Predicting treatment failure in adults and children on antiretroviral therapy

Rutherford, George W.; Anglemyer, Andrew; Easterbrook, Philippa; Horváth, Hacsi; Vitória, Marco; Penazzato, Martina; Doherty, Meg

doi:10.1097/qad.0000000000000236

Cited by 89 publications

(47 citation statements)

References 39 publications

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“…The clinical algorithms constructed in Sub-Saharan Africa (2 in Uganda and 1 in South Africa), had sensitivities ranging from 67% to76% [15–17], external validations of these algorithms are yet to be published. The sensitivity of the 2013 WHO criteria was higher in this cohort (67%) compared with previously reported data [15,16,18]. For targeting viral load testing, however, misclassification of 33% of subjects with VF cannot be accepted.…”

Section: Discussioncontrasting

confidence: 62%

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Development of an algorithm for determination of the likelihood of virological failure in HIV-positive adults receiving antiretroviral therapy in decentralized care

Reepalu

Balcha

Skogmar

et al. 2017

Global Health Action

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Background: Early identification of virological failure (VF) limits occurrence and spread of drug-resistant viruses in patients receiving antiretroviral treatment (ART). Viral load (VL) monitoring is therefore recommended, but capacities to comply with this are insufficient in many low-income countries. Clinical algorithms might identify persons at higher likelihood of VF to allocate VL resources. Objectives: We aimed to construct a VF algorithm (the Viral Load Testing Criteria; VLTC) and compare its performance to the 2013 WHO treatment failure criteria. Methods: Subjects with VL results available 1 year after ART start (n = 494) were identified from a cohort of ART-naïve adults (n = 812), prospectively recruited and followed 2011–2015 at Ethiopian health centres. VF was defined as VL≥1000 copies/mL. Variables recorded at the time of sampling, with potential association with VF, were used to construct the algorithm based on multivariate logistic regression. Results: Fifty-seven individuals (12%) had VF, which was independently associated with CD4 count <350 cells/mm3, previous ART interruption, and short mid-upper arm circumference (<24cm and <23cm, for men and women, respectively). These variables were included in the VLTC. In derivation, the VLTC identified 52/57 with VF; sensitivity 91%, specificity 43%, positive predictive value (PPV) 17%, negative predictive value (NPV) 97%. In comparison, the WHO criteria identified 38/57 with VF (sensitivity 67%, specificity 74%, PPV 25%, NPV 94%). Conclusions: The VLTC identified subjects at greater likelihood of VF, with higher sensitivity and NPV than the WHO criteria. If external validation confirms this performance, these criteria could be used to allocate limited VL resources. Due to its limited specificity, it cannot be used to determine treatment failure in the absence of a confirmatory viral load.

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Section: Discussioncontrasting

confidence: 62%

“…However, these criteria are not evidence-based, and have poor performance [18]. Alternative strategies for detection of treatment failure are therefore required for ART programs in low-income countries until universal VL monitoring is established.…”

Section: Introductionmentioning

confidence: 99%

Development of an algorithm for determination of the likelihood of virological failure in HIV-positive adults receiving antiretroviral therapy in decentralized care

Reepalu

Balcha

Skogmar

et al. 2017

Global Health Action

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“…WHO recommends VL testing as the preferred monitoring approach to diagnose and confirm treatment failure [2]. A systematic review found that current WHO clinical and immunological criteria have low sensitivity and low positive predictive value for identifying individuals with virological failure [24]; however, an evaluation from resource-limited countries found no evidence of improved mortality, reduced clinical failure or loss of treatment options when compared to programmes with VL testing [25,26]. …”

Section: Discussionmentioning

confidence: 99%

Lack of awareness of treatment failure among HIV‐1‐infected patients in Guinea‐Bissau – a retrospective cohort study

Jespersen

Hønge

Medina

et al. 2015

Journal of the International AIDS Society

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IntroductionWith more people receiving antiretroviral treatment (ART), the need to detect treatment failure and switch to second-line ART has also increased. We assessed CD4 cell counts (as a marker of treatment failure), determined the rate of switching to second-line treatment and evaluated mortality related to treatment failure among HIV-infected patients in Guinea-Bissau.MethodsIn this retrospective cohort study, adult patients infected with HIV-1 receiving ≥6 months of ART at an HIV clinic in Bissau were included from June 2005 to July 2014 and followed until January 2015. Treatment failure was defined as 1) a fall in CD4 count to baseline (or below) or 2) CD4 levels persistently below 100 cells/µL after ≥6 months of ART. Cox hazard models, with time since six months of ART as the time-varying coefficient, were used to estimate the hazard ratio for death and loss to follow-up.ResultsWe assessed 1,591 HIV-1-infected patients for immunological treatment failure. Treatment failure could not be determined in 594 patients (37.3%) because of missing CD4 cell counts. Among the remaining 997 patients, 393 (39.4%) experienced failure. Only 39 patients (9.9%) with failure were switched from first- to second-line ART. The overall switching rate was 3.1 per 100 person-years. Mortality rate was higher in patients with than without treatment failure, with adjusted hazard rate ratios (HRRs) 10.0 (95% CI: 0.9–107.8), 7.6 (95% CI: 1.6–35.5) and 3.1 (95% CI: 1.5–6.3) in the first, second and following years, respectively. During the first year of follow-up, patients experiencing treatment failure had a higher risk of being lost to follow-up than patients not experiencing treatment failure (adjusted HRR 4.4; 95% CI: 1.7–11.8).ConclusionsWe found a high rate of treatment failure, an alarmingly high number of patients for whom treatment failure could not be assessed, and a low rate of switching to a second-line therapy. These factors could lead to an increased risk of resistance development and excess mortality.

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“…6 Many rural clinics in sub-Saharan Africa therefore opt for WHO clinical staging and the widely available immunological monitoring based on CD4 cell measurement to monitor response to ART, 5,7,8 despite immunological monitoring being an imperfect way to identify treatment failure. 9 …”

Section: Introductionmentioning

confidence: 99%

Effect of a clinical decision support system on early action on immunological treatment failure in patients with HIV in Kenya: a cluster randomised controlled trial

et al. 2016

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Summary Background A clinical decision support system (CDSS) is a computer program that applies a set of rules to data stored in electronic health records to offer actionable recommendations. We aimed to establish whether a CDSS that supports detection of immunological treatment failure among patients with HIV taking antiretroviral therapy (ART) would improve appropriate and timely action. Methods We did this prospective, cluster randomised controlled trial in adults and children (aged ≥18 months) who were eligible for, and receiving, ART at HIV clinics in Siaya County, western Kenya. Health facilities were randomly assigned (1:1), via block randomisation (block size of two) with a computer-generated random number sequence, to use electronic health records either alone (control) or with CDSS (intervention). Facilities were matched by type and by number of patients enrolled in HIV care. The primary outcome measure was the difference between groups in the proportion of patients who experienced immunological treatment failure and had a documented clinical action. We used generalised linear mixed models with random effects to analyse clustered data. This trial is registered with ClinicalTrials.gov, number NCT01634802. Findings Between Sept 1, 2012, and Jan 31, 2014, 13 clinics, comprising 41 062 patients, were randomly assigned to the control group (n=6) or the intervention group (n=7). Data collection at each site took 12 months. Among patients eligible for ART, 10 358 (99%) of 10 478 patients were receiving ART at control sites and 10 991 (99%) of 11 028 patients were receiving ART at intervention sites. Of these patients, 1125 (11%) in the control group and 1342 (12%) in the intervention group had immunological treatment failure, of whom 332 (30%) and 727 (54%), respectively, received appropriate action. The likelihood of clinicians taking appropriate action on treatment failure was higher with CDSS alerts than with no decision support system (adjusted odds ratio 3.18, 95% CI 1.02–9.87). Interpretation CDSS significantly improved the likelihood of appropriate and timely action on immunological treatment failure. We expect our findings will be generalisable to virological monitoring of patients with HIV receiving ART once countries implement the 2015 WHO recommendation to scale up viral load monitoring. Funding US President’s Emergency Plan for AIDS Relief (PEPFAR), through the US Centers for Disease Control and Prevention.

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Predicting treatment failure in adults and children on antiretroviral therapy

Abstract: The 2010 WHO clinical and immunologic criteria are insensitive and have low PPV for predicting virologic failure. These data support the strong recommendation 2013 treatment guidelines that viral load testing be used to monitor for, diagnose, and confirm ART failure.

Cited by 89 publications

References 39 publications

Development of an algorithm for determination of the likelihood of virological failure in HIV-positive adults receiving antiretroviral therapy in decentralized care

Development of an algorithm for determination of the likelihood of virological failure in HIV-positive adults receiving antiretroviral therapy in decentralized care

Lack of awareness of treatment failure among HIV‐1‐infected patients in Guinea‐Bissau – a retrospective cohort study

Effect of a clinical decision support system on early action on immunological treatment failure in patients with HIV in Kenya: a cluster randomised controlled trial

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