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HIV infection in a patient with alpha-1 antitrypsin deficiency: a detrimental combination?

Potthoff, Anja Va; Münch, Janb; Kirchhoff, Frankb; Brockmeyer, Norbert Haand the Competence Network for HIV/AIDS

doi: 10.1097/QAD.0b013e3282f08b97

aDepartment of Dermatology and Allergology, St Josef Hospital of the Ruhr-University Bochum, Bochum, Germany

bInstitute of Virology, University of Ulm, Ulm, Germany.

Received 10 July, 2007

Accepted 20 July, 2007

It has recently been shown that alpha-1 antitrypsin and a specific fragment thereof inhibit HIV-1 infection in vitro, suggesting that this abundant serine protease inhibitor may play a protective role in HIV-1-infected individuals. In the present study we report the first case of an HIV-1-infected patient with alpha-1 antitrypsin deficiency. The medical history of this individual suggests a very rapid loss of CD4 T cells and thus the need for antiretroviral therapy shortly after infection. To assess the role of this serine protease inhibitor in the course of HIV-1 infection further the authors are searching for more HIV-1-infected individuals with alpha-1 antitrypsin deficiency.

Genetic host factors are known to influence the clinical course of HIV infection. Alpha-1 antitrypsin deficiency is an inherited disorder on chromosome 14 associated with emphysema and liver cirrhosis. It effects approximately one in 3000 inhabitants in Scandinavia and one in 10 000 inhabitants in other countries. Alpha-1 antitrypsin is the most abundant circulating serine protease inhibitor and its main function is to protect the lung against proteolytic damage from neutrophil elastase [1].

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Case report

A 46-year-old man who was an ex-smoker presented with deterioration of his general condition, leukopenia (3690 cells/μl) and hypergammaglobulinaemia. He tested HIV positive with a last negative HIV test 7 years earlier. The initial CD4 cell count was 271 cells/μl (29.7%) and his HIV viral load was 13 500 copies/ml. His liver enzymes were normal. In addition to HIV infection syphilis was diagnosed (Treponema pallidum haemagglutination assay >1: 20 480, Veneral Disease Research Laboratory 1: 256, fluorescence treponemal antibody absorption 19S fraction immunoglobulin M 1: 1280). The time of infection (with both HIV and syphilis) was suspected to be 8 months earlier when he had had unsafe sex with a woman, followed by a skin rash, aphtha and severe bronchitis several weeks later. Other ways of infection were denied.

His past medical history revealed severe lung emphysema caused by alpha-1 antitrypsin deficiency diagnosed 8 years earlier. He had been substituted with recombinant alpha-1 antitrypsin (Prolastin) since then. In spite of that alpha-1 antitrypsin was as low as 19 mg/dl (normal range 90–200 mg/dl) when he presented at our office. He had been hospitalized several times for lung infections during the past few years. His brother died at the age of 45 years as a result of alpha-1 antitrypsin deficiency. The patient was treated with efavirenz, abacavir and lamivudine. Syphilis was treated with ceftriaxon 1 g intravenously for 10 days. After 3 months his CD4 cell count was 516 cells/μl (51.6%) and viral load was undetectable. After 10 months efavirenz was substituted by fosamprenavir because of agitation. One year after the initiation of HAART the patient decided to stop antiretroviral therapy and his CD4 cell count dropped from 429 cells/μl (59%) to 231 cells/μl (39.5%) within one month (the viral load rose from undetectable to 11 100 copies/ml). The patient committed suicide 2 months later.

To our knowledge this is the first report of an HIV-positive patient with alpha-1 antitrypsin deficiency. The patient apparently developed low CD4 cell counts after a very short period of infection. It remains unclear whether the recurrent pneumonia should be classified as AIDS defining or whether it was caused by the underlying lung disease. No other opportunistic infections were diagnosed in the patient. Shapiro et al. [2] showed that alpha-1 antitrypsin inhibits HIV-1 in vitro. Münch et al. [3] isolated a natural HIV-1 entry inhibitor (virus inhibitory peptide) that is a fragment of alpha-1 antitrypsin, which inhibits HIV-1 with higher efficacy than the full-length protein. These results suggest that alpha-1 antitrypsin may play a protective role in HIV-1 infection. To challenge this hypothesis the authors are searching for more patients with alpha-1 antitrypsin deficiency and HIV infection (please e-mail to: or

Sponsorship: This work was supported by the German Research Foundation, NIH 5R01AI067057 and the Federal Ministry of Education and Research, German Competence Network for HIV/AIDS grant no. 01 KI 0501.

Conflicts of interest: None.

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1. Ioachimescu OC, Stoller JK. A review of alpha-1 antitrypsin deficiency. COPD 2005; 2:263–275.
2. Shapiro L, Pott GB, Ralston AH. Alpha-1-antitrypsin inhibits human immunodeficiency virus type 1. FASEB J 2001; 15:115–122.
3. Münch J, Ständker L, Adermann K, Schulz A, Schindler M, Chinnadurai R, et al. Discovery and optimization of a natural HIV-1 entry inhibitor targeting the gp 42 fusion peptide. Cell 2007; 129:263–275.
© 2007 Lippincott Williams & Wilkins, Inc.