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Double Protease Inhibitor, RTI-sparing Therapy Regimen in Naïve HIV-1-infected patients: 24-Week Virologic Response Analysis of the LORAN Trial
Ku Ulbricht*1, M Stoll1, G Behrens1, B Salzberger2, H Jessen3, A Jessen3, B Kuhlmann4, A Trein5, H Heiken1, and R Schmidt1
1Hannover Med Sch, Germany; 2Univ of Regensburg, Germany; 3Private Practice Motzstr, Berlin, Germany; 4Praxis Georgstr, Hannover; and 5Private Practice Schwabstr, Stuttgart, Germany
Background: Double-protease
inhibitor (PI) regimens are a reliable therapeutic option in salvage therapy.
However, double-PI therapy has not yet been examined as an option for treatment-naïve
patients. In the LORAN study, a 72-week, randomized trial among HAART-naïve
patients, lopinavir/ritonavir (LPV/r) is combined with either combinivir (CBV)
(zidovudine [ATZ] + lamivudine [3TC]) or atazanavir (ATV). Primary endpoints
are metabolic side effects and quality of life, secondary endpoints are virological
and immunological response.
Methods: Treatment-naïve
HIV-1-infected patients started on HAART were randomly assigned to either
treatment arm. We analyzed virological failure in both groups, defined as viral
load ≥50 copies/mL at week 24.
Results: We
present 24-week data of 67 patients focusing on virological response. Of 30
patients, 24 in the CBV-LPV/r arm show virological response (6 discontinued before
week 24) vs 15 of the 37 in the ATV-LPV/r arm (12 discontinued, 6 of them due
to virological failure). Referring to “non-completion equals failure,” the
intent-to-treat analysis revealed significant differences for virological
failure in the LPV/r-ATV arm compared to the control group: Chi-Q p = 0.015,
Fisher´s exact test, p = 0.021. With regard to 47 on-study subjects in
week 24, we observed 10 failures in the ATV-LPV/r arm vs no failure in the
CBV-LPV/r arm (Chi-Q and Fisher´s exact test: p <0.001). ATV-LPV/r
failures were on low level (9 of 10 virological failures <700 copies/mL). Pharmacokinetic
measuring showed reduced LPV concentrations in 1 of 7 tested subjects in the
double-PI failures.
Conclusions:
This is the first report of a double-PI first-line therapy. Patients in the
double-PI arm had a high rate of mostly low level virological failure. In this
setting, ATV and LPV/r are less effective than the conventional reverse
transcriptase inhibitor (RTI) -based regimens. Furthermore, significant
treatment failure of an extended PI-based combination casts a new light on PI
monotherapy in naïve patients as recently presented in the MONARK- and M03-613-study.
Further exploration of early RTI-sparing therapy with regard to
metabolic side effects and quality of life is warranted.
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