Viral Phenotype and Immune Response in Primary Human Immunodeficiency Virus Type 1 Infection

Nineteen individuals were studied for virologic and immunologic events during primary human immunodeficiency virus type 1 (HIV-l) infection. In 16 individuals only non-syncytium-inducing (NSI) isolates were detected; syncytium-inducing (SI) isolates were obtained from 3. Studies of transmitter-recipient pairs indicated that both NSI variants and SI variants were transmitted and that SI variants may be suppressed in the recipient. CD4+T cells remained in the normal range in 15 of 16 individuals with NSI isolates but rapidly declined in all 3 individuals with SI variants, 1 ofwhom was treated with zidovudine. The most marked increase in CD8+ T cells and activated CD8+ T cells was observed in individuals with the most pronounced clinical signs of acute HIV-1 infection. Activated CD8+ T cells were only transiently elevated in individuals with SI variants, suggesting that an impaired cellular anti-HIV-1 immune response plays a role in the rapid progression to AIDS.

Primary human immunodeficiency virus type 1 (HIV-1) infection has a variable clinical course. In a minority of patients this phase of infection is subclinical, but in 50%-70% an acute clinical syndrome occurs 2-4 weeks after the moment of infection, which in general lasts 1-2 weeks. Although in exceptional cases the patient may progress to AIDS very rapidly, most individuals subsequently enter a clinically asymptomatic phase and progression to AIDS occurs only after 1 to > 10 years. Previously, we demonstrated an association between the clinical course ofasymptomatic HIV-l-eseropositive individuals and the biologic phenotype of their viral isolates, Presence of syncytium-inducing (SI), T cell line tropic HIV-l variants correlated with rapid CD4+ T cell decline. In contrast, in seropositive individuals with stable CD4+ T cell numbers, only low-replicating non-syncytium-inducing (NSI) variants were observed. In longitudinal studies of seropositive asymptomatic individuals, we found that, whereas NSI variants are present throughout HIV-1 infection, SI variants generally emerge during the course ofHIV-I infection. In the present study we analyzed virologic and immuno logic events early after HIV-1 transmission. In particular we wanted to determine if and how the HIV-l biologic phenotype early after infection is related to the clinical and immunologic events during primary HIV-1 infection and thereafter.

Subjects and Methods
Subjects. Virologic and immunologic events were studied in 19 persons. Subjects 1-6 presented clinically with symptoms of acute HIV-1 infection. Subject 7, a participant of the Amsterdam cohort study on the natural course of HIV-1 infection, seroconverted during the study period. Subject 8 was accidentally infected with a small amount of blood from an individual with end-stage HIV-I-related disease. The clinical features of subjects 1-3 and 6-8 have been reported. In addition to these individuals from whom frequent blood samples were obtained, at 3-month intervals virologic and immunologic data were obtained from 11 participants in the Amsterdam cohort study who were seronegative at entry and who seroconverted during follow-up.