Table 3.
Adverse Events (MOTIVATE 1 and MOTIVATE 2 Study Populations Combined).*
| Placebo (N = 209) | Maraviroc Once Daily (N = 414) | Maraviroc Twice Daily (N = 426) | |
|---|---|---|---|
| Duration of treatment — patient-yr | 111 | 300 | 309 |
| Patients with ≥1 adverse event (of any grade) — no. of patients (%) | |||
| All causes† | 177 (85) | 375 (91) | 393 (92) |
| Related to treatment | 94 (45) | 205 (50) | 219 (51) |
| Grade 2–4 adverse events (all causes) occurring in at least 5% of patients — no. of patients (%) | |||
| Diarrhea | 20 (10) | 43 (10) | 32 (8) |
| Fatigue | 13 (6) | 13 (3) | 21 (4) |
| Fever‡ | 9 (4) | 9 (2) | 24 (6) |
| Headache§ | 12 (6) | 22 (5) | 9 (2) |
| Nausea | 15 (7) | 25 (6) | 25 (6) |
| Upper respiratory tract infection | 3 (1) | 16 (4) | 20 (5) |
| Death¶ | 2 (1) | 6 (1) | 9 (2) |
| Category C (AIDS-defining) adverse events — no. | |||
| AIDS encephalopathy | 0 | 1 | 0 |
| Cryptosporidium gastroenteritis | 1 | 1 | 0 |
| Cytomegalovirus infection | 0 | 1 | 2 |
| Esophageal candidiasis‡ | 2 | 12 | 3 |
| Herpesvirus infection | 4 | 11 | 7 |
| Kaposi’s sarcoma | 3 | 1 | 2 |
| Lymphoma|| | 2 | 2 | 2 |
| Mycobacterial infection | 0 | 0 | 1 |
| Mycobacterium avium infection | 2 | 0 | 2 |
| Pneumocystis jiroveci pneumonia | 0 | 0 | 2 |
| Pneumonia** | 4 | 3 | 1 |
| Progressive multifocal leukoencephalopathy | 1 | 0 | 1 |
| Total no. of category C events | 19 | 32 | 23 |
| No. of patients (%) | 16 (8) | 29 (7) | 23 (5) |
| Aspartate aminotransferase elevation (maximum, all causes, without regard to baseline) — no. of patients/total no. of patients (%)†† | |||
| Grade 3 (>5 to 10 × upper limit of normal) | 6/207 (3) | 12/408 (3) | 14/421 (3) |
| Grade 4 (>10 × upper limit of normal) | 0/207 | 4/408 (1) | 6/421 (1) |
| Alanine aminotransferase elevation (maximum, all causes, without regard to baseline) — no. of patients/total no. of patients (%)†† | |||
| Grade 3 (>5 to 10 × upper limit of normal) | 6/207 (3) | 16/408 (4) | 7/421 (2) |
| Grade 4 (>10 × upper limit of normal) | 1/207 (<1) | 2/408 (<1) | 4/421 (1) |
All regimens included optimized background therapy. There was no evidence of significant differences in adverse events among the study groups except as noted. Comparisons were conducted post hoc and were not adjusted for duration of treatment or multiple testing.
P = 0.01 for these values (three-way comparison).
P = 0.04 for these values (three-way comparison).
P = 0.03 for these values (three-way comparison).
Causes of death were as follows: in the placebo group, pneumonia and sudden death; in the group that received maraviroc once daily, anorexia, bacterial pneumonia, cerebrovascular accident, myocardial infarction/acute heart failure/coronary-artery atheroma, respiratory failure, and septic shock; and in the group that received maraviroc twice daily, cardiorespiratory arrest, cerebrovascular accident, chronic obstructive pulmonary disease, progression of HIV infection, hypertensive heart disease, multiple organ failure, suicide, T-cell lymphoma, unknown.
This category includes B-cell and T-cell lymphomas.
This category includes viral and bacterial pneumonias.
This category includes all patients for whom there was at least one observation of the given test while on study treatment or within 7 days of the last dose of study treatment.