CD4+ Guided Antiretroviral Treatment Interruption in HIV Infection: A Meta-Analysis

The aim of this meta-analysis study was to evaluate the relative risk of death or AIDS-defining eventsassociated to CD4+ guided treatment interruption in patients with chronic HIV infection.A search was conducted using PubMed and Cochrane Library; key words for PubMed were: “antiretroviraltherapy and interrupt*â€? in the full papers from January 1, 2000 up to and including December 31, 2007. Tolimit the publication bias, clinical trials performed on the topic of the meta-analysis were searched alsoon http://www.clinicaltrial.gov. Inclusion criteria of studies were: starting a CD4+ guided interruption ofHAART in HIV chronically infected patients with CD4+ cell count > 350 cells/mm3, age > 13 years old, andabsence of concomitant use of immunomodulatory drugs. Using a conservative approach, to be includedin the meta-analysis, studies had to have a follow up period > 100 person years to minimize the bias of atoo short observation time. The studies were classified into two categories: randomized clinical trial (onearm stops therapy and other arms continues HAART) and cohort studies. For each study measures ofeffect (hazard ratio or incidence rate ratio) were reported, when available, uncorrected and corrected forpotential confounders. Publication bias was assessed graphically through funnel plot. Pooled relativerisk and pooled risk difference were calculated by use of a random effects model following the DerSimonian-Laird method. Observational studies were considered separately and the incidence of primaryendpoint was evaluated in each study and the cumulative incidence was calculated.Of the 555 full papers found, all abstracts were screened and 58 full text articles for potential inclusion wereretrieved and 18 were retained (seven randomized clinical trials and 11 observational studies). In randomizedclinical trials, the meta-analysis showed that the pooled relative risk of AIDS-defining event or mortality was2.50 (95% CI: 1.87-3.34; p < 0.001); the pooled risk difference of AIDS-defining event or mortality was 0.02(95% CI: –0.01-0.05; p = 0.168). The respective values corrected for latest CD4+ value were 1.77 (95% CI:1.29-2.42; p 100 person years, was 0.77 (95% CI: 0.37-1.42 events per 100 person years),ranging in different studies from 0 to 3.2 events per 100 person years. This meta-analysis suggests that inpatients undergoing a treatment interruption, there is an increased risk of developing AIDS or death, and thatthis risk is decreased if a relatively high CD4+ threshold is chosen to reinitiate the treatment, while the riskdifference does not reach statistical significance.