Oxidative stress condition arises during imbalance between oxidants and antioxidants of diverse origin damaging both structure and function of tissues. Oxidative stress has been suggested as a cofactor during Human Immunodeficiency Virus Infection course involved in many aspects of disease pathogenesis as viral replication, inflammatory responses, decreased immune cell proliferation, loss of immune function, cellular apoptosis, chronic weight loss, and increased sensitivity to drug toxicity. In this review, we provide an overview of the oxidative metabolism pathways involved in HIV infection, examine the potential impact of antirretroviral toxicity on oxidative damage and argue how the response contribute to co-morbidities. Moreover, we also discuss recent reports from observational and interventional studies which have led to an increasing interest in the possible benefits of micronutrient supplementation as a cost-effective strategy for improving oxidative and nutritional status in HIV infection. The general strategy and combination of these interventions represent an important complementary deal for HIV infection treatment in the era of high active antiretroviral therapy.