回复：迷迷糊糊的疱疹系列研究----先从感叹开始
上次提到的治愈疱疹的药 isentress 确实在艾滋病人身上用后治愈了疱疹。 这个药中国也开始卖了。 有个好心的战友告诉我了， 并告诉了我电话。 可我不太敢试， 一是没有证实确实对疱疹有效 （官方证实）， 二是给艾滋人吃的药谁有胆子去试啊？
懂英文的研究下这两种药。
迷糊
Raltegravir (Isentress) and Darunavir (Prezista) Appear to Reach Therapeutic Levels in Cerebrospinal Fluid
Two newer antiretroviral drugs -- the first-in-class integrase inhibitor raltegravir (Isentress) and the next-generation boosted protease inhibitor darunavir (Prezista) -- reach effective concentrations in the cerebrospinal fluid (CSF), which may help protect the brain, according to 2 posters presented last month at the 49th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC 2009) in San Francisco.
By Liz Highleyman
Antiretroviral drugs that cross the blood-brain barrier and fight HIV within the brain may help prevent AIDS-related dementia and milder forms of neurocognitive impairment.
Scott Letendre from the University of California at San Diego and colleagues have previously published data on how well various antiretroviral drugs penetrate the brain. At ICAAC, the HIV Neurobehavioral Research Center Study Group augmented this research with findings for 2 drugs approved since the initial work.
The raltegravir analysis included 22 paired blood plasma and CSF samples from 18 individuals taking raltegravir-containing regimens. Most (94%) were men, 89% were white, and the median age was 46 years. Most (89%) had an AIDS diagnosis and 12% had hepatitis C coinfection. The median CD4 count (at the time of raltegravir measurement) was 276 cells/mm3, and just over one-quarter had < 200 cells/mm3.
The darunavir analysis included 29 paired plasma and CSF samples from 18 patients taking darunavir-containing regimens. This group was slightly more diverse, with 88% being men and 62% being white. The average age was 48 years and 19% had hepatitis C. Reflecting the population of highly treatment-experienced patients who typically use darunavir, the median CD4 count was lower, at 197 cells/mm3, with about half having < 200 cells/mm3.
Combined Results
The median CSF raltegravir concentration was 14.5 ng/mL, while the median plasma concentration was 260.9 ng/mL.
Raltegravir concentrations in CSF exceeded the 50% inhibitory concentration (IC50) for wild-type (non-mutated) HIV, with a median level 4.3 times the IC50.
Raltegravir CSF concentrations had a positive correlation with plasma levels.
62% of raltegravir recipients had undetectable plasma viral load and 95% had undetectable CSF viral load.
The median CSF darunavir concentration was 56.9 ng/mL, while the median total plasma concentration was 4094 ng/mL and the median unbound plasma concentration was 542 ng/mL (darunavir tends to bind with blood proteins, which interferes with ability to cross the blood-brain barrier).
Darunavir concentrations in CSF also exceeded the IC50 for wild-type HIV, with a median level 20.7 times the IC50.
Darunavir CSF concentrations also had a positive correlation with total plasma concentrations, but the association with unbound plasma levels was not significantly stronger.
62% of darunavir recipients had undetectable plasma viral load and 90% had undetectable CSF viral load.
Based on these findings, the researchers concluded that both raltegravir and darunavir "are in the therapeutic range for inhibition of wild-type HIV" and "should contribute to control of HIV replication in the nervous system" as a component of effective antiretroviral therapy.
It should be noted, however, that studies to date have produced conflicting data on this issue, with some indicating that regimens that fully suppress plasma HIV are protective against neurocognitive problems even if they do not enter the central nervous system (brain and spinal cord). Furthermore, drug levels in the CSF do not necessarily reflect concentrations in brain tissue.
