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Cellular HIV reservoir replenishment is not affected by blip or intermittent viremia episodes during darunavir/ritonavir monotherapy

Torres-Cornejo, Almudena; BenMarzouk-Hidalgo, Omar J.; Gutiérrez-Valencia, Alicia; Pérez-Romero, Pilar; Martín-Peña, Reyes; Ruiz-Valderas, Rosa; Viciana, Pompeyo; Lopez-Cortes, Luis F.

doi: 10.1097/QAD.0000000000000060
Clinical Science

Objective: To assess the impact of blips and persistent viremia episodes on cell-associated HIV-DNA reservoir in extensively pretreated patients receiving ritonavir-boosted darunavir monotherapy (MtDRV/rtv) for 24 months.

Design and methods: Patients from the MonDAR prospective study (NCT01606722) who received at least 6 months of MtDRV/rtv and had at least two available peripheral blood mononuclear cells (PBMCs) samples were selected and classified according to the viral outcome as continuous undetectable viremia (cUV; n = 40), blips (n = 31), intermittent viremia (IV; n = 23), and virological failure (VF, two consecutive viral loads >200 copies/ml; n = 20). Proviral HIV-DNA was quantified by real-time PCR in PBMCs samples at baseline, and months 6, 12, 18 and 24. Additionally, HIV-DNA levels were exhaustively analyzed at virological failure and blip episodes.

Results: The HIV-DNA levels remained constant during the 24 months in every group. Neither blips nor intermittent viremia influenced the HIV-DNA levels at short-term or at middle term. By contrast, virological failure episodes gave rise to a significant increase in proviral DNA (2.15 vs. 2.32 log10 HIV-DNA copies/106 PBMCs; P = 0.042). Basal proviral DNA levels more than 2 log10 copies/106 PBMCs predicted the time to viral rebound at any given cut-off point (>20, >50, and >200 copies/ml. HR: 3.02, 2.61, and 3.02, respectively; P ≤ 0.03. Besides, an adherence less than 95% was also strongly associated with virological failure (HR, 3.17; P = 0.021).

Conclusion: Blip episodes and intermittent viremia did not affect the cellular HIV reservoir dynamic during MtDRV/rtv. Higher adherence and an HIV-DNA levels less than 2 log10 copies/106 PBMCs at baseline were associated with a lower risk of virological failure.

Enfermedades Infecciosas, Microbiología y Medicina Preventiva, Hospital Universitario Virgen del Rocío. Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Av. Manuel Siurot, Sevilla, Spain.

Correspondence to Luis F. López-Cortés, Unidad Clínica de Enfermedades Infecciosas, Microbiología y Medicina Preventiva, Hospital Universitario Virgen del Rocío, Av. Manuel Siurot, s/n. 41013, Sevilla, Spain. Tel: +34 955013096; fax: +34 954624466; e-mail: lflopez@us.es

Received 8 July, 2013

Revised 28 August, 2013

Accepted 2 September, 2013

This work was partially presented at the International AIDS Society Conference, Washington DC, USA, July 23-27th 2012 (Poster LBPE21).

© 2014 Lippincott Williams & Wilkins, Inc.