AEGiS-15IAC: Genetic characterization of rebounding HIV-1 after interruption of HAART in chronic patients with suppressed viremia.

15th International AIDS Conference

Bangkok, Thailand - July 11-16, 2004

Genetic characterization of rebounding HIV-1 after interruption of HAART in chronic patients with suppressed viremia.

Int Conf AIDS 2004 Jul 11-16; 15:(abstract no. ThOrA1401)

Rusconi S, Bulgheroni E, Citterio P, Lo Cicero M, Soster F, Vigano O, Croce F, Sutton L, D'Aquila RT, Galli M, De Pasquale MP
University of Milan, Milan, Italy

BACKGROUND: Although is not surprising that viral rebound occurs in HIV-infected patients (pts) after discontinuation of HAART, the source of plasma rebounding virus remains uncertain. We examined the rebounding virus in plasma after interruption of HAART in 4 chronically infected individuals in whom successful suppression of viremia had been achieved for considerable periods of time.

METHODS: HIV RNA was extracted from blood plasma, culture supernatant and semen plasma. PBMC proviral DNA was extracted. pol region was amplified and sequenced. Phylogenetic analysis of sequences was performed by the neighbor-joining algorithm and by the Kimura method. Genetic distances were estimated by DNADIST.

RESULTS: 3 chronically infected pts with blood viremia<50 cp/ml for >2 years interrupted their treatment. A fourth patient had viremia< 50 cp/ml by bDNA and 2156 cp/ml by PCR when dropped the therapy. In 3 out of 4 pts the rebounding virus harbored mutations associated with resistance to previous regimens (41L, 70R, 184V, 219Q in RT). The sequences from each individual patient clustered together irrespectively of their source of origin w/o evidence of contamination. In 2 pts the baseline plasma sequences showed differences from the corresponding proviral DNA and the replication-competent virus isolated from CD4+ cells at matching time, suggesting that ongoing, low level replicative virus may traffic into blood from sanctuaries tissues. In 3/4 pts viral quasispecies emerging after treatment interruption showed a tighter homology: the genetic distances between pol sequences at early and later timepoints were< 5.3%.

CONCLUSIONS: We evaluated the genetic homology of rebounding virus in 4 chronically infected pts undergoing treatment interruption after a prolonged time of suppressed viremia. The data from 2 pts suggest that the virus circulating in blood when therapy was suspended may be of a different lineage than the PBMC proviral DNA. In some cases the rebounding virus at following timepoints was more genetically related and harbored resistance mutations.

Keywords: AEGIS, Antiretroviral Therapy, Highly Active, HIV-1, Viremia, Genes, pol, Virus Replication, HIV-1 Reverse Transcriptase, CD4-Positive T-Lymphocytes, Acquired Immunodeficiency Syndrome, HIV Seropositivity, Case-Control Studies, Humans, genetics, virology

040711
ThOrA1401