IL-2
This
study explores an interesting and novel concept. It explores raising CD4s with
Il-2 before initiating first-line HAART therapy. The investigators reported the
IL-2 treatment did not raise viral load but CD4 increased 232 from 440 to 660
(p=0.02).
Randomized
study of intermittent subcutaneous IL-2 therapy without antiretrovirals versus
no treatment at all
Mike Youle (Royal
Free Hospital, London) and others
This study was
designed to evaluate the virolgic and immunologic effects of IL-2 alone in
antiretroviral naÔve subjects and CDs >350. This study is an open-label,
randomized, parallel group, study comparing no treatment with IL-2--4.5 MIU or
7.5 MIU every 12 hours subcutaneously for 5 days everu 8 weeks for 24 weeks.
Subjects who received IL-2 could then continue cycles if they request. The
primary endpoints for the study were mean area under the curve (AUC) change from
baseline CD4 count and plasma HIV RNA.
36 subjects (1
female) were enrolled. The 3 arms were well matched at baseline, with median CD4
440 (nadir 399) and HIV-RNA of 4.3 log (20,000 copies/ml). Median follow-up was
9.8 months (range 0-16) and 31/36 subjects remained on study at week 24. Two
patients randomized to receive IL-2 did not start, while 6 IL-2 and 1 control
patients withdrew from study. Mean AUC change from baseline CD4 cell counts were
significantly higher (p=0.001) in recipients of IL-2 (148 cells) compared to
controls (25 cells) at week 24 and by week 48 the mean CD4 was 656 (+232) cells
and 443 (+13) (p=0.02) respectively. Mean plasma HIV-RNA levels during follow-up
and mean AUC change from baseline plasma HIV-RNA were not significantly
different between treatment arms. Six endpoints occurred in the control group
versus 2 in the IL-2 group.
Youle concluded
that this study suggests that cyclical IL-2 therapy produces sustained and
significant CD4 rises without sustained increases in HIV replication when given
without antiretrovirals in individuals with CD4 counts >350.
Structured
antiviral treatment interruption followed by daily low dose interleukin 2 (IL-2)
reveals immune response to HIV
R.
Emert^{1}, E.L. Jacobson^{2}, T. Sohn^{2}, D. Warren^{2}, K.A. Smith^{2}
^{1}Weill
Medical College of Cornell University, 525 E. 68th St., Room LC-907, New York,
NY 10021, United States, ^{2}Weill Medical College of Cornell University, New
York, United States
Background:
Most viral infections are combatted by the proliferative
expansion of antigen-selected lymphocytes, especially of the
CD8+ T cell subset. This clonal expansion is CD4+ T cell and
Interleukin-2 (IL-2) dependent.
Methods:
To test a new strategy to promote immunity to HIV, 9
individuals underwent structured interruption of Highly Active Anti-Retroviral Therapy (HAART). All were chronically
infected before treatment and were
aviremic on HAART plus daily low dose IL-2.
Results:
Upon cessation of HAART but continuation of IL-2, plasma
HIV became detectable in all subjects in 19+/-3(SEM) days, then
increased rapidly over 2 weeks (doubling time 1.6 +/- 0.2 days),
to a peak of 375,101 +/- 229,139 HIV RNA /ml. Subsequently, the
'HIV' then decreased progressively over the next 4 weeks, reaching
a low stable level of 31,707 +/- 11,851 HIV RNA molecules/ml,
less than 10% of the peak concentration (p>0.001). Coincident
with the reappearance of viremia, CD8+ T cells increased progressively,
peaking at ~200% of baseline levels (p>0.01), and then remained
at this elevated level while the plasma HIV declined progressively.
The rate of viral decay correlated with the magnitude of the
decrease in 'HIV' and with the extent of CD8+ T cell increase.
Conclusions: Contrary to previous assumptions, chronic HIV infection does not preclude the development of effective anti-viral immune reactivity. These findings indicate that a controlled trial comparing the interruption of HAART +/- IL-2 therapy is now warranted.