## 1 Introduction  
According to the World Health Organization, at the end of 2020, about 37.7 million (30.2-45.1 million) people were infected with the human immunodeficiency virus (HIV); 680,000 [480,000-1.0 million] people died from HIV-related causes and 1.5 million [1.0-2.0 million] people have acquired HIV [1]. HIV mainly targets immune cell types such as CD4 T cells, monocytes, macrophages, and natural killer (NK) cells [2,3]. Innumerable opportunistic infections associated with HIV infections include Kaposi sarcoma, Pneumocystis pneumonia, Herpes virus and _Mycobacterium tuberculosis_ (_M. tb_), all of which could result in poor patient survival [3]. These infections flourish due to a compromised immune system, which follows the depletion of CD4+ T cells. In recent years, mycobacterial infections have increased due to growing numbers of highly susceptible immunocompromised individuals arising from the AIDS epidemic. Oxidative stress and immunological dysfunction are believed to adversely impact mycobacterial outcomes, resulting in higher risks of disease relapse and mortality and a greater propensity for developing drug-resistant infections [4, 5, 6, 7]. Mycobacterial co-infection is a leading cause of mortality in HIV patients and a major contributor to antimicrobial resistance. Efavirrenz (EFA) is a drug of choice to treat HIV patients with mycobacterial infections [8]. EFA is an antiretroviral, non-nucleoside reverse transcriptase inhibitor (NNRTI) used specifically in the treatment of HIV-1 infection in combination with other antiretroviral (ARVs). These non-nucleoside reverse transcriptase inhibitors (NNRTIs) are essential components of highly active antiretroviral therapy (HAART) against HIV-1 infections. NNRTIs bind to an allosteric site of reverse transcriptase, resulting in inhibition of the enzyme activity. Implications of oxidative stress during long-term antiretroviral therapy with NNRTIs are also reported, thus complicating the existing scenario further [9]. Mechanisms of viral pathology reveal that a redox imbalance in the cells, as a result of oxidative stress, causes dysregulation in the levels of glutathione (GSH) [2; 5; 6; 7]. GSH in the reduced form is the major intracellular redox buffer, exerting its effect directly or indirectly regulating antimicrobial activity in immune cells [6]. GSH-enhancing agents elevate the cellular immune response while antagonizing the humoral response. This is accomplished mainly by favoring cytokine expression profiles of TH-1 CD4+ cells and promoting the functions of NK cells. Another explanation for the rising incidence of _M. tb_ among individuals with an HIV infection is due to decreased levels of GSH, which impairs immune cell function [10]. Our lab has previously demonstrated that rGSH directly controls _M. tb_ infection through natural killer cells and T cells [2; 11]. A therapeutic limitation to GSH is that a high dose is necessary to achieve the desired effect. GSH is known to have a short plasma half-life along with its inability to cross the cell membrane. Instead, GSH needs to be broken down into amino acids and resynthesized to GSH intracellularly--a process often impaired during viral infections [12]. Earlier clinical findings report that supplementation with liposomal glutathione (L-GSH) restored redox homeostasis, induced a cytokine balance, and improved immune responses against _M. tuberculosis_ infection [13; 14]. To overcome its biochemical and pharmacokinetic limitations, pro-GSH molecules have been proposed to restore or increase GSH levels for easier membrane transportation or constitute a source of thiols for GSH synthesis [15; 16; 17]. On the other hand, antiretroviral therapy (ARV) has reduced AIDS-related morbidity and mortality. However, several drawbacks in the current therapy still exist. Failure to target macrophages and dendritic cells that are involved in the transmission of the virus to CD4+ TH cells (helper T lymphocytes) increases the risk of relapse [18].