Role of baseline HIV-1 DNA level in highly-experienced patients receiving raltegravir, etravirine and darunavir/ritonavir regimen (ANRS139 TRIO trial).
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 log(10) copies/10(6) 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 log(10) copies/10(6) 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.
Laboratoire de Virologie, Assistance Publique-Hôpitaux de Paris (AP-HP), Groupe Hospitalier Bichat-Claude Bernard, HUPNVS, Université Paris Diderot, Paris 7, PRES Sorbonne Paris Cité, EA4409, Paris, France. charlotte.charpentier@bch.aphp.fr
Charlotte
C
Charpentier
Catherine
C
Fagard
Céline
C
Colin
Christine
C
Katlama
Jean-Michel
JM
Molina
Christine
C
Jacomet
Benoit
B
Visseaux
Anne-Marie
AM
Taburet
Françoise
F
Brun-Vézinet
Geneviève
G
Chêne
Yazdan
Y
Yazdanpanah
Diane
D
Descamps
D019380:Anti-HIV Agents / Q000494:pharmacology* / Q000627:therapeutic use; D004279:DNA, Viral / Q000378:metabolism*; D000069454:Darunavir; D015658:HIV Infections / Q000188:drug therapy / Q000821:virology*; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D009570:Nitriles; D011724:Pyridazines / Q000494:pharmacology / Q000627:therapeutic use; D011743:Pyrimidines; D011760:Pyrrolidinones / Q000494:pharmacology / Q000627:therapeutic use; D000068898:Raltegravir Potassium; D013449:Sulfonamides / Q000494:pharmacology / Q000627:therapeutic use
D019380:Anti-HIV Agents; D004279:DNA, Viral; D009570:Nitriles; D011724:Pyridazines; D011743:Pyrimidines; D011760:Pyrrolidinones; D013449:Sulfonamides; C451734:etravirine; D000068898:Raltegravir Potassium; D000069454:Darunavir