Archives of Virology
Efficacy and safety of atazanavir/ritonavir-based antiretroviral therapy for HIV-1 infected subjects: A systematic review and meta-analysis
Amr Menshawy1,2,3†, Ammar Ismail1,2,3,4†, Abdelrahman Ibrahim Abushouk3,4,5*, Hussien Ahmed3,6,7, Esraa Menshawy1,3, Ahmed Elmaraezy1,3,4, Mohamed Gadelkarim3,8, Mohamed Abdel-Maboud1,2,3, Attia Attia1,3, Ahmed Negida3,6,7
1Faculty of Medicine, Al-Azhar University, Cairo, Egypt
2Medical Research Society, Cairo University, Cairo, Egypt
3Medical Research Group of Egypt, Cairo, Egypt
4NovaMed Medical Research Association, Cairo, Egypt
5Faculty of Medicine, Ain Shams University, Cairo, Egypt
6Faculty of Medicine, Zagazig University, El-Sharkia, Egypt
7Student Research Unit, Zagazig University, El-Sharkia, Egypt
8Faculty of Medicine, Alexandria University, Alexandria, Egypt
† Both authors contributed equally to this manuscript.
*Correspondence to: Abdelrahman Ibrahim Abushouk
Faculty of Medicine, Ain Shams University, 11591, Cairo, Egypt
Address: 38 Ramsess st, Abbasia, Cairo, Egypt.
Tel: 01014295780, Fax: 020132706152,
Email:
Supplementary file 2 shows results of quality assessment for included studies.
Reason/Quotation / Risk of Bias / Miro 2015Using a centralized computer-generated process, eligible patients were randomly assigned to 1 of 3 treatment arms in a 1:1:1 ratio. / Low risk / Random sequence generation (selection bias)
Centralized computer-generated randomization. / Low risk / Allocation concealment (selection bias)
Open label study. / High risk / Blinding of participants and personnel (performance bias)
Open-label study. / High risk / Blinding of outcome assessment (detection bias)
One patient in the atazanavir/ritonavir armdid not start the study medication and was excluded from the final analysis. / Low risk / Incomplete outcome data (attrition bias)
All outcome of interest were reported. / Low risk / Selective reporting (reporting bias)
Unclear / Other bias
Reason/Quotation / Risk of Bias / Andersson 2012
patients were randomly assigned (ratio 1:1:1) to receive either LPV/r 400/100 mg twice daily, AZV/r 300/100 mg once daily, or EFV 600 mg once daily. / Low risk / Random sequence generation (selection bias)
Randomization was performed by block-randomization with a concealed predefined computer-generated randomization list. / Low risk / Allocation concealment (selection bias)
Open label study. / High risk / Blinding of participants and personnel (performance bias)
Open-label study. / High risk / Blinding of outcome assessment (detection bias)
239 of patients received the allocated treatment and were analyzed for efficacy. / Low risk / Incomplete outcome data (attrition bias)
All outcome of interest were reported. / Low risk / Selective reporting (reporting bias)
Unclear / Other bias
Reason/Quotation / Risk of Bias / Mallolas2009
Patients were randomized 1:1 either to continue their existing regimen of LPV/r or to switch to ATV/r. / Low risk / Random sequence generation (selection bias)
Not described. / Unclear / Allocation concealment (selection bias)
Open-label study. / High risk / Blinding of participants and personnel (performance bias)
Open-label study. / High risk / Blinding of outcome assessment (detection bias)
All randomized patients, except those who were found to have violated the entry criteria and those who never started the study medication, were included in the analysis. / Low risk / Incomplete outcome data (attrition bias)
All outcome of interest were reported. / Low risk / Selective reporting (reporting bias)
Unclear / Other bias
Reason/Quotation / Risk of Bias / Molina2010
Patients were randomly assigned in a one to one ratio to receive either atazanavir/ritonavir once daily, or fixed-dose lopinavir/ritonavir twice daily. / Low risk / Random sequence generation (selection bias)
Randomization was done with a computer-generated centralized randomization schedule. / Low risk / Allocation concealment (selection bias)
Open-label study. / High risk / Blinding of participants and personnel (performance bias)
Open-label study. / High risk / Blinding of outcome assessment (detection bias)
70% of patients remaining on treatment for 48 weeks. / Low risk / Incomplete outcome data (attrition bias)
All outcome of interest were reported. / Low risk / Selective reporting (reporting bias)
The study sponsor developed the study design and analysis plan with input from prospective investigators. / High risk / Other bias
Reason/Quotation / Risk of Bias / Johnson2005
Randomization was performed centrally and patients were assigned in a 1:1:1 ratio to (a) atazanavir /ritonavir (b) atazanavir/saquinavir (c) lopinavir/ritonavir / Low risk / Random sequence generation (selection bias)
Not described. / Unclear / Allocation concealment (selection bias)
Open-label study. / High risk / Blinding of participants and personnel (performance bias)
Open-label study. / High risk / Blinding of outcome assessment (detection bias)
Efficacy endpoints were assessed for all randomized patients with plasma HIV RNA levels and CD4 cell counts obtained through 4 days after the last dose of study therapy. / Low risk / Incomplete outcome data (attrition bias)
All outcome of interest were reported. / Low risk / Selective reporting (reporting bias)
This study was wholly funded by Bristol Myers Squibb. / High risk / Other bias
Reason/Quotation / Risk of Bias / Ofotokun 2015
ACTG A5257 was a Phase III, randomized, open label trial in which participants were randomly assigned 1:1:1 to receive one of three regimens. / Low risk / Random sequence generation (selection bias)
Not described. / Unclear / Allocation concealment (selection bias)
Open label study. / High risk / Blinding of participants and personnel (performance bias)
Open-label study. / High risk / Blinding of outcome assessment (detection bias)
Not described. / Unclear / Incomplete outcome data (attrition bias)
All outcome of interest were reported. / Low risk / Selective reporting (reporting bias)
Unclear / Other bias
Reason/Quotation / Risk of Bias / Martinez2014
Patients were randomly assigned in a 1: 1 ratio to receive either atazanavir or darunavir with ritonavir plus the fixed‐dose combination TDF/FTC as antiretroviral. / Low risk / Random sequence generation (selection bias)
A random sequence was generated by a computer using blocks of variable size that were balanced at each site. / Low risk / Allocation concealment (selection bias)
Open label study. / High risk / Blinding of participants and personnel (performance bias)
Open-label study. / High risk / Blinding of outcome assessment (detection bias)
Two hundred and fourteen patients were assessed for eligibility, 180 underwent randomization and
178 (ATV/r, n=90; DRV/r, n=88) received at least one dose of study drugs and were included in the analysis. / Low risk / Incomplete outcome data (attrition bias)
All outcome of interest were reported. / Low risk / Selective reporting (reporting bias)
Unclear / Other bias
Reason/Quotation / Risk of Bias / Saumoy2014
Randomized. / Low risk / Random sequence generation (selection bias)
Not described. / Unclear / Allocation concealment (selection bias)
Open-label study. / High risk / Blinding of participants and personnel (performance bias)
Open-label study. / High risk / Blinding of outcome assessment (detection bias)
Nine patients discontinued the study medication (five in the atazanavir/ritonavir arm and four in the darunavir/ritonavir arm), five owing to withdrawal of consent, three lost to follow-up and one with Kaposi’s sarcoma. Only one participant started lipid-lowering therapy during the study. / Low risk / Incomplete outcome data (attrition bias)
All outcome of interest were reported. / Low risk / Selective reporting (reporting bias)
Unclear / Other bias
Reason/Quotation / Risk of Bias / Aberg2012
Subjects were randomized in a 1:1 ratio, stratified by sex, to receive DRV/r or ATV/r, both with a fixed-dose combination of emtricitabine/tenofovir disoproxil fumarate (FTC/TDF). / Low risk / Random sequence generation (selection bias)
Not described. / Unclear / Allocation concealment (selection bias)
Open-label study. / High risk / Blinding of participants and personnel (performance bias)
Open-label study. / High risk / Blinding of outcome assessment (detection bias)
11 patients were lost from the study but all patients were included in an intention to treat analysis. / Low risk / Incomplete outcome data (attrition bias)
All outcome of interest were reported. / Low risk / Selective reporting (reporting bias)
Funding for the study and for editorial support was provided by Janssen Therapeutics. / High risk / Other bias