Table 4.
Selected adverse events and changes in clinical parameters during 48 week treatment
| Integrase inhibitor group (n=289) | Protease inhibitor group (n=286) | |
|---|---|---|
| Adverse events leading to study drug discontinuation (n)* | ||
|
| ||
| Hepatobiliary disorder | 1 | 4 |
| Gastrointestinal disorder | 3 | 4 |
| Pulmonary tuberculosis | 1 | 0 |
| Renal | 0 | 2 |
| Skin disorder | ||
| Rash | 2 | 5 |
| Toxic skin eruption | 0 | 2 |
| Dermatitis allergic | 0 | 1 |
| Stevens–Johnson | 0 | 1 |
| Drug hypersensitivity | 0 | 1 |
|
| ||
| Adverse events in ≥10%† | ||
|
| ||
| Headache | 47 (16%) | 42 (15%) |
| Upper respiratory tract infection | 147 (16%) | 42 (15%) |
| Malaria | 33 (11%) | 22 (8%) |
| Nausea | 42 (15%) | 40 (14%) |
| Vomiting | 28 (10%) | 17 (6%) |
| Jaundice | 1 (<1%) | 30 (11%) |
| Icterus | 1 (<1%) | 34 (12%) |
| Study drug related adverse events | 82 (28%) | 139 (49%) |
| Icterus | 1 (<1%) | 34 (12%) |
| Nausea | 31 (11%) | 28 (10%) |
| Vomiting | 13 (5%) | 8 (3%) |
| Diarrhoea | 8 (3%) | 11 (4%) |
| Fatigue | 5 (1%) | 13 (3%) |
| Cholestasis or jaundice | 0 | 30 (10%) |
| Decrease appetite | 9 (3%) | 3 (1%) |
| Headache | 13 (5%) | 5 (2%) |
| Dizziness | 8 (3%) | 5 (2%) |
| Dermatitis | 0 | 1 (<1%) |
| Rash | 5 (2%) | 14 (5%) |
| Serious adverse event | 3 (1%) | 5 (2%) |
|
| ||
| Grade 3 or 4 laboratory abnormality ≥2% | ||
|
| ||
| Serum amylase elevation | 5 (2%) | 6 (2%) |
| Neutropenia (<1000 cells per μL) | 5 (2%) | 9 (3%) |
| ALT elevation | 2 (1%) | 6 (2%) |
| AST elevation | 5 (2%) | 6 (2%) |
| Hyperbilirubinaemia | 2 (<1%) | 130 (46%) |
| Glycosuria | 0 | 6 (2%) |
|
| ||
| Median change in renal parameters | ||
|
| ||
| Serum creatinine (mg/mL) | 0·06 (−0·03 to 0·14) | 0·03 (−0·04 to 0·10) |
| eGFR (mL/min) | −6·1 (−16·5 to 6·0) | −2·4 (−14·4 to 7·2) |
|
| ||
| Median change in fasting lipid (mg/dL) | ||
|
| ||
| Total cholesterol | 7 (−7 to 25) | 2 (−14 to 20) |
| LDL cholesterol | 0 (−13 to 14) | −2 (−15 to 11) |
| HDL cholesterol | 4 (−3 to 11) | 3 (−3 to 10) |
| Triglycerides | 5 (−16 to 27) | 8 (−18 to 35) |
|
| ||
| Bone density and metabolism (median change from baseline) | ||
|
| ||
| Spine DXA (%) | −3·23% (−5·13 to −1·06) | −3·28% (−5·00 to −1·14) |
| Hip DXA (%) | −2·99% (−4·88 to −1·04) | −2·68% (−4·42 to −1·12) |
| Total body lean mass (g) | 866 | 397 |
| Fat mass percentage | 0·47 | 0·96 |
| Bone alkaline phosphatase (%) | 48·3% (24·4 to 77·7) | 62·0% (37·6 to 108·3) |
| CTx (%) | 15·4% (−2·9 to 35·7) | 22·9% (3·4 to 39·3) |
| Osteocalcin (%) | 68·6% (40·2 to 110·5) | 92·9% (56·1 to 146·3) |
| P1NP (%) | 71·38% (34·82 to 127·65) | 95·8% (48·12 to 147·73) |
Data are n, n (%), or median (range). Integrase inhibitor regimen was elvitegravir, cobicistat, emtricitabine, and tenofovir disoproxil fumarate; protease inhibitor regimen was ritonavir-boosted atazanavir with emtricitabine and tenofovir disoproxil fumarate. ALT=alanine aminotransferase. AST=aspartase aminotransferase. eGFR=estimated glomerular filtration rate. LDL=low density lipoprotein. HDL=high density lipoprotein. DXA=dual energy x-ray absorptiometry. CTx=C-terminal telopeptide of type 1 collagen. P1NP=N-terminal propeptide of type 1 procollagen.
More than one adverse event per participant as a reason for discontinuation, total N=24 (USA [9], Russia [10], UK [1], Portugal [2], Uganda [2]).
All adverse events (grade 1–4).