Case report

A 41-year-old HIV-infected man received lamivudine/zidovudine and nevirapine therapy. He also took isoniazid/rifampicin/pyrazinamide and ethambutol for pulmonary tuberculosis. Because skin rash appeared, nevirapine was replaced by lopinavir/ritonavir 400/100 mg twice daily. The antituberculosis regimens were replaced by rifabutin 300 mg/day and methaniazide 600 mg/day because of known interactions between lopinavir/ritonavir and rifampicin.1

Panuveitis was found in his left eye after receiving rifabutin for 86 days (Figure 1). The uveitis resolved following the discontinuation of rifabutin with the administration of topical steroids and cycloplegics. The final visual acuity recovered from hand motion to 1.0.

Figure 1
figure 1

A slit-lamp photograph shows severe cell reaction, fibrin, and a hypopyon in the anterior chamber.

Full size image

Comment

Conditions associated with uveitis in HIV-positive patients include opportunistic infection, neoplasms, inflammation due to HIV infection itself, and drug toxicities.2 The patient was negative for HLA-B27 and syphilis. Uveitis did not recur after discontinuing rifabutin for one year. Refabutin was suspected as the cause of uveitis by evidences of timing condition, lack of other causes, and resolution after stopping the implicated drug.

Rifabutin associated uveitis has been described in AIDS patients and identified as a dosage-dependent side effect.3 Adverse effects are unusual at the recommended dose of 300 mg/day.4 Clarithromycon or fluconazole was known to increase concentration of rifabutin and the incidence of rifabutin toxicities, including uveitis.5 Neither clarithromycon nor fluconazole was given to our case.

Ritonavir is a potent inhibitor of CYP3A4 and has been shown to substantially increase rifabutin concentration. Co-administration of rifabutin with ritonavir increased area under the concentration–time curve (AUC) of rifabutin and its 25-O-desacetyl metabolite by four times and 35 times, compared with administration of rifabutin alone.6 Patients receiving rifabutin and ritonavir without the reduction of dosages increased the risk of developing leucopenia, arthralgia, joint disorder, uveitis, and skin discoloration.6, 7 Because of the increased likelihood of rifabutin toxicities, the dosage of rifabutin should be reduced by at least 75% of usual dosage (300 mg once daily) or 150 mg 2–3 times a week when given with lopinavir/ritonavir.8, 9

To our knowledge, this is the first report of uveitis associated with concurrent administration of rifabutin and lopinavir/ritonavir. Our finding suggests that the dosage of rifabutin should be reduced when it is administered with lopinavir/ritonavir.