non-AIDS Deaths Research Articles

Analysis on death causes of HIV/AIDS patients in Taizhou, Zhejiang Province, 1998-2022

Objective: To understand the incidence and causes of HIV/AIDS death patients in Taizhou from 1998 to 2022. Methods: The data were collected from the AIDS Integrated Prevention and Control Information System of China Information System for Diseases Control and Prevention and Taizhou Chronic Disease Information Management System. By the end of 2022, a total of 5 126 HIV/AIDS patients living in Taizhou for a long time were included, SAS 9.4 was used for Kruskal-Wallis test, χ2 test and trend analysis. Results: From 1998 to 2022, a total of 796 HIV/AIDS patients died, with a fatality rate of 15.53% (796/5 126), in whom 52.26% (416/796) died within one year after confirmation. The proportion of HIV/AIDS patients who died within one year decreased (trend χ2=5.60, P<0.001). For the constituent of death causes, there were 140 (17.59%) deaths of AIDS, 237 (29.77%) deaths of malignant tumors, 99 (12.44%) deaths of cardiovascular disease, 58 (7.29%) deaths caused by injuries, 160 (20.10%) deaths due to other causes, and 102 (12.81%) deaths due to unknown causes. The constituent ratio of deaths of malignant tumor, cardiovascular disease and other causes increased over time (trend χ2=1.92, P=0.028; trend χ2=2.81, P=0.003; trend χ2=2.07, P=0.020). There were differences in the distribution of death causes in HIV/AIDS cases in terms of age, occupation, marital status, ethnic group, educational level and mode of transmission (all P<0.05). The average age of the death cases due to cardiovascular disease was higher than other death cases, the cases who died from AIDS had shorter survival time and the lower initial CD4+T cells after confirmation compared with all other death cases, and the time interval from confirmation to treatment in HIV/AIDS patients with unknown death causes was longer than those of all other death cases (all P<0.05). Conclusions: The constituent ratio of non-AIDS related deaths in HIV/AIDS patients in Taizhou was relatively high and showed an upward trend during 1998-2022. It is necessary to further strengthen the early screening, prevention and treatment of chronic non infectious diseases.

Hypertension in people living with HIV on combined antiretroviral therapy in rural Tanzania.

Exposure to anti-retroviral therapy in HIV infection has been associated with hypertension, but whether and to what extent HIV-related factors and anti-retroviral treatment contribute to hypertension is not well defined; in addition, data are particularly scarce in Sub-Saharan Africa. Aim of the study was to investigate prevalence and awareness of hypertension in a cohort of people living with HIV (PLWHIV) on anti-retroviral therapy in rural Tanzania, and to identify possible predictors of hypertension. A cross-sectional study on hypertension in PLWHIV was conducted at Tosamaganga District Hospital, Iringa Region, Tanzania. Subjects on anti-retroviral therapy, age 26-80 years and with monthly attendance to the HIV clinic, were considered eligible. A total number of 242 patients were included in the analysis. Sixty-two subjects (26%) had hypertension, the majority (77%) of them not aware of the condition and/or not on treatment. Older age, higher BMI and lower baseline T-CD4 count were predictors of hypertension at multivariate analysis. The results of the study suggest that hypertension screening should become part of ordinary care of PLWHIV in Tanzania, particularly in subjects with more severe immunosuppression. Leveraging already existing HIV services could be an option to prevent the burden of non-AIDS complication and related deaths.

Trends in hospitalizations and deaths in HIV-infected patients in Spain over two decades.

The prognosis of HIV infection dramatically improved after the introduction of triple antiretroviral therapy 25 years ago. Herein, we report the impact of further improvements in HIV management since then, looking at all hospitalizations in persons with HIV (PWH) in Spain. A retrospective study using the Spanish National Registry of Hospital Discharges. Information was retrieved since 1997-2018. From 79 647 783 nationwide hospital admissions recorded during the study period, 532 668 (0.67%) included HIV as diagnosis. The mean age of PWH hospitalized increased from 33 to 51 years (P < 0.001). The rate of HIV hospitalizations significantly declined after 2008. Comparing hospitalizations during the first (1997-2007) and last (2008-2018) decades, the rate of non-AIDS illnesses increased, mostly due to liver disease (from 35.9 to 38.3%), cardiovascular diseases (from 12.4 to 28.2%), non-AIDS cancers (from 6.4 to 15.5%), and kidney insufficiency (from 5.4 to 13%). In-hospital deaths occurred in 5.5% of PWH, declining significantly over time. Although most deaths were the result from AIDS conditions (34.8%), the most frequent non-AIDS deaths were liver disease (47.1%), cardiovascular events (29.2%), non-AIDS cancers (24.2%), and kidney insufficiency (20.7%). Hospital admissions in PWH significantly declined after 2008, following improvements in HIV management and antiretroviral therapy. Non-AIDS cancers, cardiovascular events and liver disease represent a growing proportion of hospital admissions and deaths in PWH.

Women from afar: an observational study of demographic characteristics and mortality among foreign-born women living with HIV in the Women's Interagency HIV Study (WIHS) in the United States 1994-2016.

IntroductionForeign‐born persons comprise ~13% of the US population. Immigrants, especially women, often face a complex set of social and structural factors that negatively impact health outcomes including greater risk of HIV infection. We described socio‐demographic, clinical and immunological characteristics and AIDs and non‐AIDS death among foreign‐born women living with HIV (FBWLWH) participating in the US Women’s Interagency HIV Study (WIHS) in the US from 1994 to 2016. We hypothesized that FBW will experience higher AIDS‐related mortality compared to US‐born women (USBW).MethodsThe WIHS is a multicenter prospective observational cohort study of mostly women living with HIV (WLWH). The primary exposure in this analysis, which focused on 3626 WLWH, was self‐reported country of birth collapsed into foreign‐born and US born. We assessed the association of birthplace with categorized demographic, clinical and immunological characteristics, and AIDS/non‐AIDS mortality of WLWH, using chi‐squared tests. Proportional hazard models examined the association of birthplace with time from enrolment to AIDS and non‐AIDS death.ResultsOf the 628 FBW, 13% were born in Africa, 29% in the Caribbean and 49% in Latin America. We observed significant differences by HIV status in socio‐demographic, clinical and immunological characteristics and mortality. For both AIDS and non‐AIDS caused deaths FBW WLWH had lower rates of death. Adjusting for year of study enrolment and other demographic/clinical characteristics mitigated FBW’s statistical survival advantage in AIDS deaths Relative Hazard (RH = 0.91 p = 0.53), but did not substantively change the survival advantage in non‐AIDS deaths RH = 0.33, p < 0.0001).ConclusionForeign‐born WLWH exhibited demographic, clinical and immunological characteristics that are significantly different compared with women born in the US or US territory. After adjusting for these characteristics, the FB WLWH had a significantly lower hazard of non‐AIDS but not AIDS mortality compared to women born in the US or a US territory. These findings of non‐increased mortality can help inform models of care to optimize treatment outcomes among FBWLWH in the United States.

Association between Use of Methadone, Other Central Nervous System Depressants, and QTc Interval-Prolonging Medications and Risk of Mortality in a Large Cohort of Women Living with or at Risk for Human Immunodeficiency Virus Infection.

To evaluate the association between use of methadone, other central nervous system (CNS) depressants, and QTc interval-prolonging medications and risk of mortality among human immunodeficiency virus (HIV)-infected and at-risk HIV-uninfected women. Multicenter, prospective, observational cohort study (Women's Interagency HIV Study [WIHS]). A total of 4150 women enrolled in the WIHS study between 1994 and 2014 who were infected (3119 women) or not infected (1031 women) with HIV. Data on medication utilization were collected from all study participants via interviewer-administered surveys at 6-month intervals (1994-2014). Mortality was confirmed by National Death Index data. With age defining the time scale for the analysis, Cox proportional hazards models were used to estimate hazard ratios (HRs) for all-cause mortality in HIV-infected and -uninfected women and non-acquired immunodeficiency syndrome (AIDS) deaths in HIV-infected women. A total of 1046 deaths were identified, of which 429 were considered non-AIDS deaths. Use of benzodiazepines, CNS depressants (excluding methadone), and number of medications with conditional QTc interval-prolonging effects were each associated with all-cause mortality in multivariate models of HIV-infected women: hazard ratio (HR) 1.28, 95% confidence interval (CI) 1.01-1.60, p=0.037; HR 1.61, 95% CI 1.35-1.92, p<0.0001; and HR 1.15 per drug, 95% CI 1.00-1.33, p=0.047, respectively. Other explanatory variables for all-cause mortality in this model included HIV viral load, CD4+ cell count, renal function, hemoglobin and albumin levels, HIV treatment era, employment status, existence of depressive symptoms, ever use of injection drugs, and tobacco smoking. Of interest, use of CNS depressants (excluding methadone) was also associated with non-AIDS deaths (HR 1.49, 95% CI 1.49-2.2, p<0.0001). Although use of benzodiazepines and conditional QT interval-prolonging medications were associated with increased risk of non-AIDS mortality (HR 1.32 and 1.25, respectively), the effect was not statistically significant (p>0.05). In this cohort of HIV-infected and at-risk HIV-uninfected women, use of benzodiazepines, CNS depressants, and conditional QTc interval-prolonging medications were associated with a higher risk of mortality independent of methadone and other well-recognized mortality risk factors. Care must be taken to assess risk when prescribing these medications in this underserved and at-risk patient population.

2244. Non-AIDS Cancers Contribute to an Increasing Proportion of Deaths in Persons Living with HIV at a Single University-Based Clinic

BackgroundMortality for people living with HIV (PLWH) has drastically decreased since the mid-1990s, and the proportion of deaths due to non-HIV-related conditions has increased.MethodsDeceased PLWH were identified within a single academic medical center. Cause of death was determined by chart review, clinic providers, and when available autopsy and toxicology data. Chart review of comorbidities, demographics and preventable causes of cancer was conducted for deaths during the period of 2013–2017.ResultsThe proportion of AIDS-related deaths decreased markedly between 1995 and 2017, while the proportion of deaths from non-AIDS cancers has increased (figure). Patients with non-AIDS cancers were older, had a higher CD4 count and greater proportion with undetectable viral load, and were more likely to be male; over 80% were current or prior smokers (table). Among all deaths from 2013 to 2017, 44% of eligible patients received colon cancer screening, 66% received cervical cancer screening, and 29% received breast cancer screening. Of patients who died from HCC, one out of six had imaging for HCC within 1 year and none within 6 months of diagnosis.ConclusionImprovements in cancer screening and preventative health measures including smoking cessation and lifestyle improvement education may help to reduce the increasing proportion of non-AIDS cancer-related deaths among PLWH. Characteristics by Cause of Death (2013–2017)HIV-Related Cancer ‡ P-value N 2224Age at death50 (44, 56)56 (53, 61)0.03Last available CD472(15, 249)207(94, 301.5)0.02Last available viral load < 50 copies5 (23)16 (67)0.004CD4 Nadir18(7, 110)77(35, 126)0.2Male14 (64)23 (96)0.009Smoking within 1 year of death9 (41)13 (54)0.8Smoking, quit 1-15 years prior to death5 (23)6 (25)Smoking, quit > 15 years prior to death1 (5)1 (4)Never smoked7 (32)4 (17)*Median (IQR) or n (%).‡ Most common: HCC (6), head/neck (4), prostate (3).Disclosures All authors: No reported disclosures.

Economic and epidemiologic impact of guidelines for early ART initiation irrespective of CD4 count in Spain.

IntroductionEmerging data suggest that early antiretroviral therapy (ART) could reduce serious AIDS and non-AIDS events and deaths but could also increase costs. In January 2016, the Spanish guidelines were updated to recommend ART at any CD4 count. However, the epidemiologic and economic impacts of early ART initiation in Spain remain unclear.MethodsThe Johns Hopkins HIV Economic-Epidemiologic Mathematical Model (JHEEM) was utilized to estimate costs, transmissions, and outcomes in Spain over 20 years. We compared implementation of guidelines for early ART initiation to a counterfactual scenario deferring ART until CD4-counts fall below 350 cells/mm3. We additionally studied the impact of early ART initiation in combination with improvements to HIV screening, care linkage and engagement.ResultsEarly ART initiation (irrespective of CD4-count) is expected to avert 20,100 [95% Uncertainty Range (UR) 11,100–83,000] new HIV cases over the next two decades compared to delayed ART (28% reduction), at an incremental health system cost of €1.05 billion [€0.66 – €1.63] billion, and an incremental cost-effectiveness ratio (ICER) of €29,700 [€13,700 – €41,200] per QALY gained. Projected ICERs declined further over longer time horizon; e.g., an ICER of €12,691 over 30 years. Furthermore, the impact of early ART initiation was potentiated by improved HIV screening among high-risk individuals, averting an estimated 41,600 [23,200–172,200] HIV infections (a 58% decline) compared to delayed ART.ConclusionsRecommendations for ART initiation irrespective of CD4-counts are cost-effective and could avert > 30% of new cases in Spain. Improving HIV diagnosis can amplify this impact.

Early Treatment of Primary HIV Infection Is Associated with Decreased Mortality.

The aim of this study was to understand factors associated with increased mortality in a cohort of primary HIV infection (PHI) in New South Wales (NSW) over three decades. Six hundred and two patients with PHI were enrolled from 1984 to 2009. Probabilistic data linkage was performed to NSW Registry of births deaths and marriages and Australian Bureau of Statistics mortality database. Mortality was measured by crude death rate. Pre highly active antiretroviral therapy (pre-HAART) era was defined as before January 1, 1997. A Cox proportional hazard model was used to identify factors associated with death. One hundred and thirty-eight deaths occurred during 6,223 person years (PY) follow-up. Overall crude death rate was 2.2 per 100 PY (95% confidence interval [CI], 1.9-2.6), 3.6 (95% CI, 3.1-4.3)in pre-HAART era and 0.20 (95% CI, 0.08-0.47) in post-HAART era. AIDS was the most frequent cause of death (52%, 72/138), all occurring in the pre-HAART era. Of non-AIDS deaths, the leading known cause was non-AIDS cancer 8% (11/138) followed by suicide 4% (6/138). On multivariate analysis, estimated date of infection in pre-HAART era and time to commencement of ART greater than 1 year post diagnosis were more likely to be associated with death (p < .05). Mortality in PHI has decreased significantly in the post-HAART era. Non-AIDS deaths due to malignancy and suicide are emerging as leading causes in this population in the post-HAART era. Time to starting ART greater than 1 year was associated with increased mortality.

Causes of death and mortality trends of all individuals reported with HIV/AIDS in Israel, 1985-2010.

BackgroundHighly active antiretroviral therapy (HAART) has changed life-expectancy and mortality trends among people living with HIV/AIDS (PLWHA) since 1996. This retrospective cohort study aimed to assess the mortality epidemiology of PLWHA in Israel and analyze the causes of death.MethodsThis cohort study included all adult Israeli-citizens PLWHA between 1985 and 2010 and crossed matched with the Civil Registry to identify those who died. Death certificates were classified into AIDS or non-AIDS deaths related-causes. Standardized mortality-ratio (SMR) represented mortality excess.ResultsOf all 5140 PLWHA who were followed-up for 36 955 person-years, 1066 (20.7%) died. The ratio of AIDS-related deaths to non-AIDS related deaths reduced from 1.2:1 before 1996 to 0.6:1 after 1997, and case-fatality rates reduced from 12.0 to 0.9%, respectively (P < 0.001). SMR were 3.0 (95% CI: 2.3–3.5) for males and 3.9 (95% CI: 3.3–4.5) for females.Fatality cases were more likely older Israeli-born males, co-infected with tuberculosis, reported before 1996 and acquired HIV by drug-injection or infected-blood products. Deaths of AIDS-related causes were common among Israeli-born gay men, while non-AIDS deaths were common among those reported after 1997 and drug users.ConclusionsDeath rates declined since HAART introduction. Yet, SMR remained high, and PLWHA infected by drug-use or blood-products have not enjoyed relative longevity.

Contribution of Oxidative Stress to Non-AIDS Events in HIV-Infected Patients.

Recognition of potentially modifiable mechanisms implicated in the pathogenesis of non-AIDS events (NAEs) might help improve outcomes of HIV-infected individuals. HIV infection has been associated with increased oxidative stress. We assessed the association between F2-isoprostanes and serious NAEs, and whether they improve the predictive performance of inflammation and coagulation biomarkers. Prospective multicenter cohort. Individuals who had an incident serious NAE and 2 sex- and age-matched participants with no events were selected. Measurement of F2-isoprostanes, highly sensitive C-reactive protein, interleukin-6, D-dimer, sCD14, sCD40, sCD163, and neopterin levels was performed in successive plasma samples collected from cohort inclusion. Biomarkers were measured in 78 participants developing serious NAEs or death, and 151 subjects with no events. Adjusted levels of F2-isoprostanes, and also of highly sensitive C-reactive protein, sCD14, and D-dimer were higher in individuals who developed serious NAEs, including or not non-AIDS deaths. The same results were observed when only samples collected since the time of achieving virological suppression were analyzed. The additive incorporation of each biomarker, ending with F2-isoprostanes, in an adjusted model was associated with a graded and significant increase in the quality of model fitting, and 94% sensitivity, 33% specificity, and 0.77 accuracy to predict serious NAEs including non-AIDS-related death. Oxidative stress is associated with a higher risk of serious NAEs, including non-AIDS deaths. This effect is independent and additive to biomarkers of inflammation, monocyte activation, and coagulation. Our results suggest that oxidative stress should be included among mechanisms to deal with to improve prognosis of HIV-infected individuals.

Survival of HIV-positive patients starting antiretroviral therapy between 1996 and 2013: a collaborative analysis of cohort studies

SummaryBackgroundHealth care for people living with HIV has improved substantially in the past two decades. Robust estimates of how these improvements have affected prognosis and life expectancy are of utmost importance to patients, clinicians, and health-care planners. We examined changes in 3 year survival and life expectancy of patients starting combination antiretroviral therapy (ART) between 1996 and 2013.MethodsWe analysed data from 18 European and North American HIV-1 cohorts. Patients (aged ≥16 years) were eligible for this analysis if they had started ART with three or more drugs between 1996 and 2010 and had at least 3 years of potential follow-up. We estimated adjusted (for age, sex, AIDS, risk group, CD4 cell count, and HIV-1 RNA at start of ART) all-cause and cause-specific mortality hazard ratios (HRs) for the first year after ART initiation and the second and third years after ART initiation in four calendar periods (1996–99, 2000–03 [comparator], 2004–07, 2008–10). We estimated life expectancy by calendar period of initiation of ART.Findings88 504 patients were included in our analyses, of whom 2106 died during the first year of ART and 2302 died during the second or third year of ART. Patients starting ART in 2008–10 had lower all-cause mortality in the first year after ART initiation than did patients starting ART in 2000–03 (adjusted HR 0·71, 95% CI 0·61–0·83). All-cause mortality in the second and third years after initiation of ART was also lower in patients who started ART in 2008–10 than in those who started in 2000–03 (0·57, 0·49–0·67); this decrease was not fully explained by viral load and CD4 cell count at 1 year. Rates of non-AIDS deaths were lower in patients who started ART in 2008–10 (vs 2000–03) in the first year (0·48, 0·34–0·67) and second and third years (0·29, 0·21–0·40) after initiation of ART. Between 1996 and 2010, life expectancy in 20-year-old patients starting ART increased by about 9 years in women and 10 years in men.InterpretationEven in the late ART era, survival during the first 3 years of ART continues to improve, which probably reflects transition to less toxic antiretroviral drugs, improved adherence, prophylactic measures, and management of comorbidity. Prognostic models and life expectancy estimates should be updated to account for these improvements.FundingUK Medical Research Council, UK Department for International Development, EU EDCTP2 programme.

Causes of Death among AIDS Patients after Introduction of Free Combination Antiretroviral Therapy (cART) in Three Chinese Provinces, 2010-2011.

IntroductionAlthough AIDS-related deaths have had significant economic and social impact following an increased disease burden internationally, few studies have evaluated the cause of AIDS-related deaths among patients with AIDS on combination anti-retroviral therapy (cART) in China. This study examines the causes of death among AIDS-patients in China and uses a methodology to increase data accuracy compared to the previous studies on AIDS-related mortality in China, that have taken the reported cause of death in the National HIV Registry at face-value.MethodsDeath certificates/medical records were examined and a cross-sectional survey was conducted in three provinces to verify the causes of death among AIDS patients who died between January 1, 2010 and June 30, 2011. Chi-square analysis was conducted to examine the categorical variables by causes of death and by ART status. Univariate and multivariate logistic regression were used to evaluate factors associated with AIDS-related death versus non-AIDS related death.ResultsThis study used a sample of 1,109 subjects. The average age at death was 44.5 years. AIDS-related deaths were significantly higher than non-AIDS and injury-related deaths. In the sample, 41.9% (465/1109) were deceased within a year of HIV diagnosis and 52.7% (584/1109) of the deceased AIDS patients were not on cART. For AIDS-related deaths (n = 798), statistically significant factors included CD4 count <200 cells/mm3 at the time of cART initiation (AOR 1.94, 95%CI 1.24–3.05), ART naïve (AOR 1.69, 95%CI 1.09–2.61; p = 0.019) and age <39 years (AOR 2.96, 95%CI 1.77–4.96).ConclusionFor the AIDS patients that were deceased, only those who initiated cART while at a CD4 count ≥200 cells/mm3 were less likely to die from AIDS-related causes compared to those who didn’t initiate ART at all.

A longitudinal population-based analysis of relationship status and mortality in KwaZulu-Natal, South Africa 2001–2011

BackgroundMortality risk is lower in married than in unmarried men and women. However, little is known about the association between mortality and relationship status in South Africa where marriage rates...

Trends in hospital deaths among human immunodeficiency virus-infected patients during the antiretroviral therapy era, 1995 to 2011.

Mortality in hospitalized human immunodeficiency virus (HIV)-infected patients is not well described. We sought to characterize in-hospital deaths among HIV-infected patients in the antiretroviral (ART) era and identify factors associated with mortality. We reviewed the medical records of hospitalized HIV-infected patients who died from January 1, 1995 to December 31, 2011 at an urban teaching hospital. We evaluated trends in early and late ART use and deaths due to acquired immunodeficiency syndrome (AIDS) and non-AIDS, and identified clinical and demographic correlates of non-AIDS deaths. In-hospital deaths declined significantly from 1995 to 2011 (P < 0.0001); those attributable to non-AIDS increased (43% to 70.5%, P < 0.0001). Non-AIDS deaths were most commonly caused by non-AIDS infection (20.3%), cardiovascular (11.3%) and liver disease (8.5%), and non-AIDS malignancy (7.8%). Patients with non-AIDS compared to AIDS-related deaths were older (median age 48 vs 40 years, P < 0.0001), more likely to be on ART (74.1% vs 55.8%, P = 0.0001), less likely to have a CD4 count of <200 cells/mm(3) (47.2% vs 97.1%, P < 0.0001), and more likely to have an HIV viral load of ≤400 copies/mL (38.1% vs 4.1%, P < 0.0001). Non-AIDS deaths were associated with 4.5 and 4.2 times greater likelihood of comorbid underlying liver and cardiovascular disease, respectively. Non-AIDS deaths increased significantly during the ART era and are now the most common cause of in-hospital deaths; non-AIDS infection, cardiovascular and liver disease, and malignancies were major contributors to mortality. Higher CD4 cell count, liver, and cardiovascular comorbidities were most strongly associated with non-AIDS deaths. Interventions targeting non-AIDS-associated conditions are needed to reduce inpatient mortality among HIV-infected patients.

Combined Antiretroviral Therapy (cART) Reduces AIDS-Related and Non- AIDS-Related Mortality: A Temporal Analysis from Time of Seroconversion (SC)

Objectives: To estimate changes of AIDS and non-AIDS mortalities from 1996 to 2010 comparing (2004-2010) vs. (1996-2003) periods from the time of HIV-seroconversion (SC). Methods: Data derived from an Italian multicentre prospective and open cohort; competing risks approach was applied estimating the cumulative incidence functions (CIF) for AIDS and non-AIDS deaths over time from SC with delayed entries in the two cART periods. Cox-cause-specific hazards models were applied to estimate relative hazards (RH) of AIDS and non-AIDS related deaths. Results: Of 2,249 individuals with known SC date followed from SC and from January 1996 to December 2010, 1,779 were survived, seroconverted or followed during 1996-2003, while 1,715 during 2004-2010. A total of 278 deaths occurred from 1996 to 2010: 197 in the early years of cART [61 (31%) non-AIDS deaths], and 81 during more recent cART period [48 (59%) non-AIDS deaths]. The CIF of AIDS related deaths was higher than CIF of non-AIDS related deaths in the early period [for instance, estimates at 15 yrs from SC: CIF of AIDS-related death = 0.15 (95% CI: 0.12-0.19 ) and CIF of non-AIDS related = 0.09 (95% CI: 0.07-0.12)], whilst in 2004-2010 period the CIF of non-AIDS related deaths was slightly higher [estimates at 15 yrs from SC: CIF of non-AIDS related = 0.03 (95% CI: 0.02-0.04) vs. CIF of AIDS-related death = 0.02 (95% CI: 0.02-0.04)]. Comparing the two periods by Cox proportional-cause-specific models, the hazard was lower for AIDS deaths than for non-AIDS related deaths [RH of non-AIDS deaths from last viral load (VL) < 200 copies/mL was 0.60 (95% CI (0.35-1.03)], while of AIDS-deaths was 0.32 (95% CI: 0.17-0.62), both RH relative to (2004-2010) vs. (1996- 2003)]. Conclusions: Considering early years of the cART period as a reference, we observed a decrease in both AIDS and non-AIDS-mortalities. In more recent cART years, non-AIDS mortality tended to decline less than AIDS-relatedmortality since HIV-SC, even after effective cART.

Association of markers of hemostasis with death in HIV-infected women.

: In HIV negatives, markers of hemostasis, including D-dimer, factor VIII, plasminogen activator inhibitor-1 antigen (PAI-1), and total protein S are associated with all-cause and cardiovascular disease mortality. In HIV positives, studies of D-dimer and factor VIII with death were limited to short follow-up; associations of PAI-1 and total protein S with death have not been examined. In 674 HIV-infected women from the Women's Interagency HIV Study, markers from the first visit after enrollment were exposures of interest in multivariate analyses of death (AIDS and non-AIDS) in separate models at 5 and 16 years. There were 87 AIDS and 44 non-AIDS deaths at 5 years, and 159 AIDS and 113 non-AIDS deaths at 16 years. An inverse association of total protein S quartiles with non-AIDS deaths was observed at 5 (P trend = 0.002) and 16 years (P trend = 0.02); there was no association with AIDS deaths. The third quartile of PAI-1 was associated with AIDS deaths at 5 [hazard ratio (HR) = 4.0; 95% confidence interval (CI): 1.9 to 8.4] and 16 years (HR = 3.4; 95% CI: 1.9 to 5.9); and with non-AIDS deaths at 5 years (HR = 4.8; 95% CI: 1.6 to 13.9). D-dimer and factor VIII were not associated with AIDS or non-AIDS death at 5 or 16 years. Lower total Protein S was a consistent marker of non-AIDS death. We found no association between D-dimer with AIDS or non-AIDS death, in contrast to previous studies showing increased short-term (<5 years) mortality, which may represent sex differences or population heterogeneity. Given longer survival on highly active antiretroviral therapy, further studies of these markers are needed to determine their prognostic value.

Impact of risk factors for specific causes of death in the first and subsequent years of antiretroviral therapy among HIV-infected patients.

Patterns of cause-specific mortality in individuals infected with human immunodeficiency virus type 1 (HIV-1) are changing dramatically in the era of antiretroviral therapy (ART). Sixteen cohorts from Europe and North America contributed data on adult patients followed from the start of ART. Procedures for coding causes of death were standardized. Estimated hazard ratios (HRs) were adjusted for transmission risk group, sex, age, year of ART initiation, baseline CD4 count, viral load, and AIDS status, before and after the first year of ART. A total of 4237 of 65 121 (6.5%) patients died (median, 4.5 years follow-up). Rates of AIDS death decreased substantially with time since starting ART, but mortality from non-AIDS malignancy increased (rate ratio, 1.04 per year; 95% confidence interval [CI], 1.0-1.1). Higher mortality in men than women during the first year of ART was mostly due to non-AIDS malignancy and liver-related deaths. Associations with age were strongest for cardiovascular disease, heart/vascular, and malignancy deaths. Patients with presumed transmission through injection drug use had higher rates of all causes of death, particularly for liver-related causes (HRs compared with men who have sex with men: 18.1 [95% CI, 6.2-52.7] during the first year of ART and 9.1 [95% CI, 5.8-14.2] thereafter). There was a persistent role of CD4 count at baseline and at 12 months in predicting AIDS, non-AIDS infection, and non-AIDS malignancy deaths. Lack of viral suppression on ART was associated with AIDS, non-AIDS infection, and other causes of death. Better understanding of patterns of and risk factors for cause-specific mortality in the ART era can aid in development of appropriate care for HIV-infected individuals and inform guidelines for risk factor management.

Life Expectancy in the Immune Recovery Era

National cohort and intercohort studies have been set to describe the differences of life expectancy (LE) of HIV-infected individuals. The aim of this study was to assess the impact of immune recovery (IR) on LE of patients with HIV undergoing combination antiretroviral therapy. In this retrospective observational study, outcome measure was LE of patients with HIV compared with LE of northern Italian population. Group categorizations were as follows: patients with no immune recovery (nIR), patients with IR, patients who are immune maintained, and pre-highly active antiretroviral therapy (HAART) and post-HAART. Abridged life tables were constructed from age-specific mortality rates (per 1000 person years) to estimate LE from the age of 20-55 years. A total of 9671 patients, 71% men, were included. After 2005, we assisted to a rapid increase in the overall rate of patients attaining IR in the community coupled with a progressive decrease of AIDS death, but not of non-AIDS deaths. In a 40-year-old patient, LE was 38.10 years [standard error (SE) = 2.60], 30.08 years (SE = 0.98), and 22.9 (SE = 0.69) in the IR, post-HAART group and nIR, respectively, compared with 41.38 years of the general Italian population. An approximately 5-year gap in LE was observed in IR patients. We describe IR at a "community" level, related to calendar year and apparent 10 years after HAART introduction. HAART community IR is significantly influencing LE and is associated with the changing clinical picture of HIV disease. An increasing gradient of LE exists between nIR, post-HAART, and IR groups, with the latter, above the age of 40 years only, reaching LE of general population.

Sudden Cardiac Death in Patients With Human Immunodeficiency Virus Infection

The aim of this study was to determine the incidence and clinical characteristics of sudden cardiac death (SCD) in patients with human immunodeficiency virus (HIV) infection. As the HIV-infected population ages, cardiovascular disease prevalence and mortality are increasing, but the incidence and features of SCD have not yet been described. The records of 2,860 consecutive patients in a public HIV clinic in San Francisco between April 2000 and August 2009 were examined. Identification of deaths, causes of death, and clinical characteristics were obtained by search of the National Death Index and/or clinic records. SCDs were determined using published retrospective criteria: 1) the International Classification of Diseases-10th Revision, code for all cardiac causes of death; and (2) circumstances of death meeting World Health Organization criteria. Of 230 deaths over a median of 3.7 years of follow-up, 30 (13%) met SCD criteria, 131 (57%) were due to acquired immune deficiency syndrome (AIDS), 25 (11%) were due to other (natural) diseases, and 44 (19%) were due to overdoses, suicides, or unknown causes. SCDs accounted for 86% of all cardiac deaths (30 of 35). The mean SCD rate was 2.6 per 1,000 person-years (95% confidence interval: 1.8 to 3.8), 4.5-fold higher than expected. SCDs occurred in older patients than did AIDS deaths (mean 49.0 vs. 44.9 years, p = 0.02). Compared with AIDS and natural deaths combined, SCDs had a higher prevalence of prior myocardial infarction (17% vs. 1%, p < 0.0005), cardiomyopathy (23% vs. 3%, p < 0.0005), heart failure (30% vs. 9%, p = 0.004), and arrhythmias (20% vs. 3%, p = 0.003). SCDs account for most cardiac and many non-AIDS natural deaths in HIV-infected patients. Further investigation is needed to ascertain underlying mechanisms, which may include inflammation, antiretroviral therapy interruption, and concomitant medications.

P1-S3.04 Death in the era of HAART: not all about AIDS

BackgroundMortality from AIDS has dramatically reduced since the introduction of effective antiretroviral therapy, Nevertheless, HIV infected individuals remain at higher risk of early death. We investigate all causes of deaths...