Blunted humoral response to influenza vaccination in patients exposed to zidovudine plus trimethoprim-sulfamethoxazole

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/mm³ 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.