<b>OBJECTIVE: </b>This article compares the effects of initiating three contemporary antiretroviral therapy (ART) regimens on progression of carotid artery intima-media thickness (IMT) over 3 years.<b>DESIGN: </b>Randomized clinical trial.<b>SETTING: </b>Multicenter (26 institutions).<b>PATIENTS: </b>ART-naive HIV-infected individuals (n = 328) without known cardiovascular disease or diabetes mellitus.<b>Intervention: </b>Random assignment to tenofovir/emtricitabine along with atazanavir/ritonavir (ATV/r), darunavir/ritonavir (DRV/r), or raltegravir (RAL).<b>MAIN OUTCOME MEASURES: </b>Right-sided carotid IMT was evaluated by B-mode ultrasonography before ART initiation, and then after 48, 96, and 144 weeks. Comparisons of yearly rates of change in carotid IMT used mixed-effects linear regression models that permitted not only evaluation of the effects of ART on carotid IMT progression but also how ART-associated changes in traditional risk factors, bilirubin, and markers of HIV infection were associated carotid IMT progression.<b>RESULTS: </b>HIV-1 RNA suppression rates were high in all arms (>85%) over 144 weeks. Modest increases in triglycerides and non-high-density lipoprotein cholesterol levels were observed in the protease inhibitor-containing arms compared with decreases with RAL. In contrast, carotid IMT progressed more slowly on ATV/r [8.2, 95% confidence interval (5.6, 10.8) μm/year] than DRV/r [12.9 (10.3, 15.5) μm/year, P = 0.013]; changes with RAL were intermediate [10.7 (9.2, 12.2) μm/year, P = 0.15 vs. ATV/r; P = 0.31 vs. DRV/r]. Bilirubin and non-high-density lipoprotein cholesterol levels appeared to influence carotid IMT progression rates.<b>CONCLUSION: </b>In ART-naive HIV-infected individuals at low cardiovascular disease risk, carotid IMT progressed more slowly in participants initiating ATV/r than those initiating DRV/r, with intermediate changes associated with RAL. This effect may be due, in part, to hyperbilirubinemia.
Los estudios de cohortes han demostrado un mayor riesgo de infarto de miocardio (MI) asociado con el uso específico de antirretrovirales, mientras que los metaanálisis de ensayos controlados aleatorios (ECA) no lo han hecho. Estas diferencias pueden deberse a sesgos inherentes en el diseño del estudio observacional oa la duración limitada de los ensayos aleatorios. Realizamos un estudio de cohorte de nuevo usuario y comparador activo que emulaba un ECA que comparaba la iniciación de varios antirretrovirales como parte de la terapia antirretroviral combinada (cART) y MI. MÉTODOS: Se incluyeron los beneficiarios de Medicaid de Carolina del Norte (NC) infectados con el virus de inmunodeficiencia humana entre 2002 y 2008 que no habían sido previamente tratados con cART. Se compararon los cocientes de riesgo (HR) y los intervalos de confianza (IC) del 95% de MI entre los receptores de abacavir y tenofovir y los receptores de lopinavir-ritonavir o atazanavir y los receptores no nucleósidos de inhibidores de la transcriptasa inversa (NNRTI). Se ajustó la confusión mediante métodos de ponderación de probabilidad inversa. RESULTADOS: Hubo 3481 NC Medicaid nuevos receptores cART que aportaron 6399 años-persona y experimentaron 38 eventos MI. Recibir abacavir en comparación con tenofovir como parte de cART se asoció con un aumento de la tasa de IM (HR no ajustada = 2,70 [IC 95% = 1,24-5,91], HR ajustado = 2,05 [0,72-5,86]). Las estimaciones puntuales también sugieren una relación entre la recepción de atazanavir o lopinavir-ritonavir en comparación con un NNRTI y MI, aunque las estimaciones eran imprecisas. Conclusiones: Se encontró un aumento en la tasa de MI entre los pacientes que inician el abacavir en comparación con el tenofovir, aunque la asociación se redujo después de un ajuste de confusión. Sin un ensayo clínico comparativo prospectivo muy grande, un estudio observacional mucho más grande de los pacientes que inician cART sería necesario para definir mejor esta aparente asociación.
OBJECTIVE: To investigate whether there is any association between exposure to atazanavir (ATV), either when boosted or unboosted by ritonavir, and myocardial infarction (MI) or stroke within the D:A:D: Study.
DESIGN: Prospective cohort collaboration.
METHODS: Poisson regression was used to investigate the association between cumulative exposure to ATV and MI/stroke risk after adjusting for known demographic and clinical confounders, as well as cumulative and recent exposure to specific antiretroviral drugs. Follow-up started on enrolment in the study and ended at the earliest of: a new MI/stroke event, death, 6 months after last clinic visit, or 1 February 2011.
RESULTS: The incidence of MI varied from 0.28 [95% confidence interval (CI) 0.26-0.30)]/100 person-years of follow-up (PYFU) in those with no exposure to ATV to 0.20 (0.12-0.32)/100 PYFU in those with more than 3 years exposure. There was no evidence of an association between cumulative exposure to ATV and MI risk, either in univariate [relative rate/year 0.96 (95% CI 0.88-1.04)] or multivariable [0.95 (0.87-1.05)] analyses. The incidence of stroke was 0.17 (0.16-0.19)/100 PYFU in those with no exposure to ATV and 0.17 (0.10-0.27)/100 PYFU in those with more than 3 years exposure. As with the MI endpoint, there was no evidence of an association with ATV exposure in either univariate [1.02 (0.98-1.05)] or multivariable [0.95 (0.87-1.05)] analyses.
CONCLUSION: These results argue against a class-wide association between exposure to HIV protease inhibitors and the risk of cardio/cerebrovascular events.
BACKGROUND: We studied the association between HIV infection, antiretroviral medications, and the risk of spontaneous intracranial hemorrhage.
METHODS: We performed a cohort and nested case control study in an administrative database. We selected all HIV-positive individuals presenting between 1985 and 2007. Each HIV-positive subject was matched with 4 HIV-negative individuals. We used a Poisson regression model to calculate rates of intracranial hemorrhage according to HIV status. We conducted a case -control study nested within the cohort of HIV-positive individuals to look at the effect of antiretroviral medications. Odds ratios for antiretroviral exposure were obtained using conditional logistic regression.
RESULTS: There were 7,053 HIV-positive and 27,681 HIV-negative subjects, representing 138,704 person-years. There were 49 incident intracranial hemorrhages, 29 in HIV-positive and 20 in HIV-negative individuals. The adjusted hazard ratio for intracranial hemorrhage in HIV-positive compared to HIV-negative patients was 3.28 (95% confidence interval [CI] 1.75-6.12). The effect was reduced to 1.99 (95% CI 0.92-4.31) in the absence of AIDS-defining conditions, and increased to 7.64 (95% CI 3.78-15.43) in subjects with AIDS-defining conditions. Hepatitis C infection, illicit drug or alcohol abuse, intracranial lesions, and coagulopathy were all strongly associated with intracranial hemorrhage (all P < .001). In the case control study, 29 cases of ICH in HIV-positive individuals were matched to 228 HIV-positive controls. None of the antiretroviral classes were associated with an increase in the odds ratio of intracranial hemorrhage.
CONCLUSIONS: The risk of intracranial hemorrhage in HIV-positive individuals seems to be mostly associated with AIDS-defining conditions, other comorbidities, or lifestyle factors. No association was found between use of antiretroviral medications and intracranial hemorrhage.
INTRODUCTION: The incidence of ischemic heart disease is higher in patients with HIV/AIDS. However, the frequency of angina pectoris in these patients is still not known. Literature about this subject is still scarce.
OBJECTIVE: To evaluate the prevalence of angina pectoris and risk factors for coronary disease and to examine the association between traditional risk factors and HIV-related risk factors and angina pectoris.
METHOD: An epidemiological cross-sectional study, analyzed as case-control study, involving 584 patients with HIV/AIDS. Angina pectoris was identified by Rose questionnaire, classified as definite or possible. Information regarding risk factors was obtained through a questionnaire, biochemical laboratory tests, medical records and anthropometric measures taken during consultations at AIDS treatment clinics in Pernambuco, Brazil, from June 2007 to February 2008. To adjust the effect of each factor in relation to others, multiple logistic regression was used.
RESULTS: There was a preponderance of men (63.2%); mean ages were 39.8 years for men, 36.8 years for women. The prevalence of definite and possible angina were 11% and 9.4%, respectively, totaling 20.4%, with independent associations between angina and smoking (OR = 2.88; 95% CI: 1.69-4.90), obesity (OR = 1.62; 95% CI: 0.97-2.70), family history of heart attack (OR = 1.70; 95% CI: 1.00-2.88), low schooling (OR = 2.11; 95% CI: 1.24-3.59), and low monthly income (OR = 2.93; 95% CI: 1.18-7.22), even after adjustment for age.
CONCLUSION: This study suggests that angina pectoris is underdiagnosed, even in patients with medical monitoring, revealing lost opportunities in identification and prevention of cardiovascular morbidity.
OBJETIVO: El abacavir uso se ha asociado con el riesgo cardiovascular, pero se desconoce si esta asociación puede explicarse en parte por los pacientes con enfermedad renal siendo tratada preferentemente con abacavir para evitar tenofovir. Nuestro objetivo fue comparar las asociaciones de abacavir y tenofovir con riesgos cardiovasculares en veteranos infectados por el VIH.
DISEÑO: Estudio de cohorte de 10 931 pacientes infectados por el VIH que inician la terapia antirretroviral en la Administración de Salud de Veteranos 1997-2007, utilizando regresión de riesgos proporcionales de supervivencia.
MÉTODOS: predictores primarios fueron la exposición a abacavir o tenofovir en los últimos 6 meses, en comparación con la no exposición a estos fármacos, respectivamente. Los resultados fueron el tiempo hasta el primer evento cardiovascular aterosclerótica, que se define como enfermedad coronaria, cerebrovascular o enfermedad arterial periférica; y el tiempo para la insuficiencia cardiaca incidente.
RESULTADOS: Más de 60 588 personas-años de observación, había 501 cardiovascular y 194 eventos de insuficiencia cardiaca. Las tasas de eventos estandarizadas por edad entre los usuarios de abacavir y tenofovir fueron 12,5 frente a 8,2 por 1000 años-persona para la enfermedad cardiovascular, y 3,9 y 3,7 por 1.000 personas-año para la insuficiencia cardíaca, respectivamente. En los modelos multivariados ajustados, incluyendo medidas de tiempo-actualizado de la función renal, uso reciente abacavir se asoció significativamente con el incidente de enfermedad cardiovascular [hazard ratio 1,48; intervalo de confianza del 95% (IC) 01.08 a 02.04]; la asociación fue similar pero no significativa para la insuficiencia cardíaca (1,45, 0,85 a 2,47). En contraste, el uso reciente tenofovir se asoció significativamente con la insuficiencia cardíaca (1.82, 01.02 a 03.24), pero no con los eventos cardiovasculares (0,78, 0,52 a 1,16).
CONCLUSIÓN: La exposición reciente abacavir se asoció de forma independiente con un mayor riesgo de eventos cardiovasculares. También se observó una asociación entre la exposición a tenofovir reciente y la insuficiencia cardíaca, la cual debe ser confirmado en estudios futuros.
Background and Purpose. It now appears clear that both HIV/AIDS and antiretroviral therapy (HAART) use are associated with higher risk of cardiovascular disease such as stroke. In this study, we evaluated the prevalence, the risk factors, and the cardiometabolic comorbidities of stroke in HIV/AIDS Central African patients. Methods. This hospital-based cross-sectional study collected clinical, laboratory, and imaging data of black Central African heterosexual, intravenous drug nonuser, and HIV/AIDS patients. Results. There were 54 men and 62 women, with a female to male ratio of 1.2 : 1. All were defined by hypercoagulability and oxidative stress. Hemorrhagic stroke was reported in 1 patient, ischemic stroke in 17 patients, and all stroke subtypes in 18 patients (15%). Younger age <45 years (P = .003), autoimmunity (P < .0001), and metabolic syndrome defined by IDF criteria (P < .0001) were associated with ischemic stroke. Conclusions. Clustering of several cardiometabolic factors, autoimmunity, oxidative stress, and lifestyle changes may explain accelerated atherosclerosis and high risk of stroke in these young black Africans with HIV/AIDS. Prevention and intervention programs are needed.
