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

By Jonathan A. C. Sterne, Margaret T. May, D. Costagliola, F. de Wolf, A. Phillips, Ross Harris, M. Funk, R. Geskus, John Gill, F. Dabis and 11 more. 2009

790 citations recorded by the source corpus.

Summary 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 μL, 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 μL. Findings Data were obtained for 21 247 patients who were followed up during the era before the introduction of combination therapy and 24 444 patients who were followed up from the start of treatment. Deferring combination therapy until a CD4 cell count of 251–350 cells per μL was associated with higher rates of AIDS and death than starting therapy in the range 351–450 cells per μL (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 μL compared with initiation at 351–450 cells per μL). Interpretation Our results suggest that 350 cells per μL 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.

Subfields: Infectious Diseases, Virology

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Citations in the corpus

Acute retroviral syndrome and high baseline viral load are predictors of rapid HIV progression among untreated Argentinean seroconverters (2011, background): “Patients with acute retroviral syndrome or high baseline viral load should be considered for treatment initiation, as our data suggest that approximately one-third of them will require treatment in the following year; new evidence also suggests benefits of earlier treatment initiation [59,60].”
Prevention of HIV-1 Infection with Early Antiretroviral Therapy (2011, neutral): “18–25 yr 145 (16) 161 (18) 154 (17) 174 (20)”
Identifying the consequences of dynamic treatment strategies: A decision-theoretic overview (2010, background): “Preliminary ﬁndings indicate that treatment should be initiated when the CD4 cell count drops below a certain level, i.e. treatment should be a function of the patient’s previous CD4 count history (Sterne et al. , 2009).”