Blunted Humoral Response to Influenza Vaccination in Patients Exposed to Zidovudine plus Trimethoprim‐Sulfamethoxazole

Abstract

Combination exposure to zidovudine plus TMP-SMX causes a clinically significant suppression of humoral immune responses to influenza vaccination in HIV-infected patients.

Trimethoprim‐Sulfamethoxazole Exposure Alters Ex Vivo Function of B Lymphocytes Isolated from Human Immunodeficiency Virus‐Infected Patients Receiving Zidovudine

“…42,43 Of interest, in both mice and humans, IgM titers are not affected by zidovudine plus TMP-SMX exposure. 36,37 This may indicate that the drugs alter the ability of B cells to undergo the isotypeswitching process from IgM to IgG. Data in our study support previous findings in that IgM production in stimulated cells was not altered with the addition of TMP-SMX.…”

“…The clinical significance of this effect was tested in our previous study of 28 HIV-infected patients with CD4 + lymphocyte counts above 350 cells/mm 3 and undetectable viral loads by measuring antibody responses to the yearly influenza vaccine. 37 Subjects receiving both zidovudine and TMP-SMX had influenza A-and influenza B-specific serum IgG values that were significantly lower than those of the control subjects. The percentage of subjects reaching an antibody titer in the immunoprotective range was significantly altered by the drug combination.…”

“…The duration of TMP-SMX exposure was chosen according to animal experiments and previously generated clinical data. [36][37][38] Patients were required to maintain diaries to track daily dosing to ensure compliance with antiretroviral therapy and TMP-SMX regimens. A 10-ml blood specimen was obtained using peripheral venipuncture from each patient on day 0 (before TMP-SMX exposure) and once during the final 3 days of TMP-SMX regimen completion (after exposure).…”

“…33,34 Studies in mice and humans have suggested that simultaneous exposure to zidovudine and TMP-SMX causes a synergistic immunotoxicity, decreasing the production of antigen-specific IgG when stimulated. [35][36][37] We speculate that this combined toxicity could contribute to the impaired antibody responses commonly observed in patients with HIV.…”

“…Results of our previous work suggest not only a decrease in number of B cells as a result of zidovudine plus TMP-SMX exposure, but also a potential alteration in their ability to produce antibodies. 36,37 In the current study, our objective was to determine the impact of TMP-SMX exposure on the functional capacity of B lymphocytes in the peripheral blood of HIVinfected patients receiving zidovudine. To address this question, we isolated peripheral B lymphocytes in patients before and after TMP-SMX exposure, and evaluated the functional capacity of B and T lymphocytes by stimulating the cells with mitogens in a series of ex vivo experiments.…”