Alopecia associated with ritonavir-boosted atazanavir therapy

Abstract

Alopecia may complicate the course of antiretroviral therapy, especially when HIV-1 protease inhibitors are used [1]. Here we report the first case of hair loss associated with ritonavir-boosted atazanavir therapy in an antiretroviral-naive patient with HIV infection. A 39-year-old Hispanic man with a history of cryptosporidiosis presented with hair loss 3 weeks after commencing combination antiretroviral therapy. He was on prophylactic therapy for Pneumocystis jiroveci pneumonia with trimethoprim–sulfamethoxazole and Mycobacterium avium complex with azithromycin for several weeks when a daily regimen of atazanavir (300 mg), ritonavir (100 mg), and emtricitabine/tenofovir (300/200 mg, fixed-dose combination) was initiated. The physical examination was remarkable only for diffuse hair loss (Fig. 1a) without skin lesions. Laboratory evaluation included a complete blood cell count and chemistry, serum folate, serum vitamin B12, serum testosterone, follicle-stimulating hormone, luteinizing hormone, and thyroid-stimulating hormone, and was only remarkable for mild anemia (hemoglobin 13.5 g/dl) and low folate levels (4.5 ng/ml). The CD4 T-lymphocyte count was 10 cells/μl, with an HIV-RNA viral load of more than 750 000 copies/ml upon initiation of antiretroviral therapy. Folate replacement therapy was started, with resolution of the anemia. The hair loss worsened, however, and folate was discontinued after 2 weeks of therapy. Alopecia caused by ritonavir-boosted atazanavir therapy was suspected, with progressive hair regrowth noted one month after the replacement of protease inhibitors by efavirenz (Fig. 1b). Emtricitabine/tenofovir was continued unchanged. After one month on the new regimen, the CD4 T-lymphocyte count was 203 cells/μl, and the HIV-RNA viral load became undetectable (< 400 copies/ml).Fig. 1: Photos of the patient showing diffuse hair loss (a), and progressive regrowth one month after the replacement of protease inhibitors by efavirenz (b).Antiretroviral-induced alopecia has been reported with the use of protease inhibitors, particularly with indinavir therapy given alone [1,2] or in combination with ritonavir [3]. Other drugs or regimens associated with this adverse event include lopinavir/ritonavir [4], zidovudine [5] and lamivudine [6]. Hair loss associated with ritonavir-boosted atazanavir therapy has not been reported to our knowledge. Alopecia occurs mostly during the first 6 months of starting protease inhibitors (median of 50 days), with some cases reported as soon as 2–3 weeks after beginning treatment [3,4]. This complication could be accompanied by other cutaneous manifestations, such as hair loss in eyelids, eyebrows, beard, axilla and pubic areas, and body hair, skin dryness, cheilitis, and paronychia [1,2]. The temporal relationship of the initiation of protease inhibitors and this patient's hair loss suggests that ritonavir-boosted atazanavir induced this abnormality. The alopecia reversed after a protease inhibitor-sparing regimen was initiated. A rechallenge would be necessary to confirm causality. The mechanism of antiretroviral-induced hair loss is unknown. In some cases, the alopecia observed in patients receiving HIV-1 protease inhibitors is indistinguishable from the toxic effects of systemic retinoid therapy [1,2]. Homologies between the C-terminal region of the cytoplasmic retinoic-acid binding protein type 1 and the catalytic site of protease inhibitors have been noted. It has been hypothesized that protease inhibitors bind to this homologous region within cytoplasmic retinoic-acid binding protein type 1 and inhibit the binding of retinoic acid [7]. Some protease inhibitors enhance the activity of retinal dehydrogenase increasing retinoic acid concentrations, which might be responsible for the retinoid-like side effects [8]. The role of immune reconstitution in this setting cannot be excluded. Alopecia usually resolves over time with discontinuation of the offending antiretroviral agent. Interestingly, hair regrowth has occurred after the replacement of indinavir by ritonavir plus saquinavir or nelfinavir [1], and of lopinavir/ritonavir by nelfinavir [4]. Therefore, protease inhibitor-induced alopecia seems to be a drug-specific rather than a drug class side effect. In summary, patients receiving ritonavir-boosted atazanavir therapy have to be monitored for alopecia, and this combination may have to be discontinued if this complication occurs and other options are available. A switch to a non-protease inhibitor regimen may not necessarily be required. Potential conflicts of interest: H.A.T. is a member of the Speakers' Bureau for GlaxoSmithKline. B.J.B. does not have a commercial interest or other association that might pose a conflict of interest. R.C.A. received grant support and honoraria for consulting and speaker programmes from GlaxoSmithKline.