compared to 10% in the cPI POWER groups. Conversely, in the RESIST studies, 23% of patients in the tipranivir/r + OB groups had viral loads below 50 copies/mL after 48 weeks, compared to 10% of patients in the cPI groups. In the darunavir/r + OB group 81% (29/36) of the ENF-naïve patients taking ENF had a viral load reduction of at least 1 log copies/mL at week 48 versus 58.5% (72/123) of the tipranavir/r + OB group. However, it must be noted that in the POWER studies, ENF use was stratiﬁed, not randomized, and patients receiving ENF were more likely to have higher baseline CD4+ T-cell counts, lower baseline viral loads and shorter duration of infections. ENF was not randomized or stratiﬁed in the RESIST studies and thus interpretations must be made with caution when comparing these studies. Pediatrics The safety and efﬁcacy of ENF has been examined in two small open-label studies involving treatment experienced children and adolescents (Church et al 2004; Wiznia et al 2007). As in the TORO studies involving adults, ENF was combined with OB therapy consisting of inhibitors of the HIV-1 reverse transcriptase and protease enzymes. These pediatric patients were followed for periods of up to 96 weeks, with frequent evaluation of T cell counts and viral load mea- surements. Suppression of plasma HIV RNA to undetectable levels ( 50 copies/mL) was uncommon, occurring in about 10% of participants. However, in the larger study, viral load was reduced by a median of 1.17 log10 copies/mL, and the median increase in T cell number was more than 100 cells/ mm3 and the CD4 T cell percentage rose by 4.7% (Wiznia et al 2007). The treatment responses were greater in children than in adolescents, perhaps reﬂecting problems with adher- ence among the older participants. Although injection site reactions were very common in pediatric patients of all ages, no patients were forced to discontinue ENF therapy because of these or other adverse events. Clinical management Dosing ENF must be administered by subcutaneous injection. ENF is in powder form and must be reconstituted with sterile water. Standard dosing for adults and adolescents greater than 16 years of age or older is 90 mg twice daily. Among children, the pharmacokinetics of ENF do not appear to be affected by age and children aged 6–16 receive two daily doses of 2 mg/kg, not to exceed 90 mg per day (Zhang et al 2007). ENF is not approved for children less than 6 years of age. There are no food restrictions and no known clinically Therapeutics and Clinical Risk Management 2008:4(2) Enfuvirtide therapy signiﬁcant interactions between ENF and other medications (Boyd et al 2003). Side effects ENF is generally well tolerated in both pediatric and adult patients (Lalezari et al 2003; Lazzarin et al 2003; Nelson et al 2005; Reynes et al 2007). Injection site reactions are the most commonly reported side-effect and occur in almost all patients. These are typically mild to moderate in severity and are rarely treatment-limiting. Other side effects include nausea, diarrhea, and fatigue. Eosinophilia has also been reported. At 96 weeks in the TORO trials, there were no new reported ENF safety issues in adults or children (Reynes et al 2007). Adherence As noted before, ENF is associated with injection site reac- tions (ISR) in nearly all patients, including redness, itching, pain, and development of nodules at the injection site. These ISR represent the most common adverse events associated with the agent that when combined with the inconvenient route of administration, represent potential barriers to adher- ence. The inferior treatment responses seen in adolescents compared to younger children in one recent trial (Wiznia et al 2007) may reﬂect problems with adherence (more reports of missed doses) seen in the former. Massaging injection sites, the use of analgesics, and other simple measures may limit ISR and improve adherence (Hu et al 2000; Clotet et al 2004). Clinical usage A consensus of recommendations concerning the use of ENF includes key points regarding resistance testing, initiation and discontinuation of therapy, safety concerns, and patient education and support is reviewed by Clotet et al (2004). The implementation of these recommendations into the day- to-day clinical practice of providers involved in the care of HIV can be critical in improving patient care and compliance with ENF therapy. ENF should be administered in conjunction with an optimized background HIV regimen. Resistance testing is recommended in patients receiving enfuvirtide in order to select an appropriate therapeutic background regimen. To this end, genotyping is currently favored as the preferred method of resistance testing for patients with chronic HIV infection (Clotet et al 2004). Susceptibility testing for ENF before initiation is not currently recommended as viruses with wild-type HR-1 can vary as much as 500-fold in susceptibility 435