enfuvirtide and Pain

The antiretroviral enfuvirtide (ENF) is injected subcutaneously using a 27-gauge needle. Injection site reactions (ISRs) can affect long-term ENF tolerability. Alternative ENF delivery methods may ameliorate ISRs.. We conducted a multicentre, open-label, randomized controlled trial in which patients receiving ENF were randomized to continue receiving ENF by a 27-gauge needle, a shorter 31-gauge needle or a gas-powered, needle-free injection device (NFID). The primary study endpoint was the proportion of participants with < grade 2 ISR induration at week 12.. Sixty patients received treatment and were included in the intention-to-treat population. The cohort was predominantly male (95%) with a mean age of 49.1 (SD +/- 7.7) years who had injected ENF for a mean of 821 (SD +/- 561) days. Response rates for ISR induration at week 12 were 38%, 25% and 42% for the 27-gauge, 31-gauge and NFID groups, respectively (all pairwise treatment comparison P-values > 0.2). There was no significant between-group difference for any ISR endpoint, except for changes in the composite ISR score (that is, no ongoing pain of > grade 1 or ISR for ongoing pain > or = grade 1 with induration ISR < grade 3 and for nodules < grade 2), which favoured the 27-gauge needle and NFID groups over the 31-gauge group (P = 0.012 and 0.047, respectively). Plasma HIV RNA load was unaffected. There were seven adverse events related to the delivery system: five attributed to the NFID. At week 12, 85% of participants elected to use the NFID.. Needle-free ENF injection offers a reasonable, reliable alternative to needle-based injecting in this population, at least in the short term.

Topics: Adult; Antiviral Agents; Australia; Enfuvirtide; Equipment Design; Female; HIV; HIV Envelope Protein gp41; HIV Infections; Humans; Injections, Jet; Injections, Subcutaneous; Male; Middle Aged; Needles; Pain; Pain Measurement; Patient Satisfaction; Peptide Fragments; RNA, Viral; Skin Diseases; Treatment Outcome; Viral Load

Antiretroviral regimens containing the fusion inhibitor enfuvirtide (ENF) are associated with sustained viral suppression and immunological benefit. However, local injection site reactions (ISR) occur in the majority of patients. The aim of this study was to determine the pathogenesis of ISRs.. Injection sites were evaluated prospectively from 30 min up to 15-30 days post-injection in ENF-experienced (Cohort I) and ENF-naive patients (Cohort II) during the first 2 weeks of therapy. Four to five injections were given in rotating abdominal sites by a nurse using a standardized technique and were rigorously evaluated.. Reactions were observed in 80-100% of patients; the majority of the reactions were mild to moderate, generally appeared within 24-48 h post-injection, and pain, induration and erythema were the most common clinical signs. Whereas most patients experienced ISRs, the overall prevalence in Cohort II was low (35% maximum). Punch biopsies of injection sites in Cohort I consisted primarily of mixed lymphocytic infiltrates with eosinophils and neutrophils. Injection vehicle (ENF buffer minus ENF) and reduced volume (2 x 0.5 ml ENF [45 mg] versus 1.0 ml [90 mg] ENF) were investigated in Cohort II. Fewer reactions appeared with vehicle and pain was absent with the smaller injection volume. Pathology was indistinguishable between ENF, vehicle and normal tissue in Cohort II patients.. These results suggest that injection technique, injection volume and peptide may influence ISR to ENF.

Topics: Abdomen; Adult; Biopsy; Cohort Studies; Enfuvirtide; HIV Envelope Protein gp41; HIV Fusion Inhibitors; HIV Infections; HIV-1; Humans; Injections, Intraperitoneal; Leukocytes; Male; Middle Aged; Pain; Peptide Fragments; Prospective Studies; Time Factors

The present study investigated the effect of enfuvirtide cross-reactive glycoprotein 41 (gp41) antibody on the efficacy or safety of enfuvirtide in patients participating in 1 of 2 24-week phase 3 clinical trials (T-20 vs. optimized regimen only [TORO] 1 and TORO 2). Serum samples from human immunodeficiency virus-infected patients receiving enfuvirtide plus optimized background (OB) and from patients receiving OB only were evaluated for enfuvirtide cross-reactive gp41 antibodies. Most patients had detectable levels of antibody at baseline; 78% of patients treated with enfuvirtide plus OB had a > or =30% decrease in level of antibody, compared with 43% of patients treated with OB only. Baseline antibody status did not influence virological responses to enfuvirtide-containing treatment. Favorable virological responses were more common among patients who experienced a > or =30% decrease from baseline than among those who experienced either an increase or a lesser decrease. A decrease in virus load correlated with a decrease in level of antibody. Safety was unaffected by the presence of positive antibody at any time point or change in level of antibody. There was no evidence that enfuvirtide cross-reactive gp41 antibody affects the efficacy or safety of enfuvirtide.

Topics: Adolescent; Adult; Cross Reactions; Drug Hypersensitivity; Enfuvirtide; HIV Antibodies; HIV Envelope Protein gp41; HIV Fusion Inhibitors; HIV Infections; HIV-1; Humans; Injections, Subcutaneous; Pain; Peptide Fragments; RNA, Viral; Skin; Viral Load