Early initiation of antiretroviral therapy linked with lower risk of cognitive impairment in HIV

Jan 18th  – Early initiation of therapy may be neuroprotective in patients recently diagnosed with HIV.

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Image: GNU2./N.Rougier. SEM of a neuron. 

1. In the era of combined antiretroviral therapy, the neurocognitive sequelae of HIV are becoming increasingly important therapeutic targets. 

2. Early initiation of therapy may be neuroprotective in patients recently diagnosed with HIV.

This study demonstrated no significant difference in the prevalence of NCI between aggressively treated HIV-infected patients and HIV-negative controls.  The study benefits from using a sample of military personnel, who receive regular HIV testing, allowing treatment to be initiated early in the course of infection.  In these patients, the regimen appears to be effective, as demonstrated by a low rate of AIDS-defining events in late-stage infection and no such events in patients with infection of a duration less than six years.  The results regarding NCI support the idea that early diagnosis and treatment may in fact lower the risk of developing HIV-associated NCI. It should be noted that the exact risk of HIV-associated NCI without early diagnosis and treatment is not known, although various studies have estimated it to be greater than what was seen in this study.

The primary limitation of this study may be its size and cross-sectional design.  While numerous relationships observed between clinical variables and NCI neared significance, ad hoc analyses were required to demonstrate any significant associations.  Moreover, the specific protocol of ART initiation in patients was not described, making it difficult to quantify how aggressively the participants were treated.  Finally, military patients are at particular risk for neurocognitive sequelae as a result of their occupation (e.g. higher risk of traumatic brain injury), which may confound some of the comparisons.  Regardless, this study provides substantial support for the increasingly popular notion that aggressive treatment of HIV may indeed have neuroprotective benefits.

Click to read the study in Neurology

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Image: GNU2./N.Rougier. SEM of a neuron. 

1. In the era of combined antiretroviral therapy, the neurocognitive sequelae of HIV are becoming increasingly important therapeutic targets. 

2. Early initiation of therapy may be neuroprotective in patients recently diagnosed with HIV.

Primer: Human immunodeficiency virus (HIV) infection represents a significant global health burden, with the most recent prevalence estimates nearing 34 million worldwide.  Though a particular problem of sub-Saharan Africa, HIV affects a large number of patients in developed countries including the United States.  Treatment is supportive, and the development of highly effective antiretroviral drug regimens in recent years has greatly extended the lifespan of patients with HIV.  Although there is some debate as to the proper time of treatment initiation, antiretroviral therapy (ART) has proven to be tremendously efficacious in combating the disease and raising CD4+ cell counts in patients with confirmed HIV infection.

As patients with HIV are living longer with ART, the neurologic complications of infection are being increasingly recognized.  HIV has long been known to have a predilection for the central nervous system.  Moreover, drug delivery to the brain is challenging due to the highly regulated transport systems of the blood-brain barrier.  While the pathophysiology of so-called “neuro-HIV” is not yet fully understood, the consequences of CNS infection are well described, most notably the syndrome of neurocognitive impairment (NCI), which often develops in patients with long-standing and/or severe infection.  The literature describing the clinical predictors of NCI in HIV infection is inconclusive, though it is generally assumed that early control of infection is an important protective strategy.  In the present study, the authors investigate the presence of NCI in HIV positive patients with varying durations of infection who were all started on ART early in their disease course in order to examine the role of aggressive treatment in preventing NCI.

Background reading:

1. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents.
2. Prediction of incident neurocognitive impairment by plasma HIV RNA and CD4 levels early after HIV seroconversion.
3. HIV-1 infection and cognitive impairment in the cART era: a review

This [cross-sectional] study: 200 HIV-infected and 50 HIV-negative military personnel participated, the former stratified into early-stage disease (<6 years since diagnosis, no history of AIDS-defining conditions, and nadir CD4 >200 cells/mm³; n=100) and late-stage disease (violating any of the aforementioned criteria; n=100). Neurocognitive impairment was present in 19% of HIV-infected patients, with no significant difference between early- and late-stage disease.  Of HIV-negative controls, 30% demonstrated NCI, which was not significantly different from the proportion of HIV-infected participants.  Plasma viral load, nadir CD4, and treatment variables were not associated with the presence of NCI.

In sum: This study demonstrated no significant difference in the prevalence of NCI between aggressively treated HIV-infected patients and HIV-negative controls.  The study benefits from using a sample of military personnel, who receive regular HIV testing, allowing treatment to be initiated early in the course of infection.  In these patients, the regimen appears to be effective, as demonstrated by a low rate of AIDS-defining events in late-stage infection and no such events in patients with infection of a duration less than six years.  The results regarding NCI support the idea that early diagnosis and treatment may in fact lower the risk of developing HIV-associated NCI. It should be noted that the exact risk of HIV-associated NCI without early diagnosis and treatment is not known, although various studies have estimated it to be greater than what was seen in this study.

The primary limitation of this study may be its size and cross-sectional design.  While numerous relationships observed between clinical variables and NCI neared significance, ad hoc analyses were required to demonstrate any significant associations.  Moreover, the specific protocol of ART initiation in patients was not described, making it difficult to quantify how aggressively the participants were treated.  Finally, military patients are at particular risk for neurocognitive sequelae as a result of their occupation (e.g. higher risk of traumatic brain injury), which may confound some of the comparisons.  Regardless, this study provides substantial support for the increasingly popular notion that aggressive treatment of HIV may indeed have neuroprotective benefits.

Click to read the study in Neurology 

By [JD] and [RR]

More from this author: The virtual lumbar puncture: MRI can predict CSF biomarker levels in patients with neurodegenerative disease, Intracranial pressure monitoring does not increase survival in patients with traumatic brain injury, PET imaging findings may precede cognitive impairment in patients at high risk for Alzheimer’s disease,Initial dexamethasone improves long-term survival in acute bacterial meningitis

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Rif Rahman: Rif is a 4th year M.D. candidate at Harvard Medical School.

Jeff Dewey: Jeff Dewey is a 4th year M.D. candidate at the Boston University School of Medicine.

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