Molecular mechanisms underpinning the protection against antiretroviral drug-induced sperm-endocrine aberrations and testicular toxicity: A review

The introduction of highly active antiretroviral therapy (HAART) has revolutionized the treatment of HIV/AIDS worldwide. The HAART approach is the combination of two or more antiretroviral drugs of different classes and are responsible for patient’s survival and declining death rates from HIV/AIDS and AIDS-related events. However, the severe and persistent reproductive side effect toxicity of HAART regimens is of great concern to patients within the reproductive age. Till date, the underlying pathophysiology of the HAART-induced reproductive toxicity remains unraveled. Nevertheless, preclinical studies show that oxidative stress and inflammation may be involved in HAART-induced sperm-endocrine deficit and reproductive aberrations. Studies are emerging demonstrating the efficacy of plant-based and non-plant products against the molecular alterations and testicular toxicity of HAART. The testicular mechanisms of mitigation by these products are associated with enhancement of testicular steroidogenesis, spermatogenesis, inhibition of oxidative stress and inflammation. This review presents the toxic effects of HAART on spermatogenesis, reproductive hormones and testis integrity. It also provides insights on the molecular mechanisms underlying the mitigation of HAART testicular toxicity by plant-based and non-plant agents. However, effect of repurposing clinical drugs to combat HAART toxicity is unknown, and more mechanistic studies are evidently needed. Altogether, plant-based and non-plant products are potential agents for prevention of rampant endocrine dysfunction and testicular toxicity of HAART.