AEGiS-15IAC: An open label study to determine the efficacy and safety of enfuvirtide in patients changing therapy to an NRTI-sparing regimen (ML16992).

15th International AIDS Conference

Bangkok, Thailand - July 11-16, 2004

An open label study to determine the efficacy and safety of enfuvirtide in patients changing therapy to an NRTI-sparing regimen (ML16992).

Int Conf AIDS 2004 Jul 11-16; 15:(abstract no. B10228)

Cooper DA, Dwyer DE, Workman C, Amin C, Miller J, Hales G, Emery S
Westmead Hospital, Sydney, Australia

BACKGROUND: NRTI adverse effects may restrict their long term use in HIV-1 therapy. The fusion inhibitor enfuvirtide may be useful in NRTI-sparing treatment regimens, although prospective data on the safety and efficacy of such regimens are limited.

METHODS: 59 HIV-1 infected, triple treatment class (NRTI, NNRTI, PI) experienced individuals with current or prior NRTI treatment limiting toxicity were enrolled in an open-label multicentre single-arm trial to receive enfuvirtide 90mg bd sc for 48 weeks. NRTI were ceased, except for tenofovir. The primary endpoint was a change in plasma HIV load over 48 weeks. Secondary endpoints were changes in CD4+ cell count, adherence to subcutaneous injections, image measurement of lipoatrophy changes, QOL, resolution of NRTI toxicity symptoms and normalisation of laboratory tests.

RESULTS: The mean age of participants was 46.8 years, 97% were male and 58% were classified as CDC-C. The mean duration of antiretroviral therapy at baseline was 9 years, with a mean exposure of 12.5 antiretroviral drugs. The mean CD4+ cell count was 242 (median 164) cells/mL and mean HIV load was log 4.5 (12/59 patients had viral loads below 400) copies/mL plasma. The mean peripheral fat mass was 3.98 kg. Baseline NRTI-related toxicities included 5 with grade 1, 27 grade 2, 21 grade 3 and 6 grade 4 toxicities. These included lipodystrophy (39/59 or 66%), peripheral neuropathy (20/59, 34%), anaemia and/or neutropenia (12/59, 20%), nausea and vomiting (9/59, 15%), diarrhoea (6/59, 10%) and headache (6/59, 10%). Other toxicities were reported in 32/59 (54%) participants. Primary protease mutations (30N, 46I, 46L, 48V, 50V, 82A, 82F, 82T, 84V, 90M) were assessed in 57/59 participants. 11 (19%) had no primary PI mutations, 10 (18%) had 1, 13 (23%) had 2, 20 (35%) had 3 and 3 (5%) patients had 4 or more mutations. The 48 week results in this heavily treatment-exposed cohort will be discussed.

Keywords: AEGIS, HIV Envelope Protein gp41, HIV Fusion Inhibitors, Peptide Fragments, CD4 Lymphocyte Count, HIV-1, Anti-HIV Agents, Antiretroviral Therapy, Highly Active, HIV Infections, Viral Load, HIV Protease Inhibitors, HIV, Drug Therapy, Combination, HIV Seropositivity, HIV-1 Reverse Transcriptase, pentafuside, Male, Humans, therapy, immunology, drug therapy

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B10228