Objective: To compare HIV-disease progression according to changes of plasma HIV RNA observed in the year following initiation of a new antiretroviral treatment.
Design: Prospective cohort treated with two nucleoside analogues or a triple combination including a protease inhibitor.
Methods: A Cox model was used to estimate the effect of viral response during the first year after initiation of treatment on the subsequent occurrence of new AIDS-defining events or death. Viral response was fitted either as HIV RNA reduction during the initial 4–12 months of treatment or reduction during the first month.
Results: Among 773 patients (47% with triple drug combination) followed for a median period of 27 months, 62 patients experienced a clinical event. Poor viral responders (at least two measurements > 3.7 log10 copies/ml during 4–12 months of treatment) had a higher risk of disease progression than good responders (RNA < 2.7 log10 copies/ml) after adjustment [hazard ratio (HR), 2.24; 95% confidence interval (CI), 1.17–4.29]. Intermediate responders (2.7 ≤ RNA ≤ 3.7 log10 copies/ml) had a risk of progression comparable with that of good responders (HR, 1.43; 95% CI, 0.64–3.22). A large initial viral reduction was also a protective factor for clinical progression (HR, 0.51 for 1 log10 copies/ml increase of the reduction; 95% CI, 0.31–0.85) and was associated with the viral response during the subsequent 4–12 month period. No patient with a reduction < 0.5 log10 copies/ml in the first month was classified as a good responder in the subsequent 4–12 month period (P < 0.01).
Conclusions: A sustained HIV RNA > 3.7 log10 copies/ml should suggest a prompt change of treatment. When the reduction in HIV RNA is < 0.5 log10 after 1 month of treatment, this action should be anticipated. A sustained HIV RNA level between 2.7 and 3.7 log10 copies/ml may permit the deferral of a change of drug regimen according to the patient's history and therapeutic options.
From the aUnité INSERM 330, Institut de Santé Publique, d'Epidémiologie et de Développement (ISPED), Université Victor Segalen, Bordeaux and the bCentre d'Information et de Soins de l'Immunodéficience Humaine, CHU de Bordeaux, France. *See Appendix.
Sponsorship: Supported in part by a grant from the Agence Nationale de Recherches sur le SIDA (Action Coordonnée no.7, Cohortes).
Correspondence to François Dabis, MD, PhD, Unité INSERM 330, Université Victor Segalen Bordeaux 2, 146 rue Léo Saignat, 33076 Bordeaux cedex, France. Tel: +33 5 57 57 14 36; fax: +33 5 57 57 11 72; email: Francois.Dabis@dim.u-bordeaux2.fr
Received: 8 December 1999;
revised: 18 January 2000; accepted: 28 January 2000.