Mortality in well controlled HIV in the continuous antiretroviral therapy arms of the SMART and ESPRIT trials compared with the general population

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

Due to the success of antiretroviral therapy (ART), it is relevant to ask whether death rates in optimally treated HIV are higher than the general population. The objective was to compare mortality rates in well controlled HIV-infected adults in the SMART and ESPRIT clinical trials with the general population. Non-IDUs aged 20-70 years from the continuous ART control arms of ESPRIT and SMART were included if the person had both low HIV plasma viral loads (≤400 copies/ml SMART, ≤500 copies/ml ESPRIT) and high CD4(+) T-cell counts (≥350 cells/μl) at any time in the past 6 months. Standardized mortality ratios (SMRs) were calculated by comparing death rates with the Human Mortality Database. Three thousand, two hundred and eighty individuals [665 (20%) women], median age 43 years, contributed 12,357 person-years of follow-up. Sixty-two deaths occurred during follow up. Commonest cause of death was cardiovascular disease (CVD) or sudden death (19, 31%), followed by non-AIDS malignancy (12, 19%). Only two deaths (3%) were AIDS-related. Mortality rate was increased compared with the general population with a CD4(+) cell count between 350 and 499 cells/μl [SMR 1.77, 95% confidence interval (CI) 1.17-2.55]. No evidence for increased mortality was seen with CD4(+) cell counts greater than 500 cells/μl (SMR 1.00, 95% CI 0.69-1.40). In HIV-infected individuals on ART, with a recent undetectable viral load, who maintained or had recovery of CD4(+) cell counts to at least 500 cells/μl, we identified no evidence for a raised risk of death compared with the general population.

Related collections

Most cited references 19

Record: found
Abstract: found
Article: not found

CD4+ count-guided interruption of antiretroviral treatment.

B. Gazzard, Richard A. Phillips, G Fätkenheuer … (2006)

Despite declines in morbidity and mortality with the use of combination antiretroviral therapy, its effectiveness is limited by adverse events, problems with adherence, and resistance of the human immunodeficiency virus (HIV). We randomly assigned persons infected with HIV who had a CD4+ cell count of more than 350 per cubic millimeter to the continuous use of antiretroviral therapy (the viral suppression group) or the episodic use of antiretroviral therapy (the drug conservation group). Episodic use involved the deferral of therapy until the CD4+ count decreased to less than 250 per cubic millimeter and then the use of therapy until the CD4+ count increased to more than 350 per cubic millimeter. The primary end point was the development of an opportunistic disease or death from any cause. An important secondary end point was major cardiovascular, renal, or hepatic disease. A total of 5472 participants (2720 assigned to drug conservation and 2752 to viral suppression) were followed for an average of 16 months before the protocol was modified for the drug conservation group. At baseline, the median and nadir CD4+ counts were 597 per cubic millimeter and 250 per cubic millimeter, respectively, and 71.7% of participants had plasma HIV RNA levels of 400 copies or less per milliliter. Opportunistic disease or death from any cause occurred in 120 participants (3.3 events per 100 person-years) in the drug conservation group and 47 participants (1.3 per 100 person-years) in the viral suppression group (hazard ratio for the drug conservation group vs. the viral suppression group, 2.6; 95% confidence interval [CI], 1.9 to 3.7; P<0.001). Hazard ratios for death from any cause and for major cardiovascular, renal, and hepatic disease were 1.8 (95% CI, 1.2 to 2.9; P=0.007) and 1.7 (95% CI, 1.1 to 2.5; P=0.009), respectively. Adjustment for the latest CD4+ count and HIV RNA level (as time-updated covariates) reduced the hazard ratio for the primary end point from 2.6 to 1.5 (95% CI, 1.0 to 2.1). Episodic antiretroviral therapy guided by the CD4+ count, as used in our study, significantly increased the risk of opportunistic disease or death from any cause, as compared with continuous antiretroviral therapy, largely as a consequence of lowering the CD4+ cell count and increasing the viral load. Episodic antiretroviral therapy does not reduce the risk of adverse events that have been associated with antiretroviral therapy. (ClinicalTrials.gov number, NCT00027352 [ClinicalTrials.gov].). Copyright 2006 Massachusetts Medical Society.

0 comments Cited 170 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

CD4+ cell count 6 years after commencement of highly active antiretroviral therapy in persons with sustained virologic suppression.

Robert Moore, Jeanne Keruly (2007)

Sustained suppression of the human immunodeficiency virus (HIV) type 1 RNA load with the use of highly active antiretroviral therapy (HAART) results in immunologic improvement, but it is not clear whether the CD4(+) cell count increases to normal levels or whether it reaches a less-than-normal plateau. We characterized the increase in the CD4(+) cell count in patients in clinical practice who maintained sustained viral suppression for up to 6 years. All patients were from the Johns Hopkins HIV Clinical Cohort, a longitudinal observational study of patients receiving primary HIV care in Baltimore, Maryland, who were observed for >1 year while receiving HAART and who had sustained suppression of the HIV RNA load at 350 cells/microL, and we assessed the development of clinical events (death and new acquired immunodeficiency syndrome-defining illness) by Kaplan-Meier analysis. A total of 655 patients were observed for a median of 46 months (range, 13-72 months). The median change from baseline to most recent CD4(+) cell count was +274 cells/microL, with 92% of patients having an increase in CD4(+) cell count. By 6 years, the median CD4(+) cell count was 493 cells/microL among patients with baseline CD4(+) cell counts 350 cells/microL. In addition to baseline CD4(+) cell count, injection drug use and older age were associated with a lesser CD4(+) cell count response, and duration of therapy was associated with a greater CD4(+) cell count response. Only patients with baseline CD4(+) cell counts >350 cells/microL returned to nearly normal CD4(+) cell counts after 6 years of follow-up. Significant increases were observed in all CD4(+) cell count strata during the first year, but there was a lower plateau CD4(+) cell count at lower baseline CD4(+) cell strata. These data suggest that waiting to start HAART at lower CD4(+) cell counts will result in the CD4(+) cell count not returning to normal levels.

0 comments Cited 136 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Markers of inflammation, coagulation, and renal function are elevated in adults with HIV infection.

Daniel Duprez, Andrew J. Ross, Henry Baker … (2010)

Human immunodeficiency virus (HIV) replication and immune activation may increase inflammation and coagulation biomarkers. Limited data exist comparing such biomarkers in persons with and without HIV infection. For persons 45-76 years of age, levels of high-sensitivity C-reactive protein (hsCRP), interleukin (IL)-6, D-dimer, and cystatin C were compared in 494 HIV-infected individuals in the Strategies for Management of Anti-Retroviral Therapy (SMART) study and 5386 participants in the Multi-Ethnic Study of Atherosclerosis (MESA) study. For persons 33-44 years of age, hsCRP and IL-6 levels were compared in 287 participants in the SMART study and 3231 participants in the Coronary Artery Development in Young Adults (CARDIA) study. hsCRP and IL-6 levels were 55% (P < . 001) and 62 (P < . 001) higher among HIV-infected participants than among CARDIA study participants. Compared with levels noted in MESA study participants, hsCRP, IL-6, D-dimer, and cystatin C levels were 50%, 152%, 94%, and 27% higher, respectively (P < . 001, for each), among HIV-infected participants. HIV-infected participants receiving antiretroviral therapy who had HIV RNA levels 400 copies/mL had levels higher (by 21% to 60%) (P < . 001) than those in the general population, for all biomarkers. hsCRP, IL-6, D-dimer, and cystatin C levels are elevated in persons with HIV infection and remain so even after HIV RNA levels are suppressed with antiretroviral therapy. Additional research is needed on the pathophysiology of HIV-induced activation of inflammatory and coagulation pathways, to guide potential interventions.