The role of the central nervous system (CNS) (brain and spinal cord) in HIV disease can be divided into two areas: diseases of the CNS caused by invading pathogens or tumors and psychological/psychiatric disease.
Infectious diseases of the CNS such as toxoplasmosis, cryptococcal meningitis, progressive multifocal leukoencephalopathy (PML), cytomegalovirus (CMV) and herpes have greatly diminished since the era of highly active antiretroviral therapy (HAART) began in 1996; so too has the incidence of tumors such as lymphoma.
These opportunistic diseases (OIs) were the result of uncontrolled HIV virus causing severe immune suppression and low T-cell counts. Effective treatment with HAART can lead to an undetectable viral load, and the immune system can and does recover.
HIV itself can infect the CNS, causing a brain infection called AIDS dementia that is directly related to the amount of virus in the CNS. While most kinds of HAART will reduce level of the virus in the CNS, 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 (often overlooked) may also result from infection with HIV.
Psychological disease is very common in people with HIV. The HIV Service and Cost Utilization Study (HSCUS) enrolled 2,864 people with HIV in 1996 at 50 sites in the United States. An analysis in 1999 showed that 50 percent of participants 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 was five times more common in people enrolled in the HSCUS study, anxiety was eight times more common, panic was four times more common, and substance abuse was also 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 it is more probable that it is because people who are depressed are more likely to stop taking their drugs or to be less adherent to their regimen. Substance abuse and drug dependence can also reduce adherence to HAART. All of these common problems present a challenge when healthcare provider and patient consider how to control HIV.
Some of the drugs commonly used 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 that 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. Studies 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 from 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 occur before HAART is begun. This should be done both initially and at periodic intervals to make sure old illness is managed and that no new issues are occurring. However, continued use of injectable drugs is not necessarily a bar to effective HAART. Two individual histories illustrate the interactions between HIV and disorders affecting the CNS.
In one case, a 35-year-old Native American was seen for a stroke that had left his left side paralyzed. A CAT scan of his brain showed a lesion that was diagnosed as being caused by toxoplasmosis. He was a long-time alcoholic and had a CD4 count of 10 and a viral load over 100,000 copies per mL of blood. He was treated with antibiotics for the toxoplasmosis, received physical therapy for his paralysis, was treated for alcoholism (with significant input from his family), treated with antidepressants for an underlying and untreated depression -- and treated with HAART (two 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 above 500.
In a second case, a 42-year-old white gay male scientist began therapy for his HIV disease with two 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 became suicidal. When his medication was changed from Sustiva to Viramune, he quickly recovered from his depression with continued good control of his viral load.
Effective treatment of HIV should consider not only the choice of HAART regimen but the underlying health of the CNS.
Trevor Hawkins, M.D. is the Medical Director of Southwest CARE Center and the Associate Clinical Professor at the University of New Mexico.
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