Cardiovascular disease risk in an urban African population: a cross-sectional analysis on the role of HIV and antiretroviral treatment.

BACKGROUND: Life expectancy is increasing in the HIV-positive population and age-related non-communicable diseases, such as cardiovascular disease, (CVD) are seen more frequently. This study investigated to what extent HIV and antiretroviral therapy (ART) is associated with CVD risk in an urban African population. METHODS: A cross-sectional study was performed in Johannesburg, South Africa, between July 2016 and November 2017. Both HIV-positive adults (ART-naïve, or on first- or second-line ART), as well as age and sex matched HIV-negative controls who were family or friends of the HIV-positive participants were included. Data were collected on demographics, cardiovascular risk factors, HIV-related characteristics, carotid intima-media thickness (CIMT) and carotid distensibility. The association between HIV, ART and CIMT and distensibility was analysed with linear regression models, adjusting for age, gender and CVD risk factors. RESULTS: The study included 548 participants, 337 (62%) females, age 38.3 ± 9.5 years of whom 104 (19.0%) were HIV-positive, ART-naïve; 94 (17.2%) were on first-line ART; 197 (35.9%) were on second-line ART; and 153 (27.9%) were HIV-negative. Participants on second-line ART had higher CIMT and lower distensibility compared to the other groups (p < 0.001). After adjustment for age, these outcomes were similar between groups. Further adjustment for CVD and HIV-related factors did not alter the findings. CONCLUSION: Neither HIV nor ART was associated with CIMT or carotid distensibility in this urban African population. Longitudinal studies are needed to fully understand the relationship between HIV and CVD across different populations.

Lipid levels, insulin resistance and cardiovascular risk over 96 weeks of antiretroviral therapy: a randomised controlled trial comparing low-dose stavudine and tenofovir.

BACKGROUND: HIV infection and antiretroviral treatment are associated with changes in lipid levels, insulin resistance and risk of cardiovascular disease (CVD). We investigated these changes in the first 96 weeks of treatment with low-dose stavudine or tenofovir regimens. METHODS: This is a secondary analysis of a double blind, randomised controlled trial performed in South-Africa, Uganda and India comparing low-dose stavudine (20 mg twice daily) with tenofovir in combination with efavirenz and lamivudine in antiretroviral-naïve adults (n = 1067) (Clinicaltrials.gov, NCT02670772). Over 96 weeks, data were collected on fasting lipids, glucose and insulin. Insulin resistance was assessed with the HOMA-IR index and 10-year CVD risk with the Framingham risk score (FRS). A generalized linear mixed model was used to estimate trends over time. RESULTS: Participants were on average 35.3 years old, 57.6% female and 91.8% Black African. All lipid levels increased following treatment initiation, with the sharpest increase in the first 24 weeks of treatment. The increase in all lipid subcomponents over 96 weeks was higher among those in the stavudine than the tenofovir group. Insulin resistance increased steadily with no difference detected between study groups. FRS rose from 1.90% (1.84-1.98%) at baseline to 2.06 (1.98-2.15%) at week 96 for the total group, with no difference between treatment arms (p = 0.144). Lipid changes were more marked in Indian than African participants. CONCLUSION: Lipid levels increased in both groups, with low-dose stavudine resulting in a worse lipid profile compared to tenofovir. Insulin resistance increased, with no difference between regimens. CVD risk increased over time and tended to increase more in the group on stavudine. The low CVD risk across both arms argues against routine lipid and glucose monitoring in the absence of other CVD risk factors. In high risk patients, monitoring may only be appropriate at least a year after treatment initiation.

Diminished impact of ethnicity as a risk factor for chronic kidney disease in the current HIV treatment era.

BACKGROUND: Chronic kidney disease (CKD) is an important comorbidity during human immunodeficiency virus (HIV) infection. Historically, HIV-associated nephropathy has been the predominant cause of CKD and has primarily been observed in people of African ancestry. This study aims to investigate the role of ethnicity in relation to CKD risk in recent years. METHODS: Analyses were performed including 16 836 patients from the Dutch AIDS Therapy Evaluation in the Netherlands (ATHENA) cohort. Baseline was defined as the first available creatinine level measurement after 1 January 2007; CKD was defined as a glomerular filtration rate of <60 mL/min/1.73 m(2). The associations between ethnicity and both prevalent CKD at baseline and incident CKD during follow-up were analyzed. RESULTS: The prevalence of baseline CKD was 2.7% (460 of 16 836 patients). Birth in a sub-Saharan African country (hereafter, "SSA origin") was significantly associated with baseline CKD (adjusted odds ratio 1.49; 95% confidence interval [CI], 1.04-2.13). During follow-up (median duration, 4.7 years; interquartile range, 2.4-5.2), the rate of incident CKD was 6.0 events per 1000 person-years. The risk of newly developing CKD was similar between patients of SSA origin and those born in Western Europe, Australia, or New Zealand (adjusted hazard ratio, 1.00; 95% CI, .63-1.59). CONCLUSIONS: Among HIV-infected patients in the Netherlands, being of SSA origin was associated with a higher baseline CKD prevalence but had no impact on newly developing CKD over time. This suggests a shift in the etiology of CKD from HIV-associated nephropathy toward other etiologies.

Carotid Intima Media Thickness in Mainly Female HIV-Infected Subjects in Rural South Africa: Association With Cardiovascular but Not HIV-Related Factors.

BACKGROUND: In sub-Saharan Africa, the number of persons living with human immunodeficiency virus (HIV) has increased immensely. In parallel, rates of noncommunicable diseases, especially cardiovascular disease, are rising rapidly in resource-limited settings. This study aims to evaluate the relation between subclinical atherosclerosis and HIV-related and traditional cardiovascular risk factors in HIV-infected patients in rural South Africa. METHODS: A cross-sectional study was performed among HIV-infected patients visiting a health center in Limpopo, South Africa. Demographic and HIV-related information was collected, and cardiovascular risk was assessed. Carotid intima media thickness (CIMT) was measured and the prevalence of subclinical atherosclerosis (CIMT >0.78 mm) was calculated. The association between cardiovascular or HIV-related determinants with CIMT was analyzed using linear and logistic regression models adjusted for age and sex. RESULTS: The median CIMT in 866 subjects (median age [interquartile range], 41 [35-48] years; 69% female) was 0.589 mm (interquartile range, 0.524-0.678 mm), and values seemed higher than in healthy Western reference populations. In fact 12% of subjects (106 of 866) had subclinical atherosclerosis. Hypertension, high body mass index, previous cardiovascular event, diabetes mellitus, total and low-density lipoprotein cholesterol, estimated glomerular filtration rate, metabolic syndrome, and the Framingham Heart Risk score were independently associated with CIMT. No HIV-related determinants were associated with CIMT. CONCLUSIONS: In a predominantly female HIV-infected population in South Africa, CIMT values are considerably high and associated with cardiovascular risk factors, rather than HIV-related factors. This finding emphasizes the need to screen for cardiovascular disease among persons with HIV infection in resource-limited settings. Ideally, this screening would be integrated into care for chronic HIV infection, posing a major challenge for the future.

Trends in body mass index in the pre-dolutegravir period in South Africa.

Background: Antiretroviral therapy (ART) is associated with weight gain, but this has been shown to be more marked with dolutegravir and other integrase strand transfer inhibitors. Objectives: We studied weight gain in people living with HIV (PLWH) on ART compared to the general population in the period before dolutegravir was introduced in a rural South African cohort. Method: Longitudinal analysis of the Ndlovu Cohort Study including 36-48 months' follow-up data. From 2014 to 2019, data were collected annually in Limpopo, rural South Africa. Linear mixed models using HIV status, demographics, ART use and cardiovascular risk factors were used to estimate trends in body mass index (BMI) over time. Results: In total, 1518 adult, non-pregnant participants were included, of whom 518 were PLWH on ART (79.8%), 135 PLWH not yet on ART (20.2%) and 865 HIV-negative. HIV-negative participants had significantly higher BMIs than PLWH on ART at all study visits. There was a significant increase in BMI in all subgroups after 36 months (PLWH on ART, BMI +1.2 kg/m2, P < 0.001; PLWH not on ART, BMI +1.8 kg/m2, P < 0.001 and HIV-negative, BMI +1.3 kg/m2, P < 0.001). Conclusion: The increase in BMI in PLWH and HIV-negative participants is a serious warning signal as obesity results in morbidity and mortality.

No Evidence for an Association of HIV and Antiviral Treatment With Changes in Framingham Cardiovascular Risk Score in the Ndlovu Cohort Study.

BACKGROUND: HIV and antiretroviral therapy (ART) have been associated with increased cardiovascular disease (CVD) risk in high-income countries. The authors studied the longitudinal association between HIV and ART and nonlaboratory Framingham Risk Score (FRS) in a middle-income country. METHODS AND RESULTS: This longitudinal analysis of the NCS (Ndlovu Cohort Study), South Africa used baseline to 36-month follow-up data. Demographics, HIV, ART status, and cardiometabolic measures were obtained. FRS was used as a CVD risk measure. Through linear mixed models, FRS trends over time and the association with HIV were studied. Analysis included 1136 participants, with 609 (54%) having HIV, and 495 (81%) taking ART. At baseline, 9.8% of participants had a high FRS. People living with HIV (PLHIV) had a 3.2% lower FRS than HIV-negative participants (P<0.001). FRS increased similarly for both groups over time. Other factors associated with FRS were secondary and higher education (ß value: -0.075, P<0.001; ß value: -0.084, P<0.001) and alcohol consumption (ß value: 0.011, P<0.001). CONCLUSIONS: CVD risk increased for all participants over 36 months, suggesting classic risk factors rather than HIV status or ART to be drivers of CVD risk. People living with HIV had a significantly lower FRS than their HIV-negative counterparts, possibly related to HIV itself or a more frequent interaction with healthcare services. No association of HIV and ART with changes in FRS over 36 months was observed, suggesting the need for research using clinical endpoints to elucidate the effects of HIV and ART on CVD risk. Population-based prevention of CVD risk factors in sub-Saharan Africa is warranted, regardless of HIV status.

Comparative performance of cardiovascular risk prediction models in people living with HIV.

Background: Current cardiovascular risk assessment in people living with HIV is based on general risk assessment tools; however, whether these tools can be applied in sub-Saharan African populations has been questioned. Objectives: The study aimed to assess cardiovascular risk classification of common cardiovascular disease (CVD) risk prediction models compared to the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) 2010 and 2016 models in people living with HIV. Method: Cardiovascular disease risk was estimated by Framingham Cardiovascular and Heart Disease (FHS-CVD, FHS-CHD), Atherosclerotic Cardiovascular Disease (ASCVD) and D:A:D 2010 and 2016 risk prediction models for HIV-infected participants of the Ndlovu Cohort Study, Limpopo, rural South Africa. Participants were classified to be at low (< 10%), moderate (10% - 20%), or high-risk (> 20%) of CVD within 10 years for general CVD and five years for D:A:D models. Kappa statistics were used to determine agreement between CVD risk prediction models. Subgroup analysis was performed according to age. Results: The analysis comprised 735 HIV-infected individuals, predominantly women (56.7%), average age 43.9 (8.8) years. The median predicted CVD risk for D:A:D 2010 and FHS-CVD was 4% and for ASCVD and FHS-CHD models, 3%. For the D:A:D 2016 risk prediction model, the figure was 5%. High 10-year CVD risk was predicted for 2.9%, 0.5%, 0.7%, 3.1% and 6.6% of the study participants by FHS-CVD, FHS-CHD, ASCVD, and D:A:D 2010 and 2016. Kappa statistics ranged from 0.34 for ASCVD to 0.60 for FHS-CVD as compared to the D:A:D 2010 risk prediction model. Conclusion: Overall, predicted CVD risk is low in this population. Compared to D:A:D 2010, CVD risk estimated by the FHS-CVD model showed similar overall results for risk classification. With the exception of the D:A:D model, all other risk prediction models classified fewer people to be at high estimated CVD risk. Prospective studies are needed to develop and validate CVD risk algorithms in people living with HIV in sub-Saharan Africa.

Corrigendum: The influence of HIV infection and antiretroviral treatment on pulmonary function in individuals in an urban setting in sub-Saharan Africa.

[This corrects the article DOI: 10.4102/sajhivmed.v22i1.1312.].

Presence of occult HBV, but near absence of active HBV and HCV infections in people infected with HIV in rural South Africa.

Human immunodeficiency (HIV), hepatitis B (HBV), and hepatitis C (HCV) viruses are endemic in Sub-Saharan Africa, but data regarding the prevalence of hepatitis co-infections in HIV-positive individuals residing there are limited. The aim of the study was to determine the prevalence of HBV, HCV, and occult HBV (presence of HBV-DNA in the absence of HBsAg) in a rural, South African cohort. The results were compared to various ethnic groups in a Dutch cohort of people infected with HIV. Antiretroviral-naïve individuals with HIV from both a rural South African clinic (n = 258), and a Dutch University hospital (n = 782), were included. Both serological (HBV and HCV) and molecular (occult HBV) assays were performed. Logistic regression analysis was used to define independent predictors of a hepatitis co-infection. HBV and HCV prevalence rates in the South African cohort were exceptionally low (0.4%, 1/242 and 0.8%, 2/242, respectively), compared to those observed in Caucasians (HBV 4.4% and HCV 10.9%) and African immigrants (HBV 8.9% and HCV 4.8%). Conversely, occult HBV was observed in a considerable proportion (10%, 6/60) of South African patients who were anti-HBc-positive but HBsAg-negative. Occult infections were less frequent in Caucasians and Africans in the Dutch cohort (3.2% and 1.4%, respectively). Independent predictors for occult HBV were not identified, but a trend towards more occult HBV at lower CD4 counts was observed. Local HBV/HCV prevalence data are needed to optimize vaccination and antiretroviral treatment strategies. Occult HBV in patients with HIV may be missed regularly when molecular analyses are not available.

The influence of HIV infection and antiretroviral treatment on pulmonary function in individuals in an urban setting in sub-Saharan Africa.

BACKGROUND: With the roll-out of antiretroviral treatment (ART), the life expectancy of people with HIV and, hence, morbidity from non-communicable diseases, including pulmonary diseases, have increased. OBJECTIVES: This research study aims to investigate whether HIV infection and ART use are associated with pulmonary function, given the high frequency of pulmonary infections, including tuberculosis (TB), associated with HIV. METHOD: Adults living with HIV (ART-naïve, on first- or second-line ART), and age and sex matched HIV-negative controls were included in a cross-sectional study in Johannesburg, South Africa. Spirometry was performed to determine lung function, measuring the forced expiratory volume in one second (FEV1), the forced vital capacity (FVC) and the FEV1/FVC ratio before (pre), and after (post), short-acting bronchodilator. The association of HIV infection and ART use with pulmonary function was analysed using linear regression models, adjusting for age, gender, body surface area (BSA), employment, education, smoking and TB. RESULTS: Overall, 548 participants (62% women) were included with a mean age of 38 (standard deviation [s.d.] 9.5) years. No effect of HIV or ART on post-FEV1 was observed in adjusted analysis. Additional adjustment for TB resulted in a higher post-FEV1 in participants on ART compared with HIV-negative participants, whereas TB was associated with a lower FEV1. No effect of HIV and ART on post-FEV1/FVC was observed. CONCLUSION: HIV infection and ART use were not associated with reduced pulmonary function in this urban African population. Tuberculosis showed a mediating effect on the association between HIV, ART and pulmonary function.

Predictors of impaired pulmonary function in people living with HIV in an urban African setting.

BACKGROUND: Studies have associated HIV with an increased risk of obstructive lung disease (OLD). OBJECTIVES: We aimed to identify the predictive factors for impaired lung function in an urban, African, HIV-positive population. METHOD: A cross-sectional study was performed in Johannesburg, South Africa, from July 2016 to November 2017. A questionnaire was administered and pre- and post-bronchodilator spirometry conducted. The predictors investigated included age, sex, antiretroviral treatment (ART) duration, body mass index, history of tuberculosis (TB) or pneumonia, occupational exposure, environmental exposure, smoking and symptoms of OLD (cough, wheeze, mucus and dyspnoea). Impaired lung function was defined as a forced expiratory volume in 1 second/forced vital capacity (FEV1/FVC) ratio of < 0.70, or below the 20th percentile of normal. RESULTS: The 98 ART-naïve participants (mean age = 34.0, standard deviation [s.d.] = 8.2), 85 participants on first-line ART (mean age = 36.9, s.d. = 6.6) and 189 participants on second-line ART (mean age = 43.5, s.d. = 7.9) were predominantly female (65.6%). Of the participants, 64 (17.2%) had impaired lung function and 308 had normal lung function. Linear regression identified age (ß = -0.003, P < 0.01), male sex (ß = -0.016, P = 0.03) and history of TB or pneumonia (ß = -0.024, P < 0.01) as independent predictors of a lower FEV1/FVC ratio. Following logistic regression, only a history of TB or pneumonia (odds ratio = 2.58, 95% confidence interval = 1.47-4.52) was significantly related to impaired lung function (area under the receiver operating characteristic curve = 0.64). CONCLUSION: Our data show that a history of TB or pneumonia predicts impaired lung function. In order to improve timely access to spirometry, clinicians should be alert to the possibility of impaired lung function in people with a history of TB or pneumonia.

Electrocardiographic and echocardiographic abnormalities in urban African people living with HIV in South Africa.

BACKGROUND: Studies from high income countries report that HIV-positive people have an impaired systolic and diastolic cardiac function compared to HIV-negative people. It is unclear if results can be translated directly to the Sub-Saharan Africa context. This study assesses electro- and echocardiographic characteristics in an urban African population, comparing HIV-positive people (treated and not yet treated) with HIV-negative controls. METHODS: We conducted a cross-sectional study in Johannesburg, South Africa. We enrolled HIV-positive participants from three randomized controlled trials that had recruited participants from routine HIV testing programs. HIV-negative controls were recruited from the community. Data were collected on demographics, cardiovascular risk factors, medical history and electrocardiographic and echocardiographic characteristics. RESULTS: In total, 394 HIV-positive participants and 153 controls were enrolled. The mean age of HIV-positive participants was 40±9 years (controls: 35±10 years), and 34% were male (controls: 50%). Of HIV-positive participants 36% were overweight or obese (controls: 44%), 23% had hypertension (controls: 28%) and 12% were current smoker (controls: 37%). Median time since HIV diagnosis was 6.0 years (IQR 2.3-10.0) and median treatment duration was 4.0 years (IQR 0.0-8.0), 50% had undetectable viral load. The frequency of anatomical cardiac abnormalities was low and did not differ between people with and without HIV. We observed no relation between HIV or anti-retroviral therapy (ART) and systolic or diastolic heart function. There was an association between ART use and corrected QT interval: +11.8 ms compared to HIV-negative controls (p<0.01) and +18.9 ms compared to ART-naïve participants (p = 0.01). We also observed a higher left ventricular mass index in participants on ART (+7.8 g/m2, p<0.01), but this association disappeared after adjusting for CD4 cell count, viral load and HIV-duration. CONCLUSION: The low number of major cardiac abnormalities in this relatively young, well managed urban African HIV-positive population is reassuring. The increase in corrected QT interval and left ventricular mass may contribute to higher cardiac mortality and morbidity in people living with HIV in the long term.

Course of Disease and Clinical Outcome of Infective Endocarditis in HIV-infected Individuals: A Systematic Review and Meta-analysis.

Infective endocarditis (IE) causes substantial morbidity and mortality if untreated. The clinical course of IE might be different in HIV-positive patients as a result of immune dysfunction. This systematic review investigates the clinical course of IE in HIV-positive compared to HIV-negative patients. A systematic search was performed in PubMed, EMBASE, and Cochrane Library and registered in PROSPERO (CRD42016048649). All articles from 1996 and onward addressing the clinical outcome of HIV-positive adults suffering from IE were reviewed and included based on predefined inclusion and exclusion criteria. A meta-analysis was performed for the outcome mortality. Twenty-three articles were included of which eight included HIVpositive patients only, and 15 compared HIV-positive to HIV-negative patients. Two studies included patients on antiretroviral therapy (ART). HIV and intravenous drug use (IVDU) were closely related. Mortality was higher in HIV-positive patients with a CD4 count below 200 cells/µl than in HIV-positive patients with a higher CD4 count, while mortality was similar for HIV-positive compared to HIV-negative patients (risk ratio = 0.86 [95% confidence interval: 0.53-1.40]). No difference was found in length of hospital stay or rehospitalization. Clinical outcomes were strongly related to the right- or left-sided endocarditis. The clinical course of IE is not different for patients with and without HIV. Clinical outcomes were mainly associated with other factors, such as IVDU and side of cardiac involvement, rather than HIV status.

Cardiovascular Disease Burden in Rural Africa: Does HIV and Antiretroviral Treatment Play a Role?: Baseline Analysis of the Ndlovu Cohort Study.

Background HIV is associated with an increased risk of cardiovascular disease (CVD) in high-income countries. Little is known about the CVD burden in sub-Saharan Africa, where 70% of the world's HIV-positive population lives. This study aims to provide insight into the burden of CVD risk in a rural setting in sub-Saharan Africa considering HIV infection and antiretroviral therapy (ART). Methods and Results A cross-sectional analysis was conducted of the baseline of the Ndlovu Cohort study including HIV-negative and HIV-positive participants in rural South Africa between 2014 and 2017. Information was collected on demographics, socioeconomic status, and CVD risk factors. Carotid intima-media thickness measurement was performed. The influence of HIV and ART on the burden of CVD was determined by comparing HIV-positive participants who were ART naive on first-line or second-line ART with HIV-negative participants. In total, 1927 participants were included, of whom 887 (46%) were HIV positive and 54% women. The median age was 38 years. Overall, 690 participants (79%) were on ART, with 613 (89%) on first-line and 77 (11%) on second-line therapy. Participants with HIV had lower values for most of the CVD risk factors but higher C-reactive protein levels than HIV-negative participants. ART-naive, HIV-positive participants had similar carotid intima-media thickness compared with HIV-negative participants but carotid intima-media thickness was increased for participants on ART aged 30 years and older compared with HIV-negative participants. Conclusions HIV-positive participants presented with a favorable CVD risk profile compared with HIV-negative participants. However, carotid intima-media thickness was increased in HIV-positive participants on ART, indicating a higher burden of subclinical CVD for the HIV-positive population.

The Utility of the Lipoprotein-Associated Phospholipase A2 (Lp-PLA2) Assay in Detecting Abnormalities in Lipid Metabolism and Cardiovascular Risk in an HIV-Infected South African Cohort.

People with HIV (PWH) have an increased prevalence of cardiovascular disease (CVD) compared to uninfected patients. Lipoprotein-associated phospholipase A2 (Lp-PLA2) catalyzes the synthesis of pro-inflammatory lipids that recruit monocytes. Current guidelines for assessing cardiovascular risk in HIV-infected patients suggest that Lp-PLA2 may be a useful surrogate marker for CVD health in this patient population. Lipoprotein-associated phospholipase A2, lipids, glucose, physical parameters, and carotid intimal-medial thickness (CIMT) were measured in 98 participants (49 HIV-uninfected, 27 antiretroviral therapy [ART]-naive PWH, and 22 ART-treated PWH). HIV viral load (VL) and CD4+ T-cell count were measured in HIV-infected participants. Lipoprotein-associated phospholipase A2 was increased in participants on protease inhibitor (PI) ART (median 50.5 vs 127.0 nmol/mL, P = .05) and correlated with age, body mass index, and cholesterol. Lipoprotein-associated phospholipase A2 was not related to Framingham risk score or CIMT but correlated directly with VL (r = .323, P = .025) and inversely with CD4+ T-cell count (r = -.727, P < .001). Lipoprotein-associated phospholipase A2 was increased in HIV-infected participants on PIs and correlated strongly with VL and CD4+ T-cell count suggesting that HIV-associated inflammation is linked to increased Lp-PLA2, providing a mechanistic link between HIV and CVD.

The association between HIV infection and pulmonary function in a rural African population.

OBJECTIVES: HIV infection has been associated with an impaired lung function in high-income countries, but the association between HIV infection and pulmonary function in Sub-Saharan Africa remains unclear. This study aims to investigate the relation between HIV infection and pulmonary function in a rural African population. METHODS: A cross-sectional study was conducted among HIV-positive and HIV-negative adults in a rural area in South Africa, as part of the Ndlovu Cohort Study. A respiratory questionnaire and post-bronchodilator spirometry were performed. Multivariable regression analysis was used to investigate whether HIV was independently associated with a decrease in post-bronchodilator FEV1/FVC ratio considering age, sex, body mass index, respiratory risk factors and a history of a pulmonary infection (tuberculosis (TB) or a pneumonia). Possible mediation by a history of pulmonary infection was tested by removing this variable from the final model. RESULTS: Two hundred and one consecutive participants were enrolled in the study in 2016, 84 (41.8%) were HIV-positive (82.1% on ART). The median age was 38 (IQR 29-51) years. Following multivariable analysis HIV was not significantly associated to a decline in post-bronchodilator FEV1/FVC ratio (ß -0.017, p 0.18). However, upon removal of a history of a pulmonary infection from the final model HIV was significantly related to post-bronchodilator FEV1/FVC ratio, ß -0.026, p 0.03. CONCLUSIONS: Pulmonary function is affected by HIV infection which most likely results from co-infection with TB or other pneumonia. Further research should focus on the influence of a pulmonary infection, most notably TB, on pulmonary function, especially as the incidence of TB is high in HIV infection.

Association between Immune Markers and Surrogate Markers of Cardiovascular Disease in HIV Positive Patients: A Systematic Review.

BACKGROUND: HIV infection is associated with an increased risk of cardiovascular disease (CVD). Chronic low-grade immune activation is likely one of the driving mechanisms. This systematic review provides an overview of the evidence addressing the relation between immune markers and surrogate markers of CVD (except CIMT) in HIV infection. METHODS: A systematic search was performed in PubMed, Embase and Cochrane Library identifying all articles from 1996 to April 2015. It addressed the relation between immune markers and surrogate markers of CVD (except Carotid Intima-media Thickness) in HIV-positive adults. Two authors, using predefined criteria, independently conducted the selection of articles, critical appraisal and extraction of the data. Analysis focused on immune markers that were assessed most frequently. The review was conducted according to the PRISMA guideline and performed as part of an overarching review registered with PROSPERO (CRD42014010516). FINDINGS: Twenty-nine articles were selected, describing 34 immune markers and nine different CVD surrogate outcomes: coronary calcium score (13 times) and flow-mediated dilation (10 times) were used most frequently. Twenty-seven studies had a cross-sectional design. CRP, IL-6 and sVCAM-1 were assessed most frequently. None of the immune markers were clearly associated with any of the surrogate CVD outcomes. No effect estimate could be calculated due to marked heterogeneity in study populations, immune markers, outcomes and statistical approaches. INTERPRETATION: This review could not identify a clear association between any of the immune markers and surrogate CVD outcomes. This may reflect a true lack of association, or may be explained by heterogeneity across studies and lack of follow-up data. Future research should focus on longitudinal studies measuring a select set of immune markers and surrogate CVD outcomes awaiting the primary outcome of clinical cardiovascular events.

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.

Pro-Inflammatory Markers in Relation to Cardiovascular Disease in HIV Infection. A Systematic Review.

BACKGROUND: In the past years many inflammatory markers have been studied in association with clinically manifest cardiovascular disease (CVD) and carotid intima-media thickness (CIMT) in HIV-infected patients, to obtain insights in the increased cardiovascular risk observed in HIV infection. This systematic review provides an oversight of the current knowledge. METHODS: A search was performed in PubMed, Embase and Cochrane in July 2014, identifying all articles from 1996 onwards addressing the relation between inflammatory markers and CVD or CIMT in HIV-positive adults. Two authors, using predefined criteria, independently conducted the selection of articles, critical appraisal and extraction of the data. Analysis was focused on the immune markers that were most frequently assessed. The review protocol was registered in the PROSPERO database at 11 July 2014 (registration number CRD42014010516). This review was performed according to the PRISMA guideline. FINDINGS: Forty articles were selected; eight addressing cardiovascular disease (CVD) and thirty-two addressing CIMT. C-reactive protein (CRP), interleukin-6 (IL-6) and d-dimer were assessed most frequently in relation to the occurrence of CVD; in four out of eight studies. All three markers were positively related to CVD in three out of four studies. Studies addressing CIMT were too heterogeneous with respect to patient populations, inflammatory markers, CIMT measurement protocols and statistical methods to allow for a formal meta-analysis to obtain summary statistics. CRP, IL-6 and soluble vascular cell adhesion molecule (sVCAM-1) were the most studied markers in relation to CIMT. None of the inflammatory markers showed an association with CIMT. INTERPRETATION: This review showed a relation between some inflammatory markers and CVD, however, no consistent relation is observed for CIMT. Statistical approaches that yields effect estimates and standardized CIMT protocols should be chosen. Further research should focus on prospective studies and a selected set of inflammatory markers.