Impact of 12 months HAART on cell-associated HIV-DNA in acute primary HIV-1 infection in the OPTIPRIM-ANRS 147 trial
Background: Early Initiation of a potent HAART at the time of primary HIV-1 infection (PHI) could block the virological and immunological storm and limit the establishment of HIV reservoirs. The randomized multicenter OPTIPRIM-ANRS147 trial was designed to evaluate the impact of a 24-month HAART initiated at the time of PHI on cell-associated HIV-DNA.
Methods: Inclusion criteria included HIV-1 western-blot with ≤ 4 antibodies, positive HIV-RNA and CD4 < 500/mm3 if PHI was asymptomatic. Patients were randomized 1:1 to receive darunavir/r, emtricitabine/tenofovir (Arm 1) or darunavir/r, emtricitabine/tenofovir (Arm 2). The primary endpoint was the between-arm difference in cell-associated HIV-DNA decrease at M24. Clinical evaluation, cART tolerability, CD4 count, HIV-RNA and HIV-DNA were collected during the trial. Hereinafter, we present the overall results of HIV-RNA and HIV-DNA decrease at 12 months. The 24 month-treatment period will be ended in July 2013.
Results: A total of 90 patients (median age: 35.5 years) were enrolled from May 2010 to July 2011, the median time from estimated date of infection was 35 days and 43% had HIV1 Western-Blot with ≤1 antibody; 92% were male and 96% had symptoms. At baseline median values for CD4, HIV-RNA and HIV-DNA were 472 cells/mm3 [IQR: 368-640], 5.4 log copies/ml [IQR: 4.9-5.8], and 3.65 log copies/106PBMC [IQR: 3.35-4.02], respectively.
Treatment was well tolerated with only 2 serious adverse effects (1 lipodystrophy, 1 acute pancreatitis), both in Arm 2. The CD4 difference at M12 was +239 cells/mm3. Plasma HIV-RNA decrease was >2 log cp/ml in 86 % subjects at M1 and HIV-RNA was < 50 cp/ml in 47%, 84%, 91% at M3, M6, and M12, respectively. Cell-associated HIV-DNA median [IQR] decrease from baseline was -0.75 [-0.94, -0.52], -1.12 [-1.33, -0.79] and -1.37 [-1.64, -1.15] log copies/106PBMC at M3 (n=73), M6 (n=63), M12 (n=39), respectively; 51.3% subjects had HIV-DNA level ≤2.3 log copies/106PBMC at M12.
Conclusion: This is the first trial showing such a rapid and intense decrease in cell-associated HIV-DNA within one year. This probably results from initiation of HAART very early after HIV infection.
A. Chéret1,2, G. Nembot3, V. Avettand-fenoël1,4, A. Mélard1,4, I. Ravaux5, B. Hoen6, C. Lascoux-Combe7, M.-L. Chaix4,8, C. Tamalet9, P. Yeni10, F. Raffi11, L. Slama12, C. Katlama13, A. Venet14, B. Autran15,16, A. Saez-Cirion17, L. Meyer3, C. Rouzioux1,4
1Paris Descartes Sorbonne-Paris-Cité University, EA 3620, Paris, France, 2Tourcoing Hospital, Infectious Diseases, Tourcoing, France, 3Faculty of Medicine Univ Paris-Sud 11, INSERM U1018, Le Kremlin-Bicêtre, France, 4AP-HP, Necker Hospital, Virology Laboratory, Paris, France, 5Timone Hospital, Infectious Diseases, Marseille, France, 6Besançon Hospital, Infectious Diseases, Besançon, France, 7AP-HP, Saint-Louis Hospital, Infectious Diseases, Paris, France, 8Paris Descartes Sorbonne-Paris-Cité, EA 3620, Paris, France, 9Timone Hospital, Virology Laboratory, Marseille, France, 10AP-HP, Bichat Hospital, Infectious Diseases, Paris, France, 11Hôtel-Dieu Hospital, Infectious Diseases, Nantes, France, 12Tenon Hospital, Infectious Diseases, Paris, France, 13AP-HP, Pitié-Salpêtrière Hospital, Infectious Diseases, Paris, France, 14INSERM, U1012, Le Kremlin-Bicêtre, France, 15Pierre & Marie Curie University, INSERM UMR-S 945, Paris, France, 16AP-HP, Pitié-Salpêtrière Hospital, Cellular and Tissular Immunology Laboratory, Paris, France, 17Pasteur Institute, Unité de Régulation des Infections Rétrovirales, Paris, France