11th Conference on Retroviruses and Opportunistic Infections San Francisco, California - February 8 - 11, 2004

Conf Retroviruses Opportunistic Infect. 2004 Feb 8-11;11th:Abstract No. 24

D Kaufmann¹, M Lichterfeld¹, M Altfeld¹, T Allen¹, M Johnston¹, P Lee¹, B Wagner¹, E Kalife¹, D Strick¹, E Rosenberg ¹ and B D Walker^1,2
1Partners AIDS Res. Ctr., Massachusetts Gen. Hosp., Boston, USA and ²Howard Hughes Med. Inst.

BACKGROUND: Early treatment of acute HIV infection with HAART, followed by supervised treatment interruption, has been associated with at least transient immune control of viremia. However, the durability of such control remains unclear.

METHODS: Here we present longitudinal follow-up of a study assessing the effect of supervised treatment interruption in the setting of acute HIV-1 infection. During acute HIV infection, 14 persons were treated and subsequently subjected to an supervised treatment interruption protocol which required re-treatment if viral load remained above 5000 copies for longer than 3 consecutive weeks, or was in excess of 50,000 copies on any single occasion.

RESULTS: Although recurrence of viremia consistently occurred when treatment was stopped, 11 of 14 (79%) subjects were able to maintain control for at least 90 days following cessation of treatment by these criteria, in spite of the lack of protective HLA alleles. Over the course of the study, a gradual increase in viremia and decline in CD4 cell counts was observed in most individuals. By an intention to treat analysis, 57%, 43%, and 21% of subjects achieved a maximal treatment interruption of 180, 360 and 720 days, respectively. The total magnitude of HIV-specific CD8 T-cell responses increased by a factor of 3.5 (p = 0.04), 2.1 (p = 0.18) and 1.78 (p = 0.21) during the first, second, and third supervised treatment interruptions, respectively; all patients had at least transient detection of lymphoproliferative responses following initial treatment, and these responses declined with recurrence of viremia. The small sample size and lack of concurrent untreated controls preclude assessment of virologic benefit from this study.

CONCLUSIONS: These data indicate that despite initial control of viremia, durable immune control in persons following treated acute infection occurs infrequently, and that larger trials will be needed to determine the potential clinical and virologic benefit of this approach. Loss of viremia control occurred in some individuals despite increase of the magnitude of HIV-specific CD8 T-cell responses during the first supervised treatment interruption. These data are relevant to current efforts to develop an AIDS vaccine designed to retard disease progression rather than prevent infection, and indicate that durable maintenance of low level viremia may be difficult to achieve.

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Copyright © 2004 - Foundation for Retrovirology and Human Health. Reproduction of this abstract (other than one copy for personal reference) must be cleared through the Foundation for Retrovirology and Human Health. Licensed (AIDSLINE) from National Library of Medicine.