Do no harm: on the ethics of testosterone replacement therapy for HIV+ persons.

This critique of the practice of

testosterone replacement therapy for

HIV+ individuals and of Wagner,

Rabkin, and Rabkin's (1997) research

on this topic focuses on (a) the dubious

ethics of stimulating sexual desire and

sexual function in persons who carry a

fatal, sexually borne pathogen, (b) our

very limited ability to ensure that

testosterone replacement therapy for

HIV+ persons will not pose significant

danger to uninfected persons, and (c) the

relative importance of quality of life

versus protection of life considerations in

research and therapy in the HIV/AIDS 

area.

The act of administering testosterone to stimulate sexual desire and function in a population of persons who carry a fatal, sexually transmitted pathogen, as reported by Wagner, Rabkin, and Rabkin (1997), requires ethical scrutiny of the most serious sort. One approach to this issue, expressed by Wagner and colleagues, is to advocate that it is humane to pursue this treatment because it helps restore quality of life to afflicted individuals and because it can be administered with care. Another approach to this issue, expressed by the current author, is that a hierarchy of concerns exists. Although improving quality of life for the afflicted is a relatively important value, protecting the lives of those who could be lethally affected as a result of testosterone replacement therapy for HIV+ persons is an additional and absolutely more important value that clearly takes precedence. Proponents of this view hold that the administration of testosterone to HIV+ persons is generally ill advised, and especially so in view of well-documented and very high rates of unprotected sexual contact among HIV+ men in the United States (e.g., Cleary et al., 1995; Fisher, 1996; Kalichman, Kelly, & Rompa, 1996; Marks et al., 1994; Sobel, Shine, DiPietro, & Rabinowitz, 1996); well-documented and very significant limits on the effectiveness of HIV-prevention counseling for persons in general (Fisher & Fisher, 1992), and for persons with HIV in particular (Cleary et al., 1995); and the fact that testosterone therapy as advocated would be offered to persons at a stage of HIV-illness progression that covaries with the increased likelihood of AIDS dementia complex and depression (Kalichman, 1995) and high viral load (Ioannidis, Cappeleri, Lau, Sacks, & Skolnik, 1996), which may be associated with increased risk behavior (Kalichman, 1995; Kelly et al., 1993) and increased infectiousness (Francis, 1992) to others. It follows from this analysis that testosterone replacement therapy should be offered only in very rare and very well-controlled and well-monitored circumstances.

Beyond these overall concerns about the ethics of testosterone replacement therapy for HIV+ individuals, specific concerns should be articulated with respect to Wagner et al.'s research on this subject. These investigators administered testosterone replacement therapy to 80 HIV+ men for 8 weeks, randomized the sample into further testosterone versus placebo conditions for an additional 4 weeks, and executed limited follow-up research on the impact of therapy and side effects that included the increased practice of unsafe sexual behavior. In the later regard, Wagner et al. communicated that 1 man reported unprotected insertive anal intercourse at baseline and that 3 men reported unprotected insertive anal intercourse at the 12-week post-test and stated that "All those who reported unprotected anal sex at baseline and/or Week 12 rated their sexual activity as posing no risk to partners" (p. 30). The partial data that the authors were able to collect on objective levels of risk actually posed by these men to their partners clearly do not rule out the possibility that testosterone replacement therapy stimulated the occurrence of unprotected insertive anal intercourse by HIV+ men with HIV-partners within the experimental interval under study. Moreover, what might have happened later among study participants who continued to receive testosterone replacement therapy for an extended period of time following completion of the research is not known, either. Although Wagner et al. followed up as many study participants as possible at 13 to 35 weeks following discharge from the study, no data on long-term unsafe sexual behavior by these HIV+ testosterone-treated men are reported.

One is not reassured by statements by HIV+ participants who received testosterone replacement therapy and who reported unprotected insertive anal intercourse that these unprotected insertive anal contacts posed no risk to their partners. Completely candid self-reports of the potentially lethal endangerment of another would not be expected, and the literature, in fact, carefully documents the cognitive distortions that some HIV+ men, and some of those who are unaware of their and their partner's HIV serostatus, use to attempt to dismiss their objectively highly risky sexual behavior (Fisher, 1996; Offir, Fisher, Williams, & Fisher, 1993). One is not reassured by Wagner et al.'s inability to follow up a number of study participants in the short term (the possibility exists that loss to short-term follow up is correlated with risky sexual behavior), and one is not reassured by the investigators' failure to report any long-term follow-up findings concerning unsafe sexual behavior by the HIV+ men who continued testosterone replacement therapy after discharge from the study and over a long period of time.

One is not required by Wagner et al.'s failure to report a priori and systematic ethics analyses of the costs and benefits of this work in relation to published ethical standards for behavioral research (e.g., American Psychological Association, 1982), published ethical standards for AIDS research (e.g., American Psychological Association, 1986), published discussions of the ethics of disclosing or not disclosing the risky sexual behavior of HIV+ individuals (e.g., Girardi, Keese, Traver, & Cooksey, 1988; Society for the Scientific Study of Sex, 1993), or in relation to the Tarasoff-based duty to warn (e.g., Tarasoff, 1976).

One is not reassured by Wagner et al.'s pilot efforts to offer testosterone therapy to HIV+ men even more widely by enrolling those who are not testosterone deficient in "testosterone addition" trials. One is not reassured by the investigators' statement that "We do not discontinue treatment for patients who report unprotected anal or vaginal sex with partners who are not HIV+ once they are in treatment" (p. 19), because of the risk that this would deter reporting such behavior, and one is not reassured that the investigators now offer safer sex counseling to those being treated, because safer sex counseling is exceedingly far from uniformly effective (e.g., Cleary et al., 1995; Fisher & Fisher, 1992; Kelly & St. Lawrence, 1988).

One does, however, gain a measure of reassurance from the candor of the authors of this report and from the care of the editor of this journal in bringing these issues to light, and some hope that this discussion will stimulate searching a priori analyses of the ethics and safety of research in this area. It is the critical imperative of health scientists to seek therapies that will improve quality of life for HIV+ individuals but that will not at the same time pose a threat to the health of the uninfected. With respect to testosterone replacement therapy for HIV+ persons, an enormous amount of work remains to be done before the achievement of this critical ethical balance.

References

American Psychological Association. (1982). Ethical principles in the conduct of research with human participants. Washington, DC: American Psychological Association.

American Psychological Association. (1986). Ethical issues in psychological research on AIDS. Journal of Homosexuality, 13(1), 109-116.

Cleary, P. D., Van Devanter, N., Steilen, M., Stuart, A., Shipton-Levy, R., McMullen, W., Rogers, T. F., Singer, F., Avorn, J., & Pindyck, J. (1995). A randomized trial of an educational and support program for HIV-infected individuals. AIDS, 9, 1271-1278.

Fisher, J. D. (1996). Dynamics of risky behavior in seropositive men who have sex with men. Invited Colloquium, Centers for Disease Control, Atlanta, GA.

Fisher, J. D., & Fisher, W. A. (1992). Changing AIDS risk behavior. Psychological Bulletin, 111, 455-474.

Francis, D. P. (1992). Public health strategies for prevention of HIV infection. In G. P. Wormser (Ed.), AIDS and other manifestations of HIV infection (pp. 659-669). New York: Raven.

Girardi, J. A., Keese, R. M., Traver, L., & Cooksey, D. R. (1988). Psychotherapist responsibility in notifying individuals at risk for exposure to HIV. The Journal of Sex Research, 25, 1-27.

Ioannidis, J. P. A., Cappeleri, J. C., Lau, J., Sacks, H. S., & Skolnik, P. R. (1996). Predictive value of viral load measurements in asymptomatic untreated HIV-1 infection: A mathematical model. AIDS, 10, 255-262.

Kalichman, S. C. (1995). Understanding AIDS. A guide for mental health professionals. Washington, DC: American Psychological Association.

Kalichman, S. C., Kelly, J. A., & Rompa, D. (1996). Continued high-risk sex among HIV seropositive men. Manuscript submitted for publication.

Kelly, J. A., Murphy, D. A., Bahr, G. R., Koob, J. J., Morgan, M. G., Kalichman, S. C., Stevenson, L. Y., Brasfield, T. L., Bernstein, B. M., & St. Lawrence, J. S. (1993). Factors associated with severity of depression and high-risk sexual behavior among persons diagnosed with human immunodeficiency virus (HIV) infection. Health Psychology, 12, 215-219.

Kelly, J. A., & St. Lawrence, J. S. (1988). The AIDS health crisis. Psychological and social interventions. New York: Plenum.

Marks, G., Ruiz, M. S., Richardson, J. L., Reed, D., Mason, H. R. C., Sotelo, M., & Turner, P. A. (1994). Anal intercourse and disclosure of HIV infection among seropositive gay and bisexual men. Journal of Acquired Immune Deficiency Syndromes, 7, 866-869.

Offir, J. T., Fisher, J. D., Williams, S. S., & Fisher, W. A. (1993). Reasons for inconsistent AIDS preventive behaviors among gay men. The Journal of Sex Research, 30, 62-69.

Sobel, E., Shine, D., DiPietro, D., & Rabinowitz, M. (1996). Condom use among HIV infected patients in South Bronx, New York. AIDS, 10, 235.

Society for the Scientific Study of Sex. (1993). Society for the Scientific Study of Sex Statement of Ethical Guidelines. The Journal of Sex Research, 30, 192-198.

Tarasoff v. Regents of the University of California. (1976). 17 Cal. 3rd 425, 131 C.R. 14.

Wagner, G., Rabkin, J., & Rabkin, R. (1997). Effects of testosterone replacement therapy on sexual interest, function, and behavior in HIV-positive men. The Journal of Sex Research, 34, 27-33.

William A. Fisher Department of Psychology, Department of Obstetrics and Gynaecology, University of Western Ontario, London, Canada

Work on this commentary was supported by research grants from the National Institute of Mental Health (1-RO1-MH46224-01), Health Canada [National Health Scientist (AIDS) Award], and Janssen-Ortho. Comments by Wendy Lewis and Michael Barrett on earlier drafts of this manuscript are acknowledged with thanks. Correspondence should be directed to William A. Fisher, Ph.D., Department of Psychology and Department of Obstetrics and Gynaecology, Social Science Centre, University of Western Ontario, London, Ontario, Canada N6A 5C2.