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-1AS MAJOR DETERMINANTS FOR HIV-1 TRANSMISSION IN HOMOSEXUAL COUPLES

To study risk factors for homosexual transmission of human immunodefic iency virus type 1 (HIV-1), we compared 10 monogamous homosexual coupl es between whom transmission of HIV-1 had occurred,vith 10 monogamous homosexual couples between whom HIV-1 transmission had not occurred de spite high-risk sexual behavior. In the group of individuals who did n ot transmit virus, peripheral cellular infectious load was lower and t he CD4(+) T-cell counts were higher than in the group of transmitters. HIV-1 RNA levels in serum did not differ between transmitters and non transmitters. 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 infectio n with non-syncytium-inducing (NSI) HIV-1 variants isolated from eithe r 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 susceptibili ty, five nonrecipients and one recipient had PBMC that were equally or even less susceptible to NSI variants than PBMC that had low suscepti bility and that were derived from healthy blood donors that were heter ozygous for a 32-bp deletion in the CCR5 gene (CCR5 Delta 32). Three o f these individuals (all nonrecipients) had a CCR5 Delta 32 heterozygo us genotype themselves, confirming an association between low suscepti bility to NSI variants and CCR5 Delta 32 heterozygosity. All three rec ipients with less susceptible PBMC had partners with a high infectious cellular load; inversely, both nonrecipients with normally susceptibl e PBMC had partners with a very low infectious cellular load. These re sults suggest that a combination of susceptibility of target cells and inoculum size upon homosexual exposure largely determines whether HIV -1 infection is established.