HIV Transmission Between Two Adolescent Brothers With Hemophilia

In July 1992, the National Hemophilia Foundation and CDC received a report from a hemophilia-treatment center of a 19-year-old man with hemophilia (patient 2) who recently had seroconverted for antibody to human immunodeficiency virus (HIV). This report summarizes the findings of an investigation by CDC and state and local public health officials, which determined he was infected with a strain of HIV nearly identical to that in his previously infected older brother (patient 1). * Case Summaries

Patient 1, who has severe factor VIII deficiency (hemophilia A), before 1985, received factor VIII concentrate made from plasma that was neither screened for HIV antibody nor heat-treated. Review of medical records indicated that in 1983 he had an episode of pharyngitis and diffuse lymph node enlargement compatible with an acute retroviral syndrome. In 1985, when first tested, HIV antibody was detected in his serum. His CD4+ T-lymphocyte count ranged from 400 to 550 cells/uL during 1987-1991 but declined to 110 cells/uL in 1992.

Patient 2 also received unscreened factor VIII concentrate before 1985 to treat severe hemophilia A. Since 1985, however, he had received only screened and heat-treated factor concentrate, and beginning in 1988, he received only concentrate that was heat-treated and monoclonally purified. HIV-antibody tests performed annually during November 1985-April 1989 were negative. When his serum was next tested in January 1992, HIV antibody was detected. A stored plasma specimen drawn in April 1991 also contained HIV antibody. His CD4+ T-lymphocyte count was 1102 cells/uL in 1985, 846 cells/uL and 500 cells/uL as measured from the same specimen in two different laboratories in 1987, and 70 cells/uL and 120 cells/uL at two different times in 1992.

The brothers have two uncles with hemophilia and HIV infection; one uncle visited their home daily to weekly but did not live with them. This uncle was HIV-seropositive when first tested in 1985. Laboratory Findings

Nucleotide sequencing of HIV-1 DNA indicated that the viral strains present in both brothers were genetically similar. Proviral DNA from peripheral blood mononuclear cells obtained from each brother and from the uncle with whom they had frequent contact was amplified by polymerase chain reaction. DNA fragments encompassing 345 nucleotides of the V3 and flanking regions of the gene encoding the HIV-1 envelope glycoprotein (gp120) were sequenced after cloning into M13 vectors. Genetic analysis indicated that two variants, or quasi-species, were present in both brothers. Variant A was the predominant species (15 of 21 clones) in patient 1 and the minor species (one of 20 clones) in patient 2, with an average intravariant nucleotide divergence of 1.8% between the two brothers. Variant B was the minor species in patient 1 (six of 21 clones) and the predominant species in patient 2 (19 of 20 clones), with an average intravariant nucleotide diversity of 3.5% in the B variants between the two brothers. The average nucleotide difference between variants A and B in the two brothers was 6.2%. Only one HIV variant was present in the uncle; that variant differed from variant A by 10.2% and variant B by 10.8%. Epidemiologic Investigation

Information concerning factor concentrate administration during the period in which patient 2 most likely was infected (October 1988 {6 months before his last negative HIV-antibody test} through April 1991) was obtained by review of medical records and interviews with the two brothers. During this period, patient 1 received factor concentrate infusions at home approximately 10 times per year and patient 2 approximately five times per year. Each brother reported always self-administering infusions and never receiving assistance from anyone else, including the other brother. They reported routinely administering their infusions at different times of the day and in different locations in their home. On the infrequent days when both received infusions on the same day, they reportedly never administered factor concentrates in the same room at the same time and never used each other's infusion equipment. Contaminated needles and other infusion equipment used were reportedly kept in one puncture-resistant container.

Both brothers recalled sharing a razor on one occasion, most likely during 1988, when they both cut themselves and bled slightly while shaving. They did not recall which brother used the razor first. Patient 2 was not aware of any other contact with his brother's blood or bloody body fluids. In October 1988, patient 1 had bleeding hemorrhoids; however, his blood reportedly never soaked through his clothing and never contaminated his sheets, toilet seats, or other environmental surfaces.

From October 1988 through April 1991, the two brothers were not hospitalized at the same time and made no visits to the dentist, emergency department, or outpatient clinic on the same day. Neither brother reported receiving tattoos, acupuncture, or injections other than factor concentrates nor recalled having had a needlestick injury or open skin lesions. During this period, the two brothers shared a bedroom and routinely slept in the same bed at night. Their mother and sister also lived in the household; the sister tested negative for HIV antibody, and the mother declined to be tested.

The brothers denied having had sex with any common sex partners or with each other. In 1990, patient 2 had unprotected sexual contact with two women; one tested negative for HIV antibody in 1992, and the other could not be located. During 1989 and 1990, patient 2 had acute gastrointestinal bleeding and received transfusions of six units of red blood cells from seronegative donors later determined not to be infected with HIV. Reported by: A Brownstein, MPH, National Hemophilia Foundation, New York City. W Fricke, MD, Center for Biologics Evaluation and Research, Food and Drug Administration. Div of HIV/AIDS, National Center for Infectious Diseases, CDC.

Editorial Note

Editorial Note: The laboratory and epidemiologic findings from this investigation indicate that patient 2 became infected with an HIV strain that had previously infected his older brother. The presence in each brother of two variants of HIV, each with DNA sequence concordance similar to that reported for other infections known to be epidemiologically related (1-3), strongly supports the hypothesis that their infections are related. However, the more than 3-year interval between seroconversion in the two brothers strongly suggests that the brothers were not infected by the same source (e.g., contaminated clotting factor concentrate administered in 1985 or earlier).

Although this investigation was unable to determine precisely how patient 2 became infected with HIV, transmission most likely occurred during the reported blood contact (i.e., the episode of razor-sharing) or other blood contact that went unrecognized or unreported. Factors accounting for an increased likelihood of blood contact included possible bleeding related to hemophilia or its treatment, the presence of used needles in the home, and the close physical contact between the brothers. However, it is also possible that transmission occurred through an exposure, such as sexual contact, that was not identified by the investigation. The limited ability of the brothers to recall events 2-3 years earlier and the inability of the investigators to independently confirm information provided by the brothers made determining the precise mode of transmission difficult.

Seventeen previous studies in the United States and Europe have examined the prevalence of HIV infection among nonsexual, nonneedlesharing household contacts of persons with HIV infection; none of the 1167 contacts who were followed for more than 1700 person-years in these studies were infected (95% confidence interval for the rate of transmission=0-0.2 infections per 100 person-years) (4). However, HIV has been transmitted in households in which opportunities existed for percutaneous, skin, or mucous-membrane contact with HIV-infected blood. This report is the second documented instance of HIV transmission between siblings with hemophilia; the first report documented opportunities for percutaneous blood exposure associated with intravenous infusions (2). Cases of HIV transmission also have been reported in households in which needles were shared for medical injections at home (5), cutaneous exposure to blood occurred during home health care (6,7), and there was presumed but undocumented blood contact between young children (3).

The findings in this report re-emphasize the need for precautions to prevent contact with blood in households and other settings -- especially those in which health care is provided. Adherence to guidelines for preventing blood exposure in health-care and other settings (8-10) may reduce the risk for blood contact and transmission of bloodborne pathogens even in homes and other settings in which the risk is already extremely low.

References

1. Ou C-Y, Ciesielski CA, Myers G, et al. Molecular epidemiology

of HIV transmission in a dental practice. Science 1992;256:1165-71.

2. CDC. HIV infection in two brothers receiving intravenous therapy for hemophilia. MMWR 1992;41:228-31.

3. Fitzgibbon JE, Gaur S, Frenkel LD, Laraque F, Edlin BR, Dubin DT. Transmission of human immunodeficiency virus type 1 with a zidovudine resistance mutation between two children. N Engl J Med 1993;329:1835-41.

4. Simonds RJ, Chanock S. Medical issues related to caring for HIV-infected children in and out of the home. Pediatr Infect Dis J 1993;12:845-52.

5. Koenig RE, Gautier T, Levy JA. Unusual intrafamilial transmission of human immunodeficiency virus. Lancet 1986;2:627.

6. Grint P, McEvoy M. Two associated cases of the acquired immunodeficiency syndrome (AIDS). Communicable Disease Report 1985;42:4.

7. CDC. Apparent transmission of human T-lymphotrophic virus type III/lymphadenopathy-associated virus from a child to a mother providing health care. MMWR 1986;35:76-9.

8. CDC. Recommendations for prevention of HIV transmission in health-care settings. MMWR 1987;36(suppl 2S).

9. CDC. Update: universal precautions for prevention of transmission of human immunodeficiency virus, hepatitis B virus, and other bloodborne pathogens in health-care settings. MMWR 1988;37:377-82,387-8. 10. Simonds RJ, Rogers MF. HIV transmission -- bringing home the message {Editorial}. N Engl J Med 1993;329:1883-5.

• Single copies of this report will be available free until December 17, 1994, from the CDC National AIDS Clearinghouse, P.O. Box 6003, Rockville, MD 20849-6003; telephone (800) 458-5231.

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