High rates of virological failure and drug resistance in perinatally HIV‐1‐infected children and adolescents receiving lifelong antiretroviral therapy in routine clinics in Togo

Salou, Mounérou; Dagnra, Anoumou; Butel, Christelle; Vidal, Nicole; Serrano, Laëtitia; Takassi, Elom; Konou, Abla A.; Houndenou, Spero; Dapam, Nina; Singo-Tokofaï, Assétina; Pitché, P.; Atakouma, Yao; Prince-David, Mireille; Delaporte, Eric; Peeters, Martine

doi:10.7448/ias.19.1.20683

Cited by 70 publications

(78 citation statements)

References 23 publications

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“…The prevalence of HIV-DRM of 90.4% in children and adolescents with virologic failure in our cohort is comparable with similar settings [9,29–30] and the adult population in our clinic [31]. The multiclass resistances, present in almost 80% of all failing patients dramatically limits future treatment options and represents an important public health concern.…”

Section: Discussionsupporting

confidence: 72%

“…The late detection of patients with treatment failure leads to the accumulation of drug resistances and dramatically limits treatment options [9,43]. The implementation and upscaling of viral load monitoring is essential to maintain treatment options and optimize health outcomes in resource-limited settings with restricted treatment possibilities [9,10,29]. …”

Section: Discussionmentioning

confidence: 99%

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Development of HIV drug resistance and therapeutic failure in children and adolescents in rural Tanzania

Muri

Gamell

Ntamatungiro

et al. 2017

Aids

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Objective:To investigate the prevalence and determinants of virologic failure and acquired drug resistance-associated mutations (DRMs) in HIV-infected children and adolescents in rural Tanzania.Design:Prospective cohort study with cross-sectional analysis.Methods:All children 18 years or less attending the paediatric HIV Clinic of Ifakara and on antiretroviral therapy (ART) for at least 12 months were enrolled. Participants with virologic failure were tested for HIV-DRM. Pre-ART samples were used to discriminate acquired and transmitted resistances. Multivariate logistic regression analysis identified factors associated with virologic failure and the acquisition of HIV-DRM.Results:Among 213 children on ART for a median of 4.3 years, 25.4% failed virologically. ART-associated DRM were identified in 90%, with multiclass resistances in 79%. Pre-ART data suggested that more than 85% had acquired key mutations during treatment. Suboptimal adherence [odds ratio (OR) = 3.90; 95% confidence interval (CI) 1.11–13.68], female sex (aOR = 2.57; 95% CI 1.03–6.45), and current nonnucleoside reverse transcriptase inhibitor-based ART (aOR = 7.32; 95% CI 1.51–35.46 compared with protease inhibitor-based) independently increased the odds of virologic failure. CD4+ T-cell percentage (aOR = 0.20; 0.10–0.40 per additional 10%) and older age at ART initiation (aOR = 0.84 per additional year of age; 95% CI 0.73–0.97) were protective (also in predicting acquired HIV-DRM). At the time of virologic failure, less than 5% of the children fulfilled the WHO criteria for immunologic failure.Conclusion:Virologic failure rates in children and adolescents were high, with the majority of ART-failing children harbouring HIV-DRM. The WHO criteria for immunologic treatment failure yielded an unacceptably low sensitivity. Viral load monitoring is urgently needed to maintain future treatment options for the millions of African children living with HIV.

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Section: Discussionsupporting

confidence: 72%

Section: Discussionmentioning

confidence: 99%

Development of HIV drug resistance and therapeutic failure in children and adolescents in rural Tanzania

Muri

Gamell

Ntamatungiro

et al. 2017

Aids

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“…Finalizando, cabe ainda alertar quanto a um problema que também poderá surgir devido não adesão ao tratamento medicamentoso, que é a resistência aos antirretrovirais, como já relatado em estudo com realizado com crianças e adolescentes infectados pelo HIV 22 . Quando há falha na regularidade e no horário de tomar os medicamentos, a pressão que a droga exerce sobre o vírus é diminuída favorecendo o aparecimento de mutações de resistência.…”

Section: Discussionunclassified

Adesão a terapia antiretroviral de crianças e adolescentes vivendo com HIV

et al. 2017

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“…Intermittent medication adherence increases the risk of treatment failure and subsequent development of drug resistance . Studies in high‐ and low‐resource settings have shown that adolescents have worse virological outcomes than other age groups . Those with chronic conditions may be more impacted by the risk‐taking behaviours that characterize adolescence than their peers without chronic medical problems in terms of impact on their health and ability to manage their illness .…”

Section: Adolescents and Treatment Outcomesmentioning

confidence: 99%

The case for viral load testing in adolescents in resource‐limited settings

et al. 2017

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Introduction The success of HIV treatment programmes globally has resulted in children with perinatally acquired HIV reaching adolescence in large numbers. The number of adolescents living with HIV is growing further due to persisting high HIV incidence rates among adolescents in low‐ and middle‐income settings, particularly in sub‐Saharan Africa. Although expanding access to HIV viral load monitoring is necessary to achieve the 90‐90‐90 targets across the HIV care continuum, implementation is incomplete. We discuss the rationale for prioritizing viral load monitoring among adolescents and the associated challenges. Discussion Adolescents with HIV are a complex group to treat successfully due to extensive exposure to antiretroviral therapy for those with perinatally acquired HIV and the challenges in sustained medication adherence in this age group. Given the high risk of treatment failure among adolescents and the limited drug regimens available in limited resource settings, HIV viral load monitoring in adolescents could prevent unnecessary and costly switches to second‐line therapy in virologically suppressed adolescents. Because adolescents living with HIV may be heavily treatment experienced, have suboptimal treatment adherence, or may be on second or even third‐line therapy, viral load testing would allow clinicians to make informed decisions about increased counselling and support for adolescents together with the need to maintain or switch therapeutic regimens. Conclusions Given scarce resources, prioritization of viral load testing among groups with a high risk of virological failure may be required. Adolescents have disproportionately high rates of virological failure, and targeting this age group for viral load monitoring may provide valuable lessons to inform broader scale‐up.

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High rates of virological failure and drug resistance in perinatally HIV‐1‐infected children and adolescents receiving lifelong antiretroviral therapy in routine clinics in Togo

Cited by 70 publications

References 23 publications

Development of HIV drug resistance and therapeutic failure in children and adolescents in rural Tanzania

Development of HIV drug resistance and therapeutic failure in children and adolescents in rural Tanzania

Adesão a terapia antiretroviral de crianças e adolescentes vivendo com HIV

The case for viral load testing in adolescents in resource‐limited settings

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