Jane P. Getchell

The Acquired Immunodeficiency Syndrome in a Cohort of Homosexual Men: A Six-Year Follow-up Study

A cohort of 6875 homosexual men, initially seen at the San Francisco City Clinic between 1978 and 1980, were studied to determine the incidence and prevalence of the acquired immunodeficiency syndrome, related conditions, and infection with the human T-lymphotropic virus, type III/lymphadenopathy-associated virus (HTLV-III/LAV). By December 1984, 2.4% of the men had the syndrome; mortality attributable to the syndrome in 1984 was 600/100 000. For each man with the syndrome in a representative sample of 474 cohort members seen in 1984, 7.5 men had generalized lymphadenopathy, 1.1 had other prodromal findings, and 0.8 had hematologic abnormalities. Prevalence of serum antibodies to HTLV-III/LAV, measured by an enzyme-linked immunosorbent assay, increased from 4.5% in 1978 to 67.4% in 1984. Of 31 persons who were seropositive and without the syndrome between 1978 and 1980, 2 developed the syndrome and 8 developed related conditions during a median follow-up of 61 months. Over a 6-year period, two thirds of cohort members were infected with HTLV-III/LAV and almost one third developed related conditions.

Risk factors for human immunodeficiency virus (HIV) infections in homosexual men.

To clarify risk factors for infection with the human immunodeficiency virus (HIV) we selected at random 785 homosexual men who had participated in studies of hepatitis B in San Francisco in 1978-80 for a follow-up study of the acquired immunodeficiency syndrome. Although most had not been contacted in over five years, 492 (63 per cent) were located and enrolled. The 240 (67 per cent) who had developed antibodies to HIV, as measured by an enzyme-linked immunosorbent assay (ELISA), were compared with 119 who had remained seronegative. In multivariate analyses, receptive anal intercourse with ejaculation by nonsteady sexual partners, many sexual partners per month, and other indicators of high levels of sexual activity were highly associated with seroconversions. None of the sexual practices that we studied appeared to offer protection against HIV infection.

Persistent Infection with Human T-Lymphotropic Virus Type III/Lymphadenopathy-Associated Virus in Apparently Healthy Homosexual Men

A group of 14 apparently health homosexual men with serologic evidence of human T-lymphotropic virus type III/lymphadenopathy-associated virus (HTLV-III/LAV) infection were studied to determine the duration of their seropositivity, their immunologic status, and the frequency of isolation of HTLV-III/LAV from their peripheral blood. The men were selected from a larger sample of patients who attended a clinic for treatment of sexually transmitted diseases in San Francisco because they did not have acquired immunodeficiency syndrome (AIDS), signs or symptoms suggestive of the prodrome of AIDS, or laboratory evidence of anemia or leukopenia. 4 or more serum samples were available from previous clinic visits. The men ranged in age from 26-41 years, and had a median number of sexual partners in the last year of 23. The estimated duration of seropositivity ranged from 4-69 months (median, 33 months). 11 of the 14 had T-helper: T-suppressor cell ratios below 1 (the lower limit of normal), and low ratios were significantly correlated with duration of seropositivity. HTLV-III/LAV was isolated in peripheral blood samples from 8 of 12 men tested. Culture-positive and culture-negative men did not differ significantly in terms of age, presence of a palpable lymph node, T helper:T-suppressor cell ratio, or duration of seropositivity. These findings suggest that some seropositive men may remain asymptomatic for at least 5 years. However, the isolation of HTLV-III/LAV from the peripheral blood of most of these men indicates persistent infection may be common among asymptomatic seropositive men at risk for AIDS. It should be assumed that these men have the potential to transmit HTLV-III/LAV infection.

Relationship between antibody to LAV/HTLV-III and the natural course of subclinical cellular immune dysfunction in homosexual men.

To assess the epidemiology and natural history of persistent generalized lymphadenopathy (PGL) and subclinical immunodeficiency in relation to serologic evidence of lymphadenopathy-associated virus/human T-lymphotropic virus type III (LAV/HTLV-III) infection, 109 homosexual men with PGL, 47 homosexual men without lymphadenopathy who attended a sexually transmitted disease (STD) clinic, 25 homosexual male university students, and 26 heterosexual men who attended the STD clinic were studied. In 1982-1983 antibody to LAV/HTLV-III was present in 97%, 35%, 21%, and 4% of the four groups, respectively (P less than .001). Subclinical immunodeficiency was more closely associated with LAV/HTLV-III seropositivity than with lymphadenopathy. Cohorts of 78 homosexual subjects with PGL, 35 homosexual subjects from STD clinic, and 15 homosexual university students were followed for median periods of 13.5, 20, and 14.5 months, respectively. The seroconversion rate was 23% per year among seronegative subjects, and 4% of seropositive subjects developed overt acquired immunodeficiency syndrome (AIDS). Among seronegative subjects, there was significant improvement in T4:T8 ratios (P = .001), whereas most seropositive subjects continued to have subnormal total counts of T4 lymphocytes and low T4:T8 ratios. Some cases of subclinical cellular immunodeficiency apparently are unrelated to LAV/HTLV-III infection, and the presence of antibody to this virus is associated with an unfavorable immunologic prognosis.

The Safety of the Hepatitis B Vaccine. Inactivation of the AIDS Virus During Routine Vaccine Manufacture

In the United States, one hepatitis B vaccine (Heptavax-B) has been licensed for the prevention of hepatitis B virus infections. Even though this vaccine has been shown to be highly effective and well tolerated in controlled trials and has been recommended for use in those at risk for acquiring infection by hepatitis B virus, many individuals have been reluctant to be immunized for fear of contracting acquired immunodeficiency syndrome (AIDS). In this study, we demonstrate that each of the three inactivation steps used in the manufacture of Heptavax-B independently will inactivate the infectivity of high-titered preparations of the AIDS virus; recipients of the hepatitis B vaccine do not develop antibodies to the AIDS virus; the hepatitis B vaccine does not contain detectable levels of nucleic acids related to the AIDS virus. These observations clearly demonstrate that vaccination with the currently available hepatitis B vaccine poses no demonstrable risk for acquiring AIDS.

Transfusion-Associated Acquired Immunodeficiency Syndrome: Evidence for Persistent Infection in Blood Donors

To investigate whether infection with human T-cell lymphotropic virus/lymphadenopathy-associated virus (HTLV-III/LAV) may be persistent in asymptomatic persons and to correlate infection with seropositivity, we performed virologic and serologic studies in 25 of 30 persons who were identified as being at high risk for the acquired immunodeficiency syndrome (AIDS) and who had donated blood to patients who later contracted transfusion-associated AIDS. High-risk donors were those who belonged to a high-risk population, had AIDS or a closely related condition, or had a low ratio of helper to suppressor T lymphocytes. We performed similar studies in 6 of the 24 patients with AIDS who had received donations from this group. HTLV-III/LAV was isolated from 22 of the 25 donors, between 12 and 52 months (mean, 28) after they had donated blood, and from all 6 recipients, between 14 and 37 months (mean, 26) after they had received blood. Of the 22 virus-positive donors, 2 have contracted AIDS, 5 have generalized lymphadenopathy, and 15 (68 per cent) remain asymptomatic. Antibodies to HTLV-III/LAV were detectable by the enzyme-linked immunosorbent assay in serum samples obtained from each person at the time the virus was isolated. We conclude that infection with HTLV-III/LAV may be persistent and asymptomatic for years. This demonstration that viremic patients may be asymptomatic supports the use of serologic screening of donated blood to supplement current procedures for the prevention of transfusion-associated AIDS.

ANTIBODIES TO HUMAN T-CELL LEUKEMIA VIRUS (HTLV) IN CHILDREN WITH ACQUIRED IMMUNE DEFICIENCY SYNDROME (AIDS)

Six children previously documented with AIDS and seven age matched controls from a similar socio-economic environment were studied for the presence of antibodies (Ab) to HTLV. Additionally, 5 adult AIDS cases and 13 similarly matched adult controls were also examined for HTLV Ab. All determinations were done blindly by two assay systems: indirect membrane immunofluorescence (IF) using HTLV infected HUT-102 cells and Ab to structural proteins of HTLV by a radioimmune precipitation assay (RIP). All 6 pediatric AIDS cases were positive for IF-Ab while negative for RIP-Ab. In contrast, 6 of 7 pediatric controls were negative for IF-Ab and all 7 negative for RIP-Ab. The IF-Ab positive control child was only weakly positive. All pediatric AIDS cases had non-specific Ab directed against infected HUT-102 cells which required absorption. None of the pediatric controls had this non-specific Ab. All 5 adult AIDS patients were positive for IF-Ab while 2 were also positive for RIP-Ab. Two of 13 adult controls were weakly positive for IF-Ab and all negative for RIP-Ab. This data supports the concept that an HTLV-like virus is important in the etiology of AIDS.