LBPE16 - Poster Exhibition
The MiniZID study: a randomized controlled trial on safety of reduced dose (400 mg) of zidovudine compared with standard dose (600 mg) in HIV-infected patients starting antiretroviral therapy
M. Rougemont1, P. Nchotu Ngang2, J.-C. Fampou2, G. Menga2, B. Stoll3, C. Delhumeau-Cartier1, A. Hill4, A. Calmy1
1University of Geneva Hospital, Division of Infectious Diseases, Geneva, Switzerland, 2National Social Insurance Hospital, Approved HIV Treatment Center, Yaounde, Cameroon, 3Institute of Global Health, Faculty of Medicine, University of Geneva, Geneva, Switzerland, 4University of Liverpool, Pharmacology Research Laboratories, Liverpool, United Kingdom
Background: Zidovudine-based therapy for HIV is a standard first-line regimen in Cameroon and the preferred second-line WHO regimen (2013). Because reducing the dose may decrease adverse effects, this study compared the safety and efficacy of standard versus reduced doses in treatment-naive HIV patients.
Methods: We conducted a prospective, randomized-control trial at one HIV clinic in Yaoundé, Cameroon (August 2011-December 2013). Adults eligible for treatment (< 350 CD4 cells) were randomized to receive 24 weeks of lamivudine plus nevirapine with either the standard dose (600 mg) or reduced dose (400 mg) of twice-daily zidovudine. At the end of follow-up we compared the proportions of participants in the two arms with: new or worsening anemia (WHO grading); grade 3 and 4 adverse events leading to switch antiretroviral; plasma HIV-RNA (pVL) of < 200 copies/mL; new AIDS-defining illness or death.
Results: The intention-to-treat analysis comprised 142 patients (AZT400=72 and AZT600=70; 59% women; median age 35 years; median BMI 23.2 kg/m2). At baseline, median (IQR) hemoglobin was 11.6 g/dl (10.8-12.8), median (IQR) CD4 cell count was 163 cells/µL (99-219) and median (IQR) plasma HIV-RNA was 5.4 log10 copies/mL (4.9-5.9). Following 24 weeks of treatment the proportion of participants with new or worsening anemia was 37.5 % for AZT400 and 32.8% for AZT600 (p=0.563). Among patients presenting with anemia, significantly fewer in the AZT400 than the AZT 600 patients required a switch in assigned treatment to tenofovir because of severe anemia (1.4% vs 11.4%; p=0·017). At 24 weeks there was no significant difference between the treatment groups in median CD4 T-cell count increases (AZT400: +126 cells/µL; AZT600: +127 cells/µL p=0.716) or in the proportion with pVL < 200 copies/mL (87.5% for AZT400 and 85.7% for AZT600, p=0.755).
Conclusions: Although we observed no difference in overall anemia rate, reduced dose zidovudine demonstrated improved safety and similar efficacy compared to standard dose zidovudine. We recommend a larger phase 3 non-inferiority clinical trial using reduced zidovudine-based ART as a second-line regimen.
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