TABLE 2.
ADVERSE EVENTS AND PERMANENT STUDY DRUG DISCONTINUATIONS
| MVC | MVC+FTC | MVC+TDF | TDF+FTC | TOTAL | |
|---|---|---|---|---|---|
| Enrolled (N) | 46 | 45 | 49 | 48 | 188 |
| Deaths | 0 | 0 | 1 | 0 | 1 |
| Permanent study drug discontinuations (participants, percent of total) | 7 (15%) | 6 (13%) | 14 (29%) | 9 (19%) | 36 (19%) |
| Time to permanent study drug discontinuation (median, [25th, 75th percentile], days) | 89 [36, 275] | 142 [94, 218] | 51 [25, 207] | 143 [55, 202] | 112 [34, 213] |
| Permanently discontinued study drugs due to adverse events | 0 | 1 | 4 | 2 | 7 |
| Serious adverse events (SAEs) | 1 | 4 (one participant with 2 events) | 8 (one participant with 2 occurrences of suicidal ideation) | 3 | 16 |
| Grade 3–4 adverse events (participants [%]; events) | 5 [11%]; 6 | 13[29%]; 16 | 9 [18%]; 15 | 8 [17%]; 11 | 35 [19%]; 48 |
| Grade 3 events – related to study drug*† | 1 | 5 | 1 | 4 | 11 |
| Grade 3 events – not related to study drug* | 4 | 10 | 11 | 6 | 31 |
| Grade 4 events – related to study drug* | 0 | 0 | 0 | 0 | 0 |
| Grade 4 events – not related to study drug* | 1 | 1 | 3 | 1 | 6 |
| Grade 3–4 Adverse event rate (per person-year; 95% confidence interval) | 0.15 (0.06, 0.36) | 0.41 (0.25, 0.69) | 0.37 (0.13, 0.54) | 0.26 (0.12, 0.58) | |
| Selected adverse events (grade 2–4, participants, percent‡) | |||||
| diarrhea | 0% | 0% | 5, 10% | 1, 2% | 6, 3% |
| nausea | 1, 2% | 3, 7% | 3, 6% | 0% | 7, 4% |
| vomiting | 0% | 1, 2% | 2, 4% | 3, 6% | 6, 3% |
| unintentional weight loss | 0% | 2, 4% | 0% | 1, 2% | 3, 2% |
| hypophosphatemia | 5, 11% | 8, 18% | 5, 10% | 6, 12% | 24, 13% |
| increased creatinine | 1, 2% | 1, 2% | 0% | 0% | 2, 1% |
MVC, maraviroc, FTC, emtricitabine, TDF, tenofovir disoproxil fumarate.
The study investigators assessed the relationship of adverse event to study drug.
Grade 3 related adverse events were: abnormal weight loss (MVC+FTC), back pain (MVC+FTC), congenital anomaly in offspring (n=2, MVC+FTC, TDF+FTC), depression (MVC+FTC), headache (TDF+FTC), hypophosphatemia (TDF+FTC), increased low-density lipoprotein (LDL) (TDF+FTC), spontaneous abortion (n=2, MVC+FTC, MVC+TDF), vitamin D deficiency (MVC only), upper limb fracture (MVC+TDF)
All events listed were predetermined to be of interest given prior reports of toxicities associated with the study medications; all are grade 2 with the exception of two grade 3 hypophosphatemia and one grade 3 weight loss.