Virological suppression in children and adolescents is not influenced by genotyping, but depends on optimal adherence to antiretroviral therapy

Abreu, Juliana Costa de; Vaz, Sara Nunes; Netto, Eduardo Martins; Brites, Carlos

doi:10.1016/j.bjid.2017.02.001

Cited by 16 publications

(13 citation statements)

References 34 publications

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“…Given that this cohort re-suppressed VL after confirmation of VF and in the absence of a drug switch, it is not surprising that they had low levels of DRMs and only 23% had confirmed resistance to at least one drug. Our findings reiterate the utility of VL and DRM monitoring, as reported in other studies, and show these may be best utilised in combination with the adherence profile especially when considering drug switch [11][12][13]. An evaluation of adherence patterns in patients with confirmed VF may be necessary before deciding to switch/change regimen.…”

Section: Discussionsupporting

confidence: 74%

Low levels of HIV-1 drug resistance mutations in patients who achieved viral re-suppression without regimen switch: a retrospective study

et al. 2020

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Background: We identified a HIV-positive cohort in virologic failure (VF) who re-suppressed without drug switch. We characterized their drug resistance mutations (DRM) and adherence profiles to learn how to better manage HIV drug resistance. A retrospective cohort study utilizing clinical data and stored samples. Patients received ART at three Nigerian treatment centres. Plasma samples stored when they were in VF were genotyped. Result: Of 126 patients with samples available, 57 were successfully genotyped. From ART initiation, the proportion of patients with adherence ≥90% increased steadily from 54% at first high viral load (VL) to 67% at confirmed VF, and 81% at time of re-suppressed VL. Sixteen (28%) patients had at least one DRM. Forty-six (81%) patients had full susceptibility to the three drugs in their first-line (1 L) regimen. Thirteen (23%) were resistant to at least one antiretroviral drug but three were resistant to drugs not used in Nigeria. Ten patients had resistance to their 1 L drug(s) and six were fully susceptible to the three drugs in the recommended second-line regimen. Conclusion: This cohort had little drug resistance mutations. We conclude that if adherence is not assured, patients could exhibit virologic failure without having developed mutations associated with drug resistance.

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Section: Discussionsupporting

confidence: 74%

Low levels of HIV-1 drug resistance mutations in patients who achieved viral re-suppression without regimen switch: a retrospective study

et al. 2020

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“…In low and middle income countries, a viral load (VL)<1000 copies/ml defines treatment success (suppression), a measure of ART efficacy, which also indicates treatment adherence and reduced risk of HIV transmission [3]. Several factors like; low adherence rate [4], WHO clinical stage 4 and TB co-infection have been highlighted to be associated with virological non-suppresion among adults [5]. Likewise, viral load suppression rates among children on ART have been shown to be low [1] and considerably poorer [6,7].…”

Section: Introductionmentioning

confidence: 99%

Factors associated with virological non-suppression among HIV-positive children receiving antiretroviral therapy at the Joint Clinical Research Centre in Lubowa, Kampala Uganda

et al. 2021

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Background While the proportion of HIV-positive children (under 15 years) enrolled on antiretroviral therapy (ART) has increased in recent years, up to 60% of children started on ART do not achieve virological suppression. We set out to determine the factors associated with virological non-suppression among children living with HIV receiving ART at a peri-urban HIV care clinic in Kampala, Uganda. Method This was a retrospective cohort study conducted at the pediatric HIV/AIDS clinic at the Joint Clinical Research Centre (JCRC) in Kampala, Uganda. Three hundred (300) HIV-positive children (0–14 years) were randomly selected from existing medical records and data on children’s socio-demographic and clinical characteristics (age at ART initiation, WHO clinical staging, and ART-induced side effects) were abstracted using a data abstraction form. Virological non-suppression was defined as a viral load ≥1000 copies/Ml of blood after six months of ART initiation. Incident rate ratios (IRRs) were determined as a measure of association between virological non-suppression and child/patient characteristics. The IRRs were obtained via a modified Poisson regression with corresponding 95% confidence intervals (95%CI). All analyses were done using statistical package, Stata version 15. Results The overall non-suppression rate among HIV-positive children on ART was 23%. Being at WHO clinical stage 4 at ART initiation [adj. IRR 2.74; 95%CI: 1.63, 4.61] and ART-induced side effects [adj. IRR 1.77; 95%CI: 1.06, 2.97] were significantly associated with non-suppression. Older age at ART initiation (age 5–9 years: [adj. IRR 0.42; 95%CI: 0.28, 0.65]; age 10–14 years: [adj. IRR 0.34; 95%CI: 0.18, 0.64] was less likely to be associated with virological non-suppression. Conclusion Nearly a quarter of HIV-positive children on ART had a non-suppressed viral load after six months of treatment. Being at WHO clinical stage 4 at ART initiation and ART-induced side effects were significantly associated with virological non-suppression while older age at ART initiation was protective. Our findings suggest a need for age-specific interventions, particularly those targeting children below five years of age, to improve virological suppression among HIV-positive children receiving ART in this setting.

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“…Additional barriers to VLS in adolescents include drug toxicity and intolerance, psychological problems (depression, anxiety, and trauma) and social barriers, including stigma, have been linked to poor treatment adherence in adolescents and young adults. [57][58][59][60] Important limitations of the study are that genotyping results after first-line ART failure were not always available in realtime to health care providers for the optimization of ART before switching to second-line regimens. In addition, limited adherence and ATV/r as second-line ART may have reduced the rate of VS 50 .…”

Section: Discussionmentioning

confidence: 99%

Drug Resistance Among Adolescents and Young Adults with Virologic Failure of First-Line Antiretroviral Therapy and Response to Second-Line Treatment

Kouamou

Varyani

Shamu³

et al. 2020

AIDS Research and Human Retroviruses

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Barriers to sustainable virologic suppression (VS) of HIV-infected adolescents and young adults include drug resistance mutations (DRMs) and limited treatment options, which may impact the outcome of second-line antiretroviral therapy (ART). We sequenced plasma viral RNA from 74 adolescents and young adults (16-24 years) failing first-line ART at Newlands Clinic, Zimbabwe between October 2015 and December 2016. We evaluated first-line nucleoside reverse transcriptase inhibitor (NRTI) susceptibility scores to first-and second-line regimens. Boosted protease inhibitor (bPI)-based ART was provided and viral load (VL) monitored for ‡48 weeks. Fisher's exact test was used to evaluate factors associated with VS on second-line regimens, defined as VL <1,000 copies/mL (VS 1,000 ) or <50 copies/mL (VS 50 ). The 74 participants on first-line ART had a median [interquartile range (IQR)] age of 18 (16-21) years and 42 (57%) were female. The mean (-standard deviation) duration on ART was 5.5 (-3.06) years and the median (IQR) log 10 VL was 4.26 (3.78-4.83) copies/mL. After switching to a second-line PI regimen, 88% suppressed to <1,000 copies/mL and 76% to <50 copies/mL at ‡48 weeks. A new NRTI was associated with increased VS 50 ( p = .031). These 74 adolescents and young adults failing first-line ART demonstrated high levels (97%) of DRMs, despite enhanced adherence counseling. Switching to new NRTIs in second-line improved VS. With the widespread adoption of generic dolutegravir, lamivudine and tenofovir combinations in Africa, genotyping to determine NRTI susceptibility, may be warranted.

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Virological suppression in children and adolescents is not influenced by genotyping, but depends on optimal adherence to antiretroviral therapy

Abstract: Despite the use of genotyping tests in guidance of a more effective antiretroviral regimen, poor adherence to ART seems to be the main determinant of low virological suppression rate for children and adolescents, in Salvador, Brazil.

Cited by 16 publications

References 34 publications

Low levels of HIV-1 drug resistance mutations in patients who achieved viral re-suppression without regimen switch: a retrospective study

Low levels of HIV-1 drug resistance mutations in patients who achieved viral re-suppression without regimen switch: a retrospective study

Factors associated with virological non-suppression among HIV-positive children receiving antiretroviral therapy at the Joint Clinical Research Centre in Lubowa, Kampala Uganda

Drug Resistance Among Adolescents and Young Adults with Virologic Failure of First-Line Antiretroviral Therapy and Response to Second-Line Treatment

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