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Blunted Humoral Response to Influenza Vaccination in Patients Exposed to Zidovudine plus Trimethoprim‐Sulfamethoxazole
Author(s) -
Feola David J.,
Garvy Beth A.,
Rapp Robert P,
Thornton Alice C.
Publication year - 2007
Publication title -
pharmacotherapy: the journal of human pharmacology and drug therapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.227
H-Index - 109
eISSN - 1875-9114
pISSN - 0277-0008
DOI - 10.1592/phco.27.7.937
Subject(s) - zidovudine , medicine , vaccination , immunology , titer , antibody , humoral immunity , influenza vaccine , sulfamethoxazole , gastroenterology , virus , viral disease , antibiotics , biology , microbiology and biotechnology
Study Objectives . 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). Design . Prospective, open‐label trial. Setting . University‐affiliated infectious diseases outpatient clinic. Patients . Twenty‐three HIV‐infected adults receiving antiretroviral therapy, with CD4 + cell counts greater than 350 cells/mm 3 and undetectable viral loads. Intervention . 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. Measurements and Main 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. Conclusion . Combination exposure to zidovudine plus TMP‐SMX causes a clinically significant suppression of humoral immune responses to influenza vaccination in HIV‐infected patients.