20th International AIDS Conference - Melbourne, Australia


LBPE19 - Poster Exhibition

HARNESS study: ritonavir-boosted atazanavir (ATV/r)+raltegravir (RAL) switch study in virologically suppressed, HIV-1-infected patients

J. van Lunzen1, A. Pozniak2, J. Gatell3, A. Antinori4, I. Klauck5, O. Serrano6, A. Baakili7, M. Yu5, P.-M. Girard8

1University Medical Center Hamburg-Eppendorf, Infectious Diseases Unit, Hamburg, Germany, 2Chelsea and Westminster Hospital, London, United Kingdom, 3Infectious Diseases & AIDS Units. Clinical Institute of Medicine & Dermatology. Hospital Clinic, University of Barcelona,, Barcelona, Spain, 4National Institute for Infectious Diseases, Rome, Italy, 5Bristol-Myers Squibb, Rueil-Malmaison, France, 6Bristol-Myers Squibb, Madrid, Spain, 7Bristol-Myers Squibb, Uxbridge, United Kingdom, 8Service des Maladies Infectieuses, Hôpital St Antoine, APHP, Paris, France

Background: Despite sustained virologic efficacy, some patients develop tolerability/safety issues during stable HAART including NRTIs. Thus, we evaluated the efficacy of a switch regimen consisting of ATV/r+RAL.
Methods: A randomized, open-label, multinational study evaluating switching from a triple-drug regimen (TDR)[including 2 NRTIs] to ATV/r 300/100mg once daily (QD)+RAL 400mg twice daily (experimental group [ExpG]) in patients with virologic suppression (HIV-1 RNA < 40 copies/mL). Patients were randomized 2:1 to the ExpG or to ATV/r 300/100mg QD+tenofovir DF/emtricitabine 300/200mg QD (reference group[RefG]). The primary endpoint was the proportion of patients with HIV-1 RNA < 40 copies/mL at Wk24.
Results: 109 patients were randomized: males 80.6% (ExpG) and 83.8% (RefG); mean CD4+ counts 588 and 631 cells/mm3, respectively. At Wk24, HIV-1 RNA < 40 copies/mL occurred in 80.6% of patients in the ExpG and 94.6% in the RefG.

HIV RNA <40 copies/mL (primary endpoint results)ATV/r+RAL; N=72 (%)ATV/r+TDF/FTC; N=37 (%)
Responder/Evaluable (ITT analysis)58/72 (80.6)35/37 (94.6)
Responder/Evaluable (observed value)58/64 (90.6)35/35 (100)
[[Table 1] Summary of efficacy results (Week 24)]

A higher rate of virologic rebound (VR)[HIV-1 RNA >40 copies/mL] was detected in the ExpG (9.7%[7/72] vs. 2.7%[1/37]) and consequently the DMC recommended stopping the trial. However, by that time all patients had reached Wk48. VR occurred at low levels (50-200 copies/mL) in 5/7 patients in the ExpG. At the time of VR, one patient in the ExpG had INI-associated resistance mutations (Y143C+N155H) and an additional patient had an INI mutation (F121Y) associated with no classical ATV-related mutations. In the RefG, no PI or INI mutation was observed in phenotypic/genotypic testing in the one patient with VR. Rates of Grade 3/4 laboratory abnormalities, including bilirubinemia, were comparable.

 ATV/r+RAL; N=72 (%)ATV/r+TDF/FTC; N=37 (%)
Discontinued from study therapy before or at Week 244/72 (5.6)0
AEs leading to treatment discontinuation3/72 (4.2)1/37 (2.7)
Grade 3-4 adverse events, Grade 3-4 total bilirubin abnormalities11/72 (15.3), 4/72 (5.6)5/37 (13.5), 3/37 (8.1)
[[Tab 2] Discontinuations and safety results (Wk24)]

Conclusions: In virologically suppressed patients on TDR, switching to ATV/r+RAL was well tolerated but resulted in more VR than in the RefG at Wk24. However, VR levels were low and major INI drug resistance occurred in only one patient.
ClinicalTrials.gov identifier NCT01332227

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