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PLOS ONE  2013 

Role of Baseline HIV-1 DNA Level in Highly-Experienced Patients Receiving Raltegravir, Etravirine and Darunavir/Ritonavir Regimen (ANRS139 TRIO Trial)

DOI: 10.1371/journal.pone.0053621

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Abstract:

Objective In the ANRS 139 TRIO trial, the use of 3 new active drugs (raltegravir, etravirine, and darunavir/ritonavir), resulted in a potent and sustained inhibition of viral replication in multidrug-resistant treatment-experienced patients. The aim of this virological sub-study of the ANRS 139 TRIO trial was to assess: (i) the evolution of HIV-1 DNA over the first year; and (ii) the association between baseline HIV-1 DNA and virological outcome. Methods Among the 103 HIV-1-infected patients included in the ANRS-139 TRIO trial, HIV-1 DNA specimens were available for 92, 84, 88, and 83 patients at Week (W)0, W12, W24, and W48, respectively. Quantification of total HIV-1 DNA was performed by using the commercial kit “Generic HIV DNA Cell” (Biocentric, Bandol, France). Results Baseline median HIV-1 DNA of patients displaying virological success (n = 61), viral blip (n = 20), and virological failure (n = 11) were 2.34 log10 copies/106 PBMC (IQR = 2.15–2.66), 2.42 (IQR = 2.12–2.48), and 2.68 (IQR = 2.46–2.83), respectively. Although not statistically significant, patients exhibiting virological success or viral blip had a tendency to display lower baseline HIV-1 DNA than patients experiencing virological failure (P = 0.06). Median decrease of HIV-1 DNA between baseline and W48 was -0.13 log10 copies/106 PBMC (IQR = -0.34 to +0.10), mainly explained by the evolution from W0 to W4. No more changes were observed in the W4-W48 period. Conclusions In highly-experienced multidrug-resistant patients, HIV-1 DNA slightly decreased during the first month and then remained stable during the first year of highly potent antiretroviral regimen. In this population, baseline HIV-1 DNA might help to better predict the virological response and to tailor clinical therapeutic management as more aggressive therapeutic choices in patients with higher baseline HIV-1 DNA.

References

[1]  Goujard C, Bonarek M, Meyer L, Bonnet F, Chaix ML, et al. (2006) CD4 cell count and HIV DNA level are independent predictors of disease progression after primary HIV type 1 infection in untreated patients. Clin Infect Dis 42: 709–715.
[2]  Rouzioux C, Hubert JB, Burgard M, Deveau C, Goujard C, et al. (2005) Early levels of HIV-1 DNA in peripheral blood mononuclear cells are predictive of disease progression independently of HIV-1 RNA levels and CD4+ T-cell counts. J Infect Dis 192: 46–55.
[3]  Lambert-Niclot S, Flandre P, Valantin MA, Peytavin G, Duvivier C, et al. (2011) Factors associated with virological failure in HIV-1-infected patients receiving darunavir/ritonavir monotherapy. J Infect Dis 204: 1211–1216.
[4]  Yazdanpanah Y, Fagard C, Descamps D, Taburet AM, Colin C, et al. (2009) High rate of virologic suppression with raltegravir plus etravirine and darunavir/ritonavir among treatment-experienced patients infected with multidrug-resistant HIV: results of the ANRS 139 TRIO trial. Clin Infect Dis 49: 1441–1449.
[5]  Fagard C, Colin C, Charpentier C, Rami A, Jacomet C, et al. (2012) Long-term efficacy and safety of raltegravir, etravirine, and darunavir/ritonavir in treatment-experienced patients: week 96 results from the ANRS 139 TRIO trial. J Acquir Immune Defic Syndr 59: 489–493.
[6]  Charpentier C, Piketty C, Laureillard D, Tisserand P, Si-Mohamed A, et al. (2012) Dynamics of HIV-1 DNA level in highly antiretroviral-experienced patients receiving raltegravir-based therapy. Eur J Clin Microbiol Infect Dis 31: 129–133.
[7]  Reigadas S, Andréola ML, Wittkop L, Cosnefroy O, Anies G, et al. (2010) Evolution of 2-long terminal repeat (2-LTR) episomal HIV-1 DNA in raltegravir-treated patients and in in vitro infected cells. J Antimicrob Chemother 65: 434–437.
[8]  Ngo-Giang-Huong N, Deveau C, Da Silva I, Pellegrin I, Venet A, et al. (2001) Proviral HIV-1 DNA in subjects followed since primary HIV-1 infection who suppress plasma viral load after one year of highly active antiretroviral therapy. AIDS 15: 665–673.
[9]  Morand-Joubert L, Marcellin F, Launay O, Guiramand-Hugon S, Gérard L, et al. (2005) Contribution of cellular HIV-1 DNA quantification to the efficacy analysis of antiretroviral therapy: a randomized comparison of 2 regimens, including 3 drugs from 2 or 3 classes (TRIANON, ANRS 081). J Acquir Immune Defic Syndr 38: 268–276.
[10]  Yerly S, Perneger TV, Vora S, Hirschel B, Perrin L (2000) Decay of cell-associated HIV-1 DNA correlates with residual replication in patients treated during acute HIV-1 infection. AIDS 14: 2805–2812.
[11]  Rong L, Perelson AS (2009) Modeling latently infected cell activation: viral and latent reservoir persistence, and viral blips in HIV-infected patients on potent therapy. PLoS Comput Biol 5: e1000533.
[12]  Ramratnam B, Mittler JE, Zhang L, Boden D, Hurley A, et al. (2000) The decay of the latent reservoir of replication-competent HIV-1 is inversely correlated with the extent of residual viral replication during prolonged anti-retroviral therapy. Nat Med 6: 82–85.

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