(011) Trimethoprim-Sulfamethoxazole-associated early neutropenia in Mexican adults living with HIV: a cohort study

Publication Number: 1007

Background: Trimethoprim/sulfamethoxazole (TMP/SMX) is the antimicrobial of first choice in the treatment and prophylaxis of Pneumocystis jirovecii pneumonia (PCP) in people living with human immunodeficiency virus (HIV). Its association with early neutropenia has been poorly documented.

Objectives: To assess the risk of early neutropenia associated with TMP/SMX use in adults living with HIV.

Methods: A new-user prospective cohort design was conducted in a third-level hospital between August 2019 and March 2020 in Mexico City. Socio-demographic, clinical, and laboratory data were collected. The follow—up started from the time patients met the inclusion criteria until the occurrence of the first neutropenia event or end of follow-up.

Inclusion criteria were hospitalized HIV patient aged 18 years or older, without neutropenia or with grade 1 or 2 neutropenia according to the CTCAE classification and with no TMP/SMX prescription in the 6 months prior to the start date. Patients exposed to any chemotherapeutic drug during the past 6 months, with chronic or acute-on-chronic kidney disease, with severe aplastic anemia or agranulocytosis and with less than 3 days of exposure to TMP/SMX were excluded.

The definition of TMP/SMX exposure was patients with TMP/SMX administered at any dose. Non-exposed were patients without any TMP/SMX dose administration.

The definition of neutropenia case for patients without baseline neutropenia was neutrophil count < 1,500/mm^3, and for patients with neutropenia at baseline, was a 20% decrease.

The risk of TMP/SMX induced early neutropenia, as well as associated factors were estimated using a bivariate model and a robust multivariate Poisson regression model. The strength of association was measured by incidence rate ratio (IRR) with 95% confidence interval.

Results: 57 patients were enrolled in the study. 40 patients were in the TMP-SMX exposed group (204.8 person-years of observation, median 26.5 days) and 17 patients were in the unexposed group (87.0 person-years of observation, median 21 days). The incidence rate of early neutropenia in the TMP/SMX exposed group versus the unexposed group was 7.81 vs 1.15 cases per 100 person-years, respectively. Current use of TMP/SMX was associated with more than 3-fold increase in the IRR of early neutropenia (adjusted IRR: 3.46; 95% CI: 0.25-47.55; p= 0.352) adjusted for stage C3 of HIV infection and neutrophil count < 1,500 cells/mm3 at hospital admission.

Conclusions: Current use of TMP/SMX in Mexican adults living with HIV was statistically non-significantly associated with an increase in the incidence rate ratio of early neutropenia.