Table 2.
Cardiovascular risks for specific antiretroviral therapies
| Study | Population | Design | Outcome |
|---|---|---|---|
| Classes | |||
| Friis-Moller et al39 | Cohort (n = 23,437) MI (n = 345) Age (median): 39 (with MI) |
D:A:D, retrospective case-control | RR of MI per year of PI exposure 1.16 (95% CI, 1.10–1.23) RR of MI per year of NNRTI exposure 1.05 (95% CI, 0.98–1.13) |
| Worm et al44 | MI (n = 580) Without MI (n = 32,728) Age (median): 49 (with MI), 44 (without MI) |
D:A:D, retrospective case-control | Adjusted RR of MI: Indinavir, cumulative exposure (per year) 1.12 (95% CI, 1.07–1.18) Lopinavir-ritonavir, cumulative exposure 1.13 (95% CI, 1.05–1.21) Nelfinavir, cumulative exposure 1.04 (95% CI, 0.98–1.11) Saquinavir, cumulative exposure 1.04 (95% CI, 0.98–1.11) Efavirenz, cumulative exposure, 1.02 (95% CI, 0.96–1.08) Nevirapine, cumulative exposure 0.97 (95% CI, 0.92–1.03) Didanosine, recent exposure 1.41 (95% CI, 1.09–1.82) Abacavir, cumulative exposure 1.07 (95% CI, 1.00–1.14); recent exposure 1.70 (95% CI, 1.17–2.47) Tenofovir, cumulative exposure 1.04 (95% CI, 0.91–1.18); recent exposure 1.14 (95% CI, 0.85–1.53) No association with zidovudine, stavudine, lamivudine, or tenofovir |
| Protease Inhibitors (older) | |||
| Holmberg et al40 | HIV+ (n = 5,672) 17,712.4 person years Age (median/range): 47 (28–67) |
HOPS, prospective observational cohort | MIs (n = 21) per number of patients Protease inhibitors: 19/3,247 No protease inhibitors 2/2,425 OR 7.1 (95% CI, 1.6–44.3) Adjusted HR 6.5 (95% CI, 0.9–47.8) |
| Jutte et al41 | HIV+ (n = 1,324) PI use (n = 373) |
Retrospective cohort | MI PI use (n = 5), 1.06/100 person years (95% CI, 0.42–2.24) No PI use (n = 3), 0.21/100 person years (95% CI, 0.06–0.54; P = 0.025) |
| Klein et al42 | HIV+ (n = 4,159) 14,823 person-years Age (median): 42 |
Retrospective cohort | Acute MI: No PI use (n = 19) PI use (n = 28) Age adjusted MI hospitalization rates: No PI exposure: 4.4 (95% CI, 2–6.7) PI exposure 4.3 (95% CI, 2.4–6.1) |
| Mary-Krause et al43 | HIV+ (n = 34,976) 88,029 person-years History of MI: Age (mean): 41.9 No MI: Age (mean): 37.7 |
FHDH, Prospective cohort | Relative hazard for MI PI 2.56 (95% CI, 1.03–6.34; P = 0.04) NRTI 0.93 (95% CI, 0.19–4.65; P = 0.93); NNRT 1.38 (95% CI, 0.67–2.83; P = 0.38) Exposure to PI: <18 months: 8.2 (95% CI, 4.7–11.7) per 10,000 patient-years 18–29 months: 15.9 (95% CI, 7.9–23.9) per 10,000 patient-years ≥30 months: 33.8 (95% CI, 15.4–52.1) per 10,000 patient-years |
| Bozzette et al48 | HIV+ (n = 36,766) Age <35 years = 17.6% 25–55 years = 71.3% >55 years = 11% |
Retrospective cohort of patients using VA services compared to typical US patients | HR for admission for cardiovascular disease for 24 months of exposure: NRTIs 0.88 (95% CI, 0.63–1.22) PIs 1.23 (95% CI, 0.78–1.93) NNRTIs 1.09 (95% CI, 0.56–2.09) |
| Davidet al49 | Case Angina (n = 8); MI (n = 8) Control (n = 32) Age (median): 43 years (ICVD); 45 years (control) |
Retrospective case-control | Number of patients with cardiovascular disease (case vs control) NNRTI Case 0 vs control 0 (P = 0.09) NRTI Case 190 vs control 130 (P = 0.02) PI Case 118 vs control 64 (P = 0.46) |
| Atazanavir | |||
| Monforte et al46 | 301,907 person-years | D:A:D study Prospective cohort | Incidence of MI No drug exposure: 0.28 (95% CI, 0.26–0.3) per 100 person-years Drug exposure (3 or more years): 0.2 (0.12–0.32) per 100 person-years |
| Didanosine | |||
| Lang et al38 | HIV+ (n = 74,958) MI (n = 423) Median age Cases (n = 289) Age (median/IQR): 47 (41–54) Age (median/IQR): 46 (40–54) |
FHDH, Prospective, observational cohort | Cumulative exposure 0.91 (95% CI, 0.82–1.01; P = 0.06) Cumulative, recent, and past exposure 0.88 (95% CI, 0.77–1.01; P = 0.07) No risk associated with lamivudine, stavudine, tenofovir,zalcitabine, zidovudine, efavirenz, or nevirapine No risk associated with indinavir +/− ritonavir, nelfinavir, saquinavir +/− ritonavir Amprenavir or fosamprenavir +/− ritonavir Cumulative: 1.57 (95% CI, 1.24–2; P = 0.001) Cumulative, recent, and past: 1.56 (95% CI, 1.21–2.01; P = 0.001) Lopinavir/ritonavir Cumulative: 1.37 (95% CI, 1.13–1.65;), P = 0.002 Cumulative, recent, and past: 1.34 (95% CI, 1.09–1.64; P = 0.005) |
| SMART/INSIGHT and D:A:D47 | HIV+ (n = 4,544) Didanosine use (n = 643) Age (median/IQR): 44 (38–50) |
Prospective cohort | HR (multivariable) in viral suppression arm CVD, major 1.06 (95% CI, 0.43–2.58) Clinical MI 1.89 (95% CI, 0.35–10.2) CVD, minor 1.03 (95% CI, 0.35–3.03) CVD, expanded definition 0.86 (95% CI, 0.40–1.85) HR (multivariable) for new ischemic abnormalities on EKG in viral suppression arm 0.81 (95% CI, 0.59–1.12) |
| Sabin et al50 | HIV+ (n = 33,347) 157,912 person-years Age (median/range): 49 (24–92) |
Prospective cohort | Cumulative exposure (per year) 1.06 (95% CI, 1.01–1.12; P = 0.03) Recent exposure (within 6 months) 1.49 (95% CI, 1.14–1.95; P = 0.003) Past exposure 1.08 (95% CI, 0.84–1.39; P = 0.54) |
| Abacavir | |||
| SMART/INSIGHT and D:A:D47 | HIV+ (n = 4,544) Abacavir use (n = 1,019) Median age: 45 (39–51) |
Prospective cohort | Adjusted HR (multivariable) in abacavir, not didanosine arm CVD, major 1.80 (95% CI, 1.04–3.11) Clinical MI 4.25 (95% CI, 1.39–13.0) CVD, minor 2.70 (95% CI, 1.51–4.83) CVD, expanded definition 1.91 (95% CI, 1.25–2.92) |
| ACTG A5001/ALLRT51 |
HIV+ (n = 5,056) Abacavir use: (n = 1,704) Median age: 37% population ≥45: 23% (n = 1,182) |
Historical Observational cohort | Hazard Ratio of exposure to abacavir and MI 1 year: 0.7 (95% CI, 0.2–2.6) 6 year: 0.6 (95% CI, 0.3–1.4) |
Abbreviations: CI, confidence interval; CVD, cardiovascular disease; D:A:D, Data Collection on Adverse Events of Anti-HIV Drugs; FHDH, French Hospital Database on HIV; HR, hazards ratio; hsCRP, high-sensitivity C-reactive protein; HIV, human immunodeficiency virus; HOPS, HIV outpatient study; ICVD, ischemic cardiovascular disease; IL6, interleukin-6; IQR, interquartile range; MI, myocardial infarction; NRTI, non-nucleoside reverse transcriptase inhibitor; NNRTI, non-nucleoside reverse transcriptase inhibitor; OR, odds ratio; PI, protease inhibitor; PY, patient-years; RR, relative risk; vs, versus; SMART, Strategies for Management of Antiretroviral Therapy.