Cause-specific mortality in HIV-positive patients who survived ten years after starting antiretroviral therapy

Objectives: To estimate mortality rates and prognostic factors in HIV-positive patients who started combination antiretroviral therapy between 1996-1999 and survived for more than ten years. Methods: We used data from 18 European and North American HIV cohort studies contributing to the Antiretroviral Therapy Cohort Collaboration. We followed up patients from ten years after start of combination antiretroviral therapy. We estimated overall and cause-specific mortality rate ratios for age, sex, transmission through injection drug use, AIDS, CD4 count and HIV-1 RNA. Results: During 50,593 person years 656/13,011 (5%) patients died. Older age, male sex, injecting drug use transmission, AIDS, and low CD4 count and detectable viral replication ten years after starting combination antiretroviral therapy were associated with higher subsequent mortality. CD4 count at ART start did not predict mortality in models adjusted for patient characteristics ten years after start of antiretroviral therapy. The most frequent causes of death (among 340 classified) were non-AIDS cancer, AIDS, cardiovascular, and liverrelated disease. Older age was strongly associated with cardiovascular mortality, injecting drug use transmission with non-AIDS infection and liver-related mortality, and low CD4 and detectable viral replication ten years after starting antiretroviral therapy with AIDS mortality. Five-year mortality risk was <5% in 60% of all patients, and in 30% of those aged over 60 years. Conclusions: Viral replication, lower CD4 count, prior AIDS, and transmission via injecting drug use continue to predict higher all-cause and AIDS-related mortality in patients treated with combination antiretroviral therapy for over a decade. Deaths from AIDS and non-AIDS infection are less frequent than deaths from other non-AIDS causes

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

Factors associated with short-term changes in HIV viral load and CD4 cell count in antiretroviral-na&#239;ve individuals.

OBJECTIVES: Among antiretroviral therapy (ART)-naive individuals, viral load levels tend to increase and CD4(+) cell counts decline over time. We sought to explore the rate of change and influence of other factors associated with these markers of HIV progression. DESIGN: An observational cohort collaboration study. METHODS: A total of 158 385 pairs of consecutive viral load and CD4(+) cell count simultaneously measured from 34 384 ART-naive individuals in the COHERE database were analysed. Annual changes and factors associated with these changes were estimated using generalized estimating equations. RESULTS: Viral load continued to rise at a mean [95% confidence interval (CI)] rate of 0.091 (0.086-0.096) log10 copies/ml per year. A faster rise in viral load was significantly associated with older age, such that for every 10 years older, it was a mean 0.022 log10 copies/ml per year greater. The mean (95% CI) CD4(+) cell count change was -78.0 (-80.1 to -76.0) cell/mul per year and it was strongly associated with a higher current viral load: for every 1 log10 copies/ml higher, CD4(+) cell count declined by an additional 37.6 cells/mul per year (P < 0.001). Current viral load was a stronger predictor of CD4(+) cell count depletion than baseline viral load. Neither sex, race nor transmission by injecting drug use was associated with change in either the viral load or CD4(+) cell count. DISCUSSION: We found that in ART-naive individuals, viral load continues to increase over time and more sharply in those who are older. Our results also suggest that higher current viral load is strongly associated with ongoing rate of CD4(+) cell count depletion

Long-term mortality in HIV-positive Individuals virally suppressed for &gt;3 years with incomplete CD4 recovery

Background.\u2003Some human immunodeficiency virus (HIV)-infected individuals initiating combination antiretroviral therapy (cART) with low CD4 counts achieve viral suppression but not CD4 cell recovery. We aimed to identify (1) risk factors for failure to achieve CD4 count >200 cells/\ub5L after 3 years of sustained viral suppression and (2) the association of the achieved CD4 count with subsequent mortality. Methods.\u2003We included treated HIV-infected adults from 2 large international HIV cohorts, who had viral suppression ( 64500 HIV type 1 RNA copies/mL) for >3 years with CD4 count 64200 cells/\ub5L at start of the suppressed period. Logistic regression was used to identify risk factors for incomplete CD4 recovery ( 64200 cells/\ub5L) and Cox regression to identify associations with mortality. Results.\u2003Of 5550 eligible individuals, 835 (15%) did not reach a CD4 count >200 cells/\ub5L after 3 years of suppression. Increasing age, lower initial CD4 count, male heterosexual and injection drug use transmission, cART initiation after 1998, and longer time from initiation of cART to start of the virally suppressed period were risk factors for not achieving a CD4 count >200 cells/\ub5L. Individuals with CD4 64200 cells/\ub5L after 3 years of viral suppression had substantially increased mortality (adjusted hazard ratio, 2.60; 95% confidence interval, 1.86-3.61) compared with those who achieved CD4 count >200 cells/\ub5L. The increased mortality was seen across different patient groups and for all causes of death. Conclusions.\u2003Virally suppressed HIV-positive individuals on cART who do not achieve a CD4 count >200 cells/\ub5L have substantially increased long-term mortality

Search for new resonances decaying to a W or Z boson and a Higgs boson in the l(+)l(-)b(b)over-bar, l nu b(b)over-bar, and nu(nu)over-barb(b)over-bar channels with pp collisions at root s=13 TeV with the ATLAS detector

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