Table 2.
Study characteristics and results.
| Study | Type of study | Population-follow-up | Drugs | Results | Outcomes |
|---|---|---|---|---|---|
| Coplan et al., 20039 | Prospective cohort | 10,986 HIV-patients which 7951 received PI therapy – 12 months | IDV, NFV, SQV Ritonavir |
RR of MI were 1.69 (0.54, 7.48) in PI-containing HAART and 1.74 (0.5, 9.0) for patients with NRTI-only regimens. | No difference in MI incidence between the PI containing or not containing groups |
| Llibre et al., 200610 | Prospective cohort | 352 HIV-patients in use of 3 antiretroviral drugs – 48 weeks | Substitution of TDF by d4T | Reduction in TC (−17.5 mg/dL; p < 0.001), LDL-C (−8.1 mg/dL; p < 0.001) and TG (−35 mg/dL; p < 0.001) at 48 weeks of follow up. | TC reduction HDL and LDL-C reduction TG reduction |
| Velenzuela et al., 200711 | Prospective cohort | 276 patients: 168 – HAART and PI 108 – HAART – 4 months |
NS | Low CVR but higher TC and TG in the subpopulation of patients who received PI | Low CVR; higher TC and TG in the subpopulation of patients who received PI |
| Brothers et al., 200912 | Prospective cohort | HIV received ABC (n = 9502) or not (n = 4672) – 24 week | ABC and NS | MI were comparable among subjects exposed n = 16 (0.168%); or not n = 11 (0.235%) to ABC-containing therapy. | CAD and MI events were similar across ABC-exposed and non-ABC-exposed groups |
| Worm et al., 201013 | Prospective cohort | 33,308 HIV-patients (D:A:D Study) – >1 year |
AZT, ddI, ddC, d4T, 3TC, ABC, TDF, IDV, NFV, LPV, SQV, NVP, EFV | Recent exposure to ABC or ddi was associated with an increased risk of MI. Cumulative exposure to IDV and LPV was associated with an increased risk of MI. | Increased risk of MI associated with IDV, LPV, ddI, ABC |
| Cahn et al., 201014 | Prospective cohort | 4010 HIV-patients receiving HAART for at least 1 month – 2 years | NS | The overall 10-year risk of CVD, as measured by the FRF, was 10.4 (24.7). The FRF score increased with duration of HAART. | 80.2% of dyslipidemia 20.2% of metabolic syndrome |
| Obel et al., 201015 | Prospective cohort | 2952 HIV-patient | ABC, AZT, d4T, ddI, 3TC | RR of MI hospitalization with ABC was 2.22 (95% CI 1.31–3.76). The risk of MI increased after initiation of ABC IRR adjusted for confounders = 2.00 (95% CI 1.10–3.64). | |
| Saint-Martin et al., 201016 | Prospective cohort | 33 ATV/r > 6 months 99 ATV/r naive controls – 18 months |
ATV/R Others |
The CIMT course significantly decreased (p = 0.018) in cases at 18 months. | CIMT significantly decreased (p = 0.018) |
| Ribaudo et al., 201117 | Prospective cohort | 1704 received ABC 3352 no ABC – 3.1 years |
NS | 6 years after ART initiation, 36 MI events were observed in 17,404 person-years. No evidence of an increased hazard of MI in subjects using ABC vs. no ABC was seen (over a 1-year period: p = 0.50; HR = 0.7 [95% CI, 0.2–2.4]). | No evidence that initial ART containing ABC increases MI risk over short-term and long-term periods |
| Durand et al., 201118 | Prospective cohort | 7053 HIV-positive patients were matched to 27,681 HIV-negative patients | ABC LPV EFV |
The drugs that were associated with an increased risk of AMI for any exposure were ABC OR = 1.79, lopinavir OR = 1.98, ritonavir OR = 2.29 and EFZ OR = 1.83. | HIV+ were at higher risk of AMI than the general population, and several ARTs were associated with an increased risk of AMI |
| Friis-Moller et al., 200319 | Prospective cohort | 17,852 patients enrolled in DAD from nine of 11 participating cohorts | PIs, NNRTIs | Increased prevalence of elevated TC among subjects receiving an NNRTI but no PI OR = 1.79, PI but no NNRTI OR = 2.35, or NNRTI + PI OR = 5.48 compared to the prevalence among antiretroviral therapy (ART)-naïve subjects. | CVD risk factors were prevalent. With the highest prevalence among patients receiving PI, NNRTI or both of these drug classes |
| Choi et al., 201121 | Prospective cohort | 10,931 HIV-infected patients initiating antiretroviral therapy in the Veterans Health Administration from 1997 to 2007 | ABC TDF |
123 cardiovascular events in 15,142 person-years of <6 months ABC use and 90 in 22 551 person-years TDF use. Incidence of any CVD event were higher in the setting of ABC use compared with TDF use or other ART (13.4 vs. 9.4 per 1000 person-years p < 0.01. | Recent ABC exposure was significantly associated with higher risk of atherosclerotic vascular events, and recent TDF exposure was significantly associated with HF |
| DAD Study Group, 200322 | Prospective cohort | 23,468 HIV-patients were enrolled from 11 previously cohorts | PIs NRTIs |
The incidence of MI increased with longer exposure to combination antiretroviral therapy (adjusted relative rate per year of exposure, 1.26 [95 percent confidence interval, 1.12 to 1.41]; p < 0.001). | Combination ART was independently associated with a 26% relative increase in MI per year of exposure |
| Masiá et al., 200723 | Prospective cohort | 245 consecutive HIV-infected patients during a 2-month period | Naïve NNRTIs PI |
Among patients on ART, peroxide concentrations (PC) were significantly lower in NNRTI regimens than in those receiving PIs ([IQR], 331.2 vs. 472.8 t∼mol/L; p = 0.003). | PC used as a marker of OS was associated with CVD factors. NNRTIs were associated with low PC vs. patients receiving PI |
| Reinsch et al., 201024 | Cohort | 698 HIV-positive patients | PIs NRTIs NNRTIs |
DD was present in 336 (48%) of the total HIV infected population. While not statistically significant, NRTI and PI use showed a trend toward a greater prevalence in the DD group. | High prevalence of DD in HIV patients was demonstrated. Traditional CVD risk factors contributed to the DD |
| Silva et al., 200925 | Cohort | 215 patients receiving HAART and 69 HAART-naive patients | G A: G B: G C: G D: G E: |
TC, HDL, TG and glucose were higher in the HAART group than in the non-HAART group p < 0.001). According to the FRS, the CVD risk was moderate to high in 11% receiving HAART. | Although the mean values for TC, HDL-c and TG were higher in the HAART group, a higher CVR was not identified in the former |
| Triant et al., 200726 | Prospective cohort | 3851 HIV and 1,044,589 non-HIV patients | PIs NRTIs NNRTIs |
AMI was identified in 189 HIV and 26,142 non-HIV patients. AMI rates were increased in HIV vs. non-HIV patients 11.13 vs. 6.98 (p < 0.001). | AMI rates and CVR factors were increased in HIV compared with non-HIV patients |
| Alvarez et al., 201027 | Prospective cohort | 4010 HIV patients | The overall prevalence of MS was 20.2% (812/4010). The 10-year risk of developing CVD was 10.4% (24.7). Patients with MS had higher CVD risk 22.2% vs. 7.4%, respectively, p < 0.001. | MS in HIV-infected patients receiving ART is comparable to populations. Patients with MS had higher estimated risk for CVD | |
| Kwiatkowska et al., 201128 | Prospective cohort | 72 HIV infected patients and 27 healthy individuals | PIs, NNRTIs, NRTIs |
HIV infected patients show more advanced subclinical atherosclerosis in the carotid arteries (cIMT and plaques incidence). Patients treated with ARV therapy for over 5 years have a higher value of cIMT. | HIV shows significant progression of subclinical atherosclerosis and incidence of atherosclerotic plaques |
| D:A:D Study Group*, 200829 | Prospective cohort | 33,347 HIV-1-infected | Associations between the rate of MI and cumulative or recent use of AZT, d4T, or 3TC. Recent use of ABC or ddI was associated with an increased rate of MI relative rate 1.90 with ABC and 1.49 with ddI [p = 0.003]). | There exists an increased risk of MI in patients exposed to ABC and ddI. The excess risk does not seem to be explained by underlying established CVD risk factors | |
| SMART/INSIGHT and DAD Study, 200830 | Prospective cohort | 4544 HIV patients | NRTIs PIs |
Use of ABC was associated with an excess risk of CVD compared with other NRTIs. Adjusted hazard ratios for clinical MI (n = 19), major CVD (MI, stroke, surgery for CAD, and CVD death; n = 70). | Current use of ABC was associated with an excess risk of CVD compared with other NRTIs. The drug may cause vascular inflammation, which may precipitate a CVD event |
| Obel et al., 200731 | Prospective cohort | 3953 HIV-infected patients and 373,856 Control subjects | PIs, NNRTIs, NRTIs |
In HAART period, the risk of ischemic heart disease (IHD) increase was substantially higher RR = 2.12. 1 year after receiving a diagnosis of HIV infection, RR of IHD was 2.38. | Compared with the general population, HIV-infected patients receiving HAART have an increased risk of IHD |
| Van Vonderen 200933 | Case–control | 55 HIV-patients ART, 22 HIV-patients ART naive 23 HIV-patients with LD 52 controls – NA |
NS | HIV infected patients had a 0.067 mm (10.8%) greater CIMT than controls. Patients exposed to ART had similar CIMT compared with ART-naive patients but 25.9% lower DC and 21.7% lower CC of the femoral artery. | HIV infection is independently associated with C-IMT and generally increased arterial stiffness |
| Lang et al., 201034 | Case–control | 289 HIV-patients with history of MI 884 HIV-patients with no history of MI – 6 years |
ABC, AZT, d4T, 3TC, TDF | Recent exposure to ABC was associated with an increased risk of MI (OR, 2.01; 95% CI, 1.11–3.64) Cumulative exposure to all PIs except SQV was associated with an increased risk of MI. | Short-term/recent exposure to ABC was associated with an increased risk of MI |
| Wand et al., 200735 | RTC | 288 ddI/d4T with EFV 305 ddI/d4T with NFV 288 ddI/d4T with EFV+ NFV – 3 years |
ddI d4T EFV NFV |
MS association with increased risk of CVD HR = 2.56 and was associated with an increased risk of T2DM (ATP-III: HR = 4.34; p = 0.001). Incident MS was associated with an increased risk of both CVD (ATP-III: HR = 2.73; p = 0.036) and T2DM (ATP-III: HR = 4.89; p < 0.0001). | Progression to MS |
| Van Vonderen et al., 200936 | RTC | 19 HIV-patients with LPV/r plus ZDV/3TC 18 LPV/r plus NVP- 3 years |
LPV/r ZDV 3TC NVP |
CIMT increased by 0.061 mm (p < 0.001) in the ZDV/3TC/LPV/r arm and by 0.044 mm (p = 0.012) in the NVP/LPV/r arm. Femoral artery DC and CC decreased in the ZDV/3TC/LPV/r arm and femoral DC decreased in the NVP/LPV/r arm. | CIMT and femoral artery stiffness increased after the initiation of HAART |
| Martınez et al., 201037 | RTC | 46 ABC/3TC 34 TDF/emtricitabine) 48 weeks |
ABC 3TC TDF Emtricitabine |
TC increased significantly in the ABC/3TC vs. TFV/ETB group, found no significant changes in the biomarkers (p = 0.12 for all comparisons) | ABC/3TC increase TCl and LDL Did not cause inflammation, endothelial dysfunction, insulin resistance |
| Murphy 201038 | RTC | 26 ATV/r 24 remained on PI regimen 24 weeks |
ATV/r Others |
Changes in the ATV/r vs. continued PI group were observed for TC (−25 vs. +1.5 mg/dl, p = 0.009), TG (−58 vs. +3.5 mg/dl, p = 0.013), and non HDL-C (−27 vs. −0.5 mg/dL, p = 0.014). | ATV/r improved lipid profile Did not change endothelial function, inflammatory and metabolic markers |
TC, total cholesterol; HDL-C and LDL-C, high and low-density lipoprotein cholesterol; TG, triglycerides; CVR, cardiovascular risk; MI, myocardial infarction; AMI, acute myocardial infarction; FRF, Framingham risk score; CAD, coronary artery disorder; CIMT, carotid intima–media thickness; LD, lipodystrophy; MS, metabolic syndrome; 3TC, lamivudine; AZT, zidovudine; d4T, stavudine; ddC, zalcitabine; ddI, didanosine; EFV, efavirenz; IDV, indinavir; LPV, lopinavir/ritonavir; NFV, nelfinavir; NVP, nevirapine; SQV, saquinavir; TDF, tenofovir; ATV/r, atazanavir; ABC, Abacavir; ETB, emtricitabine; OPG, osteoprotegerin; ADT, adiponectin.
G A: (AZT) + (3TC) + EFV; G B: AZT + 3TC + LPV e AZT + 3TC + NFV; G C: AZT + 3TC + ATV/r; G D: (d4T) + 3TC + EFV; G E: d4T + 3TC + LPV e d4T +3 TC + NFV e d4T + ddI + LPV (RTI) – reverse transcriptase inhibitors not specified (NS); not applicable (NA); relative risk (RR).