Accumulation of HIV-1 drug resistance after continued virological failure on first-line ART in adults and children in sub-Saharan Africa

Boender, T. Sonia; Kityo, Cissy; Boerma, Ragna S.; Hamers, Raph L; Ondoa, Pascale; Wellington, Maureen; Siwale, Margaret; Nankya, Immaculate; Kaudha, Elizabeth; Akanmu, Alani S; Botes, Mariëtte E.; Steegen, Kim; Calis, Job C. J.; Wit, Tobias F. Rinke de; Sigaloff, Kim C.E.

doi:10.1093/jac/dkw218

Cited by 85 publications

(70 citation statements)

References 39 publications

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“…The profile of genotypic resistances among patients receiving first-line ART was as expected [28, 29]. All patients with antiretroviral drug resistance were resistant to NNRTIs, and three quarters of them were also resistant to NRTIs.…”

Section: Discussionsupporting

confidence: 60%

Virologic Failure and Human Immunodeficiency Virus Drug Resistance in Rural Cameroon With Regard to the UNAIDS 90-90-90 Treatment Targets

Boullé

Guichet

Kouanfack

et al. 2016

Open Forum Infectious Diseases

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Background.In rural Africa, data on virologic effectiveness of antiretroviral treatment (ART) are not sufficient to assess the gap with the UNAIDS 90-90-90 treatment targets. We investigated the prevalences of unsuppressed viral load and antiretroviral drug resistance and the profile of genotypic resistance mutations among patients routinely treated in rural Cameroon.Methods.A cross-sectional study was performed in 2013–2014 among patients ≥15 years and on first-line ART for ≥6 months in a district hospital. Patients were offered free access to human immunodeficiency virus viral load testing. Genotypic drug resistance testing was done when the viral load was >1000 copies/mL. Multivariate logistic regression models were used to assess the relationship of unsuppressed viral load or antiretroviral drug resistance with sociodemographic and medical characteristics.Results.Of 407 patients (women 74.9%, median age 41.8 years, median time on ART 29.2 months), 96 (23.6%; 95% confidence interval [CI], 19.5–28.0) had unsuppressed viral load and 74 (18.2%; 95% CI, 14.6–22.3) had antiretroviral drug resistance. The prevalences of unsuppressed viral load and resistance increased with time on ART, from 12.0% and 8.0% in the 6- to 12-month group to 31.3% and 27.1% in the >72-month group, respectively. All 74 patients with antiretroviral drug resistance were resistant to nonnucleoside reverse-transcriptase inhibitors, and 57 of them were also resistant to nucleoside reverse-transcriptase inhibitors.Conclusions.Our estimations were among the highest observed in the west and central African region. The proportion of patients with virologic failure should be divided at least by 2 to reach the UNAIDS 90-90-90 treatment targets.

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Section: Discussionsupporting

confidence: 60%

Virologic Failure and Human Immunodeficiency Virus Drug Resistance in Rural Cameroon With Regard to the UNAIDS 90-90-90 Treatment Targets

Boullé

Guichet

Kouanfack

et al. 2016

Open Forum Infectious Diseases

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“…While known factors contribute to virological failure (intermittent adherence to medication resulting in nonsuppressive drug levels in a setting of ongoing viral replication, transmitted resistance), it remains unknown what proportion of those undergoing virological failure can be attributed to each factor. Studies in sub-Saharan Africa have found drug resistance mutations in 6-14% of ARTnaïve patients [11,19,20], and 84-89% of those with virological failure who initiated ART ≥12 months prior [19,21]. Results from a systematic review and metaanalysis estimated a prevalence of pretreatment nonnucleotide reverse-transcriptase inhibitor (NNRTI) resistance of 11% in southern Africa [22].…”

Section: Introductionmentioning

confidence: 99%

The role of drug resistance in poor viral suppression in rural South Africa: findings from a population-based study

et al. 2020

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Background: Understanding factors driving virological failure, including the contribution of HIV drug resistance mutations (DRM), is critical to ensuring HIV treatment remains effective. We examine the contribution of drug resistance mutations for low viral suppression in HIV-positive participants in a population-based sero-prevalence survey in rural South Africa. Methods:We conducted HIV drug resistance genotyping and ART analyte testing on dried blood spots (DBS) from HIV-positive adults participating in a 2014 survey in North West Province. Among those with virologic failure (> 5000 copies/mL), we describe frequency of DRM to protease inhibitors (PI), nucleoside reverse transcriptase inhibitors (NRTI), and non-nucleoside reverse transcriptase inhibitors (NNRTI), report association of resistance with antiretroviral therapy (ART) status, and assess resistance to first and second line therapy. Analyses are weighted to account for sampling design.Results: Overall 170 DBS samples were assayed for viral load and ART analytes; 78.4% of men and 50.0% of women had evidence of virologic failure and were assessed for drug resistance, with successful sequencing of 76/107 samples. We found ≥1 DRM in 22% of participants; 47% were from samples with detectable analyte (efavirenz, nevirapine or lopinavir). Of those with DRM and detectable analyte, 60% showed high-level resistance and reduced predicted virologic response to ≥1 NRTI/NNRTI typically used in first and second-line regimens.Conclusions: DRM and predicted reduced susceptibility to first and second-line regimens were common among adults with ART exposure in a rural South African population-based sample. Results underscore the importance of ongoing virologic monitoring, regimen optimization and adherence counseling to optimize durable virologic suppression.

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“…VL monitoring allows for early detection of virological failure (VF) before clinical disease progression and accumulation of resistance mutations has occurred [3–5]. Viral load results can also be used for adherence counselling, and may save costs by preventing unnecessary switches to 2nd line ART [6,7].…”

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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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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Accumulation of HIV-1 drug resistance after continued virological failure on first-line ART in adults and children in sub-Saharan Africa

Abstract: Patterns of drug resistance after virological failure on first-line ART are similar in adults and children in sub-Saharan Africa. Improved VL monitoring to prevent accumulation of mutations, and new drug classes to construct fully active regimens, are required.

Cited by 85 publications

References 39 publications

Virologic Failure and Human Immunodeficiency Virus Drug Resistance in Rural Cameroon With Regard to the UNAIDS 90-90-90 Treatment Targets

Virologic Failure and Human Immunodeficiency Virus Drug Resistance in Rural Cameroon With Regard to the UNAIDS 90-90-90 Treatment Targets

The role of drug resistance in poor viral suppression in rural South Africa: findings from a population-based study

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

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