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Timing of initiation of antiretroviral therapy in AIDS-free HIV-1-infected patients: a collaborative analysis of 18 HIV cohort studies

Sterne, JAC; May, M; Costagliola, D; de Wolf, F; Phillips, AN; Harris, R; Funk, MJ; ... Start Consortium, ; + view all (2009) Timing of initiation of antiretroviral therapy in AIDS-free HIV-1-infected patients: a collaborative analysis of 18 HIV cohort studies. LANCET , 373 (9672) 1352 - 1363. 10.1016/S0140-6736(09)60612-7.

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Abstract

Background The CD4 cell count at which combination antiretroviral therapy should be started is a central, unresolved issue in the care of HIV-1-infected patients. in the absence of randomised trials, we examined this question in prospective cohort studies.Methods We analysed data from 18 cohort studies of patients with HIV. Antiretroviral-naive patients from 15 of these studies were eligible for inclusion if they had started combination antiretroviral therapy (while AIDS-free, with a CD4 cell count less than 550 cells per mu L, and with no history of injecting drug use) on or after Jan 1, 1998. We used data from patients followed up in seven of the cohorts in the era before the introduction of combination therapy (1989-95) to estimate distributions of lead times (from the first CD4 cell count measurement in an upper range to the upper threshold of a lower range) and unseen AIDS and death events (occurring before the upper threshold of a lower CD4 cell count range is reached) in the absence of treatment. These estimations were used to impute completed datasets in which lead times and unseen AIDS and death events were added to data for treated patients in deferred therapy groups. We compared the effect of deferred initiation of combination therapy with immediate initiation on rates of AIDS and death, and on death alone, in adjacent CD4 cell count ranges of width 100 cells per mu L.Findings Data were obtained for 21247 patients who were followed up during the era before the introduction of combination therapy and 24444 patients who were followed up from the start of treatment. Deferring combination therapy until a CD4 cell count of 251-350 cells per mu L was associated with higher rates of AIDS and death than starting therapy in the range 351-450 Cells per mu L (hazard ratio [HR] 1.28, 95% CI 1.04-1.57). The adverse effect of deferring treatment increased with decreasing CD4 cell count threshold. Deferred initiation of combination therapy was also associated with higher mortality rates, although effects on mortality were less marked than effects on AIDS and death (HR 1.13, 0.80-1.60, for deferred initiation of treatment at CD4 cell count 251-350 cells per mu L compared with initiation at 351-450 cells per mu L).Interpretation Our results suggest that 350 cells per mu L should be the minimum threshold for initiation of antiretroviral therapy, and should help to guide physicians and patients in deciding when to start treatment.Funding UK Medical Research Council.

Type: Article
Title: Timing of initiation of antiretroviral therapy in AIDS-free HIV-1-infected patients: a collaborative analysis of 18 HIV cohort studies
DOI: 10.1016/S0140-6736(09)60612-7
Keywords: HUMAN-IMMUNODEFICIENCY-VIRUS, VIROLOGICAL TREATMENT FAILURE, BLIND CONTROLLED-TRIAL, T-LYMPHOCYTE COUNTS, SOCIETY-USA PANEL, CD4 CELL COUNTS, INFECTED PATIENTS, BASE-LINE, DISEASE PROGRESSION, PROTEASE-INHIBITOR
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Pop Health Sciences > Institute for Global Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Pop Health Sciences > Institute for Global Health > Infection and Population Health
URI: http://discovery.ucl.ac.uk/id/eprint/168611
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