JamesJ. Goedert

DETERMINANTS OF RETROVIRUS (HTLV-III) ANTIBODY AND IMMUNODEFICIENCY CONDITIONS IN HOMOSEXUAL MEN

A cohort of homosexual men at high risk of the acquired immunodeficiency syndrome (AIDS) was monitored to examine the relation between lifestyle, clinical conditions, T-lymphocyte subsets, and antibody to the AIDS-associated human retrovirus, human T-cell leukaemia virus III (HTLV-III). HTLV-III antibodies were present in 35 (53%) of the 66 subjects tested in June, 1982. 4 of the seronegative subjects had HTLV-III antibodies when re-tested one year later, a seroconversion rate of 1.2% per month. In the HTLV-III seropositive subjects, AIDS developed at a rate of 6.9% per year (minimum incidence of AIDS = 4.6% per year) and other clinical signs of immunodeficiency (lesser AIDS) at 13.1% per year. All 6 of the AIDS cases and at least 8 of the 10 lesser AIDS cases had detectable HTLV-III antibodies 1 week to 21 months before diagnosis. Of 24 other subjects with stable lymphadenopathy, 19 (79%) had or acquired HTLV-III antibodies. Lower helper T-cell counts were very closely related to HTLV-III seropositivity (r = -0.53, p = 0.0001), even in the 26 healthy subjects with no clinical abnormalities (r = -0.37, p = 0.07). In both univariate and multivariate analyses, the lifestyle risk factors for HTLV-III seropositivity were large number of homosexual partners (p less than or equal to 0.03) and receptive anal intercourse (p less than or equal to 0.03), with an apparent synergistic interaction between these two activities (chi 2 = 8.71, p = 0.003). These data suggest that frequent receptive anal intercourse with many homosexual partners predisposes to HTLV-III infection with the consequent emergence of lymphadenopathy and the various manifestations of lesser and fully fledged AIDS.

MOTHER-TO-INFANT TRANSMISSION OF HUMAN IMMUNODEFICIENCY VIRUS TYPE 1: ASSOCIATION WITH PREMATURITY OR LOW ANTI-gp120

In a prospective study of pregnant women infected with human immunodeficiency virus type 1 (HIV-1) in Brooklyn, New York, USA, 16 (29%) of 55 evaluable infants were infected with HIV-1. 9 infants had paediatric acquired immunodeficiency syndrome, 6 had less severe clinical manifestations of HIV-1 infection, and 1 was symptom-free but was seropositive for HIV-1 beyond 15 months of age. The 10 infants born at 37 weeks of gestation or earlier were at higher risk of HIV-1 infection than infants born at 38 weeks of gestation or later (60% vs 22%) but the median age at appearance of disease was approximately 5 months in both groups. The HIV-1 transmission rate was not associated with predelivery levels of maternal T cells, anti-p24, or neutralising antibodies but it was higher, among full-term infants, for those with mothers in the lowest third of the distribution of anti-gp120 levels (53%). On immunoblot, transmitting mothers lacked a gp120 band but not other bands. Protection was not associated with antibody to recombinant peptides from the hypervariable region of the major neutralising gp120 epitope, and the anti-gp120 endpoint dilution titre was similar in transmitting and non-transmitting mothers. Mothers of uninfected full-term infants appear to confer immunological protection against HIV-1 infection of their offspring by way of a high-affinity antibody to a gp120 epitope, whose specificity has importance for vaccine development and possibly perinatal immunotherapy.

AMYL NITRITE MAY ALTER T LYMPHOCYTES IN HOMOSEXUAL MEN

To evaluate the recent outbreak of Kaposis sarcoma (KS) and opportunistic infections in homosexual men, clinical, virological, and immunological data on two homosexual men with KS and on fifteen healthy homosexual volunteers were collected. Both KS patients had regularly used amyl or butyl nitrite (AN); they had low helper/suppressor (H/S) T-lymphocyte ratios before chemotherapy and high titres of antibody against cytomegalovirus (CMV). Eight of the fifteen volunteers were regular AN users; seven of the eight had low H/S ratios due to larger than normal numbers of OKT8-positive suppressor cells and smaller numbers of OKT4-positive helper cells. In all eight AN users the fluorescence profile obtained with monoclonal antibody 9.6 (which detects the sheep E-rosette receptor) was bimodal, indicating a subpopulation of T cells with increased receptor density. A similar pattern was observed when OKT8, the antibody which detects cytotoxic suppressor cells, was used. Two of the seven men who did not use AN had abnormal fluorescence with reagent 9.6, and one of these also had a low H/S ratio. CMV-antibody titres were persistently high in fourteen of the fifteen healthy men, but the titres were not related to AN use of T-cell abnormalities. The data suggest that nitrites may be immunosuppressive in the setting of repeated viral antigenic stimulation and may contribute to the high frequency of DS and opportunistic infections in homosexual men.

Effect of age at seroconversion on the natural AIDS incubation distribution

ObjectiveTo estimate the age-specific relative risk of progression from HIV seroconversion to onset of AIDS in hemophiliacs and homosexual men. DesignProspective follow-up data from HIV seroconversion to AIDS was analyzed for hemophiliacs in the Multicenter Hemophilia Cohort Study and for homosexual men in the International Registry of Seroconverters. Follow-up was censored at 1 July 1987 to obtain natural history estimates unaffected by therapies that were widely used after this date. The age-specific relative hazard of progression was estimated using nonparametric proportional hazards models and the baseline hazard function was described using spline models. ResultsAmong the 373 children and adults with hemophilia and the 1020 adult homosexual men, each 10-year increment in age at seroconversion was associated with a 1.6− and 1.4-fold increase in the hazard of progression, respectively. The effect of age was highly significant among hemophiliacs. The magnitude of the effect was consistent in different cohorts of homosexual men, although it was not nominally significant. Furthermore, there was a significant increase (1.9-fold higher) in progression rates among homosexual men above rather than below 35 years of age at seroconversion. After adjusting for age, progression rates among hemophiliacs were significantly slower, possibly because Kaposis sarcoma was rare. In both groups, the annual hazard rate increased during the first 5 years after seroconversion, but broad confidence limits prevented us from establishing hazard trends beyond this time. ConclusionsEstimates of the aggregate incubation time distribution were substantially shorter in older compared with younger individuals. The increasing risk with age was similar in hemophiliacs and homosexual men, suggesting that age is an endogenous host factor. These findings can be incorporated into newly developed backcalculation models to estimate HIV infection incidence by age group from age-specific AIDS surveillance data.

HTLV-III SEROPOSITIVITY IN EUROPEAN HAEMOPHILIACS EXPOSED TO FACTOR VIII CONCENTRATE IMPORTED FROM THE USA

77 Scottish haemophiliacs and 22 Danish haemophiliacs were serologically tested for antibodies to human T-cell leukaemia virus III (HTLV-III). Since 1979 the Scottish patients had been treated largely with factor VIII concentrate produced in Scotland, whereas all but 2 of the Danish patients had received both locally prepared concentrate and commercial concentrate made from US donor material. 15.6% of Scottish and 59.1% of Danish haemophiliacs were antibody positive (p less than 0.001). None of 11 haemophiliacs not treated in the period 1979-84 was seropositive. 2 (6.7%) of 30 subjects who had been treated with locally produced concentrate only were antibody positive, compared with 23 (39.7%) of 58 subjects who had been treated with commercial concentrate. Among 52 users of both commercially and locally produced factor VIII concentrate, seropositivity was directly correlated with the consumption of commercial concentrate (p less than 0.001) but not locally produced material. These data indicate that European haemophiliacs were exposed to HTLV-III via some factor VIII concentrates obtained from the USA.

Risks of immunodeficiency, AIDS, and death related to purity of factor VIII concentrate

In HIV-infected subjects with haemophilia, CD4 counts seem to fall more slowly in those on high-purity factor VIII (FVIII) than on intermediate-purity product. We evaluated whether risks for AIDS or death were associated with either product among 411 HIV-infected individuals. The relative hazard of AIDS was slightly elevated for both current (1.34) [corrected] and cumulative (1.01 per month) use of high-purity products (neither significant). The corresponding hazards for death were 1.49 and 1.03 (neither significant). Thus we found no evidence that high-purity FVIII concentrates retard the development of AIDS.