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San Diego, CA - Metabolic abnormalities associated with HIV infection and antiretroviral therapy are more and more prevalent as patients survive for a longer time. Despite worries of premature cardiovascular disease in those patients receiving highly active antiretroviral therapy, researchers have found that the rates of hospital admission for cardiovascular and cerebrovascular events stayed stable or even declined from 1993 to 2001 as the drugs have become more actively used. But the exposure time of these patients to the drugs has been relatively short, and the possibility remains that an increase in events will be detectable in the future.
The data come from a retrospective study of the 36766 patients who received care for HIV infection at Veterans Affairs facilities from January 1993 to June 2001. The study appears in the February 20 issue of the New England Journal of Medicine.1 Between 1995 and 2001 the researchers, led by Dr Samuel A Bozzette (Veterans Affairs San Diego Healthcare System, CA), saw the rate of admissions for cerebrovascular or cardiovascular disease decrease from 1.7 per 100 patient-years to 0.9 per 100 patient-years and the overall mortality decrease from 21.3 per 100 patient-years to 5.0 per 100 patient-years.
Number of patients admitted by year|
Year (number of patients treated for HIV) |
Admission for CVD or cerebrovascular disease |
Death from any cause |
|
1993 (16 763) | 207 | 2273 |
|
1994 (18 055) | 225 | 2860 |
|
1995 (17 717) | 234 | 2922 |
|
1996 (16 976) | 225 | 2221 |
|
1997 (16 779) | 184 | 1305 |
|
1998 (17 357) | 212 | 1104 |
|
1999 (18 183) | 198 | 1064 |
|
2000 (18 610) | 203 | 915 |
|
2001* (17 891) | 76 | 410 |
To see whether specific types of antiretroviral drugs had risks associated with them, Bozzette and his colleagues divided the patient population by drug class: nonnucleoside reverse-transcriptase inhibitors, nucleoside analogs, or protease inhibitors. Hazard ratios for cardiovascular or cerebrovascular disease for 24 months of exposure to any of these classes of drugs compared with 0 months of exposure all overlapped 1 when other covariates such as age, history of treatment for a CVD, and more advanced HIV disease were controlled for. They saw no significant effects in those receiving combinations of 2 classes of drugs.
Estimated hazard ratios for 24 months of exposure to antiretroviral drugs compared with 0 months of exposure|
Antiretroviral drug |
Admission for cardiovascular or cerebrovascular disease (95% CI) |
Admission for or death from cardiovascular or cerebrovascular disease (95% CI) |
|
Nucleoside analogs | 0.86 (0.66-1.11) | 0.88 (0.68-1.14) |
|
Protease inhibitors | 0.79 (0.54-1.14) | 0.92 (0.61-1.40) |
|
Nonnucleoside reverse-transcriptase inhibitors | 0.96 (0.55-1.68) | 1.10 (0.38-3.19) |
Study has numerous limitations
As a retrospective, observational study, there are numerous limitations to the study. The population treated in the VA hospital system was not identical to the general US population receiving care for HIV during that time. The VA population was more likely to be black (52.4% compared with 34.2%) and far more likely to be men (98.1% compared with 77.4%).
These differences may explain why this study contradicts some smaller case series that have shown an excess of MI associated with some of these drugs.
The authors are aware that most of the observations in this study were over a shorter time period than is usually required for the development of serious cardiovascular disease. "For this reason," they write, "these observations do not imply that the metabolic abnormalities associated with treated HIV are of no concern."
Given that treated HIV is associated with hyperlipidemia, insulin resistance, and changes in fat distribution that resemble syndrome X, the authors state, "It is reasonable to expect that metabolic abnormalities will be harmful to HIV-infected patients over the longer term."
Nonetheless, they conclude that "fear of accelerated vascular disease should not deter patients and providers from using the highest-quality care for HIV, as defined by the use of combination antiretroviral therapy that is compatible with current guidelines."
In an accompanying Perspective, Drs Daniel R Kuritzkes (Brigham and Women's Hospital) and Judith Currier (UCLA) essentially agree that patients at immediate risk of AIDS or death should not hesitate to use these drugs.2 But they also recommend that in patients in early stages of HIV infection the use of antiretroviral treatments less likely to produce hyperlipidemia and insulin resistance would be prudent. They recommend an emphasis on primary prevention efforts and a strategy based on the recommendations of ATP III while taking into account possible interactions between lipid-lowering agents and HIV treatments.
