Immunopathology as a result of highly active antiretroviral therapy in HIV-1-infected patients

Objective: Unusual clinical inflammatory syndromes associated with underlyi ng previously unrecognized opportunistic infections are increasingly being noted shortly after starting highly active antiretroviral therapy (HAART). This study examined the possible relationship between such unexpected disea se manifestations and in vitro parameters of microbial antigen-specific imm une reactivity in patients infected with HIV-1 who had a Mycobacterium aviu m intracellulare or Mycobacterium xenopi infection. Design: In vitro T-cell proliferation experiments were performed after spec ific stimulation of a patient's peripheral blood mononuclear cells (PBMC) w ith M. avium and M. xenopi antigen and non-specific stimulation with phytoh aemagglutinin (PHA). The results were compared with appropriate controls. Patients: Five patients who presented with unusual clinical syndromes assoc iated with M. avium or M. xenopi infection within weeks of experiencing lar ge rises in CD4+ cell counts following the initiation of antiretroviral the rapy. Results: In all patients except one, mycobacteria-specific lymphoproliferat ive responses rose significantly following HAART; this was temporally assoc iated with elevations in CD4+ cell counts and the occurrence of clinical di sease. The patient with M. xenopi infection appeared to clear his infection subsequently without antimycobacterial therapy. In three of the four patie nts with M. avium infection, antimycobacterial treatment could be stopped w ithout recurrence of infection. Conclusion: Our findings support the hypothesis that HAART may lead to clin ically relevant inflammation as a result of restoration of specific immune reactivity against microbial pathogens that are subclinically present at th e time treatment is initiated. Continuation of HAART may subsequently resul t in protective immunity and clearance of infection. (C) 1999 Lippincott Wi lliams & Wilkins.