‘Beelzebub has a devil put aside for me’ – HIV Drugs Increase The Risk Of Heart Attack
A study to assess the adverse effects of anti-retroviral drugs shows that two of the widely used HIV drugs are associated with an increased risk of heart attack/the formation of blood clots in the heart. With the use of Didanosine; the risk of developing a heart attack increases by 49%, with Abacavir; the increased risk is 90%. The effect is most pronounced in patients with a high underlying cardiovascular risk. The research findings also show that the adverse effect is reversible, if patients discontinue use of these particular drugs.
The scientists who conducted the study recommend that patients on Abacavir or Didanosine should evaluate their underlying cardiovascular risk with their doctor and discuss whether any changes to their drug regime are warranted. The scientists strongly urge HIV patients not to stop taking Abacavir or Didanosine, before they have consulted their doctor.
Since the study began in 1999, D:A:D (the Data Collection of Adverse effects of Anti-HIV Drugs Study) has examined the side-effects of anti-retroviral drugs, including a possible increase in the risk of heart attack. Recent analysis has focused on a class of drugs, not previously examined, known as the nucleoside analogues, which inhibit the HIV virus by preventing it from multiplying. This class of drugs includes Stavudine, Zidovudine, Lamivudine, Abacavir and Didanosine. Only the last two drugs in the analysis were shown to have an adverse effect with respect to heart disease.
The side-effects associated with Didanosine and Abacavir are, naturally, most significant for HIV patients who already have a high underlying cardiovascular risk. The drug effect increases an individual persons underlying risk by a factor of 1.9 for a person on Abacavir, and 1.49 for a person on Didanosine. For a person with a low underlying risk, this increase in risk is still negligible, but for someone with a high underlying cardiovacular risk, this could have serious consequences. The study shows, however, that the risk of heart attack is removed once patients stop taking the drugs. This seems to be the case, regardless of how long these drugs have been used by patients.
The D:A:D study involves over 33,000 patients from Europe, Australia and Asia. The study evaluates the incidence of heart attack among HIV-infected patients undergoing anti-retroviral treatment, and thereby enables scientists to determine whether side-effects of the anti-retroviraldrugs, including cardiovascular disease, are increased in the long-term.
The D:A:D study is headed by the Copenhagen HIV programme (CHIP) at the Department of International Health, Immunology and Microbiology, Faculty of Health Sciences, the University of Copenhagen. Professor of Virology, Jens D. Lundgren, MD, leads the Copenhagen HIV programme, which is also conducting a series of other long-term research projects to establish the optimum strategic use of the anti-retroviral drugs, examine resistance to and side-effects of these medicines, as well as developing alternative treatments.
Factors such as age, sex, smoking habits, blood pressure and cholesterol levels all contribute to a person’s underlying risk of developing a heart attack within the next 10 years. Smoking, for example, increases the risk 2-3 fold; while diabetes type 2 is associated with a 2-6 fold increased risk.
These findings have been presented at
CROI (Conference on Retroviruses and Opportunistic Infections), an international scientific conference on HIV, in Boston, USA, 3rd-6th February: Session 145 Poster
Cardiovascular, Lipid, and Metabolic Complications of ART
Session Day and Time: Tuesday, 1 – 4 pm
Predicting the Risk of Coronary Heart Disease in HIV-infected Patients: The D:A:D Risk Equation
Nina Friis-Møller*1, R Thiébaut2, P Reiss3, W El-Sadr4, S Worm1, O Kirk1, A Phillips5, C Sabin5, J Lundgren1, M Law6, and The D:A:D Study Group
1Copenhagen HIV Prgm, Hvidovre Univ Hosp, Denmark; 2INSERM E0338 & U593, ISPED, Univ Victor Segalen Bordeaux 2, France; 3ATHENA, HIV Monitoring Fndn, Academic Med Ctr, Amsterdam, The Netherlands; 4CPCPRA, Columbia Univ and Harlem Hosp, New York, NY, US; 5Royal Free Ctr for HIV Med, Royal Free and Univ Coll London, UK; and 6Australian HIV Observational Database, Natl Ctr in HIV Epidemiology and Clin Res, Sydney
Background: Prevention strategies for coronary heart disease (CHD) require reliable estimates of CHD risk. No such equations exist for HIV+ persons, where components of ART may contribute to this risk. We developed a CHD risk equation tailored to HIV+ patients.
Methods: Prospective multi-national cohort study of HIV+ subjects. Step 1 developed a model based on 9023 subjects who had full covariate data and were free of CHD at entry into the study. The risk equation to predict CHD was developed based on parametric survival models. Estimates from the risk equation and corresponding hazard ratios (HR) from a Cox model are reported. The performance of the equation was assessed on this development dataset by testing the prognostic system’s discrimination, calibration, and accuracy. The predictive performance was also compared to that of a conventional prediction model (Framingham). Step 2 will validate the model on a separate dataset (D:A:D cohort II).
Results: Over 33,594 person-years, 157 cases of CHD occurred. The best fitting parametric model was log-logistic, and included the conventional risk factors of (b-coefficient from log-logistic model with constant = 11.498 and g = 0.933; HR from Cox model): age (per 5 years older –0.334; 1.42), sex (male –0.796; 2.35), family history of CHD (–0.478; 1.66), systolic blood pressure (per 10 mmHg higher –0.050; 1.05) and smoking status (current –1.042, ex –0.456; 2.97, 1.78), the ratio of TC/HDL (per unit higher –0.144; 1.16), diabetes (fitted separately by sex due to interaction (in men –0.683, women –1.349; 1.94 and 4.04)), and in addition duration of protease inhibitor (PI) exposure (per additional year –0.114; 1.13). Age, PI exposure, and smoking status were fitted as time-updated, while all other covariates took the fixed value at baseline for the analyses. The area under the receiver-operator characteristic curve discrimination statistic was 0.78 (95%CI 0.75 to 0.82). Overall, the D:A:D equation predicted 153 CHD events, compared with 187 events predicted by the Framingham equation. Predictions were accurate in sub-groups of patients according to sex and smoking status (see the table).
Conclusions: The Framingham risk equation over-predicted CHD events in this cohort. In contrast, the D:A:D equation, developed on HIV+ subjects and incorporating PI exposure as well as conventional CHD risk parameters, accurately predicted CHD outcomes in the development dataset.