• Poster 352: Control of Viremia after Treatment Interruption (Authored by F. Lori, A. Foli, R. Maserati, E. Seminari, L. Minoli, F. Alberici, and J. Lisziewicz. Res. Inst. for Genetic & Human Therapy, Pavia, Italy, and Washington, DC; and Clin. Malattie Infettive, Policlinico S. Matteo, Pavia, Italy, and Piacenza, Italy)
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• Poster 355: Cessation of HAART Plus Daily Low-Dose Interleukin 2 to Promote Immunity to HIV (Authored by K.A. Smith, E.L. Jacobson, T. Sohn, D. Warren, R. Emert, M. Giordano, J. Ruitenberg, and C.A. Waters. New York and San Jose, CA)
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• Poster 357: Increase in Breadth and Frequency of CTL Responses after Structured Therapy Interruptions in Individuals Treated with HAART during Acute HIV-1 Infection (Authored by M. Altfeld, E.S. Rosenberg, R.L. Eldridge, S. Poon, J.S. Mukherjee, M. Phillips, P.J. Goulder, and B.D. Walker. AIDS Res. Ctr., Massachusetts Gen. Hosp. and Harvard Med. Sch., Boston)
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Poster 352: Control of Viremia after Treatment Interruption

Poster 352 looked at the question of scheduled treatment interruptions, or drug holidays and the impact on viral load and CD4 count. Two groups of patients were identified. Those on traditional three or four drug HAART regimens (eight patients) and those who have received only Hydroxyurea and ddI (PANDA cohort, nine patients). The groups were matched for length of treatment and CD4/CD8 count. 7/8 HAART patients had viral load <50/ml. All ddI/HU patients had a low but detectable viral load (mean 549/ml). The reinitiation rule was that after STI, treatment would automatically be reinitiated if the viral load went up to 10,000/ml, or the CD4 count decreased to <200. Patients discontinued drugs for 8 weeks. By week 8, all 8 subjects on HAART had failed the STI and had to reinitiate therapy (viral load increase = 2.25 log/ml). In the PANDA group, there was a small initial increase in viral load (0.27 log/ml). CD4 count decreased significantly in the HAART arm, but not in the PANDA arm. After reinitiation of HAART, all patients decreased viral load to <50/ml and CD4 count returned to baseline. After reinitiation of ddI/HU, the viral load decreased to the low but detectable levels that had been seen at baseline. CD4 count remained unchanged. This small pilot study indicates that a ddI/HU offers further benefits with respect to ongoing viral replication, even when this regimen is discontinued. This benefit was not seen in any of the patients receiving traditional HAART regimens. Whether the PANDA patients underlying immune systems or the ddI/HU regimen accounts for the observation, remains to be determined.

Poster 355: Cessation of HAART Plus Daily Low-Dose Interleukin 2 to Promote Immunity to HIV

Poster 355 looked at the question of whether low dose interleukin 2 (IL-2) provides any immunologic benefit in patients who have had their HAART regimen stopped. Nine subjects who had viral loads <50 ml, and who had been receiving HAART daily and low dose IL-2 were recruited to stop their HAART regimen, but continue the intermittent IL-2. Viral load became detectable at three weeks following treatment interruption. Mean viral load peaked at >300,000/ml and then was reduced in the absence of HAART, but continued IL-2, to a mean of 28,000/ml. This was significantly below pre-HAART (baseline levels). Although CD4 counts decreased by >20% during the peak of viral load (compared to baseline), CD8 counts increased by >200%, during the time that viral load reduction was taking place. The authors suggest that their findings may indicate that there is an IL-2-related CD8 HIV antigenic specific response, that can control viremia (viral load) independent of HAART therapy. Therefore IL-2 may be an important adjunct to HAART therapy.

Poster 357: Increase in Breadth and Frequency of CTL Responses after Structured Therapy Interruptions in Individuals Treated with HAART during Acute HIV-1 Infection

Poster 357 looked at the question of what kinds of immune responses can be seen after stopping treatment that was started during acute infection. Seven patients were identified who were acutely infected with HIV and had not developed antibodies yet. HAART was started and continued for 1 year. Cytotoxic T-cell (CTL) responses to HIV specific peptides were measured at diagnosis, during therapy and after interruption. All patients had undetectable viral loads at three months. After stopping treatment viral load rebounded within 1-8 weeks. HAART was then reinitiated. CTL responses prior to seroconversion are narrow in the spectrum of HIV peptides that are recognized. This narrow spectrum of CTL activity persisted in the presence of HAART. During treatment interruption, the breadth and magnitude of CTL responses were much greater, particularly to gag and env peptides. In addition the magnitude of CTL response were augmented to peptides that were previously recognized. In a couple of patients, repeated treatment interruption resulted in further increased in CTL response. Reinitiation of HAART resulted in all patients' viral load becoming undetectable. The authors conclude that periods of viremia (detectable viral load) may help augment the immune system's (CTL) response to control viremia.