EACS: Drugs that get into the brain work better for neurological AIDS diseases

Survival after diagnosis with AIDS-related neurological illnesses has improved since the advent of HAART, the eleventh European AIDS Conference (EACS) was told last week.

Furthermore, patients on ARV regimens which contained a higher number of drugs that crossed the ‘blood-brain barrier’ and got into the central nervous system (CNS) had better survival rates.

However the study also found that survival from two conditions – cryptococcal meningitis and progressive multifocal leukoencephalopathy (PML) - has not improved since the early days of HAART, and in the case of PML has got marginally worse since 1998.

Amongst the most feared manifestations of AIDS are those that affect the brain. However Emilie Lanoy of the French INSERM research institute told the conference that survival rates from four of them – toxoplamosis, dementia resulting from HIV encephalopathy, PML and cryptococcal meningitis – had improved dramatically since the advent of HAART. She was analysing data from the French Hospital Database of HIV, a large cohort of HIV patients.

In the pre-HAART era, she said, less than half of patients diagnosed with any of these could expect to be alive a year later, and in the case of AIDS dementia and PML that fell to one in five. The exact pre-HAART survival rates were 42%, 23%, 20% and 50% for toxoplamosis, AIDS dementia, PML and meningitis respectively between 1992 and 1995.

Survival rates immediately improved when HAART came along. One-year survival rates for the four conditions were 73%, 55%, 56% and 76% between 1996 and 1998. Since then survival from toxoplamosis and HIV dementia have continued to improve and one-year survival now stood at 80% and 70% respectively for the two conditions. Survival with AIDS-related meningitis had improved non-significantly and was now at 86%. But survival with PML had actually got marginally worse and now stood at 49%.

However she added that having drugs that crossed the blood-brain barrier in one’s HIV drug regimen improved survival rates considerably. Drugs that cross the blood-brain barrier well include AZT, d4T, abacavir, nevirapine, fosamprenavir, atazanavir and to a lesser degree indinavir and 3TC. Most other protease inhibitors penetrate poorly as do tenofovir, T20 and, oddly, efavirenz, in light of its CNS-related toxicity.

Some studies have suggested that getting drugs into the CNS is not that important in improving the prognosis of AIDS-related brain infections, and that raising the CD4 count as fast as possible is the best therapy. This certainly seemed to be the case, said Lanoy, but CNS penetration was important too.

She scored drugs on the basis of whether they had good, moderate or poor penetration into the CNS and related them to the risk of death, comparing all patients with patients who had a ‘CNS penetration score’ of more than 1.15 in their HIV drug regimen.

Having a good score dramatically improved one-year survival rates. Using 1996-98 as a baseline, the relative risk of death from toxoplamosis, AIDS dementia, PML and cryptococcal meningitis in 2002-05 were respectively 5% better, 26% better, 4% worse and 20% better. However in patients with a CNS penetration score over 1.15 in their regimens, these improved to 51%, 51%, 38% and 73% better – a dramatic improvement.