Table 2
Psychotropic/HIV drug interactions, by cytochrome P-450 isoenzyme
| CYP 3A4 | CYP 2D6 | |
|---|---|---|
| Psychotropics primarily metabolized by isoenzyme | Benzodiazepines Buspirone Carbamazepine Citalopram Clomipramine Imipramine Trazodone | Fluoxetine Fluvoxamine Mirtazapine Antipsychotics (typical and atypical) Paroxetine Sertraline Tricyclics Venlafaxine |
| HIV drugs that inhibit isoenzyme | Protease inhibitors (esp. ritonavir and indinavir) Clarithromycin Erythromycin Itraconazole Ketoconazole Macrolide antibiotics | Protease inhibitors (esp. ritonavir and nelfinavir) |
| Possible clinical effect | Increased plasma levels and increased side effects; for benzodiazepines, sedation and decreased respiratory drive | Increased plasma levels and increased side effects; for tricyclics, increased risk for cardiac conduction delay |
| HIV drugs that induce isoenzyme | Nevirapine Efavirenz Glucocorticoids Rifampin Rifabutin | None |
| Possible clinical effect | Decreased psychotropic plasma levels, decreased effectiveness | None |
| Source: Adapted and reprinted with permission from reference 1, Table 16. Copyright 2000. American Psychiatric Association | ||
The FDA approved enfuvirtide—the first of the new fusion inhibitor class of antiretroviral agents—in March 2003. Enfuvirtide prevents HIV from entering the target CD4 lymphocyte in patients who show continued viral replication despite ongoing antiretroviral therapy. This agent requires twice-daily subcutaneous injections. Because enfuvirtide can be viewed as a medication of last resort, nonresponse may be especially disheartening to an AIDS patient.
Substances of abuse also interact with HIV medications. A lethal overdose of the street drug MDMA (“Ecstasy”) has been reported in a patient treated with ritonavir.10 MDMA is metabolized primarily via CYP 2D6. Other substances of abuse metabolized by CYP 2D6 or 3A4—such as amphetamines, ketamine, heroin, cocaine, and gamma-hydroxybutyrate—may cause toxic reactions in patients being treated with protease inhibitors.
Because substance abuse is a common comorbidity of HIV infection, warn patients that using recreational drugs with antiretroviral medications can cause adverse reactions. Extensive drug interaction lists are available on patient education and physician Web sites (see Related Resources).
Table 3
Diagnostic criteria for HIV-associated minor cognitive motor disorder
Probable diagnosis (must meet all four criteria)
A possible diagnosis of minor cognitive motor disorder can be given if criteria 1-3 are present and either:
|
| Source: Reprinted with permission from reference 14 |
Lipid and hyperglycemic side effects. Antivirals— especially protease inhibitors —appear to be associated with HIV lipodystrophy, which is associated with cosmetic and serum lipid changes as well as hyperglycemia.11 Facial wasting, buffalo humps, and central intra-abdominal obesity may occur, and elevated serum cholesterol and triglycerides often require treatment with cholesterollowering “statin” drugs.
Though it is unclear whether HIV lipodystrophy increases cardiovascular disease risk, carefully consider the potential effects of psychotropics associated with weight gain, hyper-glycemia, and elevated lipids in patients receiving antiretroviral therapy.
Hepatitis. Patients at risk for HIV infection are also at risk for viral hepatitis. One-quarter of persons with HIV are coinfected with hepatitis C, primarily through IV drug use.12 Alpha-interferon treatment of hepatitis B and C has been associated with depression. SSRI treatment—such as paroxetine, 20 mg/d—can ease depressive symptoms.13
HIV-associated cognitive changes
Minor cognitive-motor disorder(Table 3) and HIV-associated dementia (Table 4) 14 are typically seen in late-stage HIV infections and are diagnoses of exclusion. Physical or neurologic examination in a patient with HIV/AIDS and altered mental status may show:
- focal deficits indicating a space-occupying lesion (eg, CNS lymphoma or toxoplasmosis)
- sensory changes that may indicate peripheral neuropathy
- ataxia or gait changes that may indicate myelopathy.
Useful neuropsychological tests include the HIV Dementia Rating Scale,15 Halstead finger-tapping test for motor speed,16 and the Trailmaking Test, which assesses psychomotor speed and sequencing ability.17
Antiretroviral therapy appears to reduce the risk of HIV-associated dementia. In a trial conducted at 42 AIDS Clinical Trials Group sites and 7 National Hemophilia Foundation sites, combination reverse transcriptase inhibitors helped preserve or improve neurologic function.18
Psychostimulants appear to improve HIV-induced brain impairment.19 Immune modulators—such as tumor necrosis factor-alpha blockers (eg, pentoxifylline)20 and interleukin-1 receptor blockers21 —have also been studied for possible beneficial effects on HIV brain disease.
HIV prevention
Because unprotected sex and IV substance use are the primary HIV transmission routes in the United States, assessing psychiatric patients’ sexual and substance use behaviors may help you prevent HIV infection. The CDC offers guidelines for HIV testing, counseling, and referral (see Related Resources).
To identify persons at risk for HIV infection, the CDC recommends asking open-ended questions about risk behaviors, such as: “What are you doing now or what have you done in the past that you think may put you at risk for HIV infection?”22
The shift of new HIV infection disproportionately into African-American and Hispanic populations suggests the need for more-intensive prevention and education in those communities. CDC guidelines emphasize the importance of using culturally sensitive language when asking about risk behavior. Some individuals may engage in same-sex behaviors but do not identify themselves as “homosexual” or “gay.” In some African-American communities, for example, being “on the down low” is used to describe men—oftentimes married—who have sex with men.