Background:  Evidence mounts that protease inhibitors (PI), and perhaps other ART, increase risk of coronary heart disease (CHD) and myocardial infarction (MI), an effect not fully explained by dyslipidemia. Interventions to manage CHD risk in HIV⁺ patients are being undertaken with some success. However, concern remains high and estimating risk is complicated by ever-changing traditional risk factors and ART regimens. Surveillance of CHD or MI event rates in HIV⁺ patients compared to HIV^– referent populations is needed.        

Methods:  We first update data from our fixed cohort of HIV⁺ and HIV^– male members of Kaiser Permanente Northern California (KPNC) followed from 1996 to June 2006 to examine the effect of HIV and PI exposure on CHD or MI hospitalizations. Separately, we provide surveillance for CHD or MI in a dynamic cohort of all HIV⁺ patients, using age- and sex-matched HIV⁻ KPNC members (1 HIV⁺ to 10 HIV⁻) as a reference. Adjusted rates and relative rates (RR) of MI hospitalization are estimated for pre-HAART (1994-1995), early HAART (1996-1999), and late HAART (2000-June 2006). Stavudien (d4T), tenofovir (TDF), and atazanavir (ATV) use over time is reported.

Results:  In the original cohort, 162 CHD events (101 MI) occurred in 30,433 person-years; rates for pre- vs post-PI exposure continue to suggest increased risk with PI exposure (CHD: 4.5 vs 7.1, p = 0.02; MI: 2.9 vs 4.4, p = 0.09). Age-adjusted RR for MI in 3 PI exposure durations compared to <2 years (ref) were 1.4 for 2 to 3.9 years, 1.8 for 4 to 5.9 years, and 1.6 for 6+ years. The overall RR for MI was 1.16 per year of PI exposure (95%CI 0.97, 1.4; p = 0.10). In the surveillance cohort (see the table), before the introduction of HAART in 1996, the RR of MI among HIV⁺ members vs HIV⁻ members (ref) was 0.85 (p = 0.65). The RR rose to 1.96 (p <0.0001) for 1996-1999 and was 1.78 (p <0.0001) for 2000-2006. Among HIV⁺ persons the RR of MI was 2.05 (p = 0.05) in 1996-1999 (vs 1994-1995) and 1.77 (p = 0.10) in 2000-2006. MI rates among HIV⁻ in these periods did not change vs 1994-1995. For 1996-2006 the RR for HIV⁺ women vs HIV⁻ women was 3.99 (p <0.001) and for HIV⁺ men vs HIV⁻ men was 1.78 (p <0.0001); d4T use declines, use of TDF and ATV go up.

Conclusions:  MI rates are higher among HIV⁺ than among HIV⁻ and appear to increase with time after PI start. The effect of HIV and its treatment on MI risk was greatest early in the HAART era, but has not continued to rise, possibly due to improved risk management and shifting to more lipid friendly regimens. We find the effect of HIV on MI is greater in women. Continued risk management and surveillance are warranted.