Mariantonietta Pisaturo1, Lorenzo Onorato1, Antonio Russo1, Salvatore Martini2, Paolo Chiodini3, Simona Signoriello3, Paolo Maggi1, Nicola Coppola4. 1. Department of Mental Health and Public Medicine - Infectious Diseases Unit, University of Campania Luigi Vanvitelli, Naples, Italy. 2. Infectious Disease Unit, University Hospital Luigi Vanvitelli, Naples, Italy. 3. Medical Statistics Unit, Department of Mental Health and Public Medicine, University of Campania Luigi Vanvitelli, Naples, Italy. 4. Department of Mental Health and Public Medicine - Infectious Diseases Unit, University of Campania Luigi Vanvitelli, Naples, Italy; Infectious Disease Unit, University Hospital Luigi Vanvitelli, Naples, Italy. Electronic address: nicola.coppola@unicampania.it.
Abstract
OBJECTIVES: Several attempts have been made to test different drug-sparing strategies to reduce the drug-burden and drug-related toxicities. The objective of this meta-analysis was to evaluate the relative risk (RR) of failure of dual therapies compared to triple therapies in HIV-naïve patients. METHODS: We searched MEDLINE, Google Scholar and the Cochrane Library. The following criteria were used: present data from original articles comparing the two treatment regimens; published from January 2007 up to January, 2020. No language or study design restriction was applied. Subjects were HIV-positive naïve patients treated with dual or triple antiretroviral therapy (ART). A systematic review and meta-analysis was performed. Treatment failure (TF) was the primary outcome evaluated; heterogeneity was assessed using the Q statistic and I2. RESULTS: Fourteen studies were included, allowing a meta-analysis on 5205 patients. The meta-analysis performed on studies that presented data at 48 weeks showed that the RR of TF (RR > 1 favouring triple therapy) in 10 studies was 1.20 (95% confidence interval (CI): 0.91-1.59, I2: 49.2%); the RR of virological failure (VF) in eight studies was 1.54 (95% CI: 0.84-2.86, I2: 54%); the RR of adverse drug reaction leading to discontinuation of the regimen at 48 weeks in eight studies was 0.76 (95% CI: 0.43-1.33, I2: 17.7%). In patients with less than 200 CD4+, the RR of TF in two studies without maraviroc was 2.09 (95% CI: 1.05-4.17, I2: 0.0%). Regarding the studies at 96 weeks there was no difference except in rate of development of resistance, RR 1.94 (95% CI: 1.06-3.53, I2: 6.2%). CONCLUSION: Dual therapies are as effective as those with three drugs, showing no difference according to the different dual therapies, except in patients with less than 200 CD4; however, they are associated with a higher selection of resistance-associated mutations at 96 weeks of therapy.
OBJECTIVES: Several attempts have been made to test different drug-sparing strategies to reduce the drug-burden and drug-related toxicities. The objective of this meta-analysis was to evaluate the relative risk (RR) of failure of dual therapies compared to triple therapies in HIV-naïve patients. METHODS: We searched MEDLINE, Google Scholar and the Cochrane Library. The following criteria were used: present data from original articles comparing the two treatment regimens; published from January 2007 up to January, 2020. No language or study design restriction was applied. Subjects were HIV-positive naïve patients treated with dual or triple antiretroviral therapy (ART). A systematic review and meta-analysis was performed. Treatment failure (TF) was the primary outcome evaluated; heterogeneity was assessed using the Q statistic and I2. RESULTS: Fourteen studies were included, allowing a meta-analysis on 5205 patients. The meta-analysis performed on studies that presented data at 48 weeks showed that the RR of TF (RR > 1 favouring triple therapy) in 10 studies was 1.20 (95% confidence interval (CI): 0.91-1.59, I2: 49.2%); the RR of virological failure (VF) in eight studies was 1.54 (95% CI: 0.84-2.86, I2: 54%); the RR of adverse drug reaction leading to discontinuation of the regimen at 48 weeks in eight studies was 0.76 (95% CI: 0.43-1.33, I2: 17.7%). In patients with less than 200 CD4+, the RR of TF in two studies without maraviroc was 2.09 (95% CI: 1.05-4.17, I2: 0.0%). Regarding the studies at 96 weeks there was no difference except in rate of development of resistance, RR 1.94 (95% CI: 1.06-3.53, I2: 6.2%). CONCLUSION: Dual therapies are as effective as those with three drugs, showing no difference according to the different dual therapies, except in patients with less than 200 CD4; however, they are associated with a higher selection of resistance-associated mutations at 96 weeks of therapy.