Efficacy and Tolerability of Tenofovir Disoproxil Fumarate Based Regimen as Compared to Zidovudine Based Regimens: A Systematic Review and Meta-Analysis

Abstract

Background: Although tenofovir (TDF)/emtricitabine (FTC)/efavirenz (EFV) and zidovudine (ZDV)/lamivudine (3TC)/efavirenz (EFV) are used as preferred first line regimen, their head-to-head comparison in terms of their efficacy and tolerability was limited. This review aimed to synthesize the best available evidence on the comparative efficacy and tolerability of the two regimens.

Methods: Seven sites and databases in addition to Google search until August 20, 2016, were searched. Only randomized clinical trials conducted on adult population were included in this study. Our primary outcome was viral load suppression while secondary outcomes were death and tolerability. Undetectable viral load is defined as <50 Human Immunodeficiency Virus (HIV) ribonucleic acid (RNA) copies/ml. Joanna Briggs institute meta-analysis of statistics assessment and review instrument (JBI-MAStARI) and critical appraisal and data extraction tool were applied for critical assessment and data extraction, respectively. We performed a random effect meta-analysis to pool the relative risk (RR) for viral load suppression (<50 HIV RNA copies/ml and <400 HIV RNA copies/ml), tolerability, and death.

Result: Data was extracted from four articles, which included a total of 2381 participants. We found superior viral load suppression among tenofovir (TDF) arm compared to zidovudine (ZDV) arm. Tenofovir arm achieves viral load <50 HIV RNA copies/ml (RR = 1.12, 95% confidence interval (CI) [1.04, 1.21], I² = 0%) higher than zidovudine arm. Similarly TDF arm is superior in viral load suppression to <400 HIV RNA copies/ml (RR = 1.19, 95% CI [1.11, 1.27], I² = 0%). Moreover, TDF based regimens were more likely to be tolerated than ZDV based regimens (4 trials, 2381 participants (RR = 1.06, 95% CI [1.02, 1.10], I² = 51%)). However, forest plot of death shows that it was not significant (RR = 0.91, 95% CI [0.51, 1.62]).

Conclusion: The use of TDF/FTC/EFV as first line regimen for naïve HIV-1 infected adult patient showed superior viral load suppression and tolerability as compared to ZDV/3TC/EFV. In order to compare the death outcome of both ZDV/3TC/EFV and TDF/FTC/EFV further research is needed.

Figure 1

Flow chart of study selection.

Figure 2

Forest plot of viral load suppression to less than 400 HIV RNA copies/ml in the TDF arm as compared to ZDV arm in ART naïve HIV-1 infected patients.

Figure 3

Forest plot of viral load suppression to less than 50 HIV RNA copies/ml in TDF arm as compared to ZDV arm in ART naïve HIV-1 infected patients.

Figure 4

Forest plot of mortality effect of TDF arm as compared to ZDV arm in ART naïve HIV-1 infected patients.

Figure 5

Forest plot of tolerability of TDF arm as compared to ZDV arm in ART naïve HIV-1 infected patients.