypes of brain-derived HIV clones: low CD4 affinity, M-tropism vs T-tropism. Ovid\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003ePharmacologic approaches to HIV-associated neurocognitive disorder: focus on CNS penetration. (Review) MDPI\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eCNS reservoir as a barrier to HIV eradication: review of anatomical and pharmacological challenges. Curr Opin Virol PubMed\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"kokilaben dhirubhai ambani hospital \u0026 research institute","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"CNS HIV Escape, CSF, HIV, RNA, MRI, VP shunt","lastPublishedDoi":"10.21203/rs.3.rs-8125428/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8125428/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cb\u003eBackground\u003c/b\u003e\u003c/p\u003e\u003cp\u003eVentriculoperitoneal (VP) shunt malfunction is a common neurosurgical problem. In contrast, central nervous system (CNS) HIV Escape is exceedingly rare and is almost never the initial presentation of HIV infection. This case highlights a unique neurosurgery\u0026ndash;infectious disease intersection where CNS HIV Escape clinically mimicked shunt failure.\u003c/p\u003e\u003cp\u003e\u003cb\u003eCase Description:\u003c/b\u003e\u003c/p\u003e\u003cp\u003eA 38-year-old male presented with severe headache, vomiting, and altered sensorium. MRI revealed obstructive hydrocephalus, for which a VP shunt was placed with subsequent clinical improvement. One year later, he developed confusion and visual blurring. MRI demonstrated diffuse periventricular hyperintensities with stable ventricular size and a functioning shunt. CSF analysis, including routine parameters, was unremarkable. However, markedly elevated CSF HIV RNA in the setting of undetectable plasma HIV RNA confirmed the diagnosis of CNS HIV Escape. The patient was started on antiretroviral therapy with high CNS penetration, resulting in significant clinical improvement.\u003c/p\u003e\u003cp\u003e\u003cb\u003eConclusion\u003c/b\u003e\u003c/p\u003e\u003cp\u003eCNS HIV Escape can closely simulate VP shunt malfunction and may rarely present as the first manifestation of HIV infection. Recognizing this uncommon entity can prevent unnecessary surgical intervention and underscores the importance of CSF viral studies in atypical neurological presentations.\u003c/p\u003e","manuscriptTitle":"CNS HIV Escape Presenting as VP Shunt Malfunction - A Rare Clinical Entity","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-11-18 08:58:26","doi":"10.21203/rs.3.rs-8125428/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"d5ca8a68-e202-4353-953c-83a5011548a3","owner":[],"postedDate":"November 18th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":58056925,"name":"Neurosurgery"}],"tags":[],"updatedAt":"2025-11-18T08:58:27+00:00","versionOfRecord":[],"versionCreatedAt":"2025-11-18 08:58:26","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8125428","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8125428","identity":"rs-8125428","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}