Background
Methods
Research design
Patients and setting
Inclusion criteria
Exclusion criteria
Effectiveness and safety assessments
Monitoring and data collection
Statistical analysis
Ethical approval
Results
Patient characteristics | n = 42 | n = 33 | |
---|---|---|---|
Age, Median (Q1-Q3) | Total | 34.0 (24–43) | 37.0 (26.7–42.7) |
Men | 30.0 (24.0–41.0) | 37.0 (26.9–42.4) | |
Women | 34.5 (26.0–44.0) | 35.6 (24.6–44.9) | |
Gender, n (%) | Male | 28 (66.7) | 21 (63.6) |
Female | 14 (33.3) | 12 (36.4) | |
Ethnicity, n (%) | Black | 7 (16.7) | 6 (18.2) |
Nonblack | 35 (83.3) | 27 (81.8) | |
Marital status, n (%) | Married | 13 (31.0) | 12 (36.4) |
Single | 29(69.0) | 21 (63.6) | |
Education, n (%) | Elementary | 10 (23.8) | 8 (24.2) |
High school | 17 (40.5) | 13 (39.4) | |
Technical education | 6 (14.3) | 5 (15.2) | |
University | 9 (21.4) | 7 (21.2) | |
Occupation, n (%) | Home | 5 (11.9) | 4 (12.1) |
Student | 6 (14.3) | 3 (9.1) | |
Unemployed | 3 (7.1) | 2 (6.1) | |
Employed | 28 (66.6) | 24 (72.7) | |
Centers for Disease Control and Prevention clinical stages | A | 35 (83.3) | 27 (81.8) |
B | 6 (14.3) | 5 (15.2) | |
C | 1 (2.4) | 1 (3.0) |
Effectiveness of generic version of abacavir/lamivudine and efavirenz
Clinical variable | Baseline | 3 months | 6 months | 12 months | |
---|---|---|---|---|---|
Viral load copies/mL | n = 42 | n = 33 | n = 33 | n = 33 | n = 33 |
Median (Q1–Q3) | 18,013 (8236–44,936) | 16,976 (7181–34,505) | 0 (0-0) | 0 (0-0) | 0 (0-0) |
≤40 copies, n (%)a | 0 (0.0) | 0 (0.0) | 28 (84.8) | 31 (93.9) | 31 (93.9) |
41-400 copies, n (%) | 0 (0.0) | 0 (0.0) | 5 (15.2) | 2 (6.1) | 2 (6.1) |
401-1.000 copies, n (%) | 1 (2.4) | 1 (3.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) |
1.001-100.000 copies, n (%) | 41 (97.6) | 32 (97.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) |
CD4 lymphocyte count (cell/mm3) | |||||
≥ 200 n (%) | 39 (92.9) | 31 (95.9) | 33 (100.0) | 33 (100.0) | 33 (100.0) |
Median (Q1–Q3)a | 373 (326–483) | 375 (333–491) | 532 (426–587) | 509 (390–558) | 545 (439–634) |
%CD4 lymphocyte | |||||
Median (Q1–Q3)a | 26.7 (20.0–32.7) | 26.7 (23.2–32.4) | 34.6 (27.0–37.7) | 37.6 (30.6–40.3) | 39.6 (34–47) |
Safety of generic version of abacavir/lamivudine and efavirenz
Baseline | 6 months | 12 months | p valuea | ||
---|---|---|---|---|---|
Clinical variable | n = 42 | n = 33 | n = 33 | n = 33 | |
Transaminase (ALT) U/L | |||||
Median (Q1–Q3) | 23 (18–32) | 23.0 (17–32) | 26.0 (18–41) | 30.0 (20–44) | 0.0452 |
Transaminase (AST) U/L | |||||
Median (Q1–Q3) | 22 (19–34) | 22.0 (20–36) | 25.0 (20–29) | 26.0 (20–32) | 0.8792 |
Serum creatinine (mg/dL) | |||||
Median (Q1–Q3) | 1.04 (0.97–1.17) | 1.05 (0.98–1.17) | 0.97 (0.90–1.06) | 0.98 (0.90–1.09) | 0.0895 |
Hemoglobin (g/dL) | |||||
Median (Q1–Q3) | 14.9 (13.1–15.8) | 14.4 (12.9–15.5) | 14.7 (13.5–15.2) | 14.6 (13.4–15.8) | 0.1983 |
Fasting total cholesterol (mg/dL) | |||||
Median (Q1–Q3) | 161.0 (140.0–177.0) | 164.0 (140–179) | 212.0 (191–231) | 226.0 (200–246) | <0.001 |
≤ 200, n (%) | 39 (92.9) | 30 (90.9) | 13 (39.4) | 9 (27.3) | <0.001 |
200–240, n (%) | 2 (4.8) | 2 (6.1) | 15 (45.4) | 14 (42.4) | |
> 240, n (%) | 1 (2.4) | 1 (3.0) | 5 (15.2) | 10 (30.3) | |
Low-density lipoprotein cholesterol –[LDL-C]– (mg/dL) | |||||
Median (Q1–Q3) | 99.8 (87.4–114.9) | 97.3 (87.4–114.9) | 132.2 (116.1–152.3) | 136.6 (115.3–155.1) | <0.001 |
≤ 130, n (%) | 37 (88.1) | 29 (87.9) | 16 (48.5) | 13 (39.4) | <0.001 |
130–160, n (%) | 5 (11.9) | 4 (12.1) | 11 (33.3) | 13 (39.4) | |
> 160, n (%) | 0 (0.0) | 0 (0.0) | 6 (8.2) | 7 (21.2) | |
High-density lipoprotein cholesterol –[HDL-C]– (mg/dL) | |||||
Median (Q1–Q3) | 38.4 (32.7–44.5) | 38.4 (33.4–46.1) | 47.0 (38.6–56.6) | 51.7 (42.8–60.3) | <0.001 |
< 40for men or <50 for women, n (%) | 27 (64.3) | 18 (54.6) | 9 (27.3) | 6 (18.1) | 0.0005 |
≥ 40 for men or ≥50 for women, n (%) | 15 (35.7) | 15 (45.4) | 24 (72.3) | 27 (81.8) | |
Total cholesterol/ HDL-cholesterol | |||||
Median (Q1–Q3) | 4.2 (3.7–5) | 4.0 (3.7–4.9) | 4.4 (3.8–5.0) | 4.3 (3.5–5.1) | 0.2348 |
< 5, n (%) | 32 (76.2) | 25 (75.8) | 25 (75.8) | 25 (75.8) | |
≥ 5, n (%) | 10 (23.8) | 8 (24.2) | 8 (24.2) | 8 (24.2) | |
Triglycerides (mg/dL) | |||||
Median (Q1–Q3) | 91 (76–126) | 95 (76–126) | 139 (99–179) | 146 (105–208) | <0.001 |
< 200, n (%) | 40 (95.2) | 32 (97.0) | 27 (81.8) | 24 (72.7) | 0.0047 |
≥ 200, n (%) | 2 (4.8) | 1 (3.0) | 6 (18.2) | 9 (27.3) | |
High-sensitivity C-reactive protein (mg/L) | |||||
Median (Q1–Q3) | 1.6 (1.1–3.4) | 1.8 (1.2–3.4) | 2.6 (1.1–4.5) | 2.3 (1–5.1) | 0.0635 |
Glycemia (mg/L) | |||||
Median (Q1–Q3) | 88 (82–94) | 88 (81–95) | 89 (86–95) | 91 (85–97) | 0.0106 |
Waist circumference (cm) | |||||
Median (interquartile range) | 85 (77–91) | 85 (77–91) | 84 (78–89) | 84 (76–90) | 0.6888 |
Cardiovascular risk according to Framingham score | |||||
Median (Q1–Q3) | −1 (−1-1) | −1 (−1-1) | 1 (−1–2) | 1 (−1–3) | 0.0002 |
< 1, n (%) | 26 (63.4) | 20 (60.6) | 14 (42.4) | 16 (48.5) | 0.0002 |
1, n (%) | 9 (21.9) | 8 (24.2) | 9 (27 .3) | 5 (15.2) | |
2, n (%) | 4 (9.8) | 3 (9.1) | 5 (15.2) | 3 (9.1) | |
3, n (%) | 1 (2.4) | 1(3.0) | 1 (3.0) | 3 (9.1) | |
4, n (%) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 1 (3.0) | |
5, n (%) | 0 (0.0) | 0 (0.0) | 1 (3.0) | 2 (6.1) | |
6, n (%) | 1 (2.4) | 1 (3.0) | 3 (9.1) | 1 (3.0) | |
8, n (%) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 1 (3.0) | |
10, n (%) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 1 (3.0) |
Adverse event in studies with regimen abacavir/lamivudine/efavirenz | Current study, N = 42 | CLASS Study [20] N = 97 (96 weeks) | CNA30024 Study [21], N = 324 | ESS30009 Study [22], N = 169 |
---|---|---|---|---|
Skin rash, n (%) | 6 (14.3) | 7 (7.2) | 21 (6.5) | 16 (9.6) |
Dizziness, n (%) | 7 (16.7) | No reported | 18 (5.6) | 9 (5.4) |
Drowsiness, n (%) | 5 (11.9) | No reported | No reported | No reported |
Depressive disorder, n (%) | 3 (7.1) | No reported | 20 (6.2) | 8 (4.8) |
Sleep disorder (insomnia), n (%) | 3 (7.1) | 8 (8.2) | 20 (6.2) | 10 (5.9) |
Dreams, n (%) | 2 (4.8) | 6 (6.2) | 15 (4.6) | No reported |
Anxiety, n (%) | 1 (2.4) | No reported | No reported | 4 (2.4) |
Tingling/Numbness (Sensation of heat) | 3 (7. 1) | No reported | No reported | No reported |
Dyspepsia or abdominal pain, n (%) | 3 (7.1) | No reported | 12 (3.7) | No reported |
Nausea, n (%) | 1 (2.4) | 4 (4.1) | 22 (6.8) | No reported |
Anorexia | 1 (2.4) | No reported | No reported | No reported |
Fatigue/weakness, n (%) | 1 (2.4) | 1 (2.4) | No reported | 7 (4.2) |
Increased cardiovascular risk - leading to study drug discontinuation | 1 (2.4) | No reported | No reported | No reported |
Vomiting, n (%) | 0 (0.0) | No reported | 7 (2.2) | No reported |
Suspected hypersensitivity to abacavir or other drug, n (%) | 0 (0.0) | 8 (8.2) | 28 (8.6) | 17 (10.1) |
Headache, n (%) | 0 (0.0) | No reported | 19 (5.9) | 10 (5.9) |
Ear, nose, and throat (ENT) Infections, n (%) | 0 (0.0) | No reported | 29 (9.0) | 11 (6.6) |
Upper respiratory tract infection, n (%) | 0 (0.0) | No reported | 13 (4.0) | 9 (5.4) |
Diarrhea, n (%) | 0 (0.0) | 1 (1.0) | 22 (6.8) | 6 (3.6) |
Viral respiratory infection, n (%) | 0 (0.0) | No reported | 21 (6.5) | No reported |
Musculoskeletal pain, n (%) | 0 (0.0) | No reported | 21 (6.5) | No reported |
Hypertriglyceridemia, n (% among 33 finished the study) | 8 (24.2) | 9 (9.3) | 18 (5.6) | No reported |
Increased Creatinine phosphokinase, n (%) | No assessed | No reported | No reported | 19 (11.4) |
Increased liver function test results, n (%) | 0 (0.0) | No reported | 13 (4.0) | 14 (8.4 %) |
Anemia, n (%) | 0 (0.0) | No reported | 7 (2.2) | No reported |
Lipids and cardiovascular risk
Discussion
Effectiveness
Type of study | Patients (n) | % of patients with viral load <50 copies/mL | Median CD4+ cell count increases [cells/mm3] | Commentary | |
---|---|---|---|---|---|
Intention-to-treat analysis | On-treatment analysis | ||||
Nonrandomized, open-label, phase IV study (Current Study, viral load <40 copies/mL)) | 42 | 73.8 | 93.9 | 172 | HLA-B*57 allele negative. 91.2 % patients with viral load <40 copies/mL, in intention-to-treat analysis; Failure |
Open-label, multicenter, randomized trial of up to 3 consecutive treatment regimens over 96 weeks in 291 subjects received abacavir/lamivudine and efavirenz, ritonavir-boosted amprenavir, or stavudine (CLASS Study) [29] | 291 | 75 (estimated values from figure 3C at 48 week) | 91 (64 of 70 patients received abacavir/lamivudine and efavirenz) | 194 | HLA-B*5701 genotype test was not screening. Results included patients with viral load <100.000 or > 100.000 copies/mL |
Multicenter, randomized, double-blind no inferiority clinical trial of abacavir with zidovudine plus lamivudine and efavirenz (CNA30024 Study) [30] | 324 | 71.7 (142 of 198 patients with viral load <100.000 copies/mL) | 89.3 % (226 of 253 patients with viral load <100.000 or > 100.000 copies/mL) | 209 | HLA-B*5701 genotype test was not screening. |
Randomized, open-label, multicenter study of abacavir/lamivudine administered with tenofovir or efavirenz (ESS30009 Study) [31] | 169 | 71.0 | 94.5 | 130 | HLA-B*5701 genotype test was not screening. The majority of subjects in the tenofovir arm switched regimens or withdrew before week 16 |
Multicenter, randomized, open-label study of abacavir/lamivudine or tenofovir/emtricitabine administered with efavirenz (ASSERT Study) [32] | 192 | 64.2 (61 of 95 patients with viral load <100.000 copies/mL) | N/D | 150 | HLA-B*5701 genotype negative. Viral load suppression as secondary efficacy endpoints |
Multicenter and randomized study of efavirenz with abacavir/lamivudine or lopinavir/r with abacavir/lamivudine (Lake Study) [33] | 63 | 56.7 | 87.0 | 193 | HLA-B*5701 genotype test was not screening. Results included patients with viral load <100.000 or > 100.000 copies/mL |
Multicenter retrospective study of tenofovir-emtricitabine or abacavir-lamivudine, administered with efavirenz for 260 weeks (TOKEN Study) [40] | 75 | N/D | 85 | 135 | HLA-B*5701 genotype negative. |