Epidemiologic Notes and Reports HIV-1 Infection and Artificial Insemination with Processed Semen

In January 1990, a health department in the United States received a report of human immunodeficiency virus type 1 (HIV-1) infection in a woman who had been artificially inseminated with semen from her HIV-1-infected, hemophilic husband. The man had tested positive for HIV-1 antibody in 1985, but his wife had been negative for HIV-1 antibody yearly since 1985, most recently in December 1988. In August, October, and December 1989, the woman was inseminated with semen from her husband.

In each of the inseminations, fresh ejaculate was processed in an attempt to remove virus from spermatozoa to avoid HIV-1 transmission. In August, the semen was centrifuged to separate cells from seminal plasma. The cellular pellet was washed and recentrifuged twice in a HEPES* buffer and introduced into the woman's uterus through a catheter placed in her cervix. In October and December, fresh ejaculate was fractionated by centrifugation through a discontinuous density gradient of polyvinylpyrrolidone-coated silica particles (Percoll((R))**) to separate motile spermatozoa from other cells and seminal plasma. The fraction containing motile spermatozoa was washed twice in buffer and introduced into the woman's uterus through a catheter. After each procedure, the woman developed mild cramping but no bleeding; she did not become pregnant. However, in January 1990, she tested positive for HIV-1 antibody by enzyme immunoassay (EIA) and Western blot.

The couple reported using latex condoms with each episode of vaginal intercourse (two to four times monthly) since 1986, denied any instances of condom breakage, and did not engage in oral or anal intercourse. The woman denied skin contact with her husband's blood or with any of the needles he used to inject himself with factor VIII concentrate. She had had no other sex partners since 1985 and had not used drugs intravenously, received blood or blood products, or worked in a health-care setting. She reported no viral illnesses between July 1988 and August 1989. In September 1989, 3 weeks after the first insemination, she was ill for 3 days with a sore throat, tinnitus, nausea, and vomiting. During late November, between the second and third inseminations, she noticed a nontender cervical lymph node. In December, 3 weeks after the third insemination, she developed a low-grade fever, abdominal cramps, and watery diarrhea that lasted 4-5 days.

The physician who performed the inseminations reported that in January 1990 a second HIV-1-discordant couple (i.e., seropositive husband with hemophilia, sero negative wife) underwent one insemination using the same density gradient centrifugation procedure. Nine weeks after the insemination, the woman was negative for HIV-1 antibody by EIA and Western blot and for proviral HIV-1 DNA by polymerase chain reaction.

To investigate the methods used to prepare semen from these men for insemination, semen from five HIV-infected men with hemophilia was processed in the same (Continued on page 255)laboratory using both procedures reported here. In four of the five semen samples, leukocytes were present before processing. Leukocytes remained in all four samples after simple centrifugation and washing and in two of three samples tested after density gradient centrifugation. In two, CD4+ lymphocytes were present after simple centrifugation and washing.

To assess the interest in insemination among HIV-discordant couples and the frequency of such procedures, 40 of the 222 hemophilia treatment centers in the United States were surveyed by telephone. Twenty-six (65%) centers reported receiving inquiries from HIV-discordant couples interested in such procedures, and 13 (33%) had referred interested couples to specialists for information or insemination; one reported a couple who had conceived without HIV-1 transmission after insemination with processed semen. In general, respondents reported that couples who sought such information were well-informed about HIV infection but were highly motivated to conceive their own children. Reported by: Epidemiology Br, Div of HIV/AIDS and Epidemiology Activity, Div of Immunologic, Oncologic, and Hematologic Diseases, Center for Infectious Diseases; Div of Field Svcs, Epidemiology Program Office, CDC.

Editorial Note

Editorial Note: The mode of HIV-1 transmission to the woman described in this report cannot be determined definitively. Although she reported symptoms suggestive of an acute retroviral syndrome, no single episode is specific enough to establish the time of infection. The possibility of sexual transmission from her husband cannot be excluded. However, the insemination procedures may have resulted in trans mission; infected leukocytes or free virus may not have been removed from the husband's semen with the procedures used.

There is no evidence that any procedure can reliably eliminate HIV from semen. HIV-1 has been isolated from the leukocyte fraction and from seminal plasma from HIV-1-infected men (1-3). Techniques for concentrating motile spermatozoa in semen (4) may remove virus associated with leukocytes and seminal plasma but have not been shown to eliminate the virus. Moreover, HIV-1 has been reported to attach to or enter spermatozoa (5,6), although this finding has been disputed (7,8).

HIV-1 transmission through intravaginal insemination with unprocessed donor semen has been reported (9,10), although data regarding the magnitude of the risk are conflicting (9-11). Whether intrauterine insemination carries a higher risk than intravaginal procedures is not known.

The investigation reported here indicates that some HIV-1-discordant couples are seeking methods of achieving conception without transmission of HIV infection. However, no data exist to support the safety of any procedure purported to remove HIV from semen. CDC recommends against insemination with semen from HIV-infected men (12).

References

1. Zagury D, Bernard J, Leibowitch J, et al. HTLV-III in cells

cultured from semen of two patients with AIDS. Science 1984;226:449-51.

2. Ho DD, Schooley RT, Rota TR, et al. HTLV-III in the semen and blood of a healthy homosexual man. Science 1984;226:451-3.

3. Levy JA. The transmission of AIDS: the case of the infected cell. JAMA 1988;259:3037-8.

4. Berger T, Marrs RP, Moyer DL. Comparison of techniques for selection of motile spermatozoa. Fertil Steril 1985;43:268-73.

5. Miller VE, Scofield VL. Sperm mediated transfer of HIV into target cells: role in AIDS transmission (Abstract). V International Conference on AIDS. Montreal, Canada, June 4-9, 1989:514.

6. Bagasra O, Freund M, Weidmann J, Harley G. Interaction of human immunodeficiency virus with human sperm in vitro. J AIDS 1988;1:431-5.

7. Pudney J. Caveats associated with identifying HIV using transmission electron microscopy. In: Alexander NJ, Gabelnick HL, Spieler JM, eds. Heterosexual transmission of AIDS: proceedings of the Second Contraceptive Research and Development (CONRAD) Program International Workshop. New York: Wiley-Liss, 1989:197-204.

8. Anderson D, Wolff H, Wenhao Z, Pudney J, Dorfman T, Mayer K. Evidence against HIV-1 attachment to human spermatozoa. Science (in press).

9. Stewart GJ, Tyler JPP, Cunningham AL, et al. Transmission of human T-cell lymphotropic virus type III (HTLV-III) by artificial insemination by donor. Lancet 1985;2:581-4. 10. Chiasson MA, Stoneburner RL, Joseph SC. Human immunodeficiency virus transmission though artificial insemination. J AIDS 1990;3:69-72. 11. Eskenazi B, Pies C, Newstetter A, Shepard C, Pearson K. HIV serology in artificially inseminated lesbians. J AIDS 1989;2:187-93. 12. CDC. Semen banking, organ and tissue transplantation, and HIV antibody testing. MMWR 1988;37:57-8,63. *4-(2-Hydroxyethyl)piperazineethanesulfonic acid. **Use of trade names is for identification only and does not imply endorsement by the Public Health Service or the U.S. Department of Health and Human Services.

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