Background: Cotrimoxazole is the main antibiotic used in primary prophylaxis for
opportunistic infections in advanced HIV infection. This drug can inhibit one of the metabolic
pathways of atazanavir (ATV), such as the cytochromes P450 (CYP) 2C8/2C9 and could interfere
with its safety and efficacy.
Objective: We studied the drug-drug interaction (DDI) between cotrimoxazole and ATV by using
therapeutic drug monitoring (TDM) and pharmacovigilance (PV) approaches.
Methods: We compared a group of patients treated with cotrimoxazole and receiving an ATV-based
regimen to controls. This historical cohort analysis used data from Dat’AIDS in HIV-infected patients
who had at least two lowest plasma concentrations (C-trough) of ATV during their outpatient
follow-up. Likewise, we used the international pharmacovigilance data from VigiBase to evaluate
the notifications of hyperbilirubinemia reported with ATV.
Results: In the TDM analysis, the two groups of patients (treated with cotrimoxazole and controls)
were almost homogeneous concerning the main baseline features. After at least six months of ATVbased
regimen, there was no significant difference in the safety threshold of the ATV C-trough
[with an adjusted odds ratio (aOR) of 1.4 (95% CI: 0.5 - 4.4)] compared to controls. We observed
similar results with the efficacy thresholds of ATV C-trough. Regarding the PV analysis, there was
no difference in hyperbilirubinemia occurring with ATV when cotrimoxazole was concomitant,
with an adjusted reporting odds ratio (aROR) of 0.9 (95% CI: 0.6 to 1.2).
Conclusion: This study showed a relevant concomitant use between Cotrimoxazole and ATV based
on TDM and PV approaches.