The United States Food and Drug Administration (FDA) has approved an extended-release formulation of nevirapine (Viramune XR).
Approval was based primarily on results from the VERxVE randomized double-blind comparison of nevirapine XR formulation, 400 mg QD, with standard immediate-release (IR) nevirapine, 200 mg BID, in ARV-naive individuals. All subjects also were treated with tenofovir + emtricitabine. At 48 weeks, HIV RNA was suppressed to <50 copies/mL in 81% of XR recipients and 76% of IR recipients; the difference was not statistically significant. CD4 cell count increases were about the same for the 2 groups. Importantly, rates of adverse effects, including rash and liver toxicity, were not more common in the XR group.
To reduce the risk of rash, nevirapine XR must be initiated with the standard nevirapine 14-day reduced-dose lead-in period, using 200 mg QD of the IR formulation. After 14 days, the XR formulation may be started, at a dosage of 400 mg QD. For persons who are switched from IR nevirapine 200 mg BID, the XR formulation (400 mg QD) may be substituted without lead-in dosing. Patients initiating either formulation of nevirapine should be monitored for liver and other toxicity per previous recommendations.
Nevirapine XR can be taken with or without food. The tablets should not be broken or crushed.
Gathe J, Bogner J, Santiago S, et al. Comparison of 48 week efficacy and safety of 400mg QD nevirapine extended release formulation (Viramune XR) versus 200mg BID nevirapine immediate release formulation (Viramune IR) in combination with Truvada in antiretroviral (ARV) naive HIV-1 infected patients (VERxVE). In: Program and abstracts of the XVIII International AIDS Conference; July 18-23, 2010; Vienna. Abstract THLBB202.
Tesamorelin for lipoaccumulation
Tesamorelin (Egrifta), an analogue of growth hormone-releasing factor, has been approved by the U.S. Food and Drug Administration for treatment of abdominal lipohypertrophy in HIV-infected adults. It is available on most formularies.
Two randomized placebo-controlled Phase III studies provided the primary data supporting tesamorelin approval. All study subjects had abdominal lipohypertrophy and were on stable ART with virologic suppression. At 26 weeks, visceral adipose tissue (VAT) had decreased by a mean of about 15% in groups treated with tesamorelin and did not change in placebo groups. At 48 weeks, for subjects continuing on an extension phase of the studies, VAT remained stable or decreased modestly in tesamorelin recipients. In patients switched from tesamorelin to placebo, however, VAT reaccumulated, to patients' pretreatment baselines. Tesamorelin also was associated with modest reductions in waist circumference, patient-reported body image measures, and lipid parameters. It had no effect on subcutaneous adipose tissue (SAT) or weight.
Tesamorelin must be administered by subcutaneous injection; recommended dosage is 2 mg daily.
Possible adverse effects include injection site reactions, edema, myalgias and arthralgias, hyperglycemia, and diabetes. Tesamorelin is contraindicated in some patients, including pregnant women (it is an FDA Pregnancy Category X drug) and those with a malignancy. Tesamorelin appears to have no significant effect on ritonavir AUC or Cmax, but there are few studies on interactions with ARVs or other drugs.
Egrifta [prescribing information]. Rockland, MA: EMD Serono; September 9, 2010.
Falutz J, Mamputu JC, Potvin D, et al. Effects of tesamorelin (TH9507), a growth hormone-releasing factor analog, in human immunodeficiency virus-infected patients with excess abdominal fat: a pooled analysis of two multicenter, double-blind placebo-controlled phase 3 trials with safety extension data. J Clin Endocrinol Metab. 2010 Sep;95(9):4291-304.
Darunavir dosage in treatment-experienced patients
The U.S. Food and Drug Administration (FDA) has approved once-daily dosing of darunavir for certain treatment-experienced adults. Specifically, it recommends that darunavir/ritonavir be given at the following dosages:
|Once daily (800/100 mg) for treatment-experienced adults who have no darunavir-associated mutations (V11I, V32I, L33F, I47V, I50V, I54L/M, T74P, L76V, I84V, and L89V)|
|Twice daily (600/100 mg) for persons with 1 or more of these mutations |
The guidance is based on data from the ODIN study, in which treatment-experienced patients with HIV RNA levels >1,000 copies/mL while on stable ART were randomized to switch to once-daily or twice-daily darunavir/ritonavir (each given with nucleoside/nucleotide analogues). Patients with any darunavir-associated resistance mutations at baseline were excluded. At 48 weeks, the difference in the rates of HIV RNA suppression for the two regimens was not statistically significant (72% vs 71%, respectively).
Note that some interacting drugs may require twice-daily dosing of darunavir/ritonavir; unfortunately, few pharmacokinetic studies have examined drug-drug interactions involving once-daily darunavir.
more on darunavir
Cahn P, Fourie J, Grinsztejn B, et al. Efficacy and safety at 48 weeks of once-daily vs twice-daily DRV/r in treatment-experienced HIV-1+ patients with no DRV resistance associated mutations: the ODIN Trial. In: Program and abstracts of the 17th Conference on Retroviruses and Opportunistic Infections; February 16-19, 2010; San Francisco. Abstract 57.