Recent abacavir use increases risk of type 1 and type 2 myocardial infarctions among adults with HIV

Background: There is persistent confusion as to whether abacavir (ABC) increases the risk of myocardial infarction (MI), and whether such risk differs by type 1 (T1MI) or 2 (T2MI) MI in adults with HIV. Methods: Incident MIs in North American Cohort Collaboration on Research and Design participants were identified from 2001 to 2013. Discrete time marginal structural models addressed channeling biases and time-dependent confounding to estimate crude hazard ratio (HR) and adjusted hazard ratio (aHR) and 95% confidence intervals; analyses were performed for T1MI and T2MI separately. A sensitivity analysis evaluated whether Framingham risk score (FRS) modified the effect of ABC on MI occurrence. Results: Eight thousand two hundred sixty-five adults who initiated antiretroviral therapy contributed 29,077 person-years and 123 MI events (65 T1MI and 58 T2MI). Median follow-up time was 2.9 (interquartile range 1.4-5.1) years. ABC initiators were more likely to have a history of injection drug use, hepatitis C virus infection, hypertension, diabetes, impaired kidney function, hyperlipidemia, low (,200 cells/mm3) CD4 counts, and a history of AIDS. The risk of the combined MI outcome was greater for persons who used ABC in the previous 6 months [aHR = 1.84 (1.17-2.91)]; and persisted for T1MI (aHR = 1.62 [1.01]) and T2MI [aHR = 2.11 (1.08-4.29)]. FRS did not modify the effect of ABC on MI (P = 0.14) and inclusion of FRS in the MSM did not diminish the effect of recent ABC use on the combined outcome. Conclusions: Recent ABC use was associated with MI after adjustment for known risk factors and for FRS. However, screening for T1MI risks may not identify all or even most persons at risk of ABC use-associated MIs

Contributions of traditional and HIV-related risk factors on non-AIDS-defining cancer, myocardial infarction, and end-stage liver and renal diseases in adults with HIV in the USA and Canada: a collaboration of cohort studies

Background: Adults with HIV have an increased burden of non-AIDS-defining cancers, myocardial infarction, end-stage liver disease, and end-stage renal disease. The objective of this study was to estimate the population attributable fractions (PAFs) of preventable or modifiable HIV-related and traditional risk factors for non-AIDS-defining cancers, myocardial infarction, end-stage liver disease, and end-stage renal disease outcomes. Methods: We included participants receiving care in academic and community-based outpatient HIV clinical cohorts in the USA and Canada from Jan 1, 2000, to Dec 31, 2014, who contributed to the North American AIDS Cohort Collaboration on Research and Design and who had validated non-AIDS-defining cancers, myocardial infarction, end-stage liver disease, or end-stage renal disease outcomes. Traditional risk factors were tobacco smoking, hypertension, elevated total cholesterol, type 2 diabetes, renal impairment (stage 4 chronic kidney disease), and hepatitis C virus and hepatitis B virus infections. HIV-related risk factors were low CD4 count (400 copies per mL), and history of a clinical AIDS diagnosis. PAFs and 95% CIs were estimated to quantify the proportion of outcomes that could be avoided if the risk factor was prevented. Findings: In each of the study populations for the four outcomes (1405 of 61 500 had non-AIDS-defining cancer, 347 of 29 515 had myocardial infarctions, 387 of 35 044 had end-stage liver disease events, and 255 of 35 620 had end-stage renal disease events), about 17% were older than 50 years at study entry, about 50% were non-white, and about 80% were men. Preventing smoking would avoid 24% (95% CI 13–35) of these cancers and 37% (7–66) of the myocardial infarctions. Preventing elevated total cholesterol and hypertension would avoid the greatest proportion of myocardial infarctions: 44% (30–58) for cholesterol and 42% (28–56) for hypertension. For liver disease, the PAF was greatest for hepatitis C infection (33%; 95% CI 17–48). For renal disease, the PAF was greatest for hypertension (39%; 26–51) followed by elevated total cholesterol (22%; 13–31), detectable HIV RNA (19; 9–31), and low CD4 cell count (13%; 4–21). Interpretation: The substantial proportion of non-AIDS-defining cancers, myocardial infarction, end-stage liver disease, and end-stage renal disease outcomes that could be prevented with interventions on traditional risk factors elevates the importance of screening for these risk factors, improving the effectiveness of prevention (or modification) of these risk factors, and creating sustainable care models to implement such interventions during the decades of life of adults living with HIV who are receiving care. Funding: National Institutes of Health, US Centers for Disease Control and Prevention, the US Agency for Healthcare Research and Quality, the US Health Resources and Services Administration, the Canadian Institutes of Health Research, the Ontario Ministry of Health and Long Term Care, and the Government of Alberta

Morbidity and survival in advanced AIDS in Rio de Janeiro, Brazil Morbidade e sobrevida em AIDS avançada no Rio de Janeiro, Brasil

Opportunistic diseases (OD) are the most common cause of death in AIDS patients. To access the incidence of OD and survival in advanced immunodeficiency, we included 79 patients with AIDS treated at Hospital Evandro Chagas (FIOCRUZ) from September 1997 to December 1999 with at least one CD4 count <=100 cells/mm³. The incidence of OD was analyzed by Poisson's regression, and survival by Kaplan Meier and Cox analysis, considering a retrospective (before CD4 <=100 cells/mm³) and a prospective (after CD4 <=100 cells/mm³) period, and controlling for demographic, clinical and laboratory characteristics. The confidence interval estipulated was 95%. Mean follow-up period was 733 days (CI = 683-782). During the study 9 (11.4%) patients died. Survival from AIDS diagnosis was a mean of 2589 days (CI = 2363-2816) and from the date of the CD4 count CD4 <=100 cells/mm³ was a mean of 1376 (CI = 1181-1572) days. Incidence of OD was 0.51 pp/y before CD4 <= 100 cells/mm³ and 0.29 pp/y after CD4 <= 100 cells/mm³. A lower number of ODs before CD4 < 100 cells/mm³ was associated with lower incidence rates after CD4 <= 100 cells/mm³. AIDS diagnosis based on CD4+ counts <= 200 cells/mm³ was associated with lower incidence rates after CD4 <= 100 cells/mm³. Baseline CD4 counts above 50 cells/mm³ (HR = 0.13) and restoration of baseline CD4+ counts above 100 cells/mm³ (HR = 0.16) were associated with a lower risk of death. Controling both variables, only restoration of baseline counts was statistically significant (HR = 0.22, p = 0.04). We found a very low incidence of OD and long survival after CD4 < 100 cells/mm³. Survival was significantly associated with restoration of baseline CD4 counts above 100 cells/mm³.<br>As doenças oportunistas (DO) são a causa mais comum de morte em pacientes com AIDS. Para acessar a incidência de DO e a sobrevida na imunodeficiência avançada, foram incluídos 79 pacientes com AIDS tratados no Hospital Evandro Chagas (FIOCRUZ) no período de Setembro de 1997 a Dezembro de 1999, com ao menos uma contagem de células CD4 <= 100/mm³. A incidência de DO foi analisada pela regressão de Poisson e a sobrevida pela analise de Kaplan Meier e Cox, considerando um período retrospectivo (anterior à contagem de CD4 <= 100 cels/mm³) e um prospectivo (após a contagem de CD4 <= 100 cels/mm³) e controlando-se características demográficas clínicas e laboratoriais. O intervalo de confiança estipulado foi o de 95%. O período médio de acompanhamento foi de 733 dias (IC = 683 - 782). Durante o estudo, nove (11,4%) pacientes morreram. A sobrevida a partir do diagnóstico de AIDS foi em média de 2589 dias (IC = 2363 - 2816) e da data da contagem de CD4 <= 100 cels/mm³ foi em média de 1376 dias (IC = 1181 - 1572). A incidência de DO foi de 0,51 pp/ano no período pré-CD4 <= 100 cels/mm³ e 0,29 pp/ano no período pós-CD4 <= 100 cels/mm³. Um menor número de DO acumuladas no período pré-CD4 <= 100 cels/mm³ foi associado com taxas de incidência menores no período pós-CD4 <= 100 cels/mm³.O diagnóstico de AIDS baseado em contagem de CD4+ <= 200 cels/mm³ foi associado com menores taxas de incidência durante o período pós-CD4 <= 100 cels/mm³. As contagens basais de células CD4 acima de 50 cel/mm³ (HR = 0,16) foram associadas a um menor risco de morte assim como a restauração da contagem basal acima de 100 cels/mm³ (HR = 0,16). Controlando-se ambas, somente a restauração da contagem basal manteve sua significância estatística (HR = 0,22, p = 0,04) Encontramos uma baixa incidência de DO durante o período pós-CD4 <= 100 cels/mm³ e uma sobrevida longa após CD4 <= 100 cels/mm³. A sobrevida foi significativamente associada com a restauração das contagens de CD4 basais