Risk, predictors, and mortality associated with non-AIDS events in newly diagnosed HIV-infected patients
ABSTRACT OBJECTIVE:: We aimed to characterize non-AIDS events (NAEs) occurring in newly diagnosed HIV-infected patients in a contemporary cohort. METHODS:: CoRIS is a prospective, multicentre cohort of HIV-infected patients antiretroviral naïve at entry, established in 2004. We evaluated the incidence of- and the mortality due to NAEs and AIDS events through October-2010. Poisson regression was used to investigate factors associated with a higher incidence of NAEs. RESULTS:: Overall, 5,185 patients (13.306 person-years of follow-up), median age (interquartile range) 36 (29-43) years, participated in the study. 86.5% patients had been diagnosed in 2004 or later. The incidence rate (IR) of NAEs was 28.93 per 1000 person-years (95% confidence interval [CI], 26.15-32.07), and of AIDS-defining events 25.23 per 1000 person-years (95% CI, 22.60-28.16). The most common NAEs were psychiatric, hepatic, malignant, renal, and cardiovascular-related. After adjustment, age, higher HIV-viral load and lower CD4 count at cohort entry were associated with the occurrence of NAEs, while likelihood significantly decreased with sexual transmission and higher educational level. Additionally, antiretroviral therapy was inversely associated with the development of some NAEs, specifically of psychiatric (IR ratio [95%CI] 0.54 [0.30-0.96]) and renal-related (IR ratio [95%CI] 0.31 [0.13-0.72]) events. 173 (3.33%) patients died during the study period. NAEs contributed to 28.9% of all deaths, with an IR (95%CI) of 3.75 (2.84-4.94) per 1000-person-years. CONCLUSION:: In patients newly diagnosed of HIV infection, NAEs are a significant cause of morbidity and mortality. Our results suggest a protective effect of antiretroviral therapy in the occurrence of NAEs, in particular of psychiatric and renal-related events.
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ABSTRACT: To summarize recent findings on the relationship between CD4 cell count metrics and selected serious clinical outcomes, and to deduce implications for CD4 cell count monitoring in treated HIV infection and the timing of combination antiretroviral therapy initiation. In treated HIV infection, a higher latest CD4 cell count is associated with a lower short-term risk of serious non-AIDS events (often composite endpoints) even in CD4 cell count strata more than 350/μl. Knowledge of alternate CD4 cell count metrics, such as CD4 cell count slope, nadir level and time spent under specific CD4 cell count thresholds, does not seem to confer additional prognostic information beyond that achieved by current CD4 cell count. Latest CD4 cell count is strongly associated with a short-term risk of infection-related non-AIDS malignancies, and serious hepatic events; however, the evidence is inconsistent for cardiovascular outcomes. Studies vary significantly in definitions of composite endpoints as well as the rigorousness of outcome ascertainment, which could explain the heterogeneity in results. Current CD4 cell count, but not other metrics, could be an important clinical tool to predict the short-term risk of serious non-AIDS events in treated HIV-positive individuals. An earlier initiation of therapy at CD4 cell count more than 350/μl or above 500/μl is likely to improve long-term CD4 cell count metrics. Whether it provides net individual clinical benefit requires a randomized trial.Current opinion in HIV and AIDS 11/2013; 9. DOI:10.1097/COH.0000000000000017 · 4.39 Impact Factor
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ABSTRACT: Objectives We aimed to characterize depression in newly diagnosed HIV-infected patients, to determine the effect of antiretroviral therapy (ART) on its incidence, and to investigate whether efavirenz use was associated with a higher risk, compared with non-efavirenz-containing regimens, in the Spanish CoRIS cohort. Methods CoRIS is a contemporary, multicentre cohort of HIV-infected patients, antiretroviral-naïve at entry, launched in 2004. Poisson regression models were used to investigate demographic, clinical and treatment-related factors associated with a higher incidence of clinically significant depression to October 2010. ResultsIn total, 5185 patients (13 089 person-years) participated in the study, of whom 3379 (65.2%) started ART during follow-up. The incidence rates of depression before and after starting ART were 11.68 [95% confidence interval (CI) 9.01–15.15] and 7.06 (95% CI 5.45–9.13) cases per 1000 person-years, respectively. After adjustment, there was an inverse association between the occurrence of depression and the initiation of ART [incidence rate ratio (IRR) 0.53; 95% CI 0.28–0.99], while the likelihood of depression increased in patients of age > 50 years (IRR 1.94; 95% CI 1.21–3.12). Longer exposure to ART was associated with a decreased IRR of depression in unadjusted and adjusted analyses. The IRR for patients receiving < 2, 2–4 and > 4 years of ART was 0.72 (95% CI 0.36–1.44), 0.10 (95% CI 0.04–0.25) and 0.05 (95% CI 0.01–0.17), respectively, compared with ART-naïve patients. This protective effect was also observed when durations of exposure to nonnucleoside reverse transcriptase inhibitor-based regimens and efavirenz-containing regimens were analysed separately. Conclusions The incidence of clinically significant depression was lower among HIV-infected patients on ART. The protective effect of ART was also observed with efavirenz-containing regimens.HIV Medicine 12/2013; 15(4). DOI:10.1111/hiv.12104 · 3.45 Impact Factor
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ABSTRACT: Despite the major advances in the management of HIV infection, HIV-infected patients still have greater morbidity and mortality than the general population. Serious non-AIDS events (SNAEs), including non-AIDS malignancies, cardiovascular events, renal and hepatic disease, bone disorders and neurocognitive impairment, have become the major causes of morbidity and mortality in the antiretroviral therapy (ART) era. SNAEs occur at the rate of 1 to 2 per 100 person-years of follow-up. The pathogenesis of SNAEs is multifactorial and includes the direct effect of HIV and associated immunodeficiency, underlying co-infections and co-morbidities, immune activation with associated inflammation and coagulopathy as well as ART toxicities. A number of novel strategies such as ART intensification, treatment of co-infection, the use of anti-inflammatory drugs and agents that reduce microbial translocation are currently being examined for their potential effects in reducing immune activation and SNAEs. However, currently, initiation of ART before advanced immunodeficiency, smoking cessation, optimisation of cardiovascular risk factors and treatment of HCV infection are most strongly linked with reduced risk of SNAEs or mortality. Clinicians should therefore focus their attention on addressing these issues prior to the availability of further data.AIDS Research and Therapy 12/2013; 10(1):29. DOI:10.1186/1742-6405-10-29 · 1.84 Impact Factor