Enfuvirtide use in routine practice is limited by its high cost and subcutaneous administration. In addition, the safety and efficacy of enfuvirtide have only been evaluated in antiretroviral-experienced subjects . In some advanced HIV patients or those whose treatment options are limited because of drug interactions or resistances, first-line enfuvirtide can be justified. We report on three patients who received enfuvirtide as first-line therapy and experienced dramatic CD4 cell count increases.
A 58-year-old man was admitted for confusion and severe dementia (Mini-Mental State 8). HIV-1 infection was discovered with a CD4 cell count of 47 cells/μl (6%) and a 5.7 log10 plasma viral load. AIDS dementia complex was diagnosed; the cerebrospinal fluid (CSF) HIV-1 load was 5.45 log10 and no other infectious agent was found in the CSF. A brain computed tomography scan and magnetic resonance imaging showed hydrocephalus and cerebral atrophy. Subcutaneous enfuvirtide injections (90 mg twice a day) were added to classic HAART (zidovudine, lamivudine, lopinavir-boosted ritonavir) because of poor compliance with oral therapy. Ten weeks later, his CD4 cell count had increased to 660 cells/μl (54%) and the plasma viral load decreased to 2.8 log10 (Fig. 1a). Three months after the initiation of HAART, the patient had recovered cognitive function (Mini-Mental State 24), the plasma viral load was less than 50 copies/ml and the CD4 cell count was 949 cells/μl (42%). One month after enfuvirtide was stopped, the plasma HIV-RNA level was still under the lower limit of quantification and the CD4 cell count decreased to 510 cells/μl (29%).
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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