Persistent Intrathecal Immune Activation in HIV-1-Infected Individuals on Antiretroviral Therapy

Yilmaz, Aylin; Price, Richard W.; Spudich, Serena; Fuchs, Dietmar; Hagberg, Lars; Gisslén, Magnus

doi:10.1097/qai.0b013e31815ace97

Cited by 97 publications

(76 citation statements)

References 32 publications

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“…These studies are corroborated by evidence that intrathecal inflammation as detected in CSF persists in the setting of long-term, systemically effective cART (Eden et al 2007;Yilmaz et al 2008). Although even in the setting of therapy that fails to successfully suppress plasma HIV RNA (Spudich et al 2006), cART usually successfully suppresses CSF HIV RNA below detectable levels, viral "escape" in the CSF may occur in up to 10% of individuals on current regimens (Eden et al 2010), and in rare cases dramatic CSF "escape" has been associated with clinically progressive neurological disease (Canestri et al 2010).…”

Section: Pathogenesis and Management Of Neuro-aidssupporting

confidence: 64%

HIV-1-Related Central Nervous System Disease: Current Issues in Pathogenesis, Diagnosis, and Treatment

Spudich¹,

González‐Scarano²

2012

Cold Spring Harbor Perspectives in Medicine

190

159

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Section: Pathogenesis and Management Of Neuro-aidssupporting

confidence: 64%

HIV-1-Related Central Nervous System Disease: Current Issues in Pathogenesis, Diagnosis, and Treatment

Spudich¹,

González‐Scarano²

2012

Cold Spring Harbor Perspectives in Medicine

190

159

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“…70 Persistent intrathecal immune activation was described in HIV-infected patients on ARV therapy having CSF HIV RNA between 2.5 and 49 copies/mL. 71 The same was reported in patients successfully treated with HAART for more than 4 years. 72 Taken together, these data suggest that inflammatory mediators released within the CNS could initiate and maintain the neurodegenerative process resulting in neuronal dysfunction and death in patients treated with HAART.…”

Section: Discussionmentioning

confidence: 66%

Cognitive function in treated HIV patients

Tozzi¹

2010

NBHIV

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Although highly active antiretroviral therapy (HAART) has reduced the incidence of HIV-associated dementia, the overall prevalence of HIV-associated neurocognitive disorders (HAND) has increased. Since treatment and prevention of HAND are becoming an increasing concern, management strategies for cognitive impairment in patients living with HIV are expected to play an important role in the near future. This review summarizes the existing literature on studies investigating cognitive functions in patients receiving antiretroviral (ARV) treatment.Most studies indicate that HAART use results in improvement of neurocognitive functions, yet milder forms of HAND are not only prevalent, but also incident in patients with persistently undetectable plasma HIV RNA. We performed a systematic review on all studies performed in patients receiving ARV treatment that included neurocognitive evaluations as study end points. Thirty-six studies were examined. Study methodology varied from cross-sectional to doubleblind, randomized, controlled designs. Aside from historic zidovudine monotherapy trials, in most studies, ARV schemes varied considerably, and in some cases, ARV regimens were not reported in detail. Only a few articles included virological studies on cerebrospinal fluid. Study duration was ,2 years in most cases. Differences in study design and presence of study limitations may account for difficulties in understanding the impact of HAART on cognition and in evaluating the effect of an individual agent or ARV regimen on cognitive functioning. The aim of the present article is to provide HIV clinicians with a comprehensive review of recent achievements and future prospects for ARV treatment and prevention of cognitive dysfunctions in HIV-infected patients.

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“…CSF neopterin concentrations also were reduced by treatment, with suppressive therapy having a greater effect than failed treatment. However, these levels do not always return to normal with suppressive treatment, indicating that low-level CNS immunoactivation can persist despite undetectable blood and CSF HIV-1 RNA levels [54,99]. Whether this might be due to continued viral replication below levels of detection within the CNS or to residual immune activation (i.e., an immunological "scar") is not yet known.…”

Section: Treatment Effects On Chronic Cns Hiv-1 Infectionmentioning

confidence: 82%

Antiretroviral Therapy and Central Nervous System HIV Type 1 Infection

2008

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Central nervous system (CNS) human immunodeficiency virus type 1 (HIV-1) infection begins during primary viremia and continues throughout the course of untreated systemic infection. Although frequently accompanied by local inflammatory reactions detectable in cerebrospinal fluid (CSF), CNS HIV-1 infection usually is not clinically apparent. In a minority of patients, CNS HIV-1 infection evolves into encephalitis during the late stages of systemic infection, which compromises brain function and presents clinically as acquired immunodeficiency syndrome dementia complex (ADC). Combination antiretroviral therapy (ART) has had a major impact on all aspects of CNS HIV-1 infection and disease. In those with asymptomatic infection, ART usually effectively suppresses HIV-1 in CSF and markedly reduces the incidence of symptomatic ADC. In those presenting with ADC, ART characteristically prevents neurological progression and leads to variable, and at times substantial, recovery. Similarly, treatment has reduced CNS opportunistic infections. With better control of these severe disorders, attention has turned to the possible consequences of chronic silent infection and the issue of whether indolent, low-grade brain injury might require earlier treatment intervention.

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Persistent Intrathecal Immune Activation in HIV-1-Infected Individuals on Antiretroviral Therapy

Cited by 97 publications

References 32 publications

HIV-1-Related Central Nervous System Disease: Current Issues in Pathogenesis, Diagnosis, and Treatment

HIV-1-Related Central Nervous System Disease: Current Issues in Pathogenesis, Diagnosis, and Treatment

Cognitive function in treated HIV patients

Antiretroviral Therapy and Central Nervous System HIV Type 1 Infection

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