The Central Nervous System (CNS) and HIV
October 15, 2002
The role of the central nervous system (brain and spinal cord) in HIV disease can be divided into 2 areas; diseases of the CNS caused by invading bugs or tumors and psychological/psychiatric disease.
Infectious diseases of the CNS such as toxoplasmosis, cryptococcal meningitis, PML, CMV and herpes have greatly diminished since the era of HAART (highly active antiretroviral therapy) began in 1996; so too has the incidence of tumors such as lymphoma.
These opportunistic infections (OIs) were the result of uncontrolled HIV virus causing severe immune suppression and low T-cell counts. Effective treatment with HAART leads to an undetectable viral load and the immune system can and does recover.
Even when the viral load is not completely suppressed, taking HAART prevents these diseases most of the time by making the HIV virus less fit. Only by selecting a number of mutations can the virus survive in the presence of HAART and these mutant forms are not as robust as the original "wild" type. Poor fitness equals less immune suppression and fewer OIs.
HIV itself infects the CNS causing a brain infection ("AIDS dementia"), which is directly related to the amount of virus in the CNS. Most kinds of HAART will reduce these CNS viral levels; however, only a few of the drugs actually get into the CNS; these are AZT, Zerit, Ziagen, Viramune and Crixivan and they are the best choices to actually treat AIDS dementia. More subtle impairment of brain function may also result from infection with HIV and is often overlooked.
Psychological disease is very common in people with HIV. The HSCUS (HIV service and cost utilization study) enrolled 2,864 people with HIV in 1966 at 50 sites in the US. An analysis in 1999 showed that 50 percent had a psychiatric disorder, 40 percent used an illicit drug other than marijuana and 12 percent were drug dependent. Compared to the general population studied with the same methods, depression in people with HIV was 5 times more common, anxiety 8 times, panic 4 times and substance abuse much higher. In a study published by Bing et al. in the Archives of Psychiatry in 2001, the incidence of depression was 36 percent in the HIV population compared to 14 percent in the general population.
Depression is a major predictor of disease progression and death in HIV, as it is in other disease states. This may be because depression directly affects the immune system but more probable is that it has this effect because people who are depressed are more likely to stop taking their drugs or to be less adherent to their regimen.
We also know that substance abuse and drug dependence can also reduce adherence to HAART. All of these common problems present a challenge when provider and patient sit down to tackle the issue of how to control HIV.
Some of the drugs we commonly use to treat HIV have a direct toxic effect on the Central and the Peripheral nervous systems.
The "D" drugs, d4T, ddI and ddC, may cause a numbness and burning pain in the feet, legs or hands which is often difficult to treat.
Efavirenz (Sustiva) is a commonly used antiviral drug which affects the CNS and often causes dizziness, abnormal dreams, poor concentration, anxiety and even hallucinations. These are worse in the first 4 weeks of therapy and then usually improve. We have shown that psychological symptoms from efavirenz often persist for 6 months or more (ICAAC 2001). A recent study presented in Barcelona showed that people with a prior psychological illness tend to have greater and more sustained CNS side effects to efavirenz.
Unless there is an urgent and critical need to start HIV therapy right away, evaluation and treatment of both mental illness and substance abuse should happen before starting HAART. This should be done both initially and at periodic intervals to make sure old illness is managed and no new issues are occurring. Continued use of injectable drugs is not necessarily a bar to effective HAART.
Case 1 is a 35-year-old Native American who was seen here with a stroke that had left his left side paralyzed. A CAT scan of his brain showed a lesion that was diagnosed as being due to toxoplasmosis. He was a long-time alcoholic and had a CD4 count of 10 and a viral load of >100,000. To cut a long story short, we treated his toxo with antibiotics, did physical therapy for his paralysis, rehab for alcoholism with great input from his family, antidepressants for an underlying and untreated depression and HAART (2 nucleosides and a protease inhibitor) for HIV. He has completely recovered from the stroke, has been sober for 4 years, has an undetectable viral load and a CD4 count of greater than 500.
Case 2 is a 42-year-old white gay male scientist who began therapy for his HIV disease with 2 nucleosides and Sustiva. He had a history of alcohol abuse and depression, both in remission. His viral load became undetectable and his CD4 count rose. However, he became severely depressed, began to drink and went out and bought a gun with the idea of shooting himself. We changed the Sustiva to Viramune and he quickly recovered from his depression with continued good control of his viral load.
Care should be taken in choosing HAART that is not only effective but is tolerable for each individual patient; one person's nectar may be another's poison!
Trevor Hawkins, M.D. is the Medical Director of Southwest CARE center and the Associate Clinical Professor at the University of New Mexico.
This article was provided by Seattle Treatment Education Project. It is a part of the publication STEP Ezine.