Background:  In the absence of antiretroviral therapy, about one third of  HIV-1 vertically infected children will develop early AIDS,while others progress more slowly to disease.The pattern of HIV-1 replication  during the  first months of life is consistent with that of a primary infection and   plays a central role in the disease outcome.Treatment with HAART during chronic infection in children and  adults, efficiently reduces the plasma HIV-1 RNA level to undetectable levels,but does not eradicate infection. In this study, the effects of early treatment with HAART  on the   course of  infection were evaluated.

Methods Six HIV-1-infected infants were enrolled;all started HAART  within 90 days of age. Median follow-up was 32 months (range 17 to 57 months). In sequentially collected samples of peripheral blood mononuclear cells (PBMC) the following parameters were determined: cell-associated  HIV-1 DNA,  intracellular levels of unspliced (US) and multiply-spliced (MS) HIV-1 mRNAs,  thymic output  by  TREC measurements,  CD4 and CD8 cell subsets. Quantification of  plasma  HIV-1 RNA levels and detection of anti-HIV-1 antibodies were performed in sequentially collected  plasma  samples.

Results: All children showed a reduction of plasma  HIV-1 RNA to undetectable levels. HIV-1 DNA persisted in 4 children,but only 2 of these had detectable US and MS HIV-1 mRNA,suggesting an ongoing viral replication. Two children remained consistently negative for all HIV-1 parameters. Thymic  output remained  fairly constant over time. Only 2 children produced autochtonous antibodies to HIV-1, while the others, having lost the maternal antibodies, remained persistently seronegative. HAART was interrupted  in a  seronegative child who had persistently undetectable levels of  HIV-1 DNA and intracellular and plasma HIV-1 RNA for more than 36 months. Within 15 days of  HAART interruption, PBMC were positive for HIV-1 DNA and HIV-1 mRNAs, and there was a rebound of plasma HIV-1 RNA. Genetic analyses revealed that the virus did not carry mutations conferring drug-resistance.

Conclusions:  Early treatment with HAART  modified the natural course of primary infection in infants by  controlling HIV-1 replication, and by reducing to below  threshold levels the viral load  required for the onset of a humoral HIV-1 immune response. Nonetheless, early HAART does not appear to prevent the establishment of a reservoir of latently infected cells.

Keywords: Pediatric; HAART; early treatment