Important note: Information in this article was accurate in 2003. The state of the art may have changed since the publication date.
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AIDS (10.17.03); Vol. 17; No. 15: P.2227-2236 - Tuesday, December 23, 2003
Ard I. van Sighem; Mark A. van de Wiel; Azra C. Ghani; Mari lle Jambroes; Peter Reiss; Inge C. Gyssens; Kees Brinkman; Joep M.A. Lange; Frank de Wolf; on behalf of the ATHENA cohort study group
Beginning in May 1998, researchers collected demographic data on ATHENA patients at entry to the study. Clinical data focused on HIV-1 infection related events according to CDC's definition, therapeutic and prophylactic drugs used for opportunistic infections, and the combination and dose of ARVs and their side effects. Additional data included measurements of plasma HIV-1 RNA concentration and CD4+ and CD8+ cell counts.
During 12,503 person-years of follow-up, 459 patients developed AIDS and 346 died. HIV-related mortality decreased from 3.8 to 0.7 per 100 person-years between 1996 and 2000. Non-HIV- related mortality did not change.
Data revealed that asymptomatic and symptomatic therapy na ve patients younger than 50 with CD4 counts above 10 x 106 and 150 x 106 cells/l, respectively, had predicted 5-year survival probabilities above 90 percent with continuous use of HAART. The limit was 450 x 106 cells/l when HAART was used during 20 weeks in each 24-week follow-up period, and 110 x 106 cells/l when patients delayed the initiation of HAART for 1 year after becoming eligible for treatment.
"The effect of treatment on disease outcome is assessed by studying therapy interruptions, which reflect both failure to suppress viral load or to increase CD4 cell counts and toxicity- driven switches," the study reported. "This analysis does not aim at drawing conclusions about the effect of a treatment strategy adopted at start of HAART. The high survival probabilities for patients with high baseline CD4 counts using interrupted HAART confirm that occasional treatment interruptions shorter than 3 months do not increase risk of death. Our results are also compatible with STI studies which show that short-term disease progression does not change or may even improve slightly. However, therapy interruptions in our cohort are largely unstructured and occur for a longer period of time... than in previous reports. Moreover, therapy may have been interrupted because of toxicity or therapy failure, the latter two being associated themselves with an increased risk of death and AIDS. Other studies have shown that therapy failure is the reason for about 10 percent of the therapy interruptions within 1 year after start of HAART, and toxicity for about 30 percent. This latter percentage increases with each calendar year following the introduction of HAART. Untangling the pure effect of STI from these other therapy interruptions is difficult in the settings of an observational cohort," the authors noted.
"Survival probabilities were high among HIV-infected patients initiating HAART at an early stage of infection," the authors found. "The best therapy strategy is therefore to start HAART at this stage of infection. However, deferring HAART in patients with high CD4 cell counts may be clinically more appropriate given toxicity and adherence problems. The lack of any change in non-HIV-related mortality suggests that toxicity has not yet become a major risk factor for death," the investigators concluded.
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