The most common CNS opportunistic infections are cerebral toxoplasmosis, cryptococcal meningitis and progressive multifocal leukoencephalopathy. Less common CNS opportunistic infections include meningitis caused by Mycobacterium tuberculosis and other fungal CNS infections, such as candidiasis, coccidioidomycosis, aspergillosis and histoplasmosis. Opportunistic viral infections involving the CNS include cytomegalovirus, herpes simplex virus and varicella-zoster virus. Acute mental status changes can also occur as a result of metabolic disturbances, such as hypoxia, fever, dehydration, electrolyte disturbances, uremia and hepatic encephalopathy.
Central nervous system involvement also occurs as a result of primary CNS lymphoma, which tends to occur late in the course of HIV infection. Central nervous system manifestations of metastatic systemic lymphoma and Kaposi's sarcoma have been reported in patients with AIDS, but are uncommon.
Finally, many antibacterial, antifungal, antineoplastic and antiviral medications, in addition to the antiretroviral therapies, have CNS side effects. An awareness of the types of pharmacological treatments used and their potential side effects is important in the evaluation of psychiatric symptoms in patients who are HIV positive. Some of the drugs more commonly used in HIV and their neuropsychiatric side effects are listed in Table 3.
Effects of HAART
The incidence and prevalence of HAD has decreased since HAART first became widely available in 1996. Data from the Multicenter AIDS Cohort study show that the incidence fell from 21% with the use of monotherapy to 10.5% with HAART regimes (Sacktor et al., 2001). The prevalence of HAD had been variably estimated from 7% to 90% in the pre-HAART era, depending on the study (Dore et al., 1999). According to a study by Maschke and colleagues, it dropped from 17.1% to 11.2% between 1995-1996 and 1997-1998 (Maschke et al., 2000). Although HAART does not eliminate HAD, patients on this regimen have less impairment in cognition, concentration, memory and psychomotor speed than their nonmedicated counterparts, with benefits appearing within one to six months of treatment initiation (Ferrando et al., 1998).
Some antiretroviral agents are associated with neuropsychiatric side effects. The nucleoside reverse transcriptase inhibitor (NRTI) zidovudine(Drug information on zidovudine) (AZT, ZDV, Retrovir) was the earliest antiretroviral drug to be used in the management of HIV. A drug with good CNS penetration, it was initially given as monotherapy in doses of 2000 mg/day, and was associated with cases of acute mania (Wright et al., 1989). Now as a part of combination therapy, reports of mania are less common at doses of 600 mg/day.
The non-NRTI (NNRTI) efavirenz(Drug information on efavirenz) (Sustiva) has been associated with many neuropsychiatric side effects, including dizziness, headache, confusion, stupor, decreased concentration, agitation, amnesia, depersonalization, hallucinations, insomnia and night terrors. Symptoms usually occur within the first month of treatment and most resolve within six to 10 weeks. One study showed increased rates of depression, nervousness, abnormal dreaming and euphoria in patients treated with efavirenz (Ruiz et al., 1999). Compared to 27% of control participants, 54% of efavirenz-treated patients suffered from nervous system adverse events. There is some evidence that the plasma level of the drug correlates with the likelihood and severity of symptoms (Marzolini et al., 2001). The other members of the NNRTI medication class, delavirdine (Rescriptor) and nevirapine(Drug information on nevirapine) (Viramune), have not been associated with significant CNS adverse effects.