Dual Antiretroviral Therapy-All Quiet Beneath the Surface?

Abstract

Infection with the human immunodeficiency virus (HIV) is characterized by progressive depletion of CD4+ lymphocytes cells as a result of chronic immune activation. Next to the decreases in the number of CD4+ cells which leads to opportunistic infections, HIV-related immune activation is associated with several prevalent comorbidities in the HIV-positive population such as cardiovascular and bone disease. Traditionally, combination antiretroviral therapy (cART) consists of three drugs with activity against HIV and is highly effective in diminishing the degree of immune activation. Over the years, questions were raised whether virological suppression could also be achieved with fewer antiretroviral drugs, i.e., dual- or even monotherapy. This is an intriguing question considering the fact that antiretroviral drugs should be used lifelong and their use could also induce cardiovascular and bone disease. Therefore, the equilibrium between drug-induced toxicity and immune activation related comorbidity is delicate. Recently, two large clinical trials evaluating two-drug cART showed non-inferiority with respect to virological outcomes when compared to triple-drug regimens. This led to adoption of dual antiretroviral therapy in current HIV treatment guidelines. However, it is largely unknown whether dual therapy is also able to suppress immune activation to the same degree as triple therapy. This poses a risk for an imbalance in the delicate equilibrium. This mini review gives an overview of the current available evidence concerning immune activation in the setting of cART with less than three antiretroviral drugs.

Keywords: HIV; antiretroviral therapy; cART; dual therapy; immune activation.

Figure 1

Three possible scenarios in the equilibrium between drug toxicity and damage from HIV-related immune activation: (A) A perfect balance between these factors with the smallest possible risk for comorbidity. (B) The reduction in the number of antiretroviral drugs diminishes the risk for drug toxicity but a flare in immune activation could lead to HIV-associated comorbidity. (C) Multiple antiretroviral drugs are able to fully suppress the virus but this poses a significant risk for cART-associated toxicity.