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Background: Viremia copy-years (VCY) has been reported as a short-term predictor of mortality. We evaluated the association of this parameter with 10-year outcome within the APROCO-COPILOTE cohort., Methods: Prospective data from 1281 HIV-1-infected patients who started a first protease inhibitor-containing regimen in 1997-1999 were analyzed. Patients with baseline plasma viral load (pVL) > 500 copies per milliliter and at least 2 pVL measures from the eighth month of follow-up were selected. VCY was calculated individually over the follow-up as the area under the pVL curve. Multivariate Cox models analyzed the relation between all-cause mortality and the following variables: age, sex, geographical origin, transmission group, HIV infection duration, ART-naive, pVL at baseline, time-dependent CD4 count, and VCY., Results: Nine hundred seventy-nine patients were followed up for a median of 10 years (interquartile range: 5-11.5). At baseline, median (interquartile range) values for duration of HIV infection, pVL, and CD4 cell count were 43 (4-95) months, 4.6 (3.9-5.2) log10 copies per milliliter, and 278 (125-416) cells per cubic millimeter, respectively. At censoring date, 77 patients (8%) had died. VCY >1.4 log10 copies × yrs/mL was an independent predictor of death (hazard ratio: 2.0; 95% confidence interval: 1.2 to 3.5), which was no longer the case after adjustment for the latest pVL value [risk ratio (RR): 1.2 for 1 additional log10 copies per milliliter; 95% confidence interval: 1.1 to 1.4]., Conclusions: VCY was associated with mortality in HIV-infected patients under combined antiretroviral therapy but did not overweigh the predictive value of the latest pVL. VCY might be more useful as a marker of persistent viral replication than for routine clinical care.

Indinavir and nelfinavir plasma levels were studied in 407 patients having plasma HIV RNA <500 copies/mL after 4 months of treatment with these drugs. For each drug, an observed/predicted (O/P) ratio was calculated between individual and mean time-adjusted population plasma drug levels. The relationship between the O/P ratio and the risk of rebound of plasma HIV RNA >500 copies/mL beyond month 4 was studied using Cox proportional hazard models. Median follow-up was 20 months. There was no association between indinavir plasma levels and risk of virologic rebound, whereas low nelfinavir + M8 (active nelfinavir metabolite) plasma levels were associated with a higher risk of virologic rebound. In multivariate analysis, the adjusted relative hazard of virologic rebound for patients with an O/P ratio of nelfinavir + M8 metabolite <0.8 compared with others was 2.2 (P = 0.01). In some patients, plasma levels of nelfinavir sufficient to achieve early viral response may not be sufficient to maintain it in the long term. This may be related to insufficient compliance with dietary recommendations. Monitoring of nelfinavir plasma levels thus seems useful, even in patients having early virologic response.

Objectives: Our objective was to describe the evolution of adherence to highly active antiretroviral therapy (HAART) over a 20-month period and its relationship with virologic success., Methods: Self-reported adherence, clinical, and virologic data were collected 4 (M4), 12 (M12), and 20 (M20) months after initiation of a protease inhibitor-containing regimen in the French APROCO cohort. At each visit, patients were classified as nonadherent, moderately, or highly adherent, and HIV plasma RNA was determined., Results: Among the 762 patients who were regularly followed until M20, the 436 patients who answered to all questionnaires, including adherence measurement, were selected for the analysis. The proportion of highly adherent patients was 55.7%, 62.2%, and 60.3% at M4, M12, and M20, respectively. A total of 137 patients (31.4%) was "always," 225 (51.6%) "sometimes," and 74 (17.0%) "never" "highly adherent" during follow-up. After multiple adjustment for known baseline predictors, virologic success after 20 months of HAART was more likely achieved in patients who were always (odds ratio [OR] 95% confidence interval [CI], 3.02 [1.64-5.58]) or sometimes (OR [95% CI], 2.15 [1.24-3.74]) "highly adherent.", Conclusion: Adherence behavior is a dynamic process. Continued adherence was associated with better response to therapy and should be encouraged to reduce the risk of virologic failure.