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Session 54 Poster Presentations
Viral Reservoirs and Transmission
Session Day and Time: Tuesday 1:30 - 3:30 pm
Room: Hall A


456
Differences in HIV-1 Replication Dynamics between Peripheral Blood and Vagina Suggest a Compartmentalized Viral Production in the Female Genital Tract
L. Andreoletti*1, N. Chomont2, G. Gresenguet3, M. Matta M. Matta4, P. Coudol4, L. Belec2,4,
1Fac de Med de Reims, France; 2INSERM U430, Paris, France; 3CNR des MST Bangui, Ctr Afrique; and 4HEGP/AP-HP, Paris, France

Background: The female genital tract is suspected to be an independent compartment of HIV-1 replication, which would have significant implications for HIV-1 transmission and for the design of systemic and mucosal vaccination against HIV.

Methods: In the present study, the levels of cell-free HIV-1 RNA and proviral DNA were determined in genital and systemic compartments of 30 clinically asymptomatic and treatment-naive African women by means of ultra-sensitive PCR-based techniques. Patients (pts) were selected from a cohort of 213 HIV-1 infected women (Bangui, Central African Republic) provided they were non-pregnant and free of cervicitis, sexual transmitted diseases, genital bleeding, and seminal pollution in the genital tract.

Results: Five (5) women (17%) only showed proviral DNA in vaginal secretions. HIV-1 RNA levels in plasma ranged from < 20 to 199,000 copies per ml (mean: 42,296 copies per ml), whereas vaginal amounts of HIV-1 RNA ranged from < 50 to 110,830 copies per ml (mean: 9,891 copies per ml). Amounts of HIV-1 DNA in blood ranged from < 5–943 copies per µg of cellular DNA (mean: 63 copies per µg), while genital proviral levels ranged from < 5–925 copies of HIV-1 DNA per µg of cellular DNA (mean: 91 copies per µg). Levels of HIV-1 RNA and HIV-1 proviral DNA in vaginal lavage samples were weakly correlated with those in paired blood samples (r = 0.45, p = 0.014; r = 0.37, p = 0.047, respectively). Levels of HIV-1 DNA in peripheral blood were strongly correlated with levels of plasma HIV-1 RNA (r = 0.76, p = 0.0001), whereas no such correlation was evidenced in vaginal secretions. Total HIV RNA loads in cervical mucus were positively correlated with cell-free HIV RNA in vaginal lavage samples (r = 0.61, p = 0.005), but not with those in plasma.

Conclusions: Our results suggest that the basal replication dynamic of HIV in the female genital tract is relatively independent from that of peripheral blood, and that genital production of cell-free and cell-associated viruses are largely unrelated in treatment-naive women. These findings further document that the female genital tract is an independent compartment of HIV-1 replication, which may result in viral or proviral populations with important genetic differences from those found in peripheral blood at the chronic phase of the infection.