Rapid reconstitution of humoral immunity against cytomegalovirus but not HIV following highly active antiretroviral therapy.
OBJECTIVE
To determine the kinetics of reduction in human cytomegalovirus (HCMV) load and specific anti-glycoprotein B (gB) immune responses in patients with concurrent HCMV DNAaemia following the initiation of highly active antiretroviral therapy (HAART).


METHODS
Sequential analysis of eleven patients with HCMV DNAaemia who received HAART and eleven control patients with HCMV DNAaemia.


METHODS
HCMV load was measured by quantitative competitive polymerase chain reaction and anti-gB, anti-HIV Env and Gag responses by an end-point dilution immunofluorescence assay using recombinant antigens expressed in insect cells. Estimates of the efficacy of the reconstituting immune system at controlling HCMV replication were based on previous dynamic models.


RESULTS
In patients initiating HAART, HCMV DNA levels in blood declined rapidly, with a median half-life of 5.2 days, consistent with an efficacy of the reconstituting immune system at inhibiting HCMV replication of 52.8-85% (median, 61%). Commensurate with this decrease, a significant increase in anti-gB titres was observed in the post-HAART period (corresponding to an average fourfold increase in titre by 1 month rising to an eightfold increase at month 3; = 0.01). No changes in titre were observed in the control group or for anti-HIV Gag antibody levels, while anti-HIV Env antibody levels decreased after HAART.


CONCLUSIONS
In patients with HCMV DNAaemia, reconstitution of humoral immunity to HCMV gB occurs rapidly following the initiation of HAART. These changes contrast with the patterns observed for anti-HIV humoral immune responses.
Deayton
Jane R
JR
Department of Virology, Royal Free Hampstead NHS Trust and Royal Free and University College School of Medicine, London, UK.
Sabin
Caroline A
CA
Britt
William B
WB
Jones
Ian M
IM
Wilson
Pauline
P
Johnson
Margaret A
MA
Griffiths
Paul D
PD
Emery
Vincent C
VC
D017088:AIDS-Related Opportunistic Infections / Q000150:complications* / Q000276:immunology; D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy / Q000276:immunology*; D000914:Antibodies, Viral / Q000276:immunology; D000917:Antibody Formation / Q000276:immunology*; D023241:Antiretroviral Therapy, Highly Active; D003587:Cytomegalovirus / Q000502:physiology; D003586:Cytomegalovirus Infections / Q000150:complications / Q000276:immunology*; D004279:DNA, Viral / Q000097:blood; D005260:Female; D015686:Gene Products, env / Q000032:analysis / Q000276:immunology; D015683:Gene Products, gag / Q000032:analysis / Q000276:immunology; D015497:HIV-1 / Q000276:immunology / Q000502:physiology; D006801:Humans; D008297:Male; D012367:RNA, Viral / Q000097:blood; D014759:Viral Envelope Proteins / Q000276:immunology; D019562:Viral Load; D014779:Virus Replication / Q000187:drug effects
D000914:Antibodies, Viral; D004279:DNA, Viral; D015686:Gene Products, env; D015683:Gene Products, gag; D012367:RNA, Viral; D014759:Viral Envelope Proteins; C040495:glycoprotein B, Simplexvirus