Non voglio aprire un nuovo thread, ma aggiungo qui questa notizia di pochi giorni fa.
Efavirenz può provocare perdite di memoria.
Uno studio del Hopkins Medicine suggerisce che Efavirenz attacca le cellule del cervello.
Nell'articolo si parla di come è stato rilevato l'hydroxiefavirenz in quantità tossiche nel cervello, e che il farmaco provoca alterazioni nelle cellule dendritiche dei neuroni, causando perdite di memoria o altri effetti neurologici. Si parla anche della possibilità di una modifica all'attuale farmaco tale da renderlo meno tossico ma ugualmente antivirale nella zona cerebrale (efavirenz è uno dei pochi ARV che arrivano fin dentro il cervello).
Qui l'articolo completo: http://www.hopkinsmedicine.org/news/med ... y_declines
HIV e demenza
Re: HIV e demenza
Quest'articolo sconvolge alcune piccole certezze.
Tuttavia l'Efavirenz, riuscendo a superare la barriera emato-encefalica, dovrebbe esercirare in contemporanea un'azione protettiva sull'accorciamento e atrofia dei neuroni (causa gli effetti citotossici dell'HIV stesso). Qui andrebbero indagati i meccanismi in dettaglio, per capire se è maggiore l'effetto protettivo o nocivo.
Dall'articolo sembra che prevalga decisamente il secondo, causa un metabolita dell'Efavirenz, altamente tossico per i neuroni.
Cominciano ad uscire sempre più farmaci in grado di entrare nel cervello (in questa tabella quelli con valore 4 e in parte con 3):
Poi, oltre al superamento dellabarriera ematico-encefalica, c'è la questione della loro distribuzione nel cervello.
Tuttavia l'Efavirenz, riuscendo a superare la barriera emato-encefalica, dovrebbe esercirare in contemporanea un'azione protettiva sull'accorciamento e atrofia dei neuroni (causa gli effetti citotossici dell'HIV stesso). Qui andrebbero indagati i meccanismi in dettaglio, per capire se è maggiore l'effetto protettivo o nocivo.
Dall'articolo sembra che prevalga decisamente il secondo, causa un metabolita dell'Efavirenz, altamente tossico per i neuroni.
Cominciano ad uscire sempre più farmaci in grado di entrare nel cervello (in questa tabella quelli con valore 4 e in parte con 3):
Poi, oltre al superamento dellabarriera ematico-encefalica, c'è la questione della loro distribuzione nel cervello.
Re: HIV e demenza
in effetti sky non so più dove ma avevo letto che l'introduzione della nevirapina era per certi versi "suggerita" come candidato sostituto dell'efavirenz.
Re: HIV e demenza
L'anno scorso sono passato dall'efavirenz (sustiva) ala nevirapina (viramune). In realtà me lo ha proposto il mio infettologo visto che non riuscivo ad addattarmi al sustiva, La mia reazione iniziale fu di rifiuto perchè non conoscevo che la nerivapina avesse una capacita di penetrazione del cervello persino maggiore. Gli risposti "faccia qualsiasi cosa, ma mi salvi il cervello"cesar78 ha scritto:in effetti sky non so più dove ma avevo letto che l'introduzione della nevirapina era per certi versi "suggerita" come candidato sostituto dell'efavirenz.
Tra gli antiretrovirali particolari non ancora ben studiati c'è il maraviroc, ma per tutt'altri motivi:
http://hivforum.info/forum/viewtopic.ph ... =maraviroc
Re: HIV e demenza
Aggiornamento su danno neurocognitivo (NCI) e infezione da HIV.
È uscito ieri su Neurology un lavoro di Nancy Crum-Cianflone, David Moore, Scott Letendre e molti altri dedicato a Low prevalence of neurocognitive impairment in early diagnosed and managed HIV-infected persons.
Poiché è accessibile solo a pagamento, vi riporto l'abstract e parte della Discussione.
DISCUSSION
We found a low prevalence of NCI among HIV-infected persons diagnosed and managed early during the course of HIV infection, and nearly identical NCI rates among earlier and later HIV-infected patients in this cohort. Of note, most patients classified as later in their course of HIV infection met criteria by a longer duration of HIV infection, but the majority had preserved CD4 counts and few had prior AIDS-defining conditions. Further, the prevalence of NCI among our HIV-infected participants was not significantly greater than a matched HIV-uninfected group.
These data provide important and novel information suggesting that the early recognition and management of HIV infection may be important in limiting NCI.
The importance of preventing NCI is severalfold as it impacts both the quantity and quality of life.
Regarding survival, HIV-infected patients with NCI are at increased risk of death, even after controlling for other medical factors.
Further, NCI can have a substantial impact on patients’ daily functioning and their ability to pursue career endeavors.
Finally, NCI may reduce antiretroviral adherence, hence adversely affecting the outcome of HIV-infected persons.
Hence, preserving cognitive function among HIV-infected persons may be an important step in further improving quality and life expectancies of patients.
During the pre-HAART era, 16% of patients with AIDS had HIV dementia, with an annual incidence of 7%. After the introduction of HAART in 1996, there was a sharp decrease in HIV dementia; however, milder forms of neurocognitive disease continued to be diagnosed.
Studies demonstrated that patients with symptomatic seroconverting illness as well as high HIV RNA levels and low CD4 counts early after infection were at highest risk.
The prevalence of NCI in the HAART era has varied in prior studies, likely related to clinical disease stage, comorbid diseases, and other factors.
A recent study found a NCI prevalence of 52% among HIV-infected patients seen at academic US HIV clinics regardless of comorbidity level.
Our study found a much lower NCI rate (19%), but was similar to a recent study evaluating HIV-infected persons with suppressed HIV RNA levels.
The relatively low prevalence in our study may be due to a combination of factors. Early diagnosis and active disease management, few comorbid conditions (low prevalence of concurrent medical conditions including HCV, illicit drug use, and alcohol), young age, frequent monitoring of vocational functioning, and the lack of AIDS events or low CD4 counts likely contributed to our low impairment rate.
Further, despite the later group having HIV for a median of 11 years, their risk of NCI remained similar to the earlier group (median 2 years). This suggests that length of HIV duration itself may not be a risk factor if patients maintain good HIV control, avoiding AIDS-defining events and low nadir CD4 counts.
In our study, HIV-infected persons had a similar prevalence of NCI compared to matched HIVuninfected persons. Further, HIV-infected patients were not more likely to be impaired in any of the 7 cognitive domains. A recent Danish study found the overall risk of severe neurocognitive disorders is now similar among HIV-positive and -negative persons. It should be noted that the HIV-negative controls in this study are likely to be an accurate control population relative to prior studies, as the military is relatively homogeneous in regards to socioeconomic status, lifestyle, and other factors such as substance abuse.
Early events in HIV infection such as loss of vital CD4 reserves and uncontrolled HIV replication may trigger irreversible CNS damage and may cause the "residual" NCI seen in long-term survivors. Prospective studies are needed to determine if early diagnosis and initiation of antiretroviral therapy would reduce the burden of NCI among HIV-infected persons.
A recent study showed that patients with early HIV infection had similar neurocognitive functioning compared to HIV-uninfected persons, suggesting that detrimental effects of HIV on the brain may not occur immediately, potentially providing an opportunity for early intervention.
Clinical trials are underway, including a substudy of the Strategic Timing of Antiretroviral Treatment (START) trial, examining neurocognitive functioning among those treated immediately compared to later in their disease course.
We did not detect strong associations between immunologic or virologic control and the presence of NCI. A low CD4 nadir was not associated with NCI as seen in other studies including a recent study which suggested that these factors may lead to structural brain damage.28 Our lack of association may reflect that few of our patients experienced very low CD4 nadirs, or that CD4 nadirs are not predictive in persons who are managed early in infection and who avoid reaching very low counts (< 200 cells/mm3). (...)
We examined the association of PI use (which may result in higher CD4 counts, but has limited CNS penetration) and found no associations between specific antiretroviral class and NCI. These data suggest a possible immunologic component, such as immune reconstitution inflammatory syndrome–like reaction, in the pathogenesis of NCI; further studies are needed.
Finally, we found no associations between HAART use and NCI. Although prior studies have shown that cognition improves shortly after HAART initiation, our data suggest that NCI may persist despite ongoing HAART use, signifying that chronic neuronal inflammation and injury may continue.
Since the benefit of HAART is incomplete, strategies to prevent the initial development of NCI are paramount. (...)
HIV-infected persons diagnosed and managed early in infection have low rates of NCI, which are comparable to those of HIV-uninfected persons. Patients with longstanding HIV infection (median > 10 years) had similar NCI rates compared to those with more recent infection, suggesting that early management and avoidance of comorbid conditions may be important in preserving cognitive function.
È uscito ieri su Neurology un lavoro di Nancy Crum-Cianflone, David Moore, Scott Letendre e molti altri dedicato a Low prevalence of neurocognitive impairment in early diagnosed and managed HIV-infected persons.
Poiché è accessibile solo a pagamento, vi riporto l'abstract e parte della Discussione.
- Objective: To describe the prevalence of neurocognitive impairment (NCI) among early diagnosed and managed HIV-infected persons (HIV+) compared to HIV-negative controls.
Methods: We performed a cross-sectional study among 200 HIV+ and 50 matched HIV-uninfected (HIV-) military beneficiaries. HIV+ patients were categorized as earlier (,6 years of HIV, no AIDSdefining conditions, and CD4 nadir .200 cells/mm3) or later stage patients (n 5 100 in each group); both groups were diagnosed early and had access to care. NCI was diagnosed using a comprehensive battery of standardized neuropsychological tests.
Results: HIV+ patients had a median age of 36 years, 91% were seroconverters (median window of 1.2 years), had a median duration of HIV of 5 years, had a CD4 nadir of 319, had current CD4 of 546 cells/mm3, and 64% were on highly active antiretroviral therapy (initiated 1.3 years after diagnosis at a median CD4 of 333 cells/mm3). NCI was diagnosed among 38 (19%, 95% confidence interval 14%–25%) HIV+ patients, with a similar prevalence of NCI among earlier and
later stage patients (18% vs 20%, p 5 0.72). The prevalence of NCI among HIV+ patients was similar to HIV- patients.
Conclusions: HIV+ patients diagnosed and managed early during the course of HIV infection had a low prevalence of NCI, comparable to matched HIV-uninfected persons. Early recognition and management of HIV infection may be important in limiting neurocognitive impairment.
DISCUSSION
We found a low prevalence of NCI among HIV-infected persons diagnosed and managed early during the course of HIV infection, and nearly identical NCI rates among earlier and later HIV-infected patients in this cohort. Of note, most patients classified as later in their course of HIV infection met criteria by a longer duration of HIV infection, but the majority had preserved CD4 counts and few had prior AIDS-defining conditions. Further, the prevalence of NCI among our HIV-infected participants was not significantly greater than a matched HIV-uninfected group.
These data provide important and novel information suggesting that the early recognition and management of HIV infection may be important in limiting NCI.
The importance of preventing NCI is severalfold as it impacts both the quantity and quality of life.
Regarding survival, HIV-infected patients with NCI are at increased risk of death, even after controlling for other medical factors.
Further, NCI can have a substantial impact on patients’ daily functioning and their ability to pursue career endeavors.
Finally, NCI may reduce antiretroviral adherence, hence adversely affecting the outcome of HIV-infected persons.
Hence, preserving cognitive function among HIV-infected persons may be an important step in further improving quality and life expectancies of patients.
During the pre-HAART era, 16% of patients with AIDS had HIV dementia, with an annual incidence of 7%. After the introduction of HAART in 1996, there was a sharp decrease in HIV dementia; however, milder forms of neurocognitive disease continued to be diagnosed.
Studies demonstrated that patients with symptomatic seroconverting illness as well as high HIV RNA levels and low CD4 counts early after infection were at highest risk.
The prevalence of NCI in the HAART era has varied in prior studies, likely related to clinical disease stage, comorbid diseases, and other factors.
A recent study found a NCI prevalence of 52% among HIV-infected patients seen at academic US HIV clinics regardless of comorbidity level.
Our study found a much lower NCI rate (19%), but was similar to a recent study evaluating HIV-infected persons with suppressed HIV RNA levels.
The relatively low prevalence in our study may be due to a combination of factors. Early diagnosis and active disease management, few comorbid conditions (low prevalence of concurrent medical conditions including HCV, illicit drug use, and alcohol), young age, frequent monitoring of vocational functioning, and the lack of AIDS events or low CD4 counts likely contributed to our low impairment rate.
Further, despite the later group having HIV for a median of 11 years, their risk of NCI remained similar to the earlier group (median 2 years). This suggests that length of HIV duration itself may not be a risk factor if patients maintain good HIV control, avoiding AIDS-defining events and low nadir CD4 counts.
In our study, HIV-infected persons had a similar prevalence of NCI compared to matched HIVuninfected persons. Further, HIV-infected patients were not more likely to be impaired in any of the 7 cognitive domains. A recent Danish study found the overall risk of severe neurocognitive disorders is now similar among HIV-positive and -negative persons. It should be noted that the HIV-negative controls in this study are likely to be an accurate control population relative to prior studies, as the military is relatively homogeneous in regards to socioeconomic status, lifestyle, and other factors such as substance abuse.
Early events in HIV infection such as loss of vital CD4 reserves and uncontrolled HIV replication may trigger irreversible CNS damage and may cause the "residual" NCI seen in long-term survivors. Prospective studies are needed to determine if early diagnosis and initiation of antiretroviral therapy would reduce the burden of NCI among HIV-infected persons.
A recent study showed that patients with early HIV infection had similar neurocognitive functioning compared to HIV-uninfected persons, suggesting that detrimental effects of HIV on the brain may not occur immediately, potentially providing an opportunity for early intervention.
Clinical trials are underway, including a substudy of the Strategic Timing of Antiretroviral Treatment (START) trial, examining neurocognitive functioning among those treated immediately compared to later in their disease course.
We did not detect strong associations between immunologic or virologic control and the presence of NCI. A low CD4 nadir was not associated with NCI as seen in other studies including a recent study which suggested that these factors may lead to structural brain damage.28 Our lack of association may reflect that few of our patients experienced very low CD4 nadirs, or that CD4 nadirs are not predictive in persons who are managed early in infection and who avoid reaching very low counts (< 200 cells/mm3). (...)
We examined the association of PI use (which may result in higher CD4 counts, but has limited CNS penetration) and found no associations between specific antiretroviral class and NCI. These data suggest a possible immunologic component, such as immune reconstitution inflammatory syndrome–like reaction, in the pathogenesis of NCI; further studies are needed.
Finally, we found no associations between HAART use and NCI. Although prior studies have shown that cognition improves shortly after HAART initiation, our data suggest that NCI may persist despite ongoing HAART use, signifying that chronic neuronal inflammation and injury may continue.
Since the benefit of HAART is incomplete, strategies to prevent the initial development of NCI are paramount. (...)
HIV-infected persons diagnosed and managed early in infection have low rates of NCI, which are comparable to those of HIV-uninfected persons. Patients with longstanding HIV infection (median > 10 years) had similar NCI rates compared to those with more recent infection, suggesting that early management and avoidance of comorbid conditions may be important in preserving cognitive function.
Re: HIV e demenza
study among 200 HIV+ and 50 matched HIV-uninfected (HIV-) military beneficiaries
Ma questi militari non erano per caso carabinieri?The prevalence of NCI among HIV+ patients was similar to HIV- patients.
Re: HIV e demenza
Non ho letto l'articolo e non ho la minima idea se la ricerca sia seria o meno, se gli effetti collaterali del DHEA-S non siano magari peggiori dei benefici che sembra apportare al sistema nervoso centrale, per quanto tempo lo si possa/debba prendere, se ci siano interazioni perverse con gli antiretrovirali, etc. etc.
Questo il comunicato stampa:
A 'neurosteroid' found to prevent brain injury caused by HIV/AIDS
New research in The FASEB Journal suggests that a network of steroid molecules found in the brain is disrupted during HIV infection, and treatment with the steroid DHEA-S prevents brain damage
Bethesda, MD—A team of scientists from Canada, Thailand and Morocco have found that DHEA-S may prevent neurocognitive impairment that affects a significant percentage of AIDS patients. In a report appearing in the February 2013 issue of The FASEB Journal, they describe how a network of steroid molecules found in the brain, termed "neurosteroids," is disrupted during HIV infection leading to brain damage. This suggests that treatment with one of these steroid molecules, called DHEA-S, may offset the disruption caused by the virus to prevent or reduce brain damage.
"From these studies, we have gained a better understanding of how HIV injures the brain during AIDS, together with developing a new treatment approach for the resulting neurological disabilities arising from HIV/AIDS," said Christopher Power, M.D., co-author of this study from the Department of Medicine at the Medical Research Centre at the University of Alberta in Edmonton, Canada.
To make their discovery, Power and colleagues initially found that neurosteroid enzyme levels were suppressed in the brains of people with HIV/AIDS and that a neurosteroid molecule, DHEA-S, prevented damage to cultured brain cells (neurons) caused by HIV. Then, using an animal model of AIDS, they showed that treatment with DHEA-S prevented neuronal damage in the brain by reducing the adverse effects of HIV. Neurosteroids have already been proposed as treatments for epilepsy, head injury, post-traumatic stress disorder and depression, and these findings extend the potential treatment applications for neurosteroid-related molecules.
"Most people know that AIDS wreaks total havoc on our immune systems," said Gerald Weissmann, M.D., Editor-in-Chief of The FASEB Journal, "but far fewer people know that the disease can also lead to noticeable brain damage. This research study offers an explanation why this occurs as well as a possible solution for preventing it. The next steps, of course, involve looking into whether or not people will benefit from some form of DHEA-S treatment."
Abstract: Neurosteroid-mediated regulation of brain innate immunity in HIV/AIDS: DHEA-S suppresses neurovirulence
Questo il comunicato stampa:
A 'neurosteroid' found to prevent brain injury caused by HIV/AIDS
New research in The FASEB Journal suggests that a network of steroid molecules found in the brain is disrupted during HIV infection, and treatment with the steroid DHEA-S prevents brain damage
Bethesda, MD—A team of scientists from Canada, Thailand and Morocco have found that DHEA-S may prevent neurocognitive impairment that affects a significant percentage of AIDS patients. In a report appearing in the February 2013 issue of The FASEB Journal, they describe how a network of steroid molecules found in the brain, termed "neurosteroids," is disrupted during HIV infection leading to brain damage. This suggests that treatment with one of these steroid molecules, called DHEA-S, may offset the disruption caused by the virus to prevent or reduce brain damage.
"From these studies, we have gained a better understanding of how HIV injures the brain during AIDS, together with developing a new treatment approach for the resulting neurological disabilities arising from HIV/AIDS," said Christopher Power, M.D., co-author of this study from the Department of Medicine at the Medical Research Centre at the University of Alberta in Edmonton, Canada.
To make their discovery, Power and colleagues initially found that neurosteroid enzyme levels were suppressed in the brains of people with HIV/AIDS and that a neurosteroid molecule, DHEA-S, prevented damage to cultured brain cells (neurons) caused by HIV. Then, using an animal model of AIDS, they showed that treatment with DHEA-S prevented neuronal damage in the brain by reducing the adverse effects of HIV. Neurosteroids have already been proposed as treatments for epilepsy, head injury, post-traumatic stress disorder and depression, and these findings extend the potential treatment applications for neurosteroid-related molecules.
"Most people know that AIDS wreaks total havoc on our immune systems," said Gerald Weissmann, M.D., Editor-in-Chief of The FASEB Journal, "but far fewer people know that the disease can also lead to noticeable brain damage. This research study offers an explanation why this occurs as well as a possible solution for preventing it. The next steps, of course, involve looking into whether or not people will benefit from some form of DHEA-S treatment."
Abstract: Neurosteroid-mediated regulation of brain innate immunity in HIV/AIDS: DHEA-S suppresses neurovirulence
Re: HIV e demenza
L'argomento della discussione prosegue qui:
http://hivforum.info/forum/viewtopic.php?f=4&t=1404
http://hivforum.info/forum/viewtopic.php?f=4&t=1404