Objective The study examined whether the benefit and adverse effects of the tenofovir-based highly active antiretroviral therapy (HAART) regimen outweigh the non-tenofovir-based regimen in the elderly population.  Methods We searched PubMed, EMBASE, Cochrane Central Library, Google Scholar, and some hand searches to identify eligible studies. Only randomized control trials on elderly HIV-positive patients on Tenofovir-based regimens living in sub-Saharan Africa were included. Studies on pregnant women or prophylactic tenofovir were excluded. The primary outcomes are viral suppression, mortality, and anemia. Two reviewers independently selected the studies, extracted data, and assessed the risk of bias. We analyzed using risk ratio, with 95% confidence intervals. A fixed effect model along with an assessment of heterogeneity was done for meta-analysis.    Results Four studies with a total of 263 participants were included. Our meta-analysis shows that there was no difference between participants on a tenofovir-based regimen and the non-tenofovir-based regimen in terms of viral suppression, mortality, anemia, and hypertension.  Our meta-analysis shows that there was no difference between participants on tenofovir based regimen and non-tenofovir based regimen in terms of viral suppression (RR=1.96, 95% CI (1.42 -2.70; I2=0%, 4 trials, 263 participants, very low certainty of evidence), mortality (RR = 2.90, 95% CI (0.12 – 69.87, I2=Not estimated, a trial, 120 participants, very low certainty of evidence), anaemia (RR=1.61, 95% CI (1.02-2.90; I2 = 0.16, 2 trials, 154 participants, very low certainty of evidence), hypertension RR = 0.76, 95% CI (0.44-1.31) I2 = Not estimated, a trial, 34 participants, low-certainty of evidence). None of the trials reported the incidence of chronic kidney disease and bone demineralization.  Conclusion There was very-low certainty evidence that no difference exists between the tenofovir-based HAART regimen and the non-tenofovir-based regimen in terms of benefits and short-term adverse outcomes. Well-designed randomized clinical trials are needed with a focus on long-term adverse effects.