HIV-related psychopharmacological interventions for people with preexisting schizophrenia follow similar guidelines for patients with new-onset psychosis associated with HIV infection. In advanced HIV infection, traditional neuroleptic agents have been found to produce modest but significant reductions in psychotic symptoms but have been eschewed for newer, atypical antipsychotics for the primary reason that such patients are very sensitive to extrapyramidal side effects due to viral involvement of the basal ganglia (American Psychiatric Association 2000; Fernandez and Levy 1993; Sewell et al. 1994). With progression of HIV, people with preexisting psychiatric conditions may thus develop new or increased side effects on medications that they were previously able to tolerate (Horwath 1996).

A large number of medications are prescribed to people with HIV infection, including antibacterial, antifungal, antineoplastic, antiretroviral, and other antiviral agents (Horwath 1996), particularly in later stages of HIV disease, when numerous present or potential complications require active treatment or prophylaxis. Any attempt to diagnose drug-induced neuropsychiatric syndromes requires an appreciation of both the therapeutic use and potential side effects of these medications. Some of these are described in the Practice Guideline for the Treatment of Patients With HIV/AIDS of the American Psychiatric Association (2000; access at http://www.psych.org), but new antiretroviral agents are being developed at a rapid pace, and existing medications to treat HIV-related infections and neoplasms are too numerous to describe fully. Neuropsychiatric side effects of antiretrovirals have been reported most commonly with efavirenz (Sustiva) and occasionally with nevirapine (Viramune).

There are many in vitro predictions of drug-drug interactions (which can be found in handheld databases, those available through hospital pharmacies, and those online at a variety of Web sites), but experienced prescribers generally find they can use the full range of psychotropic medications if they start with low doses and slowly increase the medication. Overlapping toxicities between different medications must also be taken into consideration. It is important to be aware that advanced HIV infection is associated with greater sensitivity to both the therapeutic effects and side effects of psychotropic medications, which is another reason why it is best to start with the lowest possible doses and increase medications slowly.

Drug levels, if available, should be monitored closely, especially when patients are on complex medication regimens. Recreational drugs also can affect medication levels; for dually diagnosed patients on methadone, doses of methadone often need to be adjusted, usually upward but occasionally downward depending on the antiretroviral regimen (i.e., delavirdine, nevirapine). Most psychiatric medications are metabolized by the liver and therefore may require more careful monitoring in those chronically infected with hepatitis C.

In particular, for those who manifest clinical or laboratory signs of liver failure, medication metabolism can be dangerously reduced to the point where patients may accumulate toxic levels of drugs they normally can take. In general, it is relatively safe to use most of the psychiatric medications both with HIV and HCV treatments. In the presence of HCV illness, periodic liver function tests are the standard of care. Because some psychotropics may elevate liver enzymes (e.g., valproic acid, carbamazepine, nefazodone), it is important to check these at baseline, early after initiation of therapy (2­4 weeks), and every 2­3 months thereafter. Nevertheless, data from a large retrospective study in Seattle, Washington, found that among 94 HCV seropositive patients treated with valproic acid, 81.9% showed minimal or no evidence of serum transaminase elevations (Barnes et al. 2001).

Yet combined toxicities are important to consider, particularly during treatment with medications that can have an impact on bone marrow activity (e.g., clozapine, carbamazepine, zidovudine, interferon, ribavirin) or may cause other additive side effects. Initiating interferon treatment should involve follow-up by a psychiatrist, both to evaluate the patient with schizophrenia as a candidate for long-term interferon on the basis of compliance with psychiatric therapy, and to monitor for psychiatric symptom exacerbation. Psychiatric patients, like medical patients, often are nonadherent to their medication regimen, which they may perceive as one of the few aspects of their lives they can control. It is important to time the beginning of an antiretroviral regimen with a commitment to the treatment and to help patients see that following an HIV or HCV medication regimen can be part of gaining control.

Working with a patient to promote adherence to psychotropic medications will be the best predictor of whether the patient can follow an HIV/HCV medication regimen. The clinician and infectious disease specialist must communicate about the patient’s need for and readiness to begin antiretrovirals, select in concert with the patient regimens that avoid drug­drug interactions, keep the number and doses of pills the patient has to take to the minimum necessary, and coordinate his or her treatment plans.

Conclusion
Understanding the HIV and HCV epidemics and their underpinnings among people with severe mental illness can help clinicians to recognize when their patients with schizophrenia are at risk for acquiring or transmitting these viruses and to intervene appropriately and effectively with preventive, counseling and testing, medical, and supportive services. It is critical for clinicians to receive training to enhance their knowledge and skills in these areas, to ask comfortably and nonjudgmentally about their patients’ risks rather than waiting until patients are ill to learn about risk behaviors, and continually to access up-to-date information and technical assistance about how to prevent and treat these infections among their patients.

Milton L. Wainberg, M.D.
Francine Cournos, M.D.
Karen McKinnon, M.A.
Alan Berkman, M.D.

References

1. Acuda SW, Sebit MB: Serostatus surveillance testing of HIV-I infection among Zimbabwean psychiatric inpatients in Zimbabwe. Cent Afr J Med 42:254-257, 1996
2. American Psychiatric Association: Practice Guideline for the Treatment of Patients with HIV/AIDS. Am J Psychiatry 157 (suppl):1-62, 2000
3. Ayuso-Mateos JL, Montanes F, Lastra I, et al: HIV infection in psychiatric patients: an unlinked anonymous study. Br J Psychiatry 170:181-185, 1997
4. Barnes R, Felker B, Sloan K, et al: Safety of valproic acid treatment in patients with hepatitis C. Poster presented at the 40th annual meeting of the American College of Neuropsychopharmacology, Waikoloa, HI, December 9, 2001
5. Barre-Sinoussi F, Chermann JC, Rey F, et al: Isolation of a T-lymphotropic retrovirus from a patient at risk for acquired immunodeficiency syndrome. Science 220:868-871, 1983
6. Broder S, Merigan TC, Bolognesi D (eds): Textbook of AIDS Medicine. Baltimore, MD, Williams & Wilkins, 1994
7. Brunette MF, Mercer CC, Carlson CL, et al: HIV-related services for persons with severe mental illness: policy and practice in New Hampshire community mental health. J Behav Health Serv Res 27:347-353, 2000
8. Carey MP, Carey KB, Kalichman SC: Risk for human immunodeficiency virus (HIV) infection among persons with severe mental illnesses. Clin Psychol Rev 17:271-291, 1997
9. Carmen E, Brady SM: AIDS risk and prevention for the chronic mentally ill. Hosp Community Psychiatry 41:652-657, 1990
10. Chuang HT, Atkinson M: AIDS knowledge and high-risk behaviour in the chronic mentally ill. Can J Psychiatry 41:269-272, 1996
11. Cividini A, Pistorio A, Regazzetti A, et al: Hepatitis C virus infection among institutionalized psychiatric patients: a regression analysis of indicators of risk. J Hepatol 27:455-463, 1997
12. Community Research Initiative on AIDS: HIV/hepatitis C co-infection: confronting twin epidemics. http://www.CRIANY.org, accessed January 2000
13. Corbitt G, Crosdale E, Bailey A: Protracted sero-conversion in haemophiliacs in whom infection is confirmed by p24 antigen detection and/or positive HIV PCR, in Abstracts, 7th International Conference on AIDS, Florence, Italy, 1991, p 387
14. Cournos F, McKinnon K: HIV seroprevalence among people with severe mental illness in the United States: a critical review. Clin Psychol Rev 17:259-269, 1997
15. Cournos F, Guido JR, Coomaraswamy S, et al: Sexual activity and risk of HIV infection among patients with schizophrenia. Am J Psychiatry 151:228-232, 1993
16. Fernandez F, Levy JK: The use of molindone in the treatment of psychotic and delirious patients infected with the human immunodeficiency virus: case reports. Gen Hosp Psychiatry 15:31-35, 1993
17. Gallo RC, Salahuddin SZ, Popovic M, et al: Frequent detection and isolation of cytopathic retroviruses (HTLV-III) from patients with AIDS and at risk for AIDS. Science 224:500-503, 1984
18. Goodman LA, Fallot RD: HIV risk-behavior in poor urban women with serious mental disorders: association with childhood physical and sexual abuse. Am J Orthopsychiatry 68:73-83, 1998
19. Hanson M, Kramer TH, Gross W, et al: AIDS awareness and risk behaviors among dually disordered adults. AIDS Educ Prev 4:41-51, 1992
20. Hardy AM: National health interview survey data on adult knowledge about AIDS in the United States. Public Health Rep 105:629-634, 1990
21. Herbert B: Woman battering and HIV infection, in Abstracts (TP500), HIV Infection in Women: Setting a New Agenda. Washington, DC, Philadelphia Sciences Group, 1995
22. Horwath E: Psychiatric and neuropsychiatric manifestations, in AIDS and People With Severe Mental Illness: A Handbook for Mental Health Professionals. Edited by Cournos F, Bakalar N. New Haven, CT, Yale University Press, 1996, pp 57-73
23. Horwath E, Cournos F, McKinnon K, et al: Illicit-drug injection among psychiatric patients without a primary substance use disorder. Psychiatr Serv 47:181-185, 1996
24. Kalichman SC, Kelly JA, Johnson JR, et al: Factors associated with risk for HIV infection among chronic mentally ill adults. Am J Psychiatry 151:221-227, 1994
25. Katz RC, Watts C, Santman J: AIDS knowledge and high risk behaviors in the chronic mentally ill. Community Ment Health J 30:395-402, 1994
26. Keet IP, Krol A, Koot M, et al: Predictors of rapid progression to AIDS in HIV-1 seroconverters. AIDS 7:51-57, 1993
27. Kelly JA: HIV risk reduction interventions for persons with severe mental illness. Clin Psychol Rev 17:293-309, 1997
28. Kelly JA, Murphy DA, Bahr GR, et al: AIDS/HIV risk behavior among the chronic mentally ill. Am J Psychiatry 149:886-889, 1992
29. Levy J: Pathogenesis of human immunodeficiency virus infection. Microbiol Rev 57:183-189, 1993
30. Liberman RP, Mueser KT, Wallace CJ, et al: Training skills in the psychiatrically disabled: learning coping and competence. Schizophr Bull 12:631-647, 1986
31. Lifson AR, Buchbinder SP, Sheppard HW, et al: Long-term human immunodeficiency virus infection in asymptomatic homosexual and bisexual men with normal CD4+ lymphocyte counts: immunologic and virologic characteristics. J Infect Dis 163:959-965, 1991
32. Masliah G, Achim CL, DeTeresa R, et al: The patterns of neurodegeneration in HIV encephalitis. Journal of NeuroAIDS 1:161-173, 1996
33. McDaniel JS, Purcell DW, Farber EW: Severe mental illness and HIV-related medical and neuropsychiatric sequelae. Clin Psychol Rev 17:311-325, 1997
34. McDermott BE, Sautter FJ, Winstead DK, et al: Diagnosis, health beliefs, and risk of HIV infection in psychiatric patients. Hosp Community Psychiatry 45:580-585, 1994
35. McKinnon K, Cournos F: HIV infection linked to substance use among hospitalized patients with severe mental illness. Psychiatr Serv 49:1269, 1998
36. McKinnon K, Cournos F, Sugden R, et al: The relative contributions of psychiatric symptoms and AIDS knowledge to HIV risk behaviors among people with severe mental illness. J Clin Psychiatry 57:506-513, 1996
37. McKinnon K, Cournos F, Herman R, et al: AIDS-related services and training in outpatient mental health care agencies in New York. Psychiatr Serv 50:1225-1228, 1999
38. McKinnon K, Wainberg ML, Cournos F: HIV/AIDS preparedness in mental health care agencies with high and low substance use disorder caseloads. J Subst Abuse 13:127-135, 2001
39. Mellors JW, Rinaldo CR Jr, Gupta P, et al: Prognosis in HIV-1 infection predicted by the quantity of virus in plasma. Science 272:1167-1170, 1996
40. Menon AS, Pomerantz S: Substance use during sex and unsafe sexual behaviors among acute psychiatric inpatients. Psychiatr Serv 48:1070-1072, 1997
41. Meyer JM: Prevalence of hepatitis A, hepatitis B and HIV among hepatitis C seropositive state hospital patients: results from Oregon State Hospital. J Clin Psychiatry (in press)
42. Mulder RT, Ang M, Chapman B, et al: Interferon treatment is not associated with a worsening of psychiatric symptoms in patients with hepatitis C. J Gastroenterol Hepatol 15: 300-303, 2000
43. National Digestive Diseases Information Clearinghouse: Chronic hepatitis C: current disease management. Available at: http://www.niddk.nih.gov/health/digest/pubs/chrnhepc. Accessed February 17, 2003
44. National Institutes of Health Consensus Development Conference Panel: Management of hepatitis C. Hepatology 26:2S-10S, 1997
45. O'Brien WA: Genetic and biologic basis of HIV-1 neurotropism, in HIV, AIDS and the Brain. Edited by Price RW, Perry SW. New York, Raven, 1994, pp 47-70
46. O'Brien WA, Hartigan PM, Martin D, et al: Changes in plasma HIV-1 RNA and CD4 + lymphocyte counts and the risk of progression to AIDS. N Engl J Med 334:426-431, 1996
47. Oliveira SB: Avalia'o do comportamento sexual, conhecimentos e atitudes sobre AIDS, dos pacientes internados no instituto de psiquiatria da UFRJ, in O Campo da Aten'o Psicossocial. Edited by Venncio AT, Leal EM, Delgado PG. Rio de Janeiro, Te Cor, 1997, pp 343-351
48. Oquendo M, Tricarico P: Pre- and post-HIV test counseling, in AIDS and People With Severe Mental Illness: A Handbook for Mental Health Professionals. Edited by Cournos F, Bakalar N. New Haven, CT, Yale University Press, 1996, pp 97-112
49. Otto-Salaj LL, Heckman TG, Stevenson LY, et al: Patterns, predictors and gender differences in HIV risk among severely mentally ill men and women. Community Ment Health J 34:175-190, 1998
50. Otto-Salaj LL, Kelly JA, Stevenson LY, et al: Outcomes of a randomized smallgroup HIV prevention intervention trial for people with serious mental illness. Community Ment Health J 37:123-144, 2001
51. Resnick L, Berger JR, Shapshak P, et al: Early penetration of the blood brain barrier by HTLV-III/LAV. Neurology 38:9-15, 1988
52. Rosenberg SD, Goodman LA, Osher FC, et al: Prevalence of HIV, hepatitis B, and hepatitis C in people with severe mental illness. Am J Public Health 91:31-37, 2001
53. Sewell DD, Jeste DV, McAdams LA, et al: Neuroleptic treatment of HIV-associated psychosis. Neuropsychopharmacology 10:223-229, 1994
54. Staprans SI, Feinberg MB: Natural history and immunopathogenesis of HIV-1 disease, in The Medical Management of AIDS, 5th Edition. Edited by Sande MA, Volberding PA. Philadelphia, PA, WB Saunders, 1997, pp 29-56
55. Susser E, Miller M, Valencia E, et al: Injection drug use and risk of HIV transmission among homeless men with mental illness. Am J Psychiatry 153:794-798, 1996
56. Varmus H: Retroviruses. Science 240:1427-1435, 1988
57. Vento S, Garofano T, Renzini C, et al: Fulminant hepatitis associated with hepatitis A virus superinfection in patients with chronic hepatitis C. N Engl J Med 338:286-290, 1998
58. Wainberg ML, Forstein M, Berkman A, et al: Essential medical facts for mental health practitioners, in What Mental Health Practitioners Need to Know about HIV and AIDS. Edited by Cournos F, Forstein M. San Francisco, CA, Jossey-Bass, 2000, pp 3-15
59. Warner GC: Molecular insights into HIV-1 infection, in The Medical Management of AIDS, 5th Edition. Edited by Sande MA, Volberding PA. Philadelphia, PA, WB Saunders, 1997, pp 17-28