Diffuse interstitial pulmonary opacities induced by nevirapine

Abstract

Nevirapine is a non-nucleoside reverse transcriptase inhibitor (NNRTI) used in HAART for the treatment of HIV-1 infection. The reported side effects are rash, nausea, elevated liver enzymes, Stevens–Johnson syndrome, fatigue, fever, vomiting, diarrhoea, myalgia, abdominal pain and anorexia [1]. We present here details of a patient who developed diffuse interstitial pulmonary opacities after starting nevirapine. A 47-year-old Caucasian male patient diagnosed with HIV-1 in 2004 started HAART with once daily emtricitabine/tenofovir 200/245 mg and nevirapine (first 2 weeks 200 mg and thereafter 400 mg once a day) at a CD4 cell count of 260 × 106 cells/l. His medical history mentioned a thrombosis of the vena cava inferior at birth and a recurrent venous thrombosis in 2006, a cleared hepatitis B infection and depression. After starting this HAART regimen he complained of mild fever and dry cough. After increasing the nevirapine dose he developed a skin rash and dyspnoea. Nevirapine together with emtricitabine/tenofovir was immediately stopped. Blood tests showed an increased lactate dehydrogenase level of 661 IU/l (normal value < 250 IU/l) with normal liver enzymes a C-reactive protein (CRP) level of 84 mg/l (normal value < 10 mg/l), no eosinophilia, and a CD4 cell count of 350 × 106 cells/l. His blood gas analysis was normal. His chest X-ray (Fig. 1a) showed diffuse interstitial pulmonary opacities. Although his CD4 cell count was above 200 × 106 cells/l a Pneumocystis jiroveci (carinii) infection (PCP) was suspected and we performed a bronchoalveolar lavage. Microbiological examination and culture demonstrated no PCP, nor bacteria, mycobacteria, viruses (cytomegalovirus, influenza A and B, parainfluenza 1, 2, 3, respiratory syncytial virus, adenovirus) or fungi. Serological examination yielded no antibodies against mycoplasma. Cytology showed signs of chronic inflammation with a relative lymphocytosis; however, no microorganisms were found. Considering these results, we suspected that the complaints were caused by nevirapine. The patient recovered spontaneously and a chest X-ray (Fig. 1b) after 4 weeks showed normal lung fields. HAART containing emtricitabine/tenofovir 200/245 mg and atazanavir 300 mg once a day (boosted with ritonavir 100 mg) was started without causing any side effects. We did not start with efavirenz because of his medical history of depression.Fig. 1: X-rays showing diffuse interstitial pulmonary opacities at the time the patient presented with complaints (a), and normal lung fields 4 weeks after stopping nevirapine (b).There have been reports of NNRTI-induced hypersensitivity reactions consisting of skin rash, eosinophilia and systemic symptoms (DRESS syndrome), including lymphadenopathy, interstitial nephritis, pneumonia and hepatitis [2]. So far, pulmonary involvement has only been reported for the NNRTI efavirenz [3,4]. In our patient the pulmonary symptoms started after starting nevirapine and emtricitabine/tenofovir, and resolved after stopping HAART without any other intervention. An infectious cause was excluded. Also, the restart of emtricitabine/tenofovir did not cause any complaints. These findings confirm that the symptoms of our patient can be attributed to the use of nevirapine. This case, together with the case presented by Behrens et al.[4], suggests that the development of interstitial pulmonary infiltration might be a class effect of the NNRTI and not of the individual drugs. Further data are necessary to elucidate this finding, but one should be alert in case pulmonary complaints develop during treatment with NNRTI. Conflicts of interest: None.