Silva BF, et al. - Using the methods recommended in the Preferred Reporting Items for Systematic Review and Meta-analysis Protocols, researchers conducted a systematic review with the main subclasses of highly active antiretroviral therapy describing the adverse effects of chronic treatment. Twenty-one articles with a total of 5,626 participants were reviewed. Nucleoside reverse transcriptase inhibitors (NRTIs) were the main treatment investigated in 7 studies, nonnucleoside reverse transcriptase inhibitors (NNRTIs) were the main treatment investigated in three studies, protease inhibitors (PIs) were the main treatment investigated in eight studies, and other antiretroviral drugs were the main treatment investigated in three studies. The emergence of anemia for NRTIs, NNRTIs, and PIs, as well as plasma lipid changes due to their prolonged use were the most common adverse effects on biochemical parameters. It was noted that adverse effects, such as virological and treatment failure, may differ according to biological differences among individuals.