Pharmacokinetics of Etravirine Combined with Atazanavir/Ritonavir and a Nucleoside Reverse Transcriptase Inhibitor in Antiretroviral Treatment-Experienced, HIV-1-Infected Patients

Table 4

Overview of AEs and laboratory abnormalities during the 48-week treatment session.

Incidence, ( (%))	Atazanavir/ritonavir 300/100 mg qd + one NRTI + etravirine 200 mg bid ()	Atazanavir/ritonavir 400/100 mg qd + one NRTI + etravirine 200 mg bid ()	All patients; ()
Any AE	20 (90.9)	17 (77.3)	37 (84.1)
Any treatment-related AE	5 (22.7)	5 (22.7)	10 (22.7)
Grade 3-4 AEs	4 (18.2)	4 (18.2)	8 (18.2)
AEs leading to discontinuation	2^* (9.1)	2^† (9.1)	4 (9.1)
Serious AEs	4 (18.2)	2 (9.1)	6 (13.6)
Death	1 (4.5)	0	1 (2.3)
AEs regardless of relationship to study treatment and occurring in ≥3 patients^‡
Cough	5 (22.7)	4 (18.2)	9 (20.5)
Headache	3 (13.6)	4 (18.2)	7 (15.9)
Influenza	2 (9.1)	3 (13.6)	5 (11.4)
Sinusitis	3 (13.6)	0	3 (6.8)
AEs of interest regardless of relationship to study treatment, occurring in ≥2 patients
Hepatotoxicity	5 (22.7)	5 (22.7)	5 (22.7)
Rash (any type)	3 (13.6)	2 (9.1)	5 (11.4)
Neuropsychiatric AEs	3 (13.6)	0	3 (6.8)
Treatment-emergent Grade 2–4 laboratory abnormalities occurring in ≥2 patients
Hyperbilirubinemia	8 (38.1)	6 (28.6)	14 (33.3)
Increased total cholesterol	3 (14.3)	3 (14.3)	6 (14.3)
Increased LDL-cholesterol	1 (4.8)	5 (23.8)	6 (14.3)
Hyperglycemia	4 (19.0)	1 (4.8)	5 (11.9)
Increased pancreatic amylase	1 (4.8)	3 (14.3)	4 (9.5)
Increased segmented neutrophils	2 (9.5)	2 (9.5)	4 (9.5)
Increased hemoglobin	1 (4.8)	1 (4.8)	2 (4.8)
Increased white blood cell count	2 (9.5)	0	2 (4.8)
Increased AST	1 (4.8)	1 (4.8)	2 (4.8)

AE: adverse event; AST: aspartate amino transferase; LDL: low-density lipoprotein; : number of patients per treatment group; (%): number (proportion) of patients with specified parameter; NRTI: nucleoside reverse transcriptase inhibitor.
^*One patient died (metastatic malignant melanoma), and one experienced Grade 2 maculopapular rash probably related to etravirine and atazanavir and discontinued treatment on the day of onset (eight days after the start of etravirine treatment).
^†One patient discontinued at Week 48 due to Grade 2 secondary syphilis considered not related to study medication. Another patient became pregnant and discontinued the study.
^‡Not including laboratory abnormalities reported as an AE.
AEs of special interest were selected based on their association with other antiretrovirals and relevance based on preclinical or earlier clinical data and the target population. Hepatotoxicity was considered at least possibly related to atazanavir for five and four patients in the atazanavir/ritonavir 300/100 mg qd and 400/100 mg qd treatment groups, respectively and at least possibly related to etravirine in three patients. Neuropsychiatric AEs of interest, including Grade 2 depression in one patient and Grade 2 peripheral neuropathy in two patients, were considered not serious and not related to etravirine and did not lead to discontinuation.
Grouped term including rash (not further specified), maculopapular rash and papular rash.
Two patients did not have post-dose laboratory data because they discontinued shortly after baseline.