Paper # 533 
Baseline HIV RNA Ultrasensitive Assay and Viral DNA Predict Rise in Plasma Viral Load in Patients of MONOI-ANRS 136 Trial
Anne-Geneviève Marcelin*1,2, S Lambert-Niclot1,2, G Peytavin3, C Duvivier4, M Algarte-Genin1, Y Yazdanpanah5, P-M Girard6, C Katlama1,2, V Calvez1,2, and P Flandre1,2
1INSERM U943, Paris, France; 2Univ Pierre and Marie Curie, Hosp Pitie-Salpetriere, Paris, France; 3Hosp Bichat Claude Bernard, Univ Paris 7, France; 4Inst Pasteur and Hosp Necker, Univ Paris Descartes, France; 5Hosp Tourcoing, France; and 6Hosp St Antoine, Paris, France
Background: In
patients with suppressed HIV RNA, a switch to darunavir/r (DRV/r) showed monotherapy
virologic efficacy in 87.5% of patients at week 48 in comparison with 92% of
patients in the triple standard 2 NRTI + DRV/r therapy. Our objective is to identify
patients who can successfully receive such a monotherapy strategy.
Methods: Patients
on cART with HIV RNA <400 copies/mL for at least 18 months and <50
copies/mL at screening were randomized to either continuing the standard
triple-drug DRV/r-containing regimen or switching to DRV/r monotherapy. Viremia
with a limit of quantification of 1 copy/mL was measured at screening,
baseline, and week 48. Cellular HIV DNA was also quantified at baseline. A
logistic model was used to investigate whether, in addition to other variables,
HIV RNA measured by ultrasensitive assay and HIV DNA were predictive of at
least 1 plasma HIV RNA value above 50 copies/mL through week 48 (virologic
outcome).
Results: Data
on HIV RNA ultrasensitive assays were available in 224/225 randomized patients (DRV/r
monotherapy = 111; triple-drug DRV/r = 113). Overall, 45.5% (102/224) of
patients had HIV RNA <1 copy/mL both at screening and baseline and the
median HIV DNA at baseline was 3.16 log10 copies/mL [IQR 2.8 to 3.5
log10]. Patients with HIV RNA <1 copy/mL had a lower median HIV
DNA (2.96 vs 3.26, p = 0.008) and a higher median exposure to protease
inhibitor (6.6 vs 4.3 years, p = 0.02). Overall, 52 patients (23%)
experienced at least 1 episode of HIV RNA >50 copies/mL by week 48 (30 in
the DRV/r monotherapy group and 22 in the 2 NRTI + DRV/r group, p =
0.21). Overall, full adherence (OR = 2.10; 95%CI 1.03 to 4.30), lower HIV DNA
at baseline (OR = 1.77 per 1 log10 decrease; 95%CI 1.04 to 3.00),
and a baseline ultrasensitive plasma viral load <1 copy/mL (OR = 2.58; 95%CI
1.19 to 5.61) were independently associated with maintaining HIV RNA <50
copies/mL through week 48. In the DRV/r monotherapy group, only HIV DNA (OR = 2.97;
95%CI 1.28 to 6.94) was associated with consistent HIV-1 RNA measures <50
copies/mL and only having HIV RNA <1 copy/mL (OR = 9.36; 95%CI 2.07 to 42.4)
in the 2 NRTI + DRV/r group. Similar results were found at week 96 both overall
and in the treatment group analysis.
Conclusions:
In patients receiving DRV/r monotherapy only HIV DNA viral load was a
predictive factor to maintain the HIV RNA <50 copies/mL through week 48 and week
96. This could have implications for the choice of patients who could be
treated by DRV/r monotherapy and the best timing to start this strategy.
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