Table 1.
Studies assessing the risk of acute myocardial infarction (AMI) or cardiovascular disease (CVD) from recent or cumulative exposure to abacavir.
| Author, year of publication | Study period | Cohort/Location | Study Design | Sample size (n) | Outcome (n) | Exposure (recent or cumulative) | Reference group | Statistics (95% CI) | Covariates included in the model and comments |
|---|---|---|---|---|---|---|---|---|---|
| D:A:D Study Groups, 2008 | 1999–2007 | Multinational D:A:D cohort | Prospective cohort | 33 347 | AMI (517) AMI (517) | Recent Cumulative | Other ARV agents Other ARV agents |
RR: 1.90 (1.47, 2.45) RR: 1.14 (1.08, 1.21) |
Age, sex, risk group, ethnicity, calendar year, cohort, smoking, family history of CVD, prior CVD, BMI, cumulative exposure to other ARV drugs. Further adjustment for CD4 cell count, viral load, lipid and glucose levels, blood pressure, diabetes, and lipodystrophy made little difference to the result. |
| D:A:D study Groups, 2016 | 1999–2013 | Multinational D:A:D cohort | Prospective cohort | 49 717 | AMI (941) | Current | Other ARV agents | RR: 1.98 (1.72–2.29) | Time-fixed covariates: gender, mode of HIV acquisition, ethnicity, participating clinical cohort: time-updated covariates: age, smoking status, family history of CVD, previous CVD event, BMI, cumulative exposure to the main protease inhibitors and non-NRTIs, and cumulative and current exposure to other NRTIs. |
| 1999-Feb 2008 | Multinational D:A:D cohort | Prospective cohort | 210250 person-years | AMI (672) | Current | Other ARV agents | RR: 1.97 (1.68–2.33) | Sensitivity analyses separately carried out adjusting potential causal mediators: diabetes mellitus, total and high-density lipoprotein cholesterol, triglycerides, blood pressure, antihypertensive drugs, blood glucose, Framingham score, body weight, and renal function | |
| March 2008–2013 | Multinational D:A:D cohort | Prospective cohort | 157 309 person-years | AMI (269) | Current | Other ARV agents | RR: 1.97 (1.43–2.72) | ||
| Lundgren et al., 2008 | 2002–2007 | Multinational (SMART study) | Prospective cohort | 4544 | AMI (19) CVD (70) |
Recent Recent |
Other NRTIs Other NRTIs |
HR: 4.25 (1.39, 13) HR: 1.80 (1.04, 3.11) |
Age, sex, race, baseline viral load and CD4 cell count, smoking, prior CVD, diabetes, BP-lowering drugs, hepatitis B or C virus infection, baseline use of NNRTI and PI. |
| Martin et al., 2009 | 2005–2008 | STEAL study, Australia | Randomized controlled trial | 357 | CVD (9) | Recent | Tenofovir-Emtricitabir | HR: 8.33 (1.40, 1649.58) | |
| Lang et al., 2010 | 2000–2006 | French Hospital Database | Case-control | 1173 | AMI (289) | Recent Cumulative | Not exposed to abacavir Not exposed to abacavir |
OR: 1.62 (0.93, 2.81) OR: 0.97 (0.87, 1.10) |
Cases and controls were matched for age and sex and the models were adjusted for hypertension, smoking, family history of premature coronary artery disease, cocaine or IVDU, HIV viral load, CD4:CD8 cell ratio, and exposure to other ARV drugs. |
| Obel et al., 2010 | 1995–2005 | Danish HIV Cohort Study | Prospective cohort | 2952 | AMI (67) | Current | Not exposed to abacavir | HR: 2.00 (1.10, 3.64) | Age, sex, year of diagnosis, year of HAART initiation, CD4 cell count, viral load, race, injection drug use, use of other ARV drugs, diabetes, alcoholism, COLD, hypertension, liver disease, and kidney disease. |
| Choi et al., 2011 | 1997–2007 | VA HIV Clinical Case Registry, USA | Retrospective cohort | 10 931 | CVD (501) CVD (501) AMI (NS) |
Recent Cumulative Recent |
ARV agents other than tenofovir and abacavir | HR: 1.48 (1.08, 2.04) HR: 0.93 (0.79, 1.10) HR: 1.64 (0.88, 3.08) |
Age, sex, race, calendar year, diabetes, hypertension, dyslipidemia, prevalent CVD, smoking, drug abuse, hepatitis B and C virus infection, cancer, eGFR, proteinuria, BMI, CD4 cell count, viral load, and cumulative exposure to other ARV drugs. |
| Bedimo et al., 2011 | 1996–2004 | VA HIV Clinical Case Registry, USA | Retrospective cohort | 19 424 | AMI (267) AMI (278) |
Current Cumulative | ARV agents other than tenofovir and abacavir Not exposed to abacavir |
HR: 0.67 (0.43, 1.03) HR: 1.18 (0.92, 1.50) |
Model for current exposure was adjusted for only chronic kidney disease. Model for cumulative exposure was adjusted for age, hypercholesterolemia, hypertension, diabetes, and smoking. |
| Durand et al., 2011 | 1985–2007 | RAMQ and Med-Echo Databases, Quebec | Case-control | 1209 | AMI (125) | Recent | Not exposed to abacavir | OR: 1.72 (1.10, 2.71) | Age, sex, past AMI, past stroke, chronic kidney disease, anti-diabetic drug use, lipid-lowering drug use, anti-platelet or warfarin use, hepatitis C infection, illicit drug use. |
| Rotger et al., 2013 | 2000–2009 | MAGNIFICENT Consortium | Case-control | 1875 | CAD (571) | Current | Not specified | OR: 1.56 (1.17, 2.11) | Sex-matched study and restricted to people without prior CAD. Adjusted for age, smoking, family history of CAD, cholesterol levels, hypertension or anti-hypertensives, diabetes mellitus and anti-diabetic medication, current ART exposure, cumulative exposure to lopinavir and indinavir, CD4 cell count, and HIV viral load. |
| Brouwer et al., 2014 | 2002–2008 | North Carolina Medicaid Beneficiaries | Retrospective cohort | 3481 | AMI (38) | Recent | Tenofovir | HR: 2.05 (0.72, 5.86) | Age, sex, race, calendar year, cardiovascular medication use (β-blockers, ACEI, ARB, CCB, statins), hospitalization, comorbidities including heart failure, diabetes, renal disease, cerebrovascular disease, peripheral vascular disease, and ART-regimen type. |
| Desai et al., 2015 | 1996–2009 | VA HIV Clinical Case Registry, USA | Retrospective cohort | 24 510 | CVD (934) | Current | All other ARV agents |
HR: 1.50 (1.26, 1.79) | Age, year of exposure, viral load, CD4 cell count, exposure to statins, and follow up time. |
| Young et al., 2015 | 2000–2012 | Swiss HIV Cohort Study | Prospective cohort | 11856 | CVD (365) | Recent Cumulative |
Not exposed to abacavir |
HR: 1.63 (1.14, 2.32) HR: 1.22 (0.98, 1.52) |
Age, sex, injection drug use, Caucasian ethnicity, family history of CAD, prior CVD, smoking, BMI, calendar year, cumulative exposure to other ARV drugs, hypertension, diabetes, Framingham risk score categories, CD4 cell count and viral load. |
| Palella et al., 2015 | 1995–2010 | NA-ACCORD, North America | Prospective cohort | 16733 (full study population) 6485 (ART-naive) |
AMI (301) AMI (93) |
Recent Recent |
Not recently exposed Not recently exposed |
HR: 1.34 (0.96, 1.88) HR: 1.95 (1.18, 3.45) |
Model for full study population (ART-naive and ART-experienced) was adjusted for age, sex, race, risk group, calendar year, smoking, hypertension, diabetes, renal impairment, cholesterol and triglyceride levels, statin use, CD4 count, viral load, previous PI use, and cohort. In addition to above covariates, the model for restricted study population (ART-naive) was adjusted for hepatitis C infection and history of clinical AIDS diagnosis. |
| Marcus et al., 2016 | 1998–2011 | Kaiser (KPNC&KPSC), California | Retrospective cohort | 8154 | CVD (178) | Recent | All other ARV agents |
HR: 2.2 (1.4, 3.5) | Age, sex, calendar era, years known to be HIV-infected at ART initiation, race/ethnicity, CD4 cell count, HIV viral load, risk group, previous ART experience, alcohol use, smoking, overweight/obesity, diabetes, lipid-lowering therapy, renal function, and indicator for pre-2008 and post-2008. |
| Dorjee et al., 2017 | 2009–2014 | US Insurance Claims Data | Retrospective cohort | 72 733 | CVD (714) CVD (714) |
Recent Cumulative | All other ARV agents All other ARV agents |
HR: 1.40 (1.16, 1.69) HR: 1.08 (0.89, 1.30) |
Age, sex, calendar year, smoking, body weight, substance abuse, alcohol abuse, hepatitis B and C infection, prior CVD, chronic kidney disease, hypertension, diabetes, dyslipidemia, anti-hyperglycemic agents, cardiovascular medications (ACEI, ARB, CCB, β-blockers, statins, aspirin), stroke, cancer, symptomatic HIV-disease, and exposure to specific ARV drugs. |
| Elion et al., 2018 | 2001–2013 | NA-ACCORD, North America | Prospective cohort | 8265 | AMI (123) | Recent | All other ARV agents |
HR: 1.84 (1.17, 2.91) | Age, sex, race/ethnicity, acquisition, calendar year, smoking, hepatitis C infection, hypertension, diabetes, renal function, lipid levels, statin use, CD4 cell count, HIV viral load, history of clinical AIDS |
ACEI, angiotensin converting enzyme inhibitor; ARB, angiotensin receptor blocker; ARV, antiretroviral; BMI, body mass index; BP, blood pressure; CAD, coronary artery disease; CCB, calcium channel blocker; Cl, confidence interval; COLD, chronic obstructive lung disease; eGFR, estimated glomerular filtration rate; HAART, highly active antiretroviral agent; IVDU, intravenous drug use; NNRTI, non nucleoside reverse transcriptase inhibitor; NRTI, nucleoside reverse transcriptase inhibitor; PI, protease inhibitor.