SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Abrams, D

Arduino, RC

Babiker, A

Burman, W

Clumeck, N

Cohen, CJ

Cohn, D

Cooper, D

Darbyshire, J

El-Sadr, WM

Emery, S

Fatkenheuer, G

Gazzard, B

Gordin, F

Grund, B

Hoy, J

Klingman, K

Losso, M

Lundgren, JD

Markowitz, N

Mejia, JMR

Neaton, JD

Neuhaus, J

Phillips, A

Rappoport, C

Strategies Management Antiretrovir

BACKGROUND: 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). METHODS: 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. RESULTS: 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). CONCLUSIONS: 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].)

Strategies for Management of Antiretroviral Therapy (SMART) Stud

Fätkenheuer, G

LSHTM Research Online

CD4+ count-guided interruption of antiretroviral treatment.

BACKGROUND: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).METHODS: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.RESULTS: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).CONCLUSIONS: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

UCL Discovery

English

A new epidemiologic classification system for interim myocardial infarction from serial electrocardiographic changes.

A prospective, randomized trial of structured treatment interruption for patients with chronic HIV type 1 infection. Clin Infect Dis

AIDS across Europe, 1994-1998: the EuroSIDA study. Lancet 2000;356:291-6. Strategies for management of antiretroviral therapy

Cardio- and cerebrovascular events in HIV-infected persons.

Causes of death among human immunodeficiency virus (HIV)-infected adults in the era of potent antiretroviral therapy: emerging role of hepatitis and cancers, persistent role of AIDS.

CD4-guided scheduled treatment interruptions compared with continuous therapy for patients infected with HIV-1: results of the Staccato randomised trial.

CD4-guided structured antiretroviral treatment interruption strategy in HIV-infected adults in west Africa (Trivacan ANRS 1269 trial): a randomised trial. Lancet 2006;367:1981-9. Selik RM, Byers RH Jr,

Changing patterns of mortality across Europe in patients infected with HIV-1.

Combination antiretroviral therapy and risk of myocardial infarction.

Comparisons of causes of death and mortality rates among HIV-infected persons: analysis of the pre-, early, and late HAART (highly active antiretroviral therapy) eras.

Considerations in choice of a clinical endpoint for A I D S c l i n i c a l tr i a l s

Decay characteristics of HIV-1 infected compartments during combination therapy.

Declining morbidity and mortality among patients with advanced immunodeficiency virus infection.

Discrete sequential boundaries for clinical trials.

Downloaded from www.nejm.org at

Downloaded from www.nejm.org at UNIVERSITY COLLEGE LONDON on May 12,

Effect of antiretroviral therapy on liver-related mortality in patients with HIV and hepatitis C virus coinfection.

Effect of prolonged discontinuation of successful antiretroviral therapy on CD4 T cells: a controlled, prospective study. AIDS

Fleming TR. A multiple testing procedure for clinical trials.

Guidelines for the management of chronic kidney disease in HIV-infected patients:

Highly active antiretroviral therapy (HAART) retreatment in patients on CD4-guided therapy achieved similar virologic suppression compared with patients on continuous HAART.

Is there evidence for an increase in the death rate from liver-related disease in patients with HIV?

Latent infection of CD4+ T cells provides a mechanism for lifelong persistence

Latent reservoirs of HIV: obstacles to the eradication of virus.

Liver toxicity caused by nevirapine.

National Institutes of Health. (Accessed

prediction, and natural course of HIV-1 protease-inhibitor-associated lipodystrophy, hyperlipidemia, and diabetes mellitus: a cohort study. Lancet

Sample size calculation for complex clinical trials with survival endpoints. Control Clin Trials

Structured treatment interruptions for the management of HIV infection.

The Minnesota Code manual of electrocardiographic findings.

The statistical analysis of failure time data. 2nd ed.

To stop or not to stop: that is the question, but what is the answer?

Trends in diseases reported on U.S. death certificates that mentioned HIV infection,

CD4+ count-guided interruption of antiretroviral treatment

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