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Predictors of virological rebound in HIV-1-infected patients initiating a protease inhibitor-containing regimen
  AIDS 2002; 12:21-29. Jan 4
Vincent Le Moinga,b; Genevieve Cheneb; Maria P. Carrieric; Ahmadou Alioumb; Francoise Brun-Vezinetd; Lionel Pirothe; Jill P. Cassutof; Jean-Paul Moattic; Francois Raffig; Catherine Leporta; and the Aproco Study Group*
Objective: To study the predictors of virological rebound in patients having early virological response to protease inhibitor (PI)-containing regimen.
The authors recommend using more potent regimen when viral load is high; single PI regimen may not be adequate. They found more durable responses when therapy was started at CD4 counts above 500, when immunity was preserved.
Design and methods: APROCO cohort study prospectively enrolled 1283 HIV-infected patients starting a PI-containing regimen in 1997-1999. Adherence to therapy was measured with self-administered questionnaires after 4 months of therapy (M4). Virological rebound was defined as a viral load (VL) > 500 copies/ml in patients having early virological response, defined as a VL < 500 copies/ml at M4. Predictors of time to virological rebound were studied with multivariate proportional hazards model.
Results: During a median follow-up of 20 months, virological rebound was observed in 32% of the 830 patients with early virological response. Virological rebound was more frequent when patients had received previous antiretroviral treatment [adjusted hazards ratio (HR) = 2.4; P < 0.0001], were younger (HR = 1.4 per each 10 years younger; P < 0.0001), had baseline CD4 cell count < 500 (HR = 2.3; P < 0.001), had higher baseline VL (HR = 1.4 per each log10 copies/ml higher; P < 0.001), reported low adherence to therapy at M4 (HR = 2.1; P < 0.001) or had stopped PI at M4 (HR = 1.7; P = 0.04).
Conclusion: Initiation of treatment at a stage of preserved immunity is associated with a more durable virological response under protease inhibitor. Every effort should be made to monitor and strengthen adherence to therapy, even in patients having early virological response.
At first, patients were classified as reporting high adherence if in the detailed table they reported that they had taken 100% of their prescribed doses. Among these patients, those who however declared that they had skipped a dose during the last week-end, that they had 'almost totally' followed their HAART regimen, or they had to modify several times the prescribed schedule or that they took their regimen through a unique intake were reclassified as reporting moderate adherence. Patients were also classified as reporting moderate adherence if they declared having missed no more than 20% of their prescribed doses of HAART (80-99% adherence). Finally, patients who declared that they had taken less than 80% of pills, and/or that they had 'partially' or 'not at all' followed their HAART prescriptions, were considered as reporting low adherence.
Almost half of them were antiretroviral naive; the, median baseline VL was 4.5 log10 copies/ml [interquartile range (IQR), 3.6-5.1] and median baseline CD4+ cell count was 291 (IQR, 133-436). PI prescribed at baseline was indinavir in 45.8% of patients, nelfinavir in 29.9%, ritonavir in 13.5%, saquinavir-hgc in 6.8% and a combination of PIs in 4.0%. At M4, 8.6% of patients had changed PI and 5.4% had stopped it, either temporarily or definitively. These modifications of the PI component of the regimen were due to intolerance in 69 of 116 (59.5%) patients.
Risk of rebound was higher, but not significantly so, in patients having moderate adherence compared to those reporting high adherence.
The effect of baseline CD4+ cell counts on the risk of virological rebound did not appear to be log-linear: the risk of rebound was quite uniform for the lowest counts and was significantly lower solely in the patients having a CD4+ cell count 500. In our study however, the association between baseline CD4+ cell counts and sustained virological response was not linear and was significant only when baseline CD4+ cell count was above 500.
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