Long‐term effectiveness of recommended boosted protease inhibitor‐based antiretroviral therapy in Europe

Objectives

The aim of the study was to evaluate the long‐term response to antiretroviral treatment (ART) based on atazanavir/ritonavir (ATZ/r)‐, darunavir/ritonavir (DRV/r)‐, and lopinavir/ritonavir (LPV/r)‐containing regimens.

Methods

Data were analysed for 5678 EuroSIDA‐enrolled patients starting a DRV/r‐, ATZ/r‐ or LPV/r‐containing regimen between 1 January 2000 and 30 June 2013. Separate analyses were performed for the following subgroups of patients: (1) ART‐naïve subjects (8%) at ritonavir‐boosted protease inhibitor (PI/r) initiation; (2) ART‐experienced individuals (44%) initiating the new PI/r with a viral load (VL) ≤500 HIV‐1 RNA copies/mL; and (3) ART‐experienced patients (48%) initiating the new PI/r with a VL >500 copies/mL. Virological failure (VF) was defined as two consecutive VL measurements >200 copies/mL ≥24 weeks after PI/r initiation. Kaplan–Meier and multivariable Cox models were used to compare risks of failure by PI/r‐based regimen. The main analysis was performed with intention‐to‐treat (ITT) ignoring treatment switches.

Results

The time to VF favoured DRV/r over ATZ/r, and both were superior to LPV/r (log‐rank test; P < 0.02) in all analyses. Nevertheless, the risk of VF in ART‐naïve patients was similar regardless of the PI/r initiated after controlling for potential confounders. The risk of VF in both treatment‐experienced groups was lower for DRV/r than for ATZ/r, which, in turn, was lower than for LPV/r‐based ART.

Conclusions

Although confounding by indication and calendar year cannot be completely ruled out, in ART‐experienced subjects the long‐term effectiveness of DRV/r‐containing regimens appears to be greater than that of ATZ/r and LPV/r.

     

Food insecurity may lead to incomplete HIV viral suppression and less immune reconstitution among HIV/hepatitis C virus‐coinfected people

Objectives

The aim of this study was to determine the impact of food insecurity (FI) on HIV viral load and CD4 count among people coinfected with HIV and hepatitis C virus (HCV).

Methods

This study was conducted using data from the Food Security & HIV‐HCV Sub‐Study of the Canadian Co‐Infection Cohort study. FI was measured using the adult scale of Health Canada's Household Food Security Survey Module and was classified into three categories: food security, moderate food insecurity and severe food insecurity. The association between FI, HIV viral load, and CD4 count was assessed using a stabilized inverse probability weighted marginal structural model.

Results

A total of 725 HIV/HCV‐coinfected people with 1973 person‐visits over 3 years of follow‐up contributed to this study. At baseline, 23% of participants experienced moderate food insecurity and 34% experienced severe food insecurity. The proportion of people with undetectable HIV viral load was 75% and the median CD4 count was 460 [interquartile range (IQR): 300–665] cells/μL. People experiencing severe food insecurity had 1.47 times [95% confidence interval (CI): 1.14, 1.88] the risk of having detectable HIV viral load and a 0.91‐fold (95% CI: 0.84, 0.98) increase in CD4 count compared with people who were food secure.

Conclusions

These findings provide evidence of the negative impact of food insecurity on HIV viral load and CD4 count among HIV/HCV‐coinfected people.

     

Neglect of attention to reproductive health in women with HIV infection: contraceptive use and unintended pregnancies in the Swiss HIV Cohort Study

Objectives

Women with HIV infection are mainly of reproductive age and need safe, effective and affordable contraception to avoid unintended pregnancies. The aim of this study was to evaluate contraceptive use and unintended pregnancies in this population in Switzerland.

Methods

A self‐report anonymous questionnaire on contraceptive methods, adherence to them, and unintended pregnancies was completed by women included in the Swiss HIV Cohort Study (SHCS) between November 2013 and June 2014. Sociodemographic characteristics and information related to combined antiretroviral therapy and HIV disease status were obtained from the SHCS database.

Results

Of 462 women included, 164 (35.5%) reported not using any contraception. Among these, 65 (39.6%) reported being sexually active, although 29 (44.6%) were not planning a pregnancy. Of 298 women using contraception, the following methods were reported: condoms, 219 (73.5%); oral hormonal contraception, 32 (10.7%); and intrauterine devices, 28 (9.4%). Among all women on contraception, 32 (10.7%) reported using more than one contraceptive method and 48 (16%) had an unintended pregnancy while on contraception (18, condoms; 16, oral contraception; four, other methods). Of these, 68.1% terminated the pregnancy and almost half (43.7%) continued using the same contraceptive method after the event.

Conclusions

Family planning needs in HIV‐positive women are not fully addressed because male condoms remained the predominant reported contraceptive method, with a high rate of unintended pregnancies. It is of utmost importance to provide effective contraception such as long‐acting reversible contraceptives for women living with HIV.

     

HIV prevalence among first‐presentation psychotic patients

Objectives

First‐episode psychosis is a frequent emergency department (ED) presentation that may potentially be secondary to an underlying life‐threatening HIV‐related condition. The aim of this study was to determine the prevalence of HIV infection in patients presenting with a first episode of psychosis.

Methods

Medical records of 159 consecutive African, Asian, White and mixed ethnicity patients presenting to a tertiary academic hospital ED with a first episode of psychotic features were prospectively reviewed.

Results

Of the 159 subjects, 63 (39.6%) were HIV positive. An underlying medical condition was the most common aetiology of psychosis in both HIV‐positive (84.2%) and HIV‐negative (35.4%) subjects, but was significantly more common in HIV‐positive individuals (P < 0.001). Substance‐induced psychotic disorders and other primary psychiatric disorders were significantly more common in subjects without HIV infection (P < 0.001 and P < 0.001, respectively). While there were more men in the HIV‐negative group (66.7%), gender distribution was almost equal in the HIV‐infected group (49.2% male). Overall, as well as in both groups, most subjects were of African race, were unemployed and had not completed high school.

Conclusions

Co‐occurrence of HIV infection was a frequent finding in first‐episode psychotic individuals residing in a high‐prevalence HIV setting. These individuals are more likely to have an underlying medical condition precipitating the onset of psychosis, not to have been initiated on antiretroviral therapy and to present with a low CD4 cell count and high HIV viral load.

     

Hospital‐based routine HIV testing in high‐income countries: a systematic literature review

Objectives

To produce a summary of the published evidence of the barriers and facilitators for hospital‐based routine HIV testing in high‐income countries.

Methods

Electronic databases were searched for studies, which described the offer of HIV testing to adults attending emergency departments (EDs) and acute medical units (AMUs) in the UK and US, published between 2006 and 2015. Other high‐income countries were not included, as their guidelines do not recommend routine testing for HIV. The main outcomes of interest were HIV testing uptake, HIV testing coverage, factors facilitating HIV screening and barriers to HIV testing. Fourteen studies met the pre‐defined inclusion criteria and critically appraised using mixed methods appraisal tool (MMAT).

Results

HIV testing coverage ranged from 9.7% to 38.3% and 18.7% to 26% while uptake levels were high (70.1–84% and 53–75.4%) in the UK and US, respectively. Operational barriers such as lack of time, the need for training and concerns about giving results and follow‐up of HIV positive results, were reported. Patient‐specific factors including female sex, old age and low risk perception correlated with refusal of HIV testing. Factors that facilitated the offer of HIV testing were venous sampling (vs. point‐of‐care tests), commitment of medical staff to HIV testing policy and support from local HIV specialist providers.

Conclusions

There are several barriers to routine HIV testing in EDs and AMUs. Many of these stem from staff fears about offering HIV testing due to the perceived lack of knowledge about HIV. Our systematic review highlights areas which can be targeted to increase coverage of routine HIV testing.

     

Promoting high standards of care for women living with HIV: position statement from the Women Against Viruses in Europe Working Group

Objectives

Gender‐related factors can influence management decisions, treatment outcomes and the overall long‐term wellbeing of people living with HIV (PLWH). The Women Against Viruses in Europe (WAVE) Working Group was established to promote the health and wellbeing of women living with HIV (WLWH). WAVE is part of the European AIDS Clinical Society (EACS) and organizes annual workshops to discuss different issues in the management of WLWH.

Methods

In 2016, 34 WAVE members including community representatives, HIV clinicians and researchers met to discuss standards of care for WLWH and to review current guidelines. Participants focused on three different themes: (1) access to and engagement and retention in care; (2) monitoring of women on antiretroviral therapy and management of comorbidities; and (3) review of EACS treatment guidelines.

Results

Five priority areas for optimizing the care of WLWH were identified: (1) psychosocial aspects of HIV diagnosis and care; (2) mental health and wellbeing; (3) pharmacokinetics, toxicity and tolerability of antiretroviral therapy; (4) coinfections and comorbidities; and (5) sexual and reproductive health. WAVE recommendations are provided for each of these areas, and gaps in knowledge and needs for changes in currently existing standards are discussed.

Conclusions

This position statement provides an overview of the key recommendations to optimize the care of WLWH that emerged during the 2016 WAVE workshop.

     

The world‐wide incidence of Kaposi's sarcoma in the HIV/AIDS era

Objectives

Kaposi's sarcoma (KS) is a multicentric angioproliferative cancer of endothelial origin typically occurring in the context of immunosuppression or immunodeficiency. Consequently, KS is one of the most common cancers in HIV‐infected individuals and frequently occurs among transplant recipients. Nevertheless, its incidence in different populations is not well understood.

Methods

We searched online databases for publications on KS incidence. A random‐effect meta‐analysis was performed to combine the KS incidences and incidence rate ratios (IRRs) for associated risk factors.

Results

Seventy‐six eligible studies representing 71 time periods were included. For HIV‐infected people, the overall KS incidence was 481.54 per 100 000 person‐years with a 95% confidential interval (CI) of 342.36–677.32 per 100 000 person‐years. HIV‐infected men who have sex with men (MSM) had the highest incidence of KS (1397.11 per 100 000 person‐years; 95% CI 870.55–2242.18 per 100 000 person‐years). The incidence of KS was significantly lower in female than in male individuals (IRR 3.09; 95% CI 1.70–5.62). People receiving highly active antiretroviral therapy (HAART) had a lower incidence compared with people who had never received HAART (IRR 6.57; 95% CI 1.91–24.69). The incidence of KS was 68.59 (95% CI 31.39–149.86) per 100 000 person‐years in transplant recipients, 52.94 (95% CI 39.90–70.20) per 100 000 person‐years in children with HIV infection, and 1.53 (95% CI 0.33–7.08) per 100 000 person‐years in the general population.

Conclusions

Globally, a relatively high incidence of KS was found among HIV‐seropositive people and, in particular, in HIV‐infected MSM. The introduction of HAART has largely prevented the development of KS, but it has not entirely removed the challenge of KS. In Africa, in particular, KS imposes a very heavy disease burden, which can mainly be attributed to the high prevalence of KS‐associated herpesvirus and poor access to HAART.

     

Antiretroviral pill count and clinical outcomes in treatment‐naïve patients with HIV infection

Objectives

Treatment guidelines recommend single‐tablet regimens for patients with HIV infection starting antiretroviral therapy. These regimens might be as effective and cost less if taken as separate drugs. We assessed whether the one pill once a day combination of efavirenz, emtricitabine and tenofovir reduces the risk of disease progression compared with multiple‐pill formulations of the same regimen.

Methods

We selected treatment‐naïve patients starting one‐, two‐ or three‐pill formulations of this regimen in data from the Antiretroviral Therapy Cohort Collaboration. These patients were followed until an AIDS event or death or until they modified their regimen. We analysed these data using Cox regression models, then used our models to predict the potential consequences of exposing a future population to either a one‐pill regimen or a three‐pill regimen.

Results

Among 11 739 treatment‐naïve patients starting the regimen, there were 386 AIDS events and 87 deaths. Follow‐up often ended when patients switched to the same regimen with fewer pills. After the first month, two pills rather than one was associated with an increase in the risk of AIDS or death [hazard ratio (HR) 1.39; 95% confidence interval (CI) 1.01‐1.91], but three pills rather than two did not appreciably add to that increase (HR 1.19; 95% CI 0.84‐1.68). We estimate that 77 patients would need to be exposed to a one‐pill regimen rather than a three‐pill regimen for 1 year to avoid one additional AIDS event or death.

Conclusions

This particular single‐tablet regimen is associated with a modest decrease in the risk of AIDS or death relative to multiple‐pill formulations.

     

Cerebrospinal fluid HIV RNA in persons living with HIV

Objectives

Despite adequate suppression of plasma HIV RNA, viral escape in cerebrospinal fluid (CSF) is widely reported. Rates of CSF HIV RNA escape vary in the literature. In persons living with HIV (PLWH) undergoing lumbar puncture examination for clinical reasons, we assessed rates of CSF HIV RNA escape.

Methods

Persons living with HIV attending a designated HIV neurology service undergoing CSF assessment for clinical reasons between January 2015 and April 2017 were included in the study. CSF HIV RNA escape was defined as HIV RNA ≥ 0.5 log₁₀ HIV‐1 RNA copies/mL higher than plasma HIV RNA or detectable CSF HIV RNA when plasma HIV RNA was < 20 copies/mL. Clinical factors associated with CSF HIV RNA were assessed using logistic regression modelling.

Results

Of 38 individuals, 35 were receiving antiretroviral therapy, 30 were male and their mean age was 51 years. Clinical reasons for CSF assessment included investigation for cognitive decline (n = 25), early syphilis (n = 4) and other central nervous system (CNS) conditions (n = 9). HIV RNA was detectable in plasma and CSF in seven and six individuals, respectively, with two individuals (5.3%) meeting the definition of CSF escape. Detectable CSF HIV RNA was associated with a detectable plasma HIV RNA (P < 0.001) and a history of known antiretroviral drug resistance mutations (P = 0.021).

Conclusions

The prevalence of CSF viral escape in PLWH undergoing lumbar puncture examination for clinical reasons is lower than previously reported.

     

‘Get an early check – Chrysanthemum tea’: An outcome evaluation of a multimedia campaign promoting HIV testing among men who have sex with men in Hong Kong

Objectives

‘Get an early check – chrysanthemum tea’ was a multimedia campaign promoting HIV testing targeting Chinese‐speaking men who have sex with men (MSM) in Hong Kong, China. It ran from October to December 2015. This study was carried out to investigate the level of campaign exposure among Chinese‐speaking MSM in Hong Kong and the association between uptake of HIV testing in the last 6 months and campaign exposure.

Methods

A cross‐sectional survey was conducted 6 months after the campaign was launched. Participants were Hong Kong Chinese‐speaking men aged ≥18 years who had had anal or oral sex with at least one man in their lifetime. A total of 153 eligible participants completed the anonymous self‐administered questionnaire.

Results

Among the participants, 45.8% had been exposed to the campaign and 43.1% had taken up HIV testing in the last 6 months. In multivariate logistic regression analysis, exposure to the campaign [multivariate odds ratio (ORm) 2.55; 95% confidence interval (CI) 1.25, 5.19] and having had anal intercourse with a nonregular sex partner (ORm 2.36; 95% CI 1.05, 5.31) in the last 6 months were significantly associated with uptake of HIV testing in the last 6 months.

Conclusions

The campaign had relatively good reach in the target population and may have been useful to encourage them to take up HIV testing. Future campaigns promoting HIV testing among MSM in Hong Kong are still needed. Such programmes should consider making use of viral videos, having a longer project duration and developing culturally sensitive materials for non‐Chinese‐speaking MSM.

     

CD4:CD8 ratio in children with perinatally acquired HIV‐1 infection

Objectives

In adults with horizontally acquired HIV infection, an inverted CD4:CD8 ratio is associated with persistent immune activation, size of HIV reservoir and predicts an increased risk of non‐AIDS‐defining adverse events. Normalization of this ratio with antiretroviral therapy (ART) is suboptimal in adults, despite viral suppression, and is less well described in paediatric populations. We investigated rates of CD4:CD8 ratio recovery in children with perinatally acquired HIV infection (PaHIV) on ART.

Methods

A cross‐sectional, retrospective analysis of routine clinical data in children with PaHIV (5–18 years old) attending a single UK centre was carried out.

Results

CD4:CD8 normalization was seen in 62% of children on suppressive ART. A negative correlation was found between current CD4:CD8 ratio and age at start of ART. Positive correlations were found between current CD4:CD8 ratio and total time with suppressed HIV viral load and nadir CD4 counts. Multiple linear regression analysis showed that age at start of ART was significantly associated with current CD4:CD8 ratio (standardized β = ?0.680; P < 0.001). Patient sex, ethnicity and antiretroviral regimen did not affect ratio recovery.

Conclusions

We found higher rates of CD4:CD8 ratio normalization compared with previous adult studies. Children who started ART at a younger age were more likely to recover a normal ratio. The current policy of universal treatment for all HIV‐positive adults and children will enhance immunological normalization.

     

Screening for human papillomavirus,cervical cytological abnormalities and associated risk factors in HIV‐positive and HIV‐negative women in Rwanda

Objectives

Cervical cancer is the major cause of death from cancer in Africa. We wanted to assess the prevalence of human papillomavirus (HPV) infections and associated risk factors and to determine whether HPV testing could serve as a screening method for squamous intraepithelial lesions (SILs) in Rwanda. We also wanted to obtain a broader understanding of the underlying risk factors for the establishment of HPV infection in Rwanda.

Methods

A total of 206 HIV‐positive women, 172 HIV‐negative women and 22 women with unknown HIV status were recruited at the University Teaching Hospitals of Kigali (UTHK) and of Butare (UTHB) in Rwanda. Participants underwent an interview, cervical sampling for a Thinprep Pap test and a screening test analysing 37 HPV strains.

Results

Only 27% of HIV‐positive women and 7% of HIV‐negative women had been screened for cervical cancer before. HPV16 and HPV52 were the most common HPV strains. HIV‐positive women were more commonly infected with high‐risk (HR) HPV and multitype HPV than HIV‐negative women. The sensitivity was 78% and the specificity 87% to detect high‐grade SIL (HSIL) with HPV screening. Among HIV‐negative women, being divorced was positively associated with HR‐HPV infection, while hepatitis B, Trichomonas vaginalis infection and HR‐HPV infection were factors positively associated with SILs. Ever having had gonorrhoea was positively associated with HR‐HPV infection among HIV‐positive women. HR‐HPV infection and the number of live births were positively associated with SILs.

Conclusions

The currently used quadrivalent vaccine may be insufficient to give satisfactory HPV coverage in Rwanda. HPV Screening may be effective to identify women at risk of developing cervical cancer, particularly if provided to high‐risk patients.

     

Increasing incidence of HIV‐ associated tuberculosis in Romanian injecting drug users

Background

A high prevalence of tuberculosis (TB) among HIV‐positive injecting drug users (IDUs) may fuel the TB epidemic in the general population of Romania. We determined the frequency and characteristics of TB in HIV‐infected IDUs referred to a national centre.

Methods

Prospective observational cohort study of all newly‐diagnosed HIV‐positive IDUs admitted to Victor Babes Hospital, Bucharest, between January 2009 and December 2014. Socio‐demographics, clinical characteristics and outcomes of HIV/TB co‐infected IDUs were compared to HIV‐positive IDUs without TB.

Results

170/598 (28.5%) HIV‐infected IDUs were diagnosed with TB. The prevalence increased from 12.5% in 2009 to 32.1% in 2014 (P < 0.001). HIV/TB co‐infected individuals had lower median CD4 cell counts 75 (vs. 450/mm³, P < 0.0001) and higher median HIV viral loads 5.6 log₁₀ (vs. 4.9 log₁₀, P < 0.0001) when presenting to healthcare services. 103/170 (60.6%) HIV/TB co‐infected IDUs were diagnosed with pulmonary TB. Resistant Mycobacterium tuberculosis strains were common, with 18/105 (17.1%) of patients having Multi‐Drug Resistant (MDR) disease. Higher mortality rate was associated with TB co‐infection (P < 0.0001), extra‐pulmonary TB (P = 0.0026) and extensively drug resistant TB (P = 0.024).

Conclusions

Tuberculosis (TB) is an increasing problem in HIV‐infected IDUs in Romania. Presentation is often with advanced HIV, significant TB drug resistance and consequent outcomes are poor.

     

Effect of simplification from protease inhibitors to boosted atazanavir‐based regimens in real‐life conditions

Background

Atazanavir (ATV) boosted with ritonavir (ATV/r) is a potent, well‐tolerated, once‐daily protease inhibitor (PI). Few data are available on this agent as a treatment simplification option for patients taking other PIs.

Objective

The aim of the study was to determine the effectiveness and safety of ATV‐containing regimens in patients who have simplified their antiretroviral treatment.

Methods

SIMPATAZ was a multicentre, prospective, noninterventional study in patients who had undetectable HIV RNA on their current PI‐containing therapy and who were switched to an ATV/r‐based regimen. Patients underwent a routine physical examination, and data were collected on HIV RNA levels, CD4 cell counts, liver function, lipid parameters, adverse reactions, adherence to treatment and patient satisfaction.

Results

A total of 183 patients were enrolled in the study and included in the analysis (80% were male, 29% had AIDS, and 52% were coinfected with HIV and hepatitis B virus or hepatitis C virus). The median baseline CD4 count was 514 cells/μL. Median exposure to previous HIV therapy was 8 years, and 32% of patients had a history of PI failures. Lopinavir boosted with ritonavir was the most frequent PI replaced (62%) and tenofovir+lamivudine /emtricitabine the backbone most used during the study (29%). The study drug was discontinued early by 25 patients (14%), two of whom discontinued as a result of adverse events (Hodgkin lymphoma and vomiting). Two patients died (lung cancer and myocardial infarction). At month 12, 93% of the study population had an undetectable HIV RNA viral load. Hyperbilirubinaemia >3 mg/dL and increased alanine aminotransferase levels>200 IU/L were observed in 38.5% and 4.4% of patients, respectively. Median changes from baseline to month 12 in total cholesterol, triglycerides and low‐density lipoprotein cholesterol were ?13 mg/dL (?7%; P<0.0001), ?19 mg/dL (?13%; P<0.0001) and ?7 mg/dL (?6%; P=0.021), respectively.

Conclusions

In a real‐world setting, switching from other PIs to ATV/r is a well‐tolerated and safe option for improving the lipid profile and for retaining virological response in controlled pretreated patients.

     

Rates of sustained virological response 12 weeks after the scheduled end of direct‐acting antiviral (DAA)‐based hepatitis C virus (HCV) therapy from the National German HCV registry: does HIV coinfection impair the response to DAA combination therapy?

Objectives

The European Association for the Study of the Liver (EASL) treatment recommendations for hepatitis C no longer discriminate between HIV/hepatitis C virus (HCV)‐coinfected and HCV‐monoinfected patients. However, recent data from Spain are questioning these recommendations on the basis of the findings of higher relapse rates and lower cure rates in HIV/HCV‐infected subjects. The aim of our study was to compare HCV cure rates in monoinfected and coinfected patients from Germany.

Methods

Data acquired from the Deutsches Hepatitis C‐Registry were analysed. A total of 5657 HCV‐monoinfected subjects and 488 HIV/HCV‐coinfected patients were included in the study. Rates of sustained virological response 12 weeks after the scheduled end of therapy (SVR12) were collected in both subgroups and in cirrhotic and noncirrhotic patients.

Results

HIV/HCV‐coinfected patients were more frequently male (84.6% vs. 56.4%, respectively; P < 0.001) and younger than HCV‐monoinfected subjects (46.5 ± 9 vs. 53.8 ± 12.5 years, respectively; P < 0.001). The CD4 blood cell count was > 350 cells/μL in 63.1% of HIV‐positive subjects and 88.7% were on antiretroviral therapy. SVR12 rates were 90.3% (5111 of 5657) in our HCV‐monoinfected cohort and 91.2% (445 of 488) in our coinfected patients. Liver cirrhosis was confirmed in 1667 of 5657 (29.5%) monoinfected patients and 84 of 488 (17.2%; P < 0.001) coinfected patients. SVR12 rates did not differ between HCV‐monoinfected and HIV/HCV‐coinfected patients with liver cirrhosis (87.8% vs. 89.3%, respectively; P = 0.864). A treatment duration of 8 weeks did not reduce the percentage of patients with SVR12 in either subgroup (93.7% in both groups).

Conclusions

We found high SVR12 rates in monoinfected as well as coinfected individuals. No differences were detected between the two subgroups regardless of whether there was accompanying liver cirrhosis or a shortened treatment duration.

     

High density lipoprotein cholesterol levels are an independent predictor of the progression of chronic kidney disease

Objectives

Patients with chronic kidney disease (CKD) often present with reduced plasma HDL cholesterol (HDL‐C) levels. Whether this reduction in an epiphenomenon or is involved in disease progression is unclear. The aim of this study was to investigate the relation between HDL‐C levels/function and CKD progression in patients with different degrees of disease.

Design

A total of 176 patients with CKD [glomerular filtration rate (GFR) 50.3 ± 29.1 mL min^?1] were recruited and followed for up to 84 months. Lipid profile, metabolic status and kidney function were evaluated at predetermined times. Age‐matched control subjects were selected from the PLIC study (n = 453). Scavenger receptor class B member 1 (SR‐BI) and ATP‐binding cassette transporter A1 (ABCA‐1)‐dependent efflux of cholesterol were measured in CKD patients and in age‐matched control subjects.

Results

Low HDL‐C levels, diabetes and hypertension were associated with reduced GFR. At follow‐up, low HDL‐C levels were associated with earlier entry in dialysis or doubling of the plasma creatinine level (P = 0.017); HDL‐C levels were the only lipid parameter that affected the progression of CKD (hazard ratio 0.951, 95% confidence interval 0.917–0.986, P = 0.007), independently of the presence of diabetes. Only SR‐BI‐mediated serum cholesterol efflux was significantly reduced in the group of CKD patients with low HDL‐C levels compared to the control group.

Conclusions

CKD patients with low levels of plasma HDL‐C have a poor prognosis. HDL functionality is also impaired in renal dysfunction. These data support the relevance of HDL in influencing CKD progression.

     

Personality Changes During the Transition from Cognitive Health to Mild Cognitive Impairment

Background/Objectives

Behavioral problems in individuals with Alzheimer's disease (AD ) impose major management challenges. Current prevention strategies are anchored to cognitive outcomes, but behavioral outcomes may provide another, clinically relevant opportunity for preemptive therapy. We sought to determine whether personality changes that predispose to behavioral disorders arise during the transition from preclinical AD to mild cognitive impairment (MCI ).

Design

Longitudinal observational cohort study.

Setting

Academic medical center.

Participants

Members of an apolipoprotein E (APOE ) ?4 genetically enriched cohort of Maricopa County residents who were neuropsychiatrically healthy at entry (N = 277). Over a mean interval of 7 years, 25 who developed MCI and had the Neuroticism, Extraversion, and Openness Personality Inventory—Revised (NEO ‐PI ‐R) before and during the MCI transition epoch were compared with 252 nontransitioners also with serial NEO ‐PI ‐R administrations.

Intervention

Longitudinal administration of the NEO ‐PI ‐R and neuropsychological test battery.

Measurements

Change in NEO ‐PI ‐R factor scores (neuroticism, extraversion, openness, agreeableness, conscientiousness) from entry to the epoch of MCI diagnosis or an equivalent follow‐up duration in nontransitioners.

Results

NEO ‐PI ‐R neuroticism T‐scores increased significantly more in MCI transitioners than in nontransitioners (mean 2.9, 95% confidence interval (CI ) = 0.9–4.9 vs 0, 95% CI = ?0.7–0.7, P = .02), and openness decreased more in MCI transitioners than in nontransitioners (?4.8, 95% CI = ?7.3 to ?2.4 vs ?1.0, 95% CI = ?1.6 to ?0.4, P < .001). Concurrent subclinical but statistically significant changes in behavioral scores worsened more in MCI transitioners than nontransitioners for measures of depression, somatization, irritability, anxiety, and aggressive attitude.

Conclusion

Personality and subclinical behavioral changes begin during the transition from preclinical AD to incident MCI and qualitatively resemble the clinically manifest behavioral disorders that subsequently arise in individuals with frank dementia.