Infectious cellular load in human immunodeficiency virus type 1 (HIV-1)-infected individuals and susceptibility of peripheral blood mononuclear cells from their exposed partners to non-syncytium-inducing HIV-1 as major determinants for HIV-1 transmission in homosexual couples.

To study risk factors for homosexual transmission of human immunodeficiency virus type 1 (HIV-1), we compared 10 monogamous homosexual couples between whom transmission of HIV-1 had occurred with 10 monogamous homosexual couples between whom HIV-1 transmission had not occurred despite high-risk sexual behavior. In the group of individuals who did not transmit virus, peripheral cellular infectious load was lower and the CD4+ T-cell counts were higher than in the group of transmitters. HIV-1 RNA levels in serum did not differ between transmitters and nontransmitters. Compared with peripheral blood mononuclear cells (PBMC) from normal healthy blood donors, 8 of 10 nonrecipients and only 3 of 8 recipients had PBMC with reduced susceptibility to in vitro infection with non-syncytium-inducing (NSI) HIV-1 variants isolated from either their respective partners or an unrelated individual. No difference in susceptibility was observed for infection with a syncytium-inducing variant. Among the individuals who had PBMC with reduced susceptibility, five nonrecipients and one recipient had PBMC that were equally or even less susceptible to NSI variants than PBMC that had low susceptibility and that were derived from healthy blood donors that were heterozygous for a 32-bp deletion in the CCR5 gene (CCR5 delta32). Three of these individuals (all nonrecipients) had a CCR5 delta32 heterozygous genotype themselves, confirming an association between low susceptibility to NSI variants and CCR5 delta32 heterozygosity. All three recipients with less susceptible PBMC had partners with a high infectious cellular load; inversely, both nonrecipients with normally susceptible PBMC had partners with a very low infectious cellular load. These results suggest that a combination of susceptibility of target cells and inoculum size upon homosexual exposure largely determines whether HIV-1 infection is established.

Macrophage-tropic variants initiate human immunodeficiency virus type 1 infection after sexual, parenteral, and vertical transmission.

Macrophage-tropic, non-syncytium-inducing, HIV-1 variants predominate in the asymptomatic phase of infection and may be responsible for establishing infection in an individual exposed to the mixture of HIV-1 variants. Here, genotypical and phenotypical characteristics of virus populations, present in sexual, parenteral, or vertical donor-recipient pairs, were studied. Sequence analysis of the V3 domain confirmed the presence of a homogeneous virus population in recently infected individuals. Biological HIV-1 clones were further characterized for syncytium inducing capacity on the MT2 cell line and for macrophage tropism as defined by the appearance of proviral DNA upon inoculation of monocyte-derived macrophages. Both sexual and parenteral transmission cases revealed a selective outgrowth in the recipient of the most macrophage-tropic variant(s) present in the donor. In three out of five vertical transmission cases, more than one highly macrophage-tropic virus variant was present in the child shortly after birth, suggestive of transmission of multiple variants. In three primary infection cases, homogeneous virus populations of macrophage-tropic, non-syncytium-inducing variants were present prior to seroconversion, thus excluding humoral immunity as the selective pressure in favour of macrophage-tropic variants. These observations may have important implications for vaccine development.

Orogenital sex and the transmission of HIV among homosexual men.

OBJECTIVE: To investigate the possibility of orogenital transmission of HIV. DESIGN: Cohort study on HIV infection among homosexual men. SETTING: The Municipal Health Service, Amsterdam, The Netherlands. PATIENTS, PARTICIPANTS: Homosexual men for whom the date of HIV seroconversion was known (n = 102) were included in our study. MAIN OUTCOME MEASURES: Data on the sexual behaviour of our subjects in the 6-9 months preceding HIV seroconversion were collected. In order to identify those men who consistently denied practising receptive anogenital intercourse, information was retrieved from written questionnaires and from face-to-face interviews. RESULTS: Receptive anogenital intercourse in the 6-9 months before seroconversion was denied by 20 seroconverters in their written questionnaires. However, in face-to-face interviews, 11 men later reported this sexual practice. CONCLUSIONS: Orogenital transmission of HIV appears to occur, but its frequency may be overestimated because of reluctance to report the practice of receptive anogenital intercourse.

Spread of human T-cell leukemia virus (HTLV-I) in the Dutch homosexual community.

Sequential sera of 697 homosexual men, participating in a prospective study (1984-1986) of the risk to acquire human immunodeficiency virus (HIV) or AIDS, were tested for antibodies to human T-cell leukaemia virus (HTLV-I) by particle agglutination and immunoblotting. No intravenous drug users were included in this trial. Three men (0.4%) were HTLV-I antibody positive at intake and an additional 2 at the end of the observation period, resulting in an attack rate of approximately 0.3%. One of the 3 men with HTLV-I antibodies at intake was a Brazilian. One man had an acute HTLV-I infection after sexual intercourse with a Brazilian during holiday in Brazil. No serological cross-reactivity with HIV was observed nor a relationship with other sexually transmissible viral or bacterial infections. In contrast to HIV no relationship with anogenital intercourse was noted; both primary HTLV-I infected men practiced only orogenital intercourse. This suggests that HTLV-I was imported in the Dutch homosexual community after HIV was introduced in the Netherlands. HTLV-I appears to spread slower within the homosexual community than HIV and possibly by other routes.

Hepatitis B among homosexual men in The Netherlands.

In 1980-1981 a study for the presence of markers of hepatitis B virus was done among 2, 946 homosexual men living in The Netherlands, mainly in Amsterdam. Serologic evidence of a past or present hepatitis B infection was found in 60.3% of this group, and the prevalence differed significantly among the different age groups. Of the total population studied, 4.8% were positive for HBsAg. This prevalence is very high in comparison to that in the general Dutch population, among whom the prevalence of hepatitis B is low, as is shown by the fact that the prevalence of HBsAg was 0.22% among a large group of Dutch first-time blood donors. Another blood sample was collected two to 20 months after the first sample from 316 male homosexuals who were initially negative for hepatitis B markers. It was found that 36 persons had seroconverted, most of them without clinical manifestations of hepatitis. The annual attack rate of hepatitis B in this group was calculated as 27.6% and differed significantly among the different age groups.