18th International HIV Drug Resistance Workshop Basic Principles & Clinical Implications June 9–13 2009, Fort Myers, Florida, USA

NO EVOLUTION OF HIV-1 TOTAL DNA AND 2-LTR CIRCLES AFTER 24 WEEKS OF RALTEGRAVIR-CONTAINING REGIMEN: A SUBSTUDY OF RANDOMIZED EASIERANRS 138 TRIAL

Antivir Ther 2009; 14 Suppl 1:A11 (abstract no. 9)

C Delaugerre¹, I Charreau², J Braun², ML Néré¹, N de Castro³, P Yeni⁴, JM Chennebault⁵, A Lafeuillade⁶, J Ghosn⁷, F Simon¹, JP Aboulker², JM Molina³ and the ANRS 138 study group
¹Virology Department, Paris 7 Diderot University, Saint Louis Hospital, AP-HP, Paris, France; ²INSERM SC 10, Villejuif, France; ³Infectious Diseases Department, Paris 7 Diderot University, Saint Louis Hospital, AP-HP, Paris, France; ⁴Infectious Diseases Department, Paris 7 Diderot University, Bichat-Claude Bernard Hospital, AP-HP, Paris, France; ⁵Infectious Diseases Department, CHU Angers, Angers, France; ⁶Infectious diseases and Heamatology Department, Centre Hospitalier Font Pré, Toulon, France; ⁷Internal Medicine and Infectious Diseases Department, Kremlin Bicêtre Hôpital, AP-HP, Kremlin Bicêtre, France

BACKGROUND: EASIER-ANRS 138 was a randomized non-inferiority trial that evaluated the switch from enfuvirtide to raltegravir in highly treatment-experienced HIV-1-infected patients with plasma HIV-1 RNA (pVL) <400 copies/ml. Through week 24, virological failure, defined as confirmed pVL ≥400 copies/ml, was observed in 0/82 patients in the enfuvirtide arm and 1/82 (1.2%) in the raltegravir arm (per protocol analysis). Our aim was to analyze the effect of raltegravir on the evolution of HIV-1 total DNA and episomal cDNA forms (2-LTR circles) in a subgroup of patients.

METHODS: Among the 170 patients enrolled in the trial, HIV-1 DNA quantification was measured in the first 30 patients of each arm. Viral DNA was extracted from whole blood at weeks 0 and 24. Episomal cDNA forms (2-LTR circles) were measured with primers that span the 2-LTR circle junction and total viral DNA forms were assayed using internal LTR primers.

RESULTS: Baseline characteristics for the 60 patients were: CDC stage C: 60%, median HAART duration: 14 years, median enfuvirtide duration: 2.5 years, median baseline and nadir CD4+ T-cell count: 400 cells/mm³ and 37 cells/mm³ and pVL was ≥50 copies/ml in 13% (8/60). Baseline median total DNA was 3.61 log₁₀/10⁶ PBMCs. Detection of 2-LTR circles was observed in 6 patients with a median of 89 copies/10⁶ PBMCs. At week 24, CD4+ T-cell count was 416 cells/mm³, pVL was <50 and between 50 and 400 copies/ml in 88% and 12% of patients, respectively. At week 24, total DNA was 3.68 log₁₀/10⁶ PBMCs and 2-LTR circles were detected in 3 patients (but different from baseline) with one under raltegravir. No significant change was observed between S24 and W0 in total DNA whatever the randomization group (0.01 [-0.27;0.30] and 0.02 [-0.17;0.25] log₁₀ in enfuvirtide and raltegravir, respectively; P=0.71 Wilcoxon test). There was also no difference in total DNA change in patients with baseline pVL between 50 and 400 copies/ml.

DISCUSSION: In this randomized trial, no modification in total and 2-LTR DNA was observed after 24 weeks in either raltegravir or enfuvirtide arms, suggesting that the majority of viral DNA is non-dynamic in patients with plasma controlled <400 copies/ml.

2009-06-09
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