360   In Vivo Assessment of Antiviral Reactivity in Chronic HIV Infection.

K. A. Smith*¹, E. L. Jacobson¹, T. Sohn¹, D. Warren², R. Emert¹, M. Giordano³, A. M. Dunne¹, and M. Lobo¹.
¹Cornell Univ., New York, NY;²State Univ. of New York, Brooklyn; and³SmithKline Beecham, Waterbury, CT.

Background:Chronic infection with HIV renders individuals immunodeficient in their capacity to recognize and react to HIV as defined by in vitro lymphocyte proliferation assays.

Methods:To determine whether in vivo antiviral reactivity is detectable in chronic HIV infection, viral and lymphocyte dynamics were monitored twice weekly after structured treatment interruption (STI). Chronically infected (>6 months) subjects were eligible to interrupt antiviral therapy if there was an undetectable plasma [HIV] (<50 RNA/mL) and normal [lymphocyte] while receiving antiviral therapy and daily low-dose subcutaneous interleukin 2 (IL2, 1.2 mU/M2 BSA) for at least 3 months. IL2 was continued after STI.

Results:Twenty nine (29) subjects have entered the study, 14 subjects have undergone 1 STI, and 6 have undergone 2 STIs. All subjects underwent a viral relapse upon the 1st STI. Data from the 1st 9 subjects revealed a mean time to relapse of 19 +/- 3 (SEM) days and a doubling time of plasma [HIV] of 1.6 +/- 0.2 (SEM) days. Plasma [HIV] peaked within 17 +/- 2 (SEM) days at 5.15 +/- 0.21 (SEM) log₁₀HIV RNA/mL. Subsequently, plasma [HIV] decreased with a t_1/2of 3.5 +/- 0.7 (SEM) days to 4.21 +/- 0.19 (SEM) log₁₀IV RNA/mL within 8 weeks from STI. The difference between the peak and trough [HIV] (4 successive values <25% of mean) was significant (p < 0.001, two-tailed T test). Coincident with the decline in plasma [HIV] was a transient, 24% decrease of CD4⁺T cells, while CD8⁺T cells doubled (p < 0.01, paired T test) and remained elevated until antiviral therapy was reinitiated. The mean time off antiviral therapy after the 1st STI was 120 days (range 44— 288 days). Subsequent to the 2nd STI, the peak plasma [HIV] was>10-fold lower than the 1st STI in 5/6 subjects, and the mean plasma [HIV] remained <20,000 RNA/mL in 4/5 subjects for a mean of 194 days (range 92—330 days).

Conclusions:Monitoring viral & lymphocyte dynamics after STI readily detects host antiviral reactivity in chronic HIV infection. Therefore, studies that explore therapies to augment antiviral host reactivity are now warranted prior to STI.