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

Abstract

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.

Socio-economic condition and lack of virological suppression among adults and adolescents receiving antiretroviral therapy in Ethiopia

“…Our overall study population corresponds well with recent demographic HIV data in urban parts of Ethiopia [12,13,19,66]. In agreement with other reports, we found younger age and worse perceived health to be independently associated with lack of virological suppression [9-11, 67, 68].…”

“…Lack of virological suppression during ART has been associated with advanced immunosuppression, high baseline viral load, longer ART duration, younger age and male gender [8][9][10][11][12][13]. Failure to achieve virological suppression has also been linked to various socio-demographic factors, including unstable housing, low educational status, unemployment and lack of financial or social support [14][15][16][17].…”

Performance of Galectin-9 for Identification of HIV Viremia in Adults Receiving Antiretroviral Therapy in a Resource-Limited Setting

“…We assessed the discriminatory capacity of Gal-9 in subgroups after stratification by sex and by variables that have previously been associated with VF [current CD4 count and mid-upper arm circumference (MUAC)]. 5,10,22 CD4 counts were dichotomized at 200 cells/mm 3 and 350 cells/mm 3 in 2 separate analyses, and MUAC was dichotomized at sex-specific thresholds indicating malnutrition (,23.0 cm for women and ,24.0 cm for men). 10,23 For each subgroup, the auROC values of Gal-9 in identifying those with VL $1000 copies/mL were calculated.…”

“…3 As an alternative to universal VL monitoring, targeting VL testing to persons at a higher likelihood of having nonsuppressed viremia during ART has been proposed. [4][5][6][7][8][9][10][11] Targeted VL testing requires accurate screening methods to identify such individuals, and host biomarkers reflecting viral replication could be used for this purpose. We have previously investigated the cytokine interferon-g-inducible protein 10 (IP-10/CXCL10) performance for targeted VL testing in Ethiopian ART recipients.…”

Validation of the Viral Load Testing Criteria – an algorithm for targeted viral load testing in HIV‐positive adults receiving antiretroviral therapy

“…We recently presented an algorithm for targeted VL testing, the Viral Load Testing Criteria (VLTC) . This algorithm was derived on data from a cohort of adults followed prospectively after ART initiation at Ethiopian health centres.…”