Rash occurred more commonly in treatment-experienced subjects receiving regimens containing ISENTRESS + darunavir/ritonavir compared to subjects receiving ISENTRESS without darunavir/ritonavir or darunavir/ritonavir without ISENTRESS. However, rash that was considered drug related occurred at similar rates for all three groups. These rashes were mild to moderate in severity and did not limit therapy; there were no discontinuations due to rash.

Patients with Co-existing Conditions

Patients Co-infected with Hepatitis B and/or Hepatitis C Virus

In the randomized, double-blind, placebo-controlled trials, treatment-experienced subjects (N = 114/699 or 16%) and treatment-naïve subjects (N = 34/563 or 6%) with chronic (but not acute) active hepatitis B and/or hepatitis C virus co-infection were permitted to enroll provided that baseline liver function tests did not exceed 5 times the upper limit of normal (ULN). In general the safety profile of ISENTRESS in subjects with hepatitis B and/or hepatitis C virus co-infection was similar to that in subjects without hepatitis B and/or hepatitis C virus co-infection, although the rates of AST and ALT abnormalities were higher in the subgroup with hepatitis B and/or hepatitis C virus co-infection for all treatment groups. In treatment-experienced subjects, Grade 2 or higher laboratory abnormalities that represent a worsening Grade from baseline of AST, ALT or total bilirubin occurred in 29%, 34% and 13%, respectively, of co-infected subjects treated with ISENTRESS as compared to 11%, 10% and 9% of all other subjects treated with ISENTRESS. In treatment-naïve subjects, Grade 2 or higher laboratory abnormalities that represent a worsening Grade from baseline of AST, ALT or total bilirubin occurred in 17%, 28% and 17%, respectively, of co-infected subjects treated with ISENTRESS as compared to 6%, 6% and 3% of all other subjects treated with ISENTRESS.

Table 1: Adverse ReactionsIncludes adverse experiences considered by investigators to be at least possibly, probably, or definitely related to the drug. of Moderate to Severe IntensityIntensities are defined as follows: Moderate (discomfort enough to cause interference with usual activity); Severe (incapacitating with inability to work or do usual activity). Occurring in ≥2% of Treatment-Naïve Adult Subjects Receiving ISENTRESS and at a Higher Rate Compared to Efavirenz (96 Week Analysis) System Organ Class,
Preferred Term Randomized Study Protocol 021
ISENTRESS 400 mg
Twice Daily +
Emtricitabine (+) Tenofovir
(n = 281)n = total number of subjects per treatment group
%  Efavirenz 600 mg
At Bedtime +
Emtricitabine (+) Tenofovir
(n = 282)
% 
Psychiatric Disorders
Insomnia 4 3
Table 2: Selected Grade 2 to 4 Laboratory Abnormalities Reported in Treatment-Naïve Subjects (96 Week Analysis)     Randomized Study Protocol 021
Laboratory Parameter Preferred Term (Unit) Limit ISENTRESS
400 mg
Twice Daily +
Emtricitabine
(+) Tenofovir
(N = 281)  Efavirenz
600 mg
At Bedtime +
Emtricitabine
(+) Tenofovir
(N = 282) 
ULN = Upper limit of normal range
Hematology
Absolute neutrophil count (103/μL)
Grade 2 0.75 - 0.999 3% 4%
Grade 3 0.50 - 0.749 2% 1%
Grade 4 <0.50 <1% <1%