Resistance Testing for Management of HIV Virologic Failure in Sub-Saharan Africa

Siedner, Mark J.; Moosa, Mahomed-Yunus S.; McCluskey, Suzanne M.; Gilbert, Rebecca F; Pillay, Selvan; Aturinda, Isaac; Ard, Kevin L.; Muyindike, Winnie; Musinguzi, Nicholas; Masette, Godfrey; Pillay, Melendhran; Moodley, Pravi; Brijkumar, Jaysingh; Rautenberg, Tamlyn; George, Gavin; Gandhi, Rajesh T.; Johnson, Brent A.; Sunpath, Henry; Bwana, Mwebesa; Marconi, Vincent C.

doi:10.7326/m21-2229

Cited by 13 publications

(7 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…GRT was performed using Sanger sequencing for plasma specimens with a VL >1000 copies/ml [11]. We defined HIVDR as intermediate or high-level resistance to any drug in the current ART regimen, as determined by the Stanford algorithm [12].…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Point-of-care urine tenofovir testing to predict HIV drug resistance among individuals with virologic failure

McCluskey

Govender

Adamson

et al. 2023

Aids

Self Cite

View full text Add to dashboard Cite

Objective:We sought to evaluate the utility of a point-of-care (POC) urine tenofovir (TFV) assay, developed to objectively assess adherence, to predict HIV drug resistance (HIVDR) in people failing first-line antiretroviral therapy (ART).Design:We retrospectively analyzed TFV levels as a biomarker of adherence in urine specimens collected during a clinical trial that enrolled adults with virologic failure on first-line ART in Uganda and South Africa.Methods:Urine specimens were analyzed from participants on TFV-containing regimens who had a viral load >1000 copies/ml and paired genotypic resistance test (GRT) results. We assessed recent ART TFV adherence with a qualitative POC lateral flow urine assay with a cut-off value of 1500 ng/ml. We then calculated performance characteristics of the POC urine TFV assay to predict HIVDR, defined as intermediate or high-level resistance to any component of the current ART regimen.Results:Urine specimens with paired plasma GRT results were available from 283 participants. The most common ART regimen during study conduct was emtricitabine, tenofovir disoproxil fumarate, and efavirenz. The overall prevalence of HIVDR was 86% (n = 243/283). Of those with TFV detected on the POC assay, 91% (n = 204/224) had HIVDR, vs. only 66% (n = 39/59) among those with no TFV detected (P-value < 0.001). Positive and negative predictive values of the assay to predict HIVDR were 91% and 34%, respectively.Conclusions:In populations with a high prevalence of HIVDR, the POC urine TFV assay can provide a low-cost, rapid method to guide requirements for confirmatory resistance testing and inform the need for regimen change.

show abstract

Section: Methodsmentioning

confidence: 99%

“…We conducted a diagnostic validity assessment utilizing specimens from the REVAMP clinical trial [10,11]. REVAMP enrolled adults 18 years at public-sector clinics in Uganda and South Africa who experienced virologic failure, defined as HIV-1 RNA viral load (VL) >1000 copies/ml while on first-line ART from 2016 to 2019.…”

Section: Study Design and Study Populationmentioning

confidence: 99%

Point-of-care urine tenofovir testing to predict HIV drug resistance among individuals with virologic failure

McCluskey

Govender

Adamson

et al. 2023

Aids

Self Cite

View full text Add to dashboard Cite

show abstract

“…Out of 877 participants screened for eligibility in the REVAMP trial, 37 did not meet the inclusion criteria and 840 participants were enrolled in the study [ 28 ]. Half of participants were from South Africa (n = 420) and half from Uganda (n = 420), Table 1 .…”

Section: Resultsmentioning

confidence: 99%

Determinants of health-related quality of life in people with Human Immunodeficiency Virus, failing first-line treatment in Africa

Rautenberg,

Ng,

George

et al. 2023

Health Qual Life Outcomes

Self Cite

View full text Add to dashboard Cite

Background Antiretroviral treatment improves health related quality of life (HRQoL) of people with human immunodeficiency virus (PWH). However, one third initiating first-line treatment experience virological failure and the determinants of HRQoL in this key population are unknown. Our study aims to identify determinants of among PWH failing antiretroviral treatment in sub-Saharan Africa. Methods We analysed data from a cohort of PWH having virological failure (> 1,000 copies/mL) on first-line ART in South Africa and Uganda. We measured HRQoL using the EuroQOL EQ-5D-3L and used a two-part regression model to obtain by-country analyses for South Africa and Uganda. The first part identifies risk factors that were associated with the likelihood of participants reporting perfect health (utility = 1) versus non-perfect health (utility < 1). The second part identifies risk factors that were associated with the EQ-5 L-3L utility scores for participants reporting non-perfect health. We performed sensitivity analyses to compare the results between the two-part model using tobit models and ordinary least squares regression. Results In both countries, males were more likely to report perfect health and participants with at least one comorbidity were less likely to report perfect health. In South Africa, participants with side effects and in Uganda those with opportunistic infections were also less likely to report perfect health. In Uganda, participants with 100% ART adherence were more likely to report perfect health. In South Africa, high HIV viral load, experiencing ART side effects, and the presence of opportunistic infections were each associated with lower HRQoL, whereas participants with 100% ART adherence reported higher HRQoL. In Uganda participants with lower CD4 count had lower HRQoL. Conclusion Markers of advanced disease (opportunistic infection, high viral load, low CD4), side effects, comorbidities and lack of ART adherence negatively impacted HRQoL for PWH experiencing virological failure. Trial registration ClinicalTrials.gov: NCT02787499.

show abstract

“…The high prevalence of drug resistance leaves limited potential for drug resistance testing as a means of avoiding unnecessary switches to second-line ART. Confirming this, a recent trial evaluating the clinical value of drug resistance testing alone in patients with viral rebound of NNRTI-based ART showed no benefit of implementation of drug resistance testing, in part due to the high pretest probability of NNRTI drug resistance in patients with rebound [24].…”

Section: Discussionmentioning

confidence: 98%

A randomized study of intensified antiretroviral treatment monitoring versus standard-of-care for prevention of drug resistance and antiretroviral treatment switch

Hermans

Heine²,

Schuurman

et al. 2022

Aids

View full text Add to dashboard Cite

Introduction:Standard-of-care antiretroviral treatment (ART) monitoring in low and middle-income countries consists of annual determination of HIV-RNA viral load with confirmatory viral load testing in case of viral rebound. We evaluated an intensified monitoring strategy of three-monthly viral load testing with additional drug exposure and drug resistance testing in case of viral rebound.Methods:We performed an open-label randomized controlled trial (RCT) at a rural South African healthcare clinic, enrolling adults already receiving or newly initiating first-line ART. During 96 weeks follow-up, intervention participants received three-monthly viral load testing and sequential point-of-care drug exposure testing and DBS-based drug resistance testing in case of rebound above 1000 copies/ml. Control participants received standard-of-care monitoring according to the WHO guidelines.Results:Five hundred one participants were included, of whom 416 (83.0%) were randomized at 24 weeks. Four hundred one participants were available for intention-to-treat analysis. Viral rebound occurred in 9.0% (18/199) of intervention participants and in 11.9% (24/202) of controls (P = 0.445). Time to detection of rebound was 375 days [interquartile range (IQR): 348–515] in intervention participants and 360 days [IQR: 338–464] in controls [hazard ratio: 0.88 (95% confidence interval (95% CI): 0.46–1.66]; P = 0.683]. Duration of viral rebound was 87 days [IQR: 70–110] in intervention participants and 101 days [IQR: 78–213] in controls (P = 0.423). In the control arm, three patients with confirmed failure were switched to second-line ART. In the intervention arm, of three patients with confirmed failure, switch could initially be avoided in two cases.Conclusion:Three-monthly viral load testing did not significantly reduce the duration of viraemia when compared with standard-of-care annual viral load testing, providing randomized trial evidence in support of annual viral load monitoring.

show abstract

Resistance Testing for Management of HIV Virologic Failure in Sub-Saharan Africa

Cited by 13 publications

References 32 publications

Point-of-care urine tenofovir testing to predict HIV drug resistance among individuals with virologic failure

Point-of-care urine tenofovir testing to predict HIV drug resistance among individuals with virologic failure

Determinants of health-related quality of life in people with Human Immunodeficiency Virus, failing first-line treatment in Africa

A randomized study of intensified antiretroviral treatment monitoring versus standard-of-care for prevention of drug resistance and antiretroviral treatment switch

Contact Info

Product

Resources

About