Prezista and Isentress can get into nervous system and brain to attack HIV.
An ability to get into the central nervous system (the spinal cord and brain) is a benefit not shared by all antiretrovirals. HIV does get into the central nervous system. If someone with HIV takes only antiretrovirals that do not penetrate the central nervous system, HIV will continue to hide there and make new copies of itself. If only low levels of an antiretroviral get into the central nervous system, HIV may become resistant to that drug in the spinal cord and brain.
Confusion, forgetfulness, and other mental problems trouble some people with HIV, even though their viral lead is undetectable when measured in blood outside their central nervous system. That could mean HIV remains poorly controlled in their central nervous system.
* How the studies worked. The Prezista study involved 18 people taking this protease inhibitor who had stored blood samples and cerebrospinal fluid (CSF) samples in which Prezista levels could be measured. (1) Seventeen of these people were taking Prezista twice daily, and one was taking Prezista once daily. Researchers measured Prezista levels in 29 pairs of blood samples and CSF samples from these 18 people. Then they figured how concentrations of Prezista in CSF compared with concentrations in blood.
The Isentress study involved 18 people taking this antiretroviral who had stored blood and CSF samples in which Isentress levels could be measured. (2) Researchers measured Isentress levels in 21 pairs of blood and CSF samples from these people to compare Isentress concentrations in blood and CSF.
* What the studies found. Everyone in the Prezista study had AIDS. Sixteen (88%) were men and 11 (62%) were white. Median CD4 count for the group was 197. These people had taken Prezista for a median of 7.5 months.
Prezista could be detected in all CSF samples at a median level of 56.9 ng/mL (pie chart Figure). Median total Prezista concentration in blood stood at 4094 ng/ mL. Median concentration of Prezista in blood and not bound by protein was 542 ng/mL. Prezista levels in CSF were 9.4% of Prezista blood levels unbound by protein.
Figure. The protease inhibitor Prezista and the integrase inhibitor Isentress could be detected in all CSF samples analyzed in separate studies of people taking these, anti-retrovirals. HIV could not be detected in 90% of Prezista-treated GSF samples or 95% of Isentress- treated CSF samples. Percent of CSF samples with 29 of 29 samples (100%) detectable Pezista levels Percent of CSF samples with 21 of 21 samples (100%) detectable Isenrress levels Percent of CSF samples with 26 of 29 (90%) undetectable HIV in Prezista study Percent of CSF samples with 20 of 21 (95%) undetectable HIV in Isentress study
The 50% inhibitory concentration ([IC.sub.50]) of a drug is the amount of drug needed to stop 50% of HIV in a sample from making copies of itself. The [IC.sub.50] is a standard way to measure activity of drugs. As in many studies, the Prezista and Isentress studies calculated the [IC.sub.50] of the drug against virus not resistant to Prezista or Isentress.
Prezista levels in CSF were much higher than the [IC.sub.50] in all CSF samples tested. That means Prezista would probably help control HIV in the central nervous system of these people. Indeed, viral load was too low to measure in 26 of 29 CSF samples studied (90%) as well as in 18 of 29 blood samples (62%).
Seventeen of the 18 people in the Isentress study (94%) were men, 16 (89%) were white, and 15 (83%) had AIDS. Median CD4 count in these people was 276. Sixteen people had taken other antiretrovirals before they started Isentress, which they took for a median of 4.2 months.
The researchers detected Isentress in all CSF samples at a median concentration of 14.5 ng/mL (pie chart Figure). Median Isentress blood concentration was 260.9 ng/mL. Isentress levels in CSF were 5.8% of levels in blood. Isentress levels were higher than the [IC.sub.50] in all CSF samples. Viral load could not be detected in 20 of 21 CSF samples (95%) or in 13 of 21 blood samples (62%).
* What the results mean for you. The researchers conclude that Prezista should contribute to control of HIV in the central nervous system as a part of combination antiretroviral therapy. They reach the same conclusion about Isentress. In other words, either of these antiretrovirals should help rein in HIV in the brain. As a result, including Prezista or Isentress in an antiretroviral combination may help improve mental problems caused by HIV and may help prevent such problems.
Some of the researchers who worked on these studies helped create a score that rates individual antiretrovirals for how well they get into the central nervous system. One recent study showed that this CNS penetration effectiveness (CPE) score predicted better mental function: People taking an antiretroviral combination with a higher total CPE score had fewer problems detected by standard tests of mental function. (3) But an earlier study by the physicians who created the CPE score could not show that a higher score meant better mental function. (4) Differences in the methods used in these two studies may explain the different findings. The study that found that higher CPE scores reflected better mental functioning (3) included a larger number of people and used more accurate methods for measuring changes in mental function.
More work is needed to define the ability of individual antiretrovirals to reach the brain. But everyone agrees that controlling HIV in the central nervous system is a critical goal of antiretroviral therapy. Evidence that Prezista and Isentress enter the CSF at high levels is reassuring.
(1.) Letendre S, Rossi S, Best B, et al. Darunavir concentrations in CSF exceed the median inhibitory concentration.
49th ICAAC (Interscience Conference on Antimicrobial Agents and Chemotherapy). September 12-15, 2009. San Francisco. Abstract A-1312.
(2.) Letendre S, Best B, Breidinger S, et al. Raltegravir concentrations in CSF exceed the median inhibitory concentration.
49th ICAAC (Interscience Conference on Antimicrobial Agents and Chemotherapy). September 12-15, 2009. San Francisco. Abstract A-1311.
(3.) Tozzi V, Balestra P, Salvatori MF, et al. Higher CPE score improved cognition, changes in cognition during antiretroviral therapy: comparison of 2 different ranking systems to measure antiretroviral drug efficacy on HIV-associated neurocognitive disorders. JAIDS. 2009;52:56-63.
(4.) Marra CM, Zhao Y, Clifford DB, et al. Impact of combination antiretroviral therapy on cerebrospinal fluid HIV RNAand neurocognitive performance. AIDS. 2009;23:1359-1366.
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|Title Annotation:||Latest Studies on HIV Treatment and Prevention|
|Publication:||HIV Treatment: ALERTS!|
|Date:||Oct 1, 2009|
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