Immune restoration disease in HIV patients: aberrant immune responses after antiretroviral therapy

Suppression of HIV replication by antiretroviral therapy has various effects on the immune system of HIV-infected patients. Whereas protective pathogen-specific immune responses are restored in some patients, others have persistent immunodeficiency or produce immunopathological responses against opportunistic pathogens that cause immune restoration disease (IRD). Significant morbidity and even mortality may result from IRDs associated with infections by mycobacteria, herpesviruses, hepatitis viruses or the JC virus. Preliminary evidence from our studies suggests that immune responses in patients with IRD may be dysregulated and affected by immunogenetic factors. Thus, herpesvirus IRDs were associated with increased plasma levels of bioavailable interleukin-6 and soluble CD30, while mycobacterial and herpesvirus IRDs were associated with a major histocompatibility complex gene haplotype and/or alleles of particular cytokine genes. A greater understanding of pathogenic mechanisms and the immunogenetics of IRDs may lead to improved preventive and management strategies.