Immunopathology as a result of highly active antiretroviral therapy in HIV-1-infected patients.
OBJECTIVE
Unusual clinical inflammatory syndromes associated with underlying 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 disease manifestations and in vitro parameters of microbial antigen-specific immune reactivity in patients infected with HIV-1 who had a Mycobacterium avium intracellulare or Mycobacterium xenopi infection.


METHODS
In vitro T-cell proliferation experiments were performed after specific stimulation of a patient's peripheral blood mononuclear cells (PBMC) with M. avium and M. xenopi antigen and non-specific stimulation with phytohaemagglutinin (PHA). The results were compared with appropriate controls.


METHODS
Five patients who presented with unusual clinical syndromes associated with M. avium or M. xenopi infection within weeks of experiencing large rises in CD4+ cell counts following the initiation of antiretroviral therapy.


RESULTS
In all patients except one, mycobacteria-specific lymphoproliferative responses rose significantly following HAART; this was temporally associated with elevations in CD4+ cell counts and the occurrence of clinical disease. The patient with M. xenopi infection appeared to clear his infection subsequently without antimycobacterial therapy. In three of the four patients with M. avium infection, antimycobacterial treatment could be stopped without recurrence of infection.


CONCLUSIONS
Our findings support the hypothesis that HAART may lead to clinically relevant inflammation as a result of restoration of specific immune reactivity against microbial pathogens that are subclinically present at the time treatment is initiated. Continuation of HAART may subsequently result in protective immunity and clearance of infection.
Foudraine
N A
NA
National AIDS Therapy Evaluation Center, Department of Internal Medicine, Academic Medical Center, University of Amsterdam, The Netherlands.
Hovenkamp
E
E
Notermans
D W
DW
Meenhorst
P L
PL
Klein
M R
MR
Lange
J M
JM
Miedema
F
F
Reiss
P
P
D017088:AIDS-Related Opportunistic Infections / Q000188:drug therapy / Q000276:immunology* / Q000382:microbiology; D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D008297:Male; D009165:Mycobacterium Infections, Nontuberculous / Q000188:drug therapy / Q000276:immunology* / Q000382:microbiology; D015270:Mycobacterium avium-intracellulare Infection / Q000188:drug therapy / Q000276:immunology* / Q000382:microbiology; D019912:Mycobacterium xenopi / Q000276:immunology*
D019380:Anti-HIV Agents