Blunted humoral response to influenza vaccination in patients exposed to zidovudine plus trimethoprim-sulfamethoxazole.
OBJECTIVE
To determine as proof of principle the effect of combination exposure to zidovudine plus trimethoprim-sulfamethoxazole (TMP-SMX) on humoral immune responses to influenza vaccination in patients with human immunodeficiency virus (HIV).


METHODS
Prospective, open-label trial.


METHODS
University-affiliated infectious diseases outpatient clinic.


METHODS
Twenty-three HIV-infected adults receiving antiretroviral therapy, with CD4+ cell counts greater than 350 cells/mm3 and undetectable viral loads.


METHODS
Patients were assigned to one of four treatment groups: zidovudine (6 patients), TMP-SMX (7), zidovudine plus TMP-SMX (5), or neither drug (5); TMP-SMX was given as a 28-day course. Patients were subsequently immunized with the yearly influenza vaccine, and humoral responses were compared among groups 20-24 days after vaccination.


RESULTS
Antibody responses to influenza A and B were measured, and total and activated T and B cell percentages in the peripheral blood were determined. Mean influenza B-specific serum immunoglobulin (Ig)G titers were significantly lower in patients receiving TMP-SMX alone (0.98 +/- 0.60 reference value, p=0.010) or the combination of zidovudine plus TMP-SMX (0.73 +/- 0.29 reference value, p=0.003) compared with those receiving neither drug (1.95 +/- 0.38 reference value). This corresponded to a significantly lower percentage of patients in the combination group that achieved immunoprotective titers to influenza B compared with the group who received neither drug (control group; 20% vs 100%, p=0.048). In addition, the relationship between serum IgG titer and CD4+ cell count was statistically significantly different for patients exposed to zidovudine plus TMP-SMX versus control patients for both influenza A and B (F statistics 8.72 and 11.70, respectively, compared with critical F value 7.26 for p<0.025). Likewise, the relationship between influenza B serum IgG and CD4+ cell count was different among patients who received TMP-SMX versus those who did not receive TMP-SMX (F statistic 5.95 compared with critical F value 4.56 for p<0.025). No significant differences were observed among T and B cell percentages in the blood.


CONCLUSIONS
Combination exposure to zidovudine plus TMP-SMX causes a clinically significant suppression of humoral immune responses to influenza vaccination in HIV-infected patients.
Feola
David J
DJ
Department of Pharmacy Practice and Science, University of Kentucky Chandler Medical Center, Lexington, Kentucky 40536-0082, USA. djfeol2@email.uky.edu
Garvy
Beth A
BA
Rapp
Robert P
RP
Thornton
Alice C
AC
D000328:Adult; D019380:Anti-HIV Agents / Q000009:adverse effects*; D000890:Anti-Infective Agents / Q000009:adverse effects*; D018791:CD4 Lymphocyte Count; D005260:Female; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D009980:Influenza A virus / Q000276:immunology; D009981:Influenza B virus / Q000276:immunology; D007252:Influenza Vaccines; D008297:Male; D008875:Middle Aged; D015662:Trimethoprim, Sulfamethoxazole Drug Combination / Q000009:adverse effects*; D015215:Zidovudine / Q000009:adverse effects*
D019380:Anti-HIV Agents; D000890:Anti-Infective Agents; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D007252:Influenza Vaccines; D015215:Zidovudine; D015662:Trimethoprim, Sulfamethoxazole Drug Combination