Search

OBJECTIVE To describe the time from first viral rebound on highly active antiretroviral therapy to first treatment change, identify factors associated with more rapid switching, and investigate whether treatment changes are in line with treatment guidelines. DESIGN AND SETTING A multicentre cohort study. METHODS We described the time to first treatment switch among individuals experiencing confirmed virological rebound after initiating highly active antiretroviral therapy; factors associated with more rapid switching were identified using proportional hazards regression and predictors of a switch in line with guidelines were identified using logistic regression. RESULTS Thirty-four percent of the 694 patients experiencing virological rebound remained on a failing regimen for more than 6 months. Factors associated with more rapid switching were lower CD4 cell count (hazard ratio, 0.84 /100 cells/mul higher, P < 0.001), higher viral load (1.29 /log10 copies/ml higher, P < 0.001), older age (1.06 /5 years older, P = 0.07), and changing/adding drugs to the regimen prior to rebound (1.16, P = 0.16). Two hundred and eighteen of the 394 treatment changes (55%) were in line with guidelines; those receiving nonnucleoside reverse transcriptase inhibitor-containing regimens were more likely to make changes in line with guidelines (adjusted odds ratio, 2.80, P < 0.001), whereas those who had previously added drugs to their regimen were less likely to make changes in line with guidelines (0.15, P = 0.001). CONCLUSION A substantial minority of patients remain on a failing highly active antiretroviral therapy regimen for periods of 6 months or longer without adding new drugs. Changes made are often not in line with treatment guidelines, raising concerns about the development of resistance and long-term clinical outcomes in these individuals.

Objective: We investigated whether previous treatment interruptions are associated with a raised risk of viral rebound in individuals who have attained virological suppression.Methods: All patients achieving an undetectable viral load while on therapy were followed until viral rebound or the time of the last viral load. Poisson regression was used to describe the independent impact of treatment interruptions on rebound rates.Results: A total of 12 977 patients from the United Kingdom Collaborative HIV Cohort (UK CHIC) Study achieved a viral load of less than 50 copies/ml. These patients contributed a total of 37 314 person-years of follow-up. The overall rebound rate was 8.07 (7.78, 8.36) per 100 person-years. In adjusted analyses, rates of viral rebound were up to 64% higher (rate ratio 1.64; 1.43, 1.88) in those who had previously interrupted therapy compared with those who had not. Patients who had interrupted at detectable viral loads had upto a 74% (1.74; 1.42, 2.14) higher chance of rebounding compared with those who had not interrupted with a detectable viral load. We found no evidence to suggest interrupting treatment at an undetectable viral load was associated with viral rebound.Conclusion: Among patients with an undetectable viral load, having previously interrupted therapy while the viral load was detectable is associated with a raised risk of rebound. (C) 2008 Wolters Kluwer Health | Lippincott Williams & Wilkins.

To evaluate the efficacy and toxicity of salvage regimens containing ritonavir and saquinavir in patients failing highly active antiretroviral therapy (HAART), and to correlate outcome with plasma concentrations of protease inhibitors.Prospective, non-randomized interventional study.Thirty extensively pretreated HIV-infected patients with virological failure under HAART were treated with ritonavir (400 mg twice daily) and saquinavir (600 mg twice daily) and at least one reverse transcriptase inhibitor. HIV-RNA, CD4 cell counts and plasma concentrations of protease inhibitors were determined, and patients were monitored for toxicity at monthly intervals.Six patients showed complete virological success (HIV-RNA200 copies/ml at week 12) which was sustained for a median follow-up of 6.3 months. Partial virological response (decrease of HIV-RNA of1 log10 at week 12) was achieved by a further three patients. Patients with a virological response had significantly higher CD4 cell increases than patients without virological response (mean increase at week 12: 66x10(6) cells/l versus 6x10(6) cells/l; P = 0.01). No clinical events were observed during 6 months of follow-up. Neither the use of a non-nucleoside reverse transcriptase inhibitor (NNRTI) nor the number of newly introduced drugs influenced the virological response. Plasma concentrations of protease inhibitors did not statistically differ between patients with and without success. Toxicity included gastrointestinal disturbances, lipid abnormalities and liver dysfunction.In extensively pretreated patients, salvage regimens containing ritonavir and saquinavir had only limited and short-term anti-HIV activity and were associated with substantial toxicity. Plasma concentrations of saquinavir were not predictive for virological response.

Objective: To determine the rate of virological treatment failure with protease inhibitor therapy in unselected patients and to assess underlying risk factors. Design and setting: Retrospective study in two German tertiary care treatment centres. Patients: A total of 198 HIV-infected patients treated with protease inhibitors in 1996. Main outcome measures: Levels of HIV RNA 1-6 months after start of treatment; definition of treatment failure of < 1 log 10 reduction in plasma HIV RNA within 6 months after starting protease inhibitor therapy; multivariate analysis of risk factors for treatment failures. Results: A total of 226 treatment episodes with protease inhibitors were evaluable (saquinavir, 83; ritonavir, 47; indinavir, 96). The rate of virological treatment failure was 44% (saquinavir, 64%; ritonavir, 38%; indinavir, 30%). In a multivariate analysis, the following independent risk factors for virological failure were found: CD4 cell count, pretreatment with antiretroviral drugs (number), and protease inhibitor (compound). The relative risk reduction for each CD4 cell count increase was 0.997 (P = 0.012), 2.64 for pretreatment with one or two drugs versus no drug (P = 0.05), 2.97 for pretreatment with more than two drugs versus no drug (P = 0.05), and 4.62 for treatment with saquinavir versus indinavir (P = 0.001). Conclusion: An unexpectedly high rate of virological treatment failure of protease inhibitor therapy was found in an unselected cohort of HIV-infected patients. Response to antiretroviral combination therapy in normal clinical practice may considerably differ from results of randomized clinical trials. Further studies are warranted to find optimal treatment strategies for both initial and salvage therapy.