Objective
The aim of the study was to characterize the causes, trends and determinants of severe morbidity in a large cohort of HIV‐infected patients between 2000 and 2004.
Method
Severe morbid ...events were defined as medical events associated with hospitalization or death. Epidemiological and biological data were recorded at the time of the morbid event. Trends were estimated using Poisson regression.
Results
Among 3863 individuals followed between 2000 and 2004, 1186 experienced one or more severe events, resulting in 1854 hospitalizations or deaths. The severe events recorded included bacterial infections (21%), AIDS events (20%), psychiatric events (10%), cardiovascular events (9%), digestive events including cirrhosis (7%), viral infections (6%) and non‐AIDS cancers (5%). Between 2000 and 2004, the incidence rate of AIDS events decreased from 60 to 20 per 1000 person‐years, that of bacterial infections decreased from 45 to 24 per 1000 person‐years, and that of psychiatric events decreased from 26 to 14 per 1000 person‐years (all P<0.01), whereas the incidences of cardiovascular events and of non‐AIDS cancers remained stable at 14 and 10 per 1000 person‐years, on average, respectively.
Conclusion
Severe morbidity has shifted from AIDS‐related to non‐AIDS‐related events during the course of HIV infection in developed countries. Limiting endpoints to AIDS events and death is insufficient to describe HIV disease progression in the era of combination antiretroviral therapy.
Objectives
Many HIV‐infected patients with chronic hepatitis C virus (HCV) infection do not receive treatment for HCV infection, often because of contraindications or poor adherence to anti‐HIV ...therapy. The aim of this study was to identify factors influencing guideline‐based HCV treatment initiation in a large cohort of HIV/HCV‐coinfected patients.
Methods
Between 2005 and 2011, 194 (40.5%) of 479 coinfected patients not previously treated for HCV infection started this treatment based on current recommendations, i.e. a Metavir score > F1 for liver fibrosis; HCV genotype 2 or 3 infection; or HCV genotype 1 or 4 infection and low HCV viral load (< 800 000 IU/mL), whatever the fibrosis score. Clinical and biological data were compared between patients who started HCV therapy during follow‐up and those who did not.
Results
In multivariate analyses, good adherence to treatment for HIV infection, as judged by the patient's physician, was associated with HCV treatment initiation odds ratio (OR) 2.37; 95% confidence interval (CI) 1.17–4.81; P = 0.017, whereas patients with children (OR 0.53; 95% CI 0.30–0.91; P = 0.022) and those with cardiovascular disease or respiratory distress (OR 0.10; 95% CI 0.01–0.78; P = 0.03) were less likely to be treated.
Conclusions
Adherence to treatment for HIV infection, as judged by the patient's physician, appears to have a major influence on the decision to begin treatment for HCV infection in coinfected patients. This calls for specific therapeutic education and adherence support in order to ensure timely anti‐HCV therapy in this population.
Causes of acquired thrombotic thrombocytopenic purpura (TTP) are multiple and rarely iatrogenic.
A 40-year-old, HIV and hepatitis C virus co-infected woman was treated with interferon and ribavirine ...and developed a TTP confirmed by the presence of anti-ADAMTS 13 antibodies. The outcome was favourable when treatment was discontinued and rituximab infusion administered.
The occurrence of anemia and thrombocytopenia in patients treated with interferon and ribavirine is not always related to direct toxicities of these treatments. The ADAMS 13 testing may help the clinician to diagnose iatrogenic acquired TTP.
The multicenter national Mortalité 2005 survey aimed at describing the distribution of causes of death among HIV-infected adults in France in 2005 and its changes as compared with 2000.
Physicians ...involved in the management of HIV infection notified deaths and documented the causes using a standardized questionnaire similar to the previous survey performed in 2000.
Overall, 1042 deaths were notified in 2005 (vs 964 in 2000): with median age, 46 years (vs 41 years); men, 76%; and median last CD4 cell count, 161/mm (vs 94). The proportion of underlying causes of death due to AIDS decreased (36% in 2005 vs 47% in 2000), and the proportion of cancer not related to AIDS or hepatitis (17% vs 11%), liver related disease (15% vs 13%: hepatitis C, 11%, and hepatitis B, 2%), cardiovascular disease (8% vs 7%), or suicide (5% vs 4%) increased. Among the 375 AIDS-related deaths, the most frequent event was non-Hodgkin lymphoma (28%). Among cancers not related to AIDS or hepatitis, the most frequent localizations were lung (31%) and digestive tract (14%). Among the 154 liver-related deaths, 24% were due to hepatocarcinoma.
The heterogeneity of causes of death among HIV-infected adults was confirmed and intensified in 2005, with 3 causes following AIDS: cancers and liver-related and cardiovascular diseases.
Objectives
HIV‐infected patients are at risk of atherosclerosis and cardiovascular diseases. In a 12‐month follow‐up study, we aimed to investigate changes in carotid intima–media thickness (IMT), a ...surrogate marker of atherosclerosis, and its determinants in HIV‐1‐infected patients.
Methods
Our multicentre prospective longitudinal cohort study included 346 HIV‐infected patients, for each of whom two IMT measurements were taken by B‐mode ultrasonography at baseline (M0) and 1 year later (M12).
Results
We observed a significant but moderate increase in the common carotid artery (CCA) median IMT, from 0.54 to 0.56 mm (P<10−4), i.e. an increase of 0.020 mm (95% confidence interval 0.012–0.029). There was a significant association between cross‐sectional CCA IMT measures at M12 and conventional cardiovascular risk factors (higher CCA IMT with older age, P<10−4; male gender, P=0.02; tobacco consumption, P=0.05), as well as higher CD4 cell count at M12 (>median 455 cells/μL, P=0.01). Only CD4 cell count at M0 was strongly and positively associated with the variation in IMT between M0 and M12 (P=4 × 10−3). IMT progression was +0.0020 mm for the lowest quartile of CD4 cell count distribution at M0, i.e. 3–253 cells/μL, +0.010 mm for 253–402 cells/μL, +0.043 mm for 402–590 cells/μL, and +0.028 mm for 590–2270 cells/μL. No association was found with type or duration of antiretroviral exposure.
Conclusions
Conventional cardiovascular risk factors are major determinants of IMT evolution. The link between immunological status and carotid IMT requires further study.
Background.
Several antiretroviral agents (ARVs) are associated with chronic renal impairment, but the extent of such adverse events among human immunodeficiency virus (HIV)–positive persons with ...initially normal renal function is unknown.
Methods.
D:A:D study participants with an estimated glomerular filtration rate (eGFR) of ≥90 mL/min after 1 January 2004 were followed until they had a confirmed eGFR of ≤70 mL/min (the threshold below which we hypothesized that renal interventions may begin to occur) or ≤60 mL/min (a value indicative of moderately severe chronic kidney disease CKD) or until the last eGFR measurement during follow-up. An eGFR was considered confirmed if it was detected at 2 consecutive measurements ≥3 months apart. Predictors and eGFR-related ARV discontinuations were identified using Poisson regression.
Results.
Of 22 603 persons, 468 (2.1%) experienced a confirmed eGFR of ≤70 mL/min (incidence rate, 4.78 cases/1000 person-years of follow-up 95% confidence interval {CI}, 4.35–5.22) and 131 (0.6%) experienced CKD (incidence rate, 1.33 cases/1000 person-years of follow-up 95% CI, 1.10–1.56) during a median follow-up duration of 4.5 years (interquartile range IQR, 2.7–6.1 years). A current eGFR of 60–70 mL/min caused significantly higher rates of discontinuation of tenofovir (adjusted incidence rate ratio aIRR, 1.72 95% CI, 1.38–2.14) but not other ARVs compared with a current eGFR of ≥90 mL/min. Cumulative tenofovir use (aIRR, 1.18/year 95% CI, 1.12–1.25) and ritonavir-boosted atazanavir use (aIRR, 1.19/year 95% CI, 1.09–1.32) were independent predictors of a confirmed eGFR of ≤70 but were not significant predictors of CKD whereas ritonavir-boosted lopinavir use was a significant predictor for both end points (aIRR, 1.11/year 95% CI, 1.05–1.17 and 1.22/year 95% CI, 1.16–1.28, respectively). Associations were unaffected by censoring for concomitant ARV use but diminished after discontinuation of these ARVs.
Conclusions.
Tenofovir, ritonavir-boosted atazanavir, and ritonavir-boosted lopinavir use were independent predictors of chronic renal impairment in HIV-positive persons without preexisting renal impairment. Increased tenofovir discontinuation rates with decreasing eGFR may have prevented further deteriorations. After discontinuation, the ARV-associated incidence rates decreased.
Les causes de purpura thrombotique thrombocytopénique (PTT) acquis sont multiples et d’origine médicamenteuse rare.
Une femme de 40ans co-infectée par le virus de l’immunodéficience humaine (VIH) et ...le virus de l’hépatite C (VHC) et traitée par interféron et ribavirine développait un tableau de PTT confirmé par la présence d’anticorps anti-ADAMTS 13. L’évolution était favorable à l’arrêt du traitement et après administration de rituximab.
L’apparition d’une anémie et d’une thrombopénie sous interféron et ribavirine ne sont donc pas toujours liées à la toxicité directe de ces traitements. Le dosage de l’ADAMTS 13 peut permettre d’argumenter un diagnostic de PTT iatrogène.
Causes of acquired thrombotic thrombocytopenic purpura (TTP) are multiple and rarely iatrogenic.
A 40-year-old, HIV and hepatitis C virus co-infected woman was treated with interferon and ribavirine and developed a TTP confirmed by the presence of anti-ADAMTS 13 antibodies. The outcome was favourable when treatment was discontinued and rituximab infusion administered.
The occurrence of anemia and thrombocytopenia in patients treated with interferon and ribavirine is not always related to direct toxicities of these treatments. The ADAMS 13 testing may help the clinician to diagnose iatrogenic acquired TTP.
The features of paradoxical reactions (PR) that occurred in non-HIV infected patients treated with antituberculous drugs are diverse. We report four new cases of such PR and review the literature.
...Were included all consecutive patients with PR that occurred in non-HIV infected patients who were treated for tuberculosis and followed-up in the department of internal medicine and infectious diseases between January 1st, 2009 and July 31st, 2010.
Three of the patients were male. Their median age was 28.5 years. Tuberculous locations were pulmonary (two instances) and extrapulmonary (three instances). Paradoxical reactions occurred after a median of 5.5 weeks after initiation of antituberculous treatment. The PR presented as hypercalcemia (n=1), spondylitis of the 9th thoracic vertebra (n=1), intracerebral tuberculoma (n=1), pericardial effusion (n=1) and adenitis (n=3). Lymphopenia was present in three patients. Three out of the four patients received corticosteroid. Outcome was favorable in three patients.
Pardoxical reactions are more common in patients who present with extrapulmonary tuberculosis. Intracerebral tuberculomas and spondylitis may be asymptomatic. Prescription of corticosteroids remains controversial except for intracerebral tuberculoma.
Whether or not the association between some antiretrovirals used in HIV infection and chronic kidney disease is cumulative is a controversial topic, especially in patients with initially normal renal ...function. In this study, we aimed to investigate the association between duration of exposure to antiretrovirals and the development of chronic kidney disease in people with initially normal renal function, as measured by estimated glomerular filtration rate (eGFR).
In this prospective international cohort study, HIV-positive adult participants (aged ≥16 years) from the D:A:D study (based in Europe, the USA, and Australia) with first eGFR greater than 90 mL/min per 1·73 m(2) were followed from baseline (first eGFR measurement after Jan 1, 2004) until the occurrence of one of the following: chronic kidney disease; last eGFR measurement; Feb 1, 2014; or final visit plus 6 months (whichever occurred first). Chronic kidney disease was defined as confirmed (>3 months apart) eGFR lower than 60 mL/min per 1·73 m(2). The primary outcome was the occurrence of chronic kidney disease. Poisson regression was used to estimate the incidence rate of chronic kidney disease associated with cumulative exposure to tenofovir disoproxil fumarate, ritonavir-boosted atazanavir, ritonavir-boosted lopinavir, other ritonavir-boosted protease inhibitors, or abacavir.
Between Jan 1, 2004, and July 26, 2013, 23,905 eligible individuals from the D:A:D study were included. Participants had a median baseline eGFR of 110 mL/min per 1·73 m(2) (IQR 100-125), a median age of 39 years (33-45), and median CD4 cell count of 441 cells per mm(3) (294-628). During a median follow-up of 7·2 years (IQR 5·1-8·9), 285 (1%) of 23,905 people developed chronic kidney disease (incidence 1·76 per 1000 person-years of follow-up 95% CI 1·56-1·97). After adjustment, we recorded a significant increase in chronic kidney disease associated with each additional year of exposure to tenofovir disoproxil fumarate (adjusted incidence rate ratio 1·14 95% CI 1·10-1·19, p<0·0001), ritonavir-boosted atazanavir (1·20 1·13-1·26, p<0·0001), and ritonavir-boosted lopinavir (1·11 1·06-1·16, p<0·0001), but not other ritonavir-boosted protease inhibitors or abacavir.
In people with normal renal function, the annual incidence of chronic kidney disease increased for up to 6 years of exposure to tenofovir disoproxil fumarate, ritonavir-boosted atazanavir, or ritonavir-boosted lopinavir therapy. Although the absolute number of new cases of chronic kidney disease was modest, treatment with these antiretrovirals might result in an increasing and cumulative risk of chronic kidney disease. Patients on potentially nephrotoxic antiretrovirals or at high risk of chronic kidney disease should be closely monitored.
The Highly Active Antiretroviral Therapy Oversight Committee.
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