Association between antiretroviral exposure and renal impairment among HIV-positive persons with normal baseline renal function: the D:A:D 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.

Antiretroviral drug-related liver mortality among HIV-positive persons in the absence of hepatitis B or C virus coinfection: the data collection on adverse events of anti-HIV drugs study.

BACKGROUND: Liver diseases are the leading causes of death in human immunodeficiency virus (HIV)-positive persons since the widespread use of combination antiretroviral treatment (cART). Most of these deaths are due to hepatitis C (HCV) or B (HBV) virus coinfections. Little is known about other causes. Prolonged exposure to some antiretroviral drugs might increase hepatic mortality. METHODS: All patients in the Data Collection on Adverse Events of Anti-HIV Drugs study without HCV or HBV coinfection were prospectively followed from date of entry until death or last follow-up. In patients with liver-related death, clinical charts were reviewed using a structured questionnaire. RESULTS: We followed 22 910 participants without hepatitis virus coinfection for 114 478 person-years. There were 12 liver-related deaths (incidence, 0.10/1000 person-years); 7 due to severe alcohol use and 5 due to established ART-related toxicity. The rate of ART-related deaths in treatment-experienced persons was 0.04/1000 person-years (95% confidence interval, .01, .10). CONCLUSIONS: We found a low incidence of liver-related deaths in HIV-infected persons without HCV or HBV coinfection. Liver-related mortality because of ART-related toxicity was rare.

Non-AIDS defining cancers in the D:A:D Study--time trends and predictors of survival: a cohort study.

BACKGROUND: Non-AIDS defining cancers (NADC) are an important cause of morbidity and mortality in HIV-positive individuals. Using data from a large international cohort of HIV-positive individuals, we described the incidence of NADC from 2004-2010, and described subsequent mortality and predictors of these. METHODS: Individuals were followed from 1st January 2004/enrolment in study, until the earliest of a new NADC, 1st February 2010, death or six months after the patient's last visit. Incidence rates were estimated for each year of follow-up, overall and stratified by gender, age and mode of HIV acquisition. Cumulative risk of mortality following NADC diagnosis was summarised using Kaplan-Meier methods, with follow-up for these analyses from the date of NADC diagnosis until the patient's death, 1st February 2010 or 6 months after the patient's last visit. Factors associated with mortality following NADC diagnosis were identified using multivariable Cox proportional hazards regression. RESULTS: Over 176,775 person-years (PY), 880 (2.1%) patients developed a new NADC (incidence: 4.98/1000PY [95% confidence interval 4.65, 5.31]). Over a third of these patients (327, 37.2%) had died by 1st February 2010. Time trends for lung cancer, anal cancer and Hodgkin's lymphoma were broadly consistent. Kaplan-Meier cumulative mortality estimates at 1, 3 and 5 years after NADC diagnosis were 28.2% [95% CI 25.1-31.2], 42.0% [38.2-45.8] and 47.3% [42.4-52.2], respectively. Significant predictors of poorer survival after diagnosis of NADC were lung cancer (compared to other cancer types), male gender, non-white ethnicity, and smoking status. Later year of diagnosis and higher CD4 count at NADC diagnosis were associated with improved survival. The incidence of NADC remained stable over the period 2004-2010 in this large observational cohort. CONCLUSIONS: The prognosis after diagnosis of NADC, in particular lung cancer and disseminated cancer, is poor but has improved somewhat over time. Modifiable risk factors, such as smoking and low CD4 counts, were associated with mortality following a diagnosis of NADC.

Diabetes mellitus, preexisting coronary heart disease, and the risk of subsequent coronary heart disease events in patients infected with human immunodeficiency virus: the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D Study).

BACKGROUND: Although guidelines in individuals not infected with the human immunodeficiency virus (HIV) consider diabetes mellitus (DM) to be a coronary heart disease (CHD) equivalent, there is little information on its association with CHD in those infected with HIV. We investigated the impact of DM and preexisting CHD on the development of a new CHD episode among 33,347 HIV-infected individuals in the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D Study). METHODS AND RESULTS: Over 159,971 person-years, 698 CHD events occurred. After adjustment for gender, age, cohort, HIV transmission, ethnicity, family history of CHD, smoking, and calendar year, the rate of a CHD episode was 7.52 times higher (Poisson regression, 95% CI 6.02 to 9.39, P=0.0001) in those with preexisting CHD than in those without preexisting CHD, but it was only 2.41 times higher (95% CI 1.91 to 3.05, P=0.0001) in those with preexisting DM compared with those without DM. No statistical interactions were apparent between either diagnosis and sex; although older people with DM had an increased CHD rate compared with younger people, older people with preexisting CHD had a lower event rate. A statistically significant interaction between preexisting DM and CHD (P=0.003) suggested that the CHD rate in those with preexisting CHD and DM is lower than expected on the basis of the main effects alone. CONCLUSIONS: DM and preexisting CHD are both important risk factors for CHD events in HIV-infected individuals. There is a need for targeted interventions to reduce the risk of CHD in both high-risk groups of HIV-infected individuals.

Use of nucleoside reverse transcriptase inhibitors and risk of myocardial infarction in HIV-infected patients enrolled in the D:A:D study: a multi-cohort collaboration.

BACKGROUND: Whether nucleoside reverse transcriptase inhibitors increase the risk of myocardial infarction in HIV-infected individuals is unclear. Our aim was to explore whether exposure to such drugs was associated with an excess risk of myocardial infarction in a large, prospective observational cohort of HIV-infected patients. METHODS: We used Poisson regression models to quantify the relation between cumulative, recent (currently or within the preceding 6 months), and past use of zidovudine, didanosine, stavudine, lamivudine, and abacavir and development of myocardial infarction in 33 347 patients enrolled in the D:A:D study. We adjusted for cardiovascular risk factors that are unlikely to be affected by antiretroviral therapy, cohort, calendar year, and use of other antiretrovirals. FINDINGS: Over 157,912 person-years, 517 patients had a myocardial infarction. We found no associations between the rate of myocardial infarction and cumulative or recent use of zidovudine, stavudine, or lamivudine. By contrast, recent-but not cumulative-use of abacavir or didanosine was associated with an increased rate of myocardial infarction (compared with those with no recent use of the drugs, relative rate 1.90, 95% CI 1.47-2.45 [p=0.0001] with abacavir and 1.49, 1.14-1.95 [p=0.003] with didanosine); rates were not significantly increased in those who stopped these drugs more than 6 months previously compared with those who had never received these drugs. After adjustment for predicted 10-year risk of coronary heart disease, recent use of both didanosine and abacavir remained associated with increased rates of myocardial infarction (1.49, 1.14-1.95 [p=0.004] with didanosine; 1.89, 1.47-2.45 [p=0.0001] with abacavir). INTERPRETATION: There exists an increased risk of myocardial infarction in patients exposed to abacavir and didanosine within the preceding 6 months. The excess risk does not seem to be explained by underlying established cardiovascular risk factors and was not present beyond 6 months after drug cessation.

[Amputation of an arm due to infection with Vibrio vulnificus after beach holiday].

Infection with Vibrio vulnificus is a rare condition with approximately 11 cases reported in the Danish literature. It is characterized by soft tissue infection/wound, necrotizing fasciitis and septicaemia. In this case report we present a patient admitted with a rapid progression and sepsis consistent with V. vulnificus infection but with no informa-tion of water exposure. The initial treatment was surgery and sepsis management including broad-spectrum antibiotics. On day eight the patient's right arm was amputated. On day 16 the patient was discharged from the intensive care unit, and on day 32 the patient was transferred to a local hospital.

Atazanavir is not associated with an increased risk of cardio- or cerebrovascular disease events.

OBJECTIVE: To investigate whether there is any association between exposure to atazanavir (ATV), either when boosted or unboosted by ritonavir, and myocardial infarction (MI) or stroke within the D:A:D: Study. DESIGN: Prospective cohort collaboration. METHODS: Poisson regression was used to investigate the association between cumulative exposure to ATV and MI/stroke risk after adjusting for known demographic and clinical confounders, as well as cumulative and recent exposure to specific antiretroviral drugs. Follow-up started on enrolment in the study and ended at the earliest of: a new MI/stroke event, death, 6 months after last clinic visit, or 1 February 2011. RESULTS: The incidence of MI varied from 0.28 [95% confidence interval (CI) 0.26-0.30)]/100 person-years of follow-up (PYFU) in those with no exposure to ATV to 0.20 (0.12-0.32)/100 PYFU in those with more than 3 years exposure. There was no evidence of an association between cumulative exposure to ATV and MI risk, either in univariate [relative rate/year 0.96 (95% CI 0.88-1.04)] or multivariable [0.95 (0.87-1.05)] analyses. The incidence of stroke was 0.17 (0.16-0.19)/100 PYFU in those with no exposure to ATV and 0.17 (0.10-0.27)/100 PYFU in those with more than 3 years exposure. As with the MI endpoint, there was no evidence of an association with ATV exposure in either univariate [1.02 (0.98-1.05)] or multivariable [0.95 (0.87-1.05)] analyses. CONCLUSION: These results argue against a class-wide association between exposure to HIV protease inhibitors and the risk of cardio/cerebrovascular events.

Associations between immune depression and cardiovascular events in HIV infection.

OBJECTIVE: To consider associations between the latest/nadir CD4 cell count, and time spent with CD4 cell count less than 200 cells/µl (duration of immune depression), and myocardial infarction (MI), coronary heart disease (CHD), stroke, or cardiovascular disease (CVD) (CHD or stroke) in 33 301 HIV-positive individuals. DESIGN: Longitudinal cohort study. METHODS: Analyses were undertaken using Poisson regression. To investigate whether analyses of stroke were robust to the type of endpoint, we additionally included stroke-like events and rejected strokes into the stroke endpoint. RESULTS: Participants experienced 716 MI, 1056 CHD, 303 stroke, and 1284 CVD events. Whereas there was no evidence of a higher MI/CHD risk in those with lower latest/nadir CD4 cell counts after adjustment [current CD4 <100 cells/µl: relative rate (95% confidence interval) 0.96 (0.62-1.50) for MI, 0.89 (0.30-2.36) for CHD; nadir CD4 <100 cells/µl: 1.36 (0.57-3.23) for MI, 0.98 (0.45-2.16) for CHD], stroke and CVD rates were higher in those with a latest CD4 cell count less than 100 cells/µl [2.26 (1.29-3.94) and 1.14 (0.84-1.56), respectively]. All events occurred less frequently in those who had not experienced immune depression, although evidence for a linear association with duration of immune depression was weak. The association between stroke risk and the latest CD4 cell count strengthened as stroke-like and rejected strokes were included; conversely, associations with established stroke risk factors weakened. CONCLUSION: We do not find strong evidence that HIV-positive individuals with a low CD4 cell count are more likely to experience MI/CHD. Although strokes appear to occur more commonly at low CD4 cell counts, this may be partly explained by misclassification or other biases.

Predicting the short-term risk of diabetes in HIV-positive patients: the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study.

INTRODUCTION: HIV-positive patients receiving combination antiretroviral therapy (cART) frequently experience metabolic complications such as dyslipidemia and insulin resistance, as well as lipodystrophy, increasing the risk of cardiovascular disease (CVD) and diabetes mellitus (DM). Rates of DM and other glucose-associated disorders among HIV-positive patients have been reported to range between 2 and 14%, and in an ageing HIV-positive population, the prevalence of DM is expected to continue to increase. This study aims to develop a model to predict the short-term (six-month) risk of DM in HIV-positive populations and to compare the existing models developed in the general population. METHODS: All patients recruited to the Data Collection on Adverse events of Anti-HIV Drugs (D:A:D) study with follow-up data, without prior DM, myocardial infarction or other CVD events and with a complete DM risk factor profile were included. Conventional risk factors identified in the general population as well as key HIV-related factors were assessed using Poisson-regression methods. Expected probabilities of DM events were also determined based on the Framingham Offspring Study DM equation. The D:A:D and Framingham equations were then assessed using an internal-external validation process; area under the receiver operating characteristic (AUROC) curve and predicted DM events were determined. RESULTS: Of 33,308 patients, 16,632 (50%) patients were included, with 376 cases of new onset DM during 89,469 person-years (PY). Factors predictive of DM included higher glucose, body mass index (BMI) and triglyceride levels, and older age. Among HIV-related factors, recent CD4 counts of <200 cells/µL and lipodystrophy were predictive of new onset DM. The mean performance of the D:A:D and Framingham equations yielded AUROC of 0.894 (95% CI: 0.849, 0.940) and 0.877 (95% CI: 0.823, 0.932), respectively. The Framingham equation over-predicted DM events compared to D:A:D for lower glucose and lower triglycerides, and for BMI levels below 25 kg/m(2). CONCLUSIONS: The D:A:D equation performed well in predicting the short-term onset of DM in the validation dataset and for specific subgroups provided better estimates of DM risk than the Framingham.

HIV infection, aging and cardiovascular disease: epidemiology and prevention.

In the developed world, HIV infection is now well managed with very effective and less toxic antiretroviral treatment. HIV-positive patients therefore are living longer, but are now faced by challenges associated with aging. Several non-AIDS associated morbidities are increased in this population, including cardiovascular disease (CVD). It is suggested that CVD occurs earlier among HIV-positive patients compared with HIV-negative patients, and at a higher rate. Several factors have been proposed to contribute to this. First, the traditional CVD risk factors are highly prevalent in this population. High rates of smoking, dyslipidaemia and a family history of CVD have been reported. This population is also aging, with estimates of more than 25% of HIV-positive patients in the developed world being over the age of 50. Antiretroviral treatment, both through its effect on lipids and through other, sometimes less well understood, mechanisms, has been linked to increased CVD risk. HIV infection, especially untreated, is a further contributing factor to increased CVD risk in HIV-positive patients. As the HIV-positive population continues to age, the risk of CVD will continue to increase. Guidelines for the management and prevention of CVD risk have been developed, and are largely modelled on those used in the general population. However, the data currently suggest that these interventions, such as the use of lipid-lowering medications and smoking cessation programs, remain quite low. A better understanding the mechanisms of CVD risk in this aging population and further efforts in improving uptake of prevention strategies will remain an important research area.

The metabolic syndrome in HIV.

The metabolic syndrome (MS) is a term used to describe the clustering of risk factors for cardiovascular disease (CVD), including elevated triglyceride (TG), low high density lipoprotein cholesterol (HDL), hypertension, hyperglycemia/ insulin resistance and intra-abdominal obesity. This paper discusses why the prevalence of MS in the setting of HIV has been reported to range from 7-45% and how antiretroviral drugs might contribute to the development of MS. The MS has been reported to be a 'CVD risk enhancer', and much debate is ongoing on the independent risk of CVD associated with the MS. Based on a limited number of studies on MS in HIV with clinical end-points, there is no data to support that the MS is independently associated with an increased risk of CVD.

Risk factors for fatality in HIV-infected patients with dideoxynucleoside-induced severe hyperlactataemia or lactic acidosis.

BACKGROUND: Lactic acidosis (LA) and severe hyperlactataemia (HL) are infrequent but serious complications of antiretroviral therapy that have been associated with a high fatality rate. METHODS: In a multinational retrospective cohort study, LA was defined as arterial blood pH<7.35, bicarbonate <20 mmol/l and lactate above normal, and HL as confirmed blood lactate >5 mmol/l. Logistic regression was used to identify factors associated with fatality. Sensitivity and specificity of different case definitions as predictors of death were compared. RESULTS: The overall case-fatality rate was 19/110 (17.3%), but among acidotic patients it was 33% (16/49 cases). There were 10 asymptomatic patients and none of them died as a consequence of the event. The median lactate for fatal, non-fatal and all patients was 8.3 mmol/l (IQR 7.2-13.1), 6.4 mmol/l (IQR 5.4-7.8) and 6.7 mmol/l (IQR 5.5-8.1), respectively. After adjusting for age and current CD4(+) T-cell count, lactate >7 mmol/l (OR 6.27, 95% CI 1.13-34.93), blood bicarbonate <12 mmol/l (OR 10.02 relative to >18 mmol/l, 95% CI 1.33-75.65) and concurrent opportunistic infections (OR 8.69, 95% CI 1.45-52.22) were independently associated with case fatality. Blood lactate >7 mmol/l showed a sensitivity of 84% for fatality with a specificity of 60%, whereas bicarbonate <12 mmol/l showed a better specificity (85%) but a poorer sensitivity (42%). Bicarbonate <18 mmol/l appears to be as good as lactate <7 mmol/l at predicting death (sensitivity 90% and specificity 54%). CONCLUSIONS: Our data suggest that blood lactate >7 mmol/l and blood bicarbonate <18 mmol/l appear to predict death and might help clinicians in selecting patients who may benefit from more intense monitoring.

Elevated triglycerides and risk of myocardial infarction in HIV-positive persons.

OBJECTIVES: To explore the relationship between elevated triglyceride levels and the risk of myocardial infarction (MI) in HIV-positive persons after adjustment for total cholesterol (TC), high-density lipoprotein-cholesterol (HDL-C) and nonlipid risk factors. BACKGROUND: Although elevated triglyceride levels are commonly noted in HIV-positive individuals, it is unclear whether they represent an independent risk factor for MI. METHODS: The incidence of MI during follow-up was stratified according to the latest triglyceride level. Multivariable Poisson regression models were used to describe the independent association between the latest triglyceride level and MI risk after adjusting for TC and HDL-C, nonlipids cardiovascular disease (CVD) risk factors, HIV and treatment-related factors. RESULTS: The 33,308 persons included in the study from 1999 to 2008 experienced 580 MIs over 178,835 person-years. Unadjusted, the risk of MI increased by 67% [relative risk (RR) 1.67, 95% confidence interval 1.54-1.80] per doubling in triglyceride level. After adjustment for the latest TC and HDL-C level, the RR dropped to 1.33 (95% confidence interval 1.21-1.45); this effect was further attenuated by other CVD risk factors and the RR was reduced to 1.17 (95% confidence interval 1.06-1.29). In models that additionally adjusted for HIV and treatment factors, the risk was further diminished, although remained significant (RR 1.11, 95% confidence interval 1.01-1.23). CONCLUSION: Higher triglyceride levels were marginally independently associated with an increased risk of MI in HIV-positive persons, although the extent of reduction in RR after taking account of latest TC, latest HDL-C and other confounders suggests that any independent effect is small.

Role of biomarkers in predicting CVD risk in the setting of HIV infection?

PURPOSE OF REVIEW: The purpose of this review is to present recent results on biomarkers and risk of cardiovascular disease (CVD) in the general population and to review studies of biomarkers among individuals with HIV infection. RECENT FINDINGS: Several inflammatory as well as lipid biomarkers are associated with risk of CVD. Biomarkers associated with inflammation such as C-reactive protein and interleukin-6 have been suggested to improve risk stratification among intermediate-risk persons; however, their routine use is not recommended in the general population. Both biomarkers have recently been reported elevated in patients with HIV. Additionally, interleukin-6 and D-dimer have been reported to predict overall mortality among individuals with HIV. However, the utility of other biomarkers to predict CVD among individuals with HIV infection is not clear. SUMMARY: The risk of CVD is increasing in the HIV-infected population and will increase as this population continues to age. Identification of intermediate-risk individuals using biomarkers will be an important tool for clinicians in the future to be able to treat HIV-infected individuals aggressively. Future studies of biomarkers among individuals with HIV will be needed to help determine the utility of specific markers in predicting CVD risk as well as the mechanism underlying increased CVD risk in the setting of HIV infection.

High prevalence of the metabolic syndrome in HIV-infected patients: impact of different definitions of the metabolic syndrome.

INTRODUCTION: This study describes the characteristics of the metabolic syndrome in HIV-positive patients in the Data Collection on Adverse Events of Anti-HIV Drugs study and discusses the impact of different methodological approaches on estimates of the prevalence of metabolic syndrome over time. METHODS: We described the prevalence of the metabolic syndrome in patients under follow-up at the end of six calendar periods from 2000 to 2007. The definition that was used for the metabolic syndrome was modified to take account of the use of lipid-lowering and antihypertensive medication, measurement variability and missing values, and assessed the impact of these modifications on the estimated prevalence. RESULTS: For all definitions considered, there was an increasing prevalence of the metabolic syndrome over time, although the prevalence estimates themselves varied widely. Using our primary definition, we found an increase in prevalence from 19.4% in 2000/2001 to 41.6% in 2006/2007. Modification of the definition to incorporate antihypertensive and lipid-lowering medication had relatively little impact on the prevalence estimates, as did modification to allow for missing data. In contrast, modification to allow the metabolic syndrome to be reversible and to allow for measurement variability lowered prevalence estimates substantially. DISCUSSION: The prevalence of the metabolic syndrome in cohort studies is largely based on the use of nonstandardized measurements as they are captured in daily clinical care. As a result, bias is easily introduced, particularly when measurements are both highly variable and may be missing. We suggest that the prevalence of the metabolic syndrome in cohort studies should be based on two consecutive measurements of the laboratory components in the syndrome definition.

HBV or HCV coinfections and risk of myocardial infarction in HIV-infected individuals: the D:A:D Cohort Study.

BACKGROUND: Data on a link between HCV or HBV infection and the development of cardiovascular disease among HIV-negative and HIV-positive individuals are conflicting. We sought to investigate the association between HBV or HCV infection and myocardial infarction in HIV-infected individuals. METHODS: The prospective observational database of the D:A:D collaboration of 11 cohorts of HIV-infected individuals, including 212 clinics in Europe, the United States and Australia was used. Multivariate Poisson regression was used to assess the effect of HCV or HBV infection on the development of myocardial infarction after adjustment for potential confounders, including cardiovascular risk factors, diabetes mellitus and exposure to antiretroviral therapy. RESULTS: Of 33,347 individuals, 517 developed a myocardial infarction over 157,912 person-years, with an event rate of 3.3 events/1,000 person-years (95% confidence interval [CI] 3.0-3.6). Event rates (95% CIs) per 1,000 person-years in those who were HCV-seronegative and HCV-seropositive were 3.3 (3.0-3.7) and 2.7 (2.2-3.3), respectively, and for those who were HBV-seronegative, had inactive infection or had active infection were 3.2 (2.8-3.5), 4.2 (3.1-5.2) and 2.8 (1.8-3.9), respectively. After adjustment, there was no association between HCV seropositivity (rate ratio 0.86 [95% CI 0.62-1.19]), inactive HBV infection (rate ratio 1.07 [95% CI 0.79-1.43]) or active HBV infection (rate ratio 0.78 [95% CI 0.52-1.15]) and the development of myocardial infarction. CONCLUSIONS: We found no association between HBV or HCV coinfection and the development of myocardial infarction among HIV-infected individuals.

Factors associated with specific causes of death amongst HIV-positive individuals in the D:A:D Study.

OBJECTIVE: To investigate any emerging trends in causes of death amongst HIV-positive individuals in the current cART era, and to investigate the factors associated with each specific cause of death. DESIGN: An observational multicentre cohort study. METHODS: All HIV-positive individuals included in one of the cohorts in the Data Collection on Adverse Events of Anti-HIV drugs (D:A:D) Study were included. The association between HIV-specific and non HIV-specific risk factors and death were studied using multivariable Poisson regression. RESULTS: We observed 2482 deaths in 180,176 person-years (PY) on 33,308 individuals [rate/1000 PY = 13.8 (95% CI 13.2-14.3)]. Primary causes of death were: AIDS (n = 743; rate/1000 PY = 4.12), liver-related (341; 1.89), CVD-related (289; 1.60), non-AIDS malignancy (286; 1.59). The overall rate of death fell from 16.9 in 1999/2000 to 9.6/ 1000 PY in 2007/2008. Smoking was associated with CVD and non-AIDS cancers, HBV and HCV co-infection with liver-related deaths, and hypertension with liver-related and CVD deaths. Diabetes was a risk factor for all specific causes of death except non-AIDS cancers, and higher current HIV RNA for AIDS-related deaths. Lower CD4 cell counts were associated with a higher risk of death from all specific causes of death. CONCLUSION: Multiple potentially modifiable traditional and HIV-specific risk factors for death of HIV-infected persons were identified. The maximum reduction in mortality in HIV-infected populations will require that each of these factors be appropriately addressed. No trends in terms of emerging causes of unexpected deaths were observed, although monitoring will continue.

Presence of the metabolic syndrome is not a better predictor of cardiovascular disease than the sum of its components in HIV-infected individuals: data collection on adverse events of anti-HIV drugs (D:A:D) study.

OBJECTIVE: It is much debated whether the metabolic syndrome contributes additional information over and above that provided by the individual components of the syndrome alone. Among HIV-infected individuals, we investigated whether any particular combinations of the components included in the definition of the metabolic syndrome are associated with a higher risk of cardiovascular disease (CVD). RESEARCH DESIGN AND METHODS: We followed 33,347 HIV-infected individuals in a prospective observational study. The effect of combinations of components of the metabolic syndrome (low HDL cholesterol, high triglycerides, high BMI, hypertension, and diabetes) on the risk of CVD was assessed by Poisson regression incorporating interactions between each component pair and adjusting for age, sex, family history of CVD, smoking status, calendar year, and exposure to antiretroviral therapy. We reduced the risk of type 1 errors by randomly splitting the data set for training (70% of sample) and validation (remaining 30%). RESULTS: In the training data set, 671 patients experienced a CVD event over 110,652 person-years. Unadjusted, the presence of metabolic syndrome at study enrollment (>or=3 of the factors) was associated with a 2.89 higher risk of CVD (95% CI 2.34-3.59; P = 0.0001) compared with individuals without the metabolic syndrome. After adjustment for the individual components, the metabolic syndrome as an entity no longer predicted the risk of CVD (adjusted relative risk 0.85; 95% CI 0.61-1.17; P = 0.32). No significant positive interactions were found among the components of the metabolic syndrome. CONCLUSIONS: The presence of the metabolic syndrome in HIV-infected individuals did not appear to increase the CVD risk over and above that conferred by the components of the syndrome separately.

Conventional cardiovascular risk factors in HIV infection: how conventional are they?

PURPOSE OF REVIEW: To describe the prevalence of traditional cardiovascular disease risk factors in HIV-infected individuals and to describe the impact of these factors outcomes. RECENT FINDINGS: Patients living with HIV in the developed world are ageing and a large number are male. As would be expected for a population of this age, many individuals report a family history of cardiovascular disease, a small proportion have already experienced a cardiovascular event and an increasing proportion has type 2 diabetes mellitus. Smoking rates range from 35 to 72%, and an increasing proportion of HIV-infected individuals have dyslipidaemia. Studies suggest that these traditional risk factors will play as important a role in the development of cardiovascular disease in these individuals as in the general population. Thus, whilst the predicted 10-year cardiovascular disease risk remains relatively low at present, it is likely to increase as this population survives to older ages. Despite treatment guidelines recommending interventions to prevent cardiovascular disease in these individuals, uptake of such interventions is low. SUMMARY: Due to the high prevalence of traditional cardiovascular disease risk factors, HIV-infected individuals will be at increased risk of the disease as they age. Measures to prevent further development of cardiovascular disease should be initiated in this group.