Increased duration of viral suppression is associated with lower viral rebound rates in patients with previous treatment failures

Benzie, Andrew; Bansi, Loveleen; Sabin, Caroline; Portsmouth, Simon; Hill, Teresa; Johnson, Margaret; Gilson, Richard; Easterbrook, Philippa; Gazzard, Brian; Fisher, Martin; Orkin, Chloe; Dunn, David; Delpech, Valérie; Taylor, Graham P.; Walsh, John; Phillips, Andrew

doi:10.1097/qad.0b013e3281532ca7

Cited by 34 publications

(41 citation statements)

References 17 publications

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“…After adjustment, time since last viral rebound was highly predictive of virological failure after starting new ARVs, consistent with findings from other studies. For example, Benzie et al [16] reported that up to 4 years of sustained viral suppression was necessary in patients with previous treatment failures for them to achieve rebound rates similar to those of patients with no prior treatment failures. The greatest risk of viral rebound has been shown to be in the first few months after initial suppression [14], and therefore it follows that increasing time since last virological rebound decreased the risk of virological failure after baseline.…”

Section: Discussionmentioning

confidence: 99%

“…This proportion has increased in recent years [11][12][13]; however, viral replication is still not fully controlled in all patients at all times. Previous analyses have found that a patient is most likely to fail in the first few months after initial viral suppression [14], that increasing time with viral suppression decreases the risk of rebound [15,16], and that treatment interruptions with detectable viral load [17] increase the risk of rebound, as does pre-cART exposure to nucleoside reverse transcriptase inhibitor (NRTI) regimens [15,18]. Additionally, low CD4 cell counts, high viral load, a slow virological response to cART and prior AIDS diagnosis were linked to lack of durable viral load undetectability [19,20].…”

Section: Introductionmentioning

confidence: 99%

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History of viral suppression on combination antiretroviral therapy as a predictor of virological failure after a treatment change^*

et al. 2010

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ObjectivesHIV-infected persons experience different patterns of viral suppression after initiating combination antiretroviral therapy (cART). The relationship between such differences and risk of virological failure after starting a new antiretroviral could help with patient monitoring strategies. MethodsA total of 1827 patients on cART starting at least one new antiretroviral from 1 January 2000 while maintaining a suppressed viral load were included in the analysis. Poisson regression analysis identified factors predictive of virological failure after baseline in addition to traditional demographic variables. Baseline was defined as the date of starting new antiretrovirals. ResultsFour hundred and fifty-one patients (24.7%) experienced virological failure, with an incidence rate (IR) of 7.3 per 100 person-years of follow-up (PYFU) [95% confidence interval (CI) 6.7-8.0]. After adjustment, patients who had rebounded in the year prior to baseline had a 2.4-times higher rate of virological failure after baseline (95% CI 1.77-3.26; Po.0001), while there was no increased incidence in patients whose last viral rebound was 43 years prior to baseline [Incidence rate ratio (IRR) 1.06; 95% CI 0.75-1.50; P 5 0.73] compared with patients who had never virally rebounded. Patients had an 86% (95% CI 1.36-2.55; Po.0001), 53% (95% CI 1.06-2.04; P 5 0.02) and 5% (95% CI 0.80-1.38; P 5 0.72) higher virological failure rate after baseline if they were virally suppressed o50%, 50-70% and 70-90% of the time they were on cART prior to baseline, respectively, compared with those virally suppressed 490% of the time. DiscussionIntensive monitoring after a treatment switch is required in patients who have rebounded recently or have a low percentage of time suppressed while on cART. Consideration should be given to increasing the provision of adherence counselling. IntroductionTreatment guidelines for HIV-1 infection state that suppression of viral load below the level of quantification (normally 50 HIV-1 RNA copies/mL) is one of the key goals of combination antiretroviral therapy (cART) and should be one of the deciding factors when planning a patient's treatment strategy [1][2][3][4]. However, a substantial number of patients fail to achieve viral suppression in the first 6 DOI: 10.1111DOI: 10. /j.1468DOI: 10. -1293DOI: 10. .2009 (2010), 11, 469-478 469 months after starting cART [5] and many others go on to experience viral rebound at some time thereafter [6]. With increasing numbers of episodes of viral failure, the goal of viral suppression becomes harder to achieve [7]. Patients experience different immunological and virological responses after initiating cART [5,8,9]. In clinical practice, earlier studies found that around 70-80% of patients starting cART achieve an undetectable viral load [10]. This proportion has increased in recent years [11][12][13]; however, viral replication is still not fully controlled in all patients at all times. Previous analyses have found that a patient is most likely to fail in the first few mon...

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

History of viral suppression on combination antiretroviral therapy as a predictor of virological failure after a treatment change^*

et al. 2010

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“…Individuals were again included in the analysis if and when they next achieved a viral load o50 copies/mL whilst receiving cART and hence started a new suppression episode. At the start of each suppression episode, the number of previous ARV regimens that had been failed was calculated using a definition from a previous study [10]. A treatment regimen was failed on each date an individual experienced a viral load 4400 copies/mL and there was an ARV they hadn't failed previously in a current regimen they had been receiving for 416 weeks.…”

Section: Methodsmentioning

confidence: 99%

“…However, the expected duration of viral suppression in this situation remains unclear. A recent study by Benzie et al [10] for the UK Collaborative HIV Cohort (CHIC) found a strong association between a higher number of previous treatment regimens failed and raised risk of viral rebound.…”

Section: Introductionmentioning

confidence: 99%

Factors associated with viral rebound among highly treatment‐experienced HIV‐positive patients who have achieved viral suppression

Smith

Dauer

et al. 2008

HIV Medicine

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ObjectiveMore and more highly treatment-experienced patients are achieving viral suppression. However, the durability of suppression remains unclear. MethodsPatients from Royal Free Hospital (London, UK) and JW Goethe University Hospital (Frankfurt, Germany) who had failed 1 antiretroviral (ARV) regimen in all three main drug classes and 3 previous ARV regimens and subsequently achieved viral load o50 HIV-1 RNA copies/mL were included. They were followed until stopping pre-combination antiretroviral therapy, end of followup or viral rebound (two viral loads 4400 copies/mL). ResultsTwo hundred and forty-seven patients contributed 723 person-years and 114 viral rebounds [rate 5 15.8 per 100 person-years; 95% confidence interval (CI) 12. 9-18.7]. More recent calendar years of viral suppression [relative risk (RR) 5 0.90 per year later; 95% CI 0.81-1.00; P 5 0.05] and greater number of ARVs in the regimen not previously failed (RR 5 0.78 per 1 ARV more; 95% CI 0.65-0.95; P 5 0.01) were associated with lower viral rebound rates. At 0-1, 1-2, 2-3 and 43 years after achieving suppression, the rebound rates were 30.9, 9.2, 4.3 and 3.5 per 100 person-years, respectively. Compared to 0-1 years, the adjusted RRs (95% CIs) after 1-2, 2-3 and 43 years were 0.33 (0.18-0.58), 0.21 (0.09-0.48) and 0.14 (0.06-0.33), respectively (Po0.0001). ConclusionsAlthough rebound rates are high, especially in the first year after viral suppression, this risk reduces substantially if highly treatment-experienced patients can maintain viral suppression.Keywords: antiretroviral therapy, three-class failure, viral rebound IntroductionThe availability of new antiretrovirals (ARVs) for the treatment of HIV infection has enabled many highly treatment-experienced patients to achieve viral suppression [1][2][3][4][5][6][7][8][9]. However, the expected duration of viral suppression in this situation remains unclear. A recent study by Benzie et al. [10] for the UK Collaborative HIV Cohort (CHIC) found a strong association between a higher number of previous treatment regimens failed and raised risk of viral rebound.Prior exposure to monotherapy or dual therapy [11,12] has been shown to be associated with increased rebound rate. Several authors, including Benzie et al., have also found an association between longer time since viral suppression and a decreased rate of viral rebound [10,12,13]. Interestingly, Benzie et al. found that as the time since viral suppression achievement increased, the risk of rebound declined more rapidly among those with more extensive previous treatment failure. Other factors have also been found to be associated with viral rebound, such as pre-combination antiretroviral therapy (cART), viral load [13][14][15] 19The aim of this study was to investigate the factors associated with viral rebound in highly treatment-experienced patients who have achieved virological suppression, in order to better understand the period of suppression required for the likelihood of rebound to reach a level seen in patients with no or less ext...

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“…Entre los efectos adversos como causa de cambio de terapia destacaron la alergia y las dislipidemias; estas últimas son importantes pues su incidencia se mantiene similar a pesar de nuevos medicamentos. Las consecuencias cardiovasculares de la tri-terapia han sido destacadas en muchas series 5,7,8 aunque no pudieron ser evaluadas sistemáticamente en esta población. Otro efecto adverso frecuentemente descrito en este grupo fue la lipodistrofia, especialmente la atrofia del tejido graso de la cara y las extremidades.…”

Section: Discussionunclassified

Una década de terapia anti-retroviral: Perfil de pacientes con 10 años de triterapia de alta efectividad

Wilson

Wolff

2012

Rev. chil. infectol.

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A decade of antiretroviral therapy: a profile of patients with 10 years of highly effective triple therapyIntroduction: Highly effective antiretroviral triple therapy (TAR 3 ) has led to a significant increase in survival of patients (pts) infected with human immunodeficiency virus. In 1999 it was started in the Chilean public health system, including Arriarán Foundation (FA) access to TAR 3 , reaching full coverage since 2003. By October 31, 2009 124 pts had reached 10 years of uninterrupted TAR 3 in FA.Objective: To describe and analyze the profile of pts, their therapeutic regimen (s) and clinical outcomes during 10 years of TAR 3 . Methods: Retrospective descriptive study. We reviewed the records of pts who had reached 10 years of uninterrupted TAR 3 in FA. Demographic data, baseline and virological staging at start of TAR 3 , comorbidities and complications were recorded. Drug regimens used were analyzed, as well as toxicity, virological and immunological outcomes, frequency and reasons for change in therapy. Complications were classified as opportunistic and not opportunistic during this evolution and the latest known clinical and laboratory data were registered. A database program based on Excel was used. Results: 121/124 pts were available for analysis, 76.8% male, male-female ratio was 3.3:1. Baseline median age: 36 years (20-69); CD4 cells 176/ mm 3 (8-1,224) with 65.3% < 200; median viral load (VL): 60,078 copies/ml (1,100-7,900,000); 36.3% were in clinical AIDS stage. Patients received an average of 3.5 therapies regimens during the decade (range, 1 [14 pts, 11.5%] to 7 [3 pts, 2.4%]), with average duration of 42 months each and a median of 36 months. As initial TAR 3 regimen 2 backbone nucleoside analogues (ITRN) was the most frequent, with a protease inhibitor (PI) in 51.2% and non-nucleoside RTIs (NNRTIs) in 38.8%. Adverse reactions were the main reason for change of therapy (24.7%), followed by virological failure (24.2%) and treatment simplification (16.6%). At the latest assessment, all with ≥ 10 years of TAR 3 median CD4 was 602 cells/mm 3 , 11 pts (9%) had CD4 < 200/mm 3 ; 85.2% had undetectable VL (< 80 copies/mL); the remaining 14.8% had a median of 1,800 copies/mL. Only 2 pts (1.7%) were in AIDS clinical stage. Current regimens were 2 NRTI plus 1 NNRTI in 61 pts (50.4%), 2 or more NRTI plus 1 PI in 46 (38%). Seventy two pts (60.3%) had chronic comorbidities at latest follow up. Dyslipidemia, hypertension, diabetes mellitus and renal failure were the most frequent conditions; 17 pts (14%) had clinical lipodystrophy secondary to TAR 3 . Conclusion: Achieving a decade of TAR 3 is already a reality and in the short term will be routine. This is rarely achieved with the initial therapeutic regimen. The major obstacles to prolonged maintenance of a single therapeutic regimen have been adverse effects and virological failure, although current drugs with better efficacy and safety profile may allow longer use for each regimen. Despite the difficulty of treating these pts, they can achieve long-ter...

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Increased duration of viral suppression is associated with lower viral rebound rates in patients with previous treatment failures

Abstract: After around 4 years of viral suppression rebound rates in individuals with multiple prior treatment failures approach those of individuals with no prior treatment failure.

Cited by 34 publications

References 17 publications

History of viral suppression on combination antiretroviral therapy as a predictor of virological failure after a treatment change^*

History of viral suppression on combination antiretroviral therapy as a predictor of virological failure after a treatment change^*

Factors associated with viral rebound among highly treatment‐experienced HIV‐positive patients who have achieved viral suppression

Una década de terapia anti-retroviral: Perfil de pacientes con 10 años de triterapia de alta efectividad

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Increased duration of viral suppression is associated with lower viral rebound rates in patients with previous treatment failures

Abstract: After around 4 years of viral suppression rebound rates in individuals with multiple prior treatment failures approach those of individuals with no prior treatment failure.

Cited by 34 publications

References 17 publications

History of viral suppression on combination antiretroviral therapy as a predictor of virological failure after a treatment change*

History of viral suppression on combination antiretroviral therapy as a predictor of virological failure after a treatment change*

Factors associated with viral rebound among highly treatment‐experienced HIV‐positive patients who have achieved viral suppression

Una década de terapia anti-retroviral: Perfil de pacientes con 10 años de triterapia de alta efectividad

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Product

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History of viral suppression on combination antiretroviral therapy as a predictor of virological failure after a treatment change^*

History of viral suppression on combination antiretroviral therapy as a predictor of virological failure after a treatment change^*