AEGiS-14IAC: Quantitation of HIV-1 DNA forms with the second template switch (HIV-1 STS DNA) in peripheral blood predicts disease progression in HIV-1 infection independently of plasma RNA load.

14th International AIDS Conference

Barcelona, Spain - July 7-12, 2002

Quantitation of HIV-1 DNA forms with the second template switch (HIV-1 STS DNA) in peripheral blood predicts disease progression in HIV-1 infection independently of plasma RNA load.

Int Conf AIDS 2002 Jul 7-12; 14:(abstract no. ThOrA1382)

Kostrikis LG, Touloumi G, Karanicolas R, Pantazis N, Anastassopoulou C, Karafoulidou A, Goedert J, Hatzakis A
Athens University Medical School, Athens, Greece

BACKGROUND: A number of studies have identified several forms of HIV-1 DNA in peripheral-blood T-cells and lymph nodes in untreated HIV-1-infected individuals and in patients whose plasma HIV-1 RNA load is suppressed by long-term potent antiretroviral therapy. However, it remains to be established whether the concentration of HIV-1 DNA in cells has any implications in the progression of HIV-1 disease in the absence of highly effective antiretroviral therapy.

METHODS: We measured the concentration of HIV-1 DNA forms, which have undergone the second template switch (HIV-1 STS DNA) in PBMC samples with real time PCR and molecular beacons in 130 patients with hemophilia in the Multicenter Hemophilia Cohort Study. We assessed the influence of baseline HIV-1 STS DNA levels on the progression of HIV-1 disease by Kaplan-Meier and Cox's regression analysis.

RESULTS: Among the patients who progressed to AIDS, the median (IQR) levels of STS HIV-1 DNA in PBMC, were significantly higher compared to those who remained AIDS-free during the 16 years of follow-up [1,017 (235 to 6,059) and 286 (31 to 732) copies per million PBMC respectively; p<0.0001]. The progression rates of death and development of AIDS varied significantly (log-rank p<0.001) by quartile distribution of HIV-1 STS DNA levels. By adjusting for age at seroconversion, baseline CD4+ T-cell counts, plasma viral load and T cell receptor excision circles (TREC) the relative hazard (RH) (95% CI) of death and AIDS was significantly increased with higher HIV-1 STS DNA levels [adjusted RH=1.84 (1.30 to 2.59) and 2.62 (1.75 to 3.93) per tenfold per million PBMC increase, respectively].

CONCLUSIONS: Our findings show that the concentration of HIV-1 STS DNA in PBMC had an independent strong effect on the clinical outcome of HIV-1 disease and it may have important implications on the virological response to highly effective antiretroviral therapy.

Keywords: AEGIS, Disease Progression, HIV Infections, Viral Load, CD4 Lymphocyte Count, HIV-1, Acquired Immunodeficiency Syndrome, RNA, Viral, Plasma, RNA, Polymerase Chain Reaction, Receptors, Antigen, T-Cell, Leukocytes, Mononuclear, T-Lymphocytes, Human, Blood

020707
ThOrA1382