A 41-year-old HIV-positive man was admitted for abdominal pain, diarrhoea and fever. Three years earlier, he had received zidovudine, lamivudine, nevirapine then zidovudine, lamivudine, and lopinavir/ritonavir for 2 years. At the time of admission, abdominal and hepatic tuberculosis was diagnosed in this untreated patient, and an antituberculosis regimen was started; the CD4 cell count was 16 cells/μl (4%) and the plasma viral load was 5.5 log10. Renal insufficiency, with a serum creatinine level of 500 μmol/l, was attributed to HIV acute nephropathy. Because of this nephropathy and the detection of a Y181C mutation, the initial antiviral regimen was changed to abacavir, lamivudine, enfuvirtide (90 mg twice a day; Fig. 1b). Six weeks later, his clinical status and biological parameters had greatly improved; the CD4 cell count reached 81 cells/μl (11%), the viral load decreased to 3 log10 and the serum creatinine level declined to 112 μmol/l.
A 57-year-old man was hospitalized for cachexia, diarrhoea and confusion. HIV-1 infection and encephalitis associated with disseminated tuberculosis were diagnosed, with a CD4 cell count of 15 cells/μl (5%) and a viral load of 6.2 log10. Zidovudine, lamivudine, and lopinavir/ritonavir were prescribed. Three days later, zidovudine was withdrawn because of severe neutropenia (400 cells/μl) and was replaced by didanosine. Two weeks later, lopinavir/ritonavir was switched to enfuvirtide (90 mg twice a day) because of confusion and gastric intolerance. After one month of this treatment, the CD4 cell count reached 38% (52 cells/μl), whereas the viral load, after a transient slump (3.2 log10/ml), rebounded to 5.0 log10 (Fig. 1c). The patient died 6 weeks after the initiation of HAART from aspiration pneumonitis.
These three cases illustrate different situations in which first-line enfuvirtide could be a valid alternative. Subcutaneous administration allows its use when oral intake is uncertain because of non-adherence or digestive intolerance. The second advantage is the absence of known drug interactions in patients with concomitant opportunistic infections. Moreover, enfuvirtide may be able to reinforce HAART efficacy when a rapid control of advanced HIV infection is crucial. The pivotal phase III TORO trials showed that CD4 cell counts increased from inclusion by 91 × 106 cells/l at week 48 . There is no study in naive patients, but our first patient showed an unusually fast improvement of immunological functions when receiving enfuvirtide. Furthermore, after stopping enfuvirtide, the viral load remained controlled but the CD4 cell count dropped sharply. Although all three patients benefited immunologically, patient 3's improvement persisted independently of the virological response. How this cumulative immunological efficacy is achieved remains unknown; perhaps through less activation-induced and envelope-induced cell death . Regardless of the quantitative improvement, it seems important to note the clinical improvement in two of these AIDS patients; a regression of neurological symptoms in one and a rapid recovery of renal function in the other.
First-line enfuvirtide demonstrated efficacy on immunological responses in our three patients, and dramatically improved the clinical course of two of them. This strategy may avoid other opportunistic infections and complications of this wasting disease. These case reports may enable, if not encourage, clinicians to use enfuvirtide in HAART combinations in specific clinical situations.
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© 2006 Lippincott Williams & Wilkins, Inc.
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