BACKGROUND: Treatment strategies for patients in whom HIV replication is not suppressed after exposure to several drug classes remain unclear. We aimed to assess the inter-relations between viral load, CD4-cell count, and clinical outcome in patients who had experienced three-class virological failure. METHODS: We undertook collaborative joint analysis of 13 HIV cohorts from Europe, North America, and Australia, involving patients who had had three-class virological failure (viral load >1000 copies per mL for >4 months). Regression analyses were used to quantify the associations between CD4-cell-count slope, HIV-1 RNA concentration, treatment information, and demographic characteristics. Predictors of death were analysed by Cox's proportional-hazards models. FINDINGS: 2488 patients were included. 2118 (85%) had started antiretroviral therapy with single or dual therapy. During 5015 person-years of follow-up, 276 patients died (mortality rate 5.5 per 100 person-years; 3-year mortality risk 15.3% (95% CI 13.5-17.3). Risk of death was strongly influenced by the latest CD4-cell count with a relative hazard of 15.8 (95% CI 9.28-27.0) for counts below 50 cells per microL versus above 200 cells per microL. The latest viral load did not independently predict death. For any given viral load, patients on treatment had more favourable CD4-cell-count slopes than those off treatment. For patients on treatment and with stable viral load, CD4-cell counts tended to be increasing at times when the current viral load was below 10000 copies per mL or 1.5 log10 copies per mL below off-treatment values. INTERPRETATION: In patients for whom viral-load suppression to below the level of detection is not possible, achievement and maintenance of a CD4-cell count above 200 per microL becomes the primary aim. Treatment regimens that maintain the viral load below 10000 copies per mL or at least provide 1.5 log10 copies per mL suppression below the off-treatment value do not seem to be associated with appreciable CD4-cell-count decline.
BACKGROUND: Treatment strategies for patients in whom HIV replication is not suppressed after exposure to several drug classes remain unclear. We aimed to assess the inter-relations between viral load, CD4-cell count, and clinical outcome in patients who had experienced three-class virological failure. METHODS: We undertook collaborative joint analysis of 13 HIV cohorts from Europe, North America, and Australia, involving patients who had had three-class virological failure (viral load >1000 copies per mL for >4 months). Regression analyses were used to quantify the associations between CD4-cell-count slope, HIV-1 RNA concentration, treatment information, and demographic characteristics. Predictors of death were analysed by Cox's proportional-hazards models. FINDINGS: 2488 patients were included. 2118 (85%) had started antiretroviral therapy with single or dual therapy. During 5015 person-years of follow-up, 276 patients died (mortality rate 5.5 per 100 person-years; 3-year mortality risk 15.3% (95% CI 13.5-17.3). Risk of death was strongly influenced by the latest CD4-cell count with a relative hazard of 15.8 (95% CI 9.28-27.0) for counts below 50 cells per microL versus above 200 cells per microL. The latest viral load did not independently predict death. For any given viral load, patients on treatment had more favourable CD4-cell-count slopes than those off treatment. For patients on treatment and with stable viral load, CD4-cell counts tended to be increasing at times when the current viral load was below 10000 copies per mL or 1.5 log10 copies per mL below off-treatment values. INTERPRETATION: In patients for whom viral-load suppression to below the level of detection is not possible, achievement and maintenance of a CD4-cell count above 200 per microL becomes the primary aim. Treatment regimens that maintain the viral load below 10000 copies per mL or at least provide 1.5 log10 copies per mL suppression below the off-treatment value do not seem to be associated with appreciable CD4-cell-count decline.
Authors: Allan R Tenorio; Hongyu Jiang; Yu Zheng; Barbara Bastow; Daniel R Kuritzkes; John A Bartlett; Steven G Deeks; Alan L Landay; Sharon A Riddler Journal: AIDS Res Hum Retroviruses Date: 2009-02 Impact factor: 2.205
Authors: Frederick L Altice; Duncan Smith-Rohrberg Maru; R Douglas Bruce; Sandra A Springer; Gerald H Friedland Journal: Clin Infect Dis Date: 2007-08-13 Impact factor: 9.079
Authors: Matthew Bidwell Goetz; Monique R Ferguson; Xueliang Han; Greg McMillan; Marty St Clair; Keith A Pappa; Daniel R McClernon; William A O'Brien Journal: J Acquir Immune Defic Syndr Date: 2006-12-15 Impact factor: 3.731
Authors: Emilie Lanoy; Margaret May; Amanda Mocroft; Andrew Phillip; Amy Justice; Geneviève Chêne; Hansjakob Furrer; Timothy Sterling; Antonella D'Arminio Monforte; Lluís Force; John Gill; Ross Harris; Robert S Hogg; Jürgen Rockstroh; Mike Saag; Pavel Khaykin; Frank de Wolf; Jonathan A C Sterne; Dominique Costagliola Journal: AIDS Date: 2009-10-23 Impact factor: 4.177