Background
Methods
Eligibility criteria
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Types of studies: Randomised, quasi-randomised trials and prospective cohort studies.
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Types of participants: adult (> 18 years) people living with HIV (PLHIV) of either sex.
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Types of intervention: Any form of statin use regardless of indication, including but not limited to primary or secondary prevention of cardiovascular disease.
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Types of comparator: no statin or placebo
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Types of outcome measures: All-cause mortality.
Information sources and search strategy
Study selection and data extraction
Risk of bias assessment
Statistical analysis
Sensitivity analyses
Results
Study selection and characteristics
Study | Study period | Study design | Country | Setting/population | Indication | CVD risk | Male (%) | Age (mean/median) | Sample size | Statin therapy | Multivariate analysis (adjusted) |
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Moore et al., [40] 2011 | 1998 to 2009 | Cohort | USA | Johns Hopkins HIV Clinical Cohort | Primary prevention | Antihypertensive use: 29.3%, total cholesterol: 166 (141–194) mg/dL | 67.2 | 43 (36–49) | 1538 | Atorvastatin. Pravastatin, rosuvastatin [15.5%] | CD4, HIV-1 RNA, haemoglobin and cholesterol levels at the start of HAART, age, race, HIV risk group, prior use of ART, year of HAART start, NNRTI vs. PI-based ART, prior AIDS-defining illness, and viral hepatitis coinfection |
*Drechsler et al., [36] 2013 | 1995 to 2009 | Cohort | USA | Veteran Affairs’ Clinical Case Registry | Primary prevention | Smokers: 50% | 98 | 46.8 (40.6–52.9) | 25,884 | Atorvastatin, rosuvastatin [35%] | Age, gender, race, HCV-co-infection, hypertension, smoking, BMI, CD4 strata, LDL-strata |
*Knobel et al., [37] 2013 | 2002–2013 | Cohort | Spain | HIV clinic in Barcelona | Primary prevention | Framingham score > 20%: 8.5%, ever smokers: 67% | 72.2 | 42.09 (9.29) | 733 | Not reported [21%] | Baseline CD4 cell count, baseline viral load, undetectable viral load at follow-up, Framingham risk score, age, HIV transmission group, chronic liver disease, and smoking status |
Overton et al., [41] 2013 | 2000–2013 | Cohort | USA | Adult AIDS Clinical Trials Group Longitudinal Linked Randomized Trials (ALLRT) | Primary prevention | Framingham score > 10%: 10%, current smokers: 38% | 83 | 39 (33–46) | 3601 | Not reported [13%] | Age, sex, race/ethnicity, intravenous drug history, history of coronary artery disease (CAD), hepatitis B coinfection, systolic BP, eGFR, glucose, current use of lipid-lowering drugs other than statins, HIV-1 RNA, CD4 count, current smoking, and waist-to-hip ratio. |
Rasmussen et al., [42] 2015 | 1998–2009 | Cohort | Denmark | Danish HIV Cohort Study (DHCS) | Primary prevention | Total cholesterol > 5 mmol/L: 28.3% | 73.1 | 39.3 (33.0–46.3) | 1738 | Not reported [10%] | Age intervals (time-updated), gender, race, HIV-transmission group, hepatitis C status, calendar year of HAART initiation, AIDS defining illnesses prior to HAART, ART use before initiating HAART, CD4 cell count, viral load and cholesterol at HAART initiation. |
Krask et al., [38] 2015 | 2000–2015 | Cohort | USA | Nutrition For Healthy Living (NFHL) | Primary prevention | Framingham score: 6.5, hypertensive: 35%, diabetic: 7%, smokers: 47%, metabolic syndrome: 23% | 68 | 44.3 (7.7) | 438 | Not reported [15%] | Race, HBV, HCV, LDL, CD4 cell count, age, smoking, statin duration |
Lang et al., [39] 2015 | 2000–2009 | Cohort | France | French Hospital Database on HIV (FHDH-ANRS CO4) | Primary prevention | Current smokers: 42.1%, hypertensive 13.7%, diabetics: 10.1% | 88.9 | 50.5 (10) | 1776 | Not reported [8%] | Stepwise multivariable model using age, gender, HIV transmission group, current CD4 and CD8 T cell counts, CD4 T cell nadir, CD4/CD8 T cell ratio, CD4 T cell nadir/CD8 T cell ratio, plasma HIV-1 RNA level, AIDS status, the haemoglobin level, body mass index (BMI), smoking status, hypertension or use of antihypertensive treatment, diabetes or use of antidiabetic treatment, anti-HCV antibodies and HBs antigen status, non-AIDS malignancy (CIM-10 definition), liver failure, chronic kidney disease, cirrhosis, and pulmonary embolism. |
Quality assessment of included studies
Effects of statins on all-cause mortality
Posterior mean (95% CrI) | Number of studies | I2 | Probability HR < 1 | |
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Main analysis | 0.67 (0.39, 0.96) | 7 | 63% | 97% |
Down-weight low quality studies (20%/70%)a | 0.82 (0.49, 1.35) | 7 | 49% | 80% |
Down-weight low quality studies (50%/80%)b | 0.76 (0.50, 1.13) | 7 | 43% | 92% |
Exclude low quality studies | 0.81(0.49, 1.37) | 4 | 45% | 81% |
‘Sceptical’ prior | 0.88 (0.69, 1.14) | 7 | 62% | 85% |
Factor | Ratio of Hazard Ratio (95% Credible Interval) |
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Sample size (per 1000 people) | 1.02 (0.97 to 1.06) |
Publication year | 1.20 (0.85 to 1.71) |
Cohort follow-up period | 1.16 (0.93 to 1.38) |
Statin use (%) | 1.01 (0.95 to 1.06) |
Male (%) | 1.02 (0.98 to 1.05) |
Age (mean, years) | 1.08 (0.98 to 1.18) |
Europe vs. North America studies | 0.94 (0.31 to 2.27) |