Gender differences in the use of cardiovascular interventions in HIV-positive persons; the D:A:D Study

Peer reviewe

Development and Validation of a Risk Score for Chronic Kidney Disease in HIV Infection Using Prospective Cohort Data from the D:A:D Study

Ristola M. on työryhmien DAD Study Grp ; Royal Free Hosp Clin Cohort ; INSIGHT Study Grp ; SMART Study Grp ; ESPRIT Study Grp jäsen.Background Chronic kidney disease (CKD) is a major health issue for HIV-positive individuals, associated with increased morbidity and mortality. Development and implementation of a risk score model for CKD would allow comparison of the risks and benefits of adding potentially nephrotoxic antiretrovirals to a treatment regimen and would identify those at greatest risk of CKD. The aims of this study were to develop a simple, externally validated, and widely applicable long-term risk score model for CKD in HIV-positive individuals that can guide decision making in clinical practice. Methods and Findings A total of 17,954 HIV-positive individuals from the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study with >= 3 estimated glomerular filtration rate (eGFR) values after 1 January 2004 were included. Baseline was defined as the first eGFR > 60 ml/min/1.73 m2 after 1 January 2004; individuals with exposure to tenofovir, atazanavir, atazanavir/ritonavir, lopinavir/ritonavir, other boosted protease inhibitors before baseline were excluded. CKD was defined as confirmed (>3 mo apart) eGFR In the D:A:D study, 641 individuals developed CKD during 103,185 person-years of follow-up (PYFU; incidence 6.2/1,000 PYFU, 95% CI 5.7-6.7; median follow-up 6.1 y, range 0.3-9.1 y). Older age, intravenous drug use, hepatitis C coinfection, lower baseline eGFR, female gender, lower CD4 count nadir, hypertension, diabetes, and cardiovascular disease (CVD) predicted CKD. The adjusted incidence rate ratios of these nine categorical variables were scaled and summed to create the risk score. The median risk score at baseline was -2 (interquartile range -4 to 2). There was a 1: 393 chance of developing CKD in the next 5 y in the low risk group (risk score = 5, 505 events), respectively. Number needed to harm (NNTH) at 5 y when starting unboosted atazanavir or lopinavir/ritonavir among those with a low risk score was 1,702 (95% CI 1,166-3,367); NNTH was 202 (95% CI 159-278) and 21 (95% CI 19-23), respectively, for those with a medium and high risk score. NNTH was 739 (95% CI 506-1462), 88 (95% CI 69-121), and 9 (95% CI 8-10) for those with a low, medium, and high risk score, respectively, starting tenofovir, atazanavir/ritonavir, or another boosted protease inhibitor. The Royal Free Hospital Clinic Cohort included 2,548 individuals, of whom 94 individuals developed CKD (3.7%) during 18,376 PYFU (median follow-up 7.4 y, range 0.3-12.7 y). Of 2,013 individuals included from the SMART/ESPRIT control arms, 32 individuals developed CKD (1.6%) during 8,452 PYFU (median follow-up 4.1 y, range 0.6-8.1 y). External validation showed that the risk score predicted well in these cohorts. Limitations of this study included limited data on race and no information on proteinuria. Conclusions Both traditional and HIV-related risk factors were predictive of CKD. These factors were used to develop a risk score for CKD in HIV infection, externally validated, that has direct clinical relevance for patients and clinicians to weigh the benefits of certain antiretrovirals against the risk of CKD and to identify those at greatest risk of CKD.Peer reviewe

HIV and Cognitive Impairment in Clinical Practice : The Evaluation of a Stepwise Screening Protocol in Relation to Clinical Outcomes and Management

Neurocognitive impairment (NCI) is an increasingly important comorbidity in an ageing HIV+ population. Despite the lack of available treatment modalities, screening for NCI is recommended. In the UMC Utrecht, yearly NCI screening is done using the Montreal Cognitive Assessment (MoCA) tool and the HIV Dementia Scale (HDS). The aim of this study was to evaluate this screening protocol in relation to clinical outcomes and management. A retrospective cohort study was performed in suppressed adult HIV+ patients. Apart from the MoCa and the HDS, the Utrecht Scale for Evaluation of Rehabilitation-Participation (USER-P) and the Hospital Anxiety and Depression Scale (HADS) were performed. Patients scoring below average on cognitive screening tests or with subjective cognitive complaints were further evaluated using a standardized protocol, including optimizing cART and checking for somatic disorders. In patients with cognitive complaints and participation restrictions, cognitive rehabilitation was proposed. Two hundred eighty-six patients were screened. The vast majority were MSM with an average age of 49 years. One hundred forty-four out of 286 patients (50%) had an abnormal test score and/or had subjective cognitive complaints. Restrictions in participation were present in 23% of patients. Six patients on Efavirenz switched their regimes, as this drug is known for its potential central nervous system (CNS) side effects. A depressive component was present in 58 patients (40%). Five patients had a clinical relevant laboratory abnormality. Moreover, six patients were referred for cognitive rehabilitation, which resulted in a 100% success rate in set goals in the five evaluable patients. Although the protocol was not fully adhered to in all patients, it did result in detectable underlying causes of NCI in 59% of patients, and 21% was referred for further treatment. Moreover, cognitive rehabilitation appears to be a very successful intervention for patients with NCI who experience subjective complaints and participation restrictions

HIV and Cognitive Impairment in Clinical Practice : The Evaluation of a Stepwise Screening Protocol in Relation to Clinical Outcomes and Management

Neurocognitive impairment (NCI) is an increasingly important comorbidity in an ageing HIV+ population. Despite the lack of available treatment modalities, screening for NCI is recommended. In the UMC Utrecht, yearly NCI screening is done using the Montreal Cognitive Assessment (MoCA) tool and the HIV Dementia Scale (HDS). The aim of this study was to evaluate this screening protocol in relation to clinical outcomes and management. A retrospective cohort study was performed in suppressed adult HIV+ patients. Apart from the MoCa and the HDS, the Utrecht Scale for Evaluation of Rehabilitation-Participation (USER-P) and the Hospital Anxiety and Depression Scale (HADS) were performed. Patients scoring below average on cognitive screening tests or with subjective cognitive complaints were further evaluated using a standardized protocol, including optimizing cART and checking for somatic disorders. In patients with cognitive complaints and participation restrictions, cognitive rehabilitation was proposed. Two hundred eighty-six patients were screened. The vast majority were MSM with an average age of 49 years. One hundred forty-four out of 286 patients (50%) had an abnormal test score and/or had subjective cognitive complaints. Restrictions in participation were present in 23% of patients. Six patients on Efavirenz switched their regimes, as this drug is known for its potential central nervous system (CNS) side effects. A depressive component was present in 58 patients (40%). Five patients had a clinical relevant laboratory abnormality. Moreover, six patients were referred for cognitive rehabilitation, which resulted in a 100% success rate in set goals in the five evaluable patients. Although the protocol was not fully adhered to in all patients, it did result in detectable underlying causes of NCI in 59% of patients, and 21% was referred for further treatment. Moreover, cognitive rehabilitation appears to be a very successful intervention for patients with NCI who experience subjective complaints and participation restrictions

Factors associated with presenting late or with advanced HIV disease in the Netherlands, 1996 2014: Results from a national observational cohort

Objectives: Early testing for HIV and entry into care are crucial to optimise treatment outcomes of HIV-infected patients and to prevent spread of HIV. We examined risk factors for presentation with late or advanced disease in HIV-infected patients in the Netherlands. Methods: HIV-infected patients registered in care between January 1996 and June 2014 were selected from the ATHENA national observational HIV cohort. Risk factors for late presentation and advanced disease were analysed by multivariable logistic regression. Furthermore, geographical differences and time trends were examined. Results: Of 20 965 patients, 53% presented with latestage HIV infection, and 35% had advanced disease. Late presentation decreased from 62% (1996) to 42% (2013), while advanced disease decreased from 46% to 26%. Late presentation only declined significantly among men having sex with men (MSM; p <0.001), but not among heterosexual males (p=0.08) and females (p=0.73). Factors associated with late presentation were: heterosexual male (adjusted OR (aOR), 1.59; 95% CI 1.44 to 1.75 vs MSM), injecting drug use (2.00; CI 1.69 to 2.38), age .50 years (1.46; CI 1.33 to 1.60 vs 30.49 years), region of origin (South-East Asia 2.14; 1.80 to 2.54, sub-Saharan Africa 2.11; 1.88 to 2.36, Surinam 1.59; 1.37 to 1.84, Caribbean 1.31; 1.13 to 1.53, Latin America 1.23; 1.04 to 1.46 vs the Netherlands), and location of HIV diagnosis (hospital 3.27; 2.94 to 3.63, general practitioner 1.66; 1.50 to 1.83, antenatal screening 1.76; 1.38 to 2.34 vs sexually transmitted infection clinic). No association was found for socioeconomic status or level of urbanisation. Compared with Amsterdam, 2 regions had higher adjusted odds and 2 regions had lower odds of late presentation. Results were highly similar for advanced disease. Conclusions: Although the overall rate of late presentation is declining in the Netherlands, targeted programmes to reduce late HIV diagnoses remain needed for all risk groups, but should be prioritised for heterosexual males, migrant populations, people aged ≥50 years and certain regions in the Netherlands

Risk for non-AIDS-defining and AIDS-defining cancer of early versus delayed initiation of antiretroviral therapy: A multinational prospective cohort study

Background: Immediate initiation of antiretroviral therapy (ART) regardless of CD4 cell count reduces risk for AIDS and non-AIDS-related events in asymptomatic, HIV-positive persons and is the standard of care. However, most HIV-positive persons initiate ART when their CD4 count decreases below 500 × 109 cells/L. Consequences of delayed ART on risk for non-AIDS-defining and AIDS-defining cancer, one of the most common reasons for death in HIV, are unclear. Objective: To estimate the long-term risk difference for cancer with the immediate ART strategy. Design: Multinational prospective cohort study. Setting: The D:A:D (Data collection on Adverse events of anti-HIV Drugs) study, which included HIV-positive persons from Europe, Australia, and the United States. Participants: 8318 HIV-positive persons with at least 1 measurement each of CD4 cell count and viral load while ART-naive (study period, 2006 to 2016). Measurements: The parametric g-formula was used, with adjustment for baseline and time-dependent confounders (CD4 cell count and viral load), to assess the 10-year risk for non-AIDS-defining and AIDS-defining cancer of immediate versus deferred (at CD4 counts &lt; 350 and &lt; 500 × 109 cells/L) ART initiation strategies. Results: During 64 021 person-years of follow-up, 231 cases of non-AIDS-defining cancer and 272 of AIDS-defining cancer occurred among HIV-positive persons with a median age of 36 years (interquartile range, 29 to 43 years). With immediate ART, the 10-year risk for non-AIDS-defining cancer was 2.97% (95% CI, 2.37% to 3.50%) and that for AIDS-defining cancer was 2.50% (CI, 2.37% to 3.38%). Compared with immediate ART initiation, the 10-year absolute risk differences when deferring ART to CD4 counts less than 500 × 109 cells/L and less than 350 × 109 cells/L were 0.12 percentage point (CI, -0.01 to 0.26 percentage point) and 0.29 percentage point (CI, -0.03 to 0.73 percentage point), respectively, for non-AIDS-defining cancer and 0.32 percentage point (CI, 0.21 to 0.44 percentage point) and 1.00 percentage point (CI, 0.67 to 1.44 percentage points), respectively, for AIDS-defining cancer. Limitation: Potential residual confounding due to observational study design. Conclusion: In this young cohort, effects of immediate ART on 10-year risk for cancer were small, and further supportive data are needed for non-AIDS-defining cancer. Primary Funding Source: Highly Active Antiretroviral Therapy Oversight Committee