12th Conference on Retroviruses and Opportunistic Infections Boston, Massachusetts - February 22-25, 2005

Conf Retrovir Opportunistic Infect 2005 Feb 22-25;12:abstract no. 49

J Kajdas¹, D Watson², G Siberry¹, A Ahonkhai¹, R Ashworth¹, T Quinn¹, S Ray¹, and Deborah Persaud^1
1Johns Hopkins Univ, Baltimore, MD, USA and ²Univ of Maryland, Baltimore, USA

BACKGROUND: The persistence of HIV-1 in latent reservoirs despite effective HAART has resulted in a shift in the adult treatment guidelines from “hit early, hit hard” to delaying therapy until threshold levels of CD4 and viral loads are reached. In HIV-1-infected infants, the optimal time to initiate HAART has not been defined. However, the high rates of progression to AIDS or death in the first year of life has led some experts to recommend HAART for all infected infants diagnosed in the first year of life. We examined the extent to which HAART started in early infancy impacts on viral diversity and divergence in the HIV-1 pol and env genes of biologic clones retained in the resting CD4+ T-cell reservoir after years of suppressive HAART when compared with pre-HAART viral variants.

METHODS: We performed extensive clonal (n = 340) analysis of the HIV-1 pol (1.5 kb) and env (gp 120) genes from plasma virus at peak viremia (mean age, 2 months; range 0. 6 to 3.1 months) in early-treated infants and compared them to replication-competent HIV-1 clones cultured from the resting CD4+ T-cell latent reservoir during HAART (median 2.2 years; range 0.7 to 4.9 years). In 6 of the 12 infected infants studied to date, multiple biologic HIV-1 clones were recovered longitudinally during HAART and pre-HAART plasma was available for genotyping of pol and env. We were thus able to compare viral diversity and divergence in pre-HAART viral variants at peak viremia to viral clones cultured longitudinally from resting CD4+ T cells in early-treated infants.

RESULTS: Using comprehensive clonal analysis of both the pol and env genes in pre-HAART plasma and latent reservoir clones cultured during HAART, we observed that early-treated infants exhibited little or no viral diversity or divergence for pol (range 0.0% to 0.4%) or env (0.1 to 0.7%). Even in the case with maximum diversity and divergence in env, the median variation observed in pre-HAART plasma was 0.7%; range 0.14 to 1.1 % and for the latent reservoir clones 0.6%; range 0.07 to 1.24%. In addition, with over up to 4.9 years of HAART, little or no change in HIV-1 divergence was observed in the pol and env genes.

CONCLUSIONS: HAART initiated in early infancy is highly effective in arresting HIV-1 evolution in pol and env. The persistence of a homogeneous pool of HIV-1 variants due to early effective HAART has important implications for therapeutic HIV-1 vaccine strategy.

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Copyright © 2005 - 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.