Paul Bellman is one of the most concerned doctors in the US on the subject of how to rescue HIV patients who have ran out of options. Here is a manuscript he wrote for patients and medical students on the subject that I highly recommend for all to read:
This study really worries me. Median CD4 cells were in the 400, and half were naive. So these are not sick patients. I wish they had defined what mild cognitive impairment is. I forget faces, names, things to do, sometimes important personal data, etc. At 48 years old, I have the feeling that this is not normal. Studies like this one just feed that concern….
They say that may be most of the HIV meds we are taking may not be penetrating the central nervous system as well as they should, and thus we may be losing mental capacity with time.
I wonder if anyone is doing studies with the use of Alzheimer drugs for HIV related cognitive impairment….
Link:The prevalence and incidence of neurocognitive impairment in the HAART era (08/30/07)
The study conclusions:
“….By the most conservative estimate, an assessment of neurocognitive function revealed that 26% of subjects selected from the ALLRT study were cognitively impaired at their baseline Neuroscreen….226 (58%) had a follow-up visit at which their test scores indicated they were neurologically unimpaired. This may be related to the favorable effects of HAART on neurological function
There was a relationship between immunological status and prevalent neurocognitive impairment, but we did not find substantial evidence to suggest that virological factors were associated with prevalent neurocognitive impairment….
the observed decline in neurocognitive functioning despite ART is consistent with the hypothesis that viral replication in the CNS may not be well controlled in some patients treated with HAART, perhaps because antiretroviral drugs may not penetrate adequately into the CNS…”
If you are thinking about obtaining TMC 125 (Etravirine, a new non nucleoside yet to be approved) via Tibotec’s expanded access program (EAP) and you have developed resistance to non nucleosides in the past (Sustiva, Viramune, Rescriptor), be aware that it is very difficult to know if TMC 125 will work for your virus since the mutations that predict its efficacy may not be present in your genotype. Non nucleoside old mutations are “archived” and may not show up in your current genotype or phenotype tests. In fact, many people with past non nucleoside resistance show complete sensitivity to non-nucleosides years after developing resistance and not using that drug class. Doctors sometimes try to search old charts to see if they can pull out old genotype test results from a time when the patient was on non-nucleosides and failing. In many instances, that information is not found. We are also learning that TMC 125 specific mutations were not included in genotype tests years ago, so looking for old patient charts may be a moot subject.
We know from studies so far that TMC 125 is not effective in people with previously accumulated and extensive NNRTI resistance, but it can still work in those with more limited mutations.
My suggestion is that if you are going to start TMC 125, make sure that you are not gambling about assuming drug sensitivity, so NEVER start it with only one fully active agent but TWO. This will ensure that you have enough of an active background for viral suppression and sustained response in case that you may not have sensitivity to TMC 125.
Possible combinations :
No resistance to Prezista but resistance to Fuzeon: Darunavir (Prezista) + TMC 125 + Raltegravir (Merck integrase available via expanded access as of Aug 2007) + nukes (approved agents + two EAPs)
If you have resistance to Prezista and Fuzeon and have an R5 tropic virus: Maraviroc+ TMC 125+ Raltegravir + nukes (approved agents + two EAPs)
If you do not have resistance to Fuzeon or Prezista: Fuzeon + TMC 125 + Prezista + nukes ( all approved agents + one EAP)
If you have resistance to Prezista but not Fuzeon: Fuzeon + TMC 125 + raltegravir (approved agents plus two EAPs)
If you do not have a R5 only tropic virus and have resistance to Fuzeon and Prezista: TMC 125 + raltegravir + ???…you may want to wait
If you have resistance to Prezista, Fuzeon, and have a R5 tropic virus: TMC 125 + Maraviroc +raltegravir
A lot of these combinations have not been fully researched. So far, we have some knowledge of interaction data between these agents and the only contraindication that I have seen is TMC 125 + Tipranavir (Aptivus)
Message: a new agent may not be an active agent, so be cautious and combine agents in such a way that you do not take too many chances. Make sure that you have a doctor who knows the data on these agents, potential interactions, and how to deal with lacking resistance information.