SESOTHO trial (“Switch Either near Suppression Or THOusand”) – switch to second-line versus WHO-guided standard of care for unsuppressed patients on first-line ART with viremia below 1000 copies/mL: protocol of a multicenter, parallel-group, open-label, randomized clinical trial in Lesotho, Southern Africa

Amstutz, Alain; Nsakala, Bienvenu Lengo; Vanobberghen, Fiona; Muhairwe, Josephine; Glass, Tracy R.; Achieng, Beatrice; Sepeka, Mamorena; Tlali, Katleho; Sao, Lebohang; Thin, Kyaw; Klimkait, Thomas; Battegay, Manuel; Labhardt, Niklaus Daniel

doi:10.1186/s12879-018-2979-y

Cited by 8 publications

(8 citation statements)

References 27 publications

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“…More importantly the WHO recognizes that this threshold has not been proven to be optimal for detecting treatment failure [27]. Various studies have proven that this threshold significantly misclassifies patients and undermines the large subset of patients who require clinical intervention [28, 29]. In this particular study 24(7.5%) of the patients had detectable viral load (≥ 150 copies /ml) but have not been given attention regarding this.…”

Section: Discussionmentioning

confidence: 99%

Predictors of treatment failure, time to switch and reasons for switching to second line antiretroviral therapy in HIV infected children receiving first line anti-retroviral therapy at a Tertiary Care Hospital in Ethiopia

Haile

Berha

2019

BMC Pediatr

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BackgroundTreatment failure and delay in switching to second line regimen are major concerns in the treatment of HIV infected children in a resource limited setting. The aim of this study was to determine the prevalence and predictors of first line antiretroviral therapy (ART) regimen failure, reasons and time taken to switch to second line antiretroviral (ARV) medications after treatment failure among HIV-infected children.MethodsA retrospective cohort study was conducted February 2003 to May 2018 in HIV-clinic at Tikur Anbessa Specialized Hospital (TASH), Ethiopia. All HIV infected children ≤15 years of age and who were taking first line ART for at least 6 months were included. Data abstraction format was used to collect the data from patients’ chart and registry. Binary and multivariable logistic regression statistics were used.ResultsOut of 318 enrolled HIV-infected children, the prevalence of treatment failure was found to be 22.6% (72/318), among these 37 (51.4%) had only immunologic failure, 6 (8.3%) had only virologic failure and 24 (33.3%) had both clinical and immunological failure. The mean time taken to modify combination antiretroviral therapy (cART) regimen was 12.67 (4.96) weeks after treatment failure was confirmed. WHO Stage 3 and 4 [Adjusted Odds Ratio (AOR), 3.64, 95% CI 1.76–7.56], not having both parents as primary caretakers [AOR, 2.72 95% CI, 1.05–7.06], negative serology of care takers [AOR, 2.69 95% CI, 1.03–7.03], and cART initiation at 11 month or younger were predicting factors of treatment failure. Of the 141 (47.9%) children who had regimen switching or substitution, treatment failure (44.4%) and replacement of stavudine (d4T) (30.8%) were major reasons. Only 6.6% patients had received PMTCT service.ConclusionOne fifth of the patients had experienced treatment failure. Advanced WHO stage at baseline, not being taken care of by mother and father, negative sero-status caretakers, and younger age at initiation of cART were the predictors of treatment failure. PMTCT service uptake was very low. There was a significant time gap between detection of treatment failure and initiation of second line cART. Half of the patients encountered regimen switching or substitution of cART due to treatment failure and replacement of stavudine (d4T).

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Section: Discussionmentioning

confidence: 99%

Predictors of treatment failure, time to switch and reasons for switching to second line antiretroviral therapy in HIV infected children receiving first line anti-retroviral therapy at a Tertiary Care Hospital in Ethiopia

Haile

Berha

2019

BMC Pediatr

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“…Recruitment lasted from August 1, 2017, until August 7, 2019, when the target sample size was achieved. A detailed study protocol has been published previously [ 21 ]. Eligible participants were individuals living with HIV, taking non-nucleoside reverse transcriptase inhibitor (NNRTI)-based first-line ART (standard first-line regimen in most resource-limited countries at that time) for at least six mo, presenting two consecutive VLs ≥100 copies/mL with the second VL between 100 and 999 copies/mL, and providing written informed consent to participate.…”

Section: Methodsmentioning

confidence: 99%

“…Details of our sample size calculation have been published previously [ 21 ]. Assuming a two-sided type-1 error of 5% and a power of 90%, 80 individuals (40 per group) were needed to detect a 35% difference in viral suppression.…”

Section: Methodsmentioning

confidence: 99%

Switch to second-line versus continued first-line antiretroviral therapy for patients with low-level HIV-1 viremia: An open-label randomized controlled trial in Lesotho

Amstutz

Nsakala²,

Vanobberghen

et al. 2020

PLoS Med

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Background Current World Health Organization (WHO) antiretroviral therapy (ART) guidelines define virologic failure as two consecutive viral load (VL) measurements ≥1,000 copies/mL, triggering empiric switch to next-line ART. This trial assessed if patients with sustained low-level HIV-1 viremia on first-line ART benefit from a switch to second-line treatment. Methods and findings This multicenter, parallel-group, open-label, superiority, randomized controlled trial enrolled patients on first-line ART containing non-nucleoside reverse transcriptase inhibitors (NNRTI) with two consecutive VLs ≥100 copies/mL, with the second VL between 100–999 copies/mL, from eight clinics in Lesotho. Consenting participants were randomly assigned (1:1), stratified by facility, demographic group, and baseline VL, to either switch to second-line ART (switch group) or continued first-line ART (control group; WHO guidelines). The primary endpoint was viral suppression (<50 copies/mL) at 36 weeks. Analyses were by intention to treat, using logistic regression models, adjusted for demographic group and baseline VL. Between August 1, 2017, and August 7, 2019, 137 individuals were screened, of whom 80 were eligible and randomly assigned to switch ( n = 40) or control group ( n = 40). The majority of participants were female (54 [68%]) with a median age of 42 y (interquartile range [IQR] 35–51), taking tenofovir disoproxil fumarate/lamivudine/efavirenz (49 [61%]) and on ART for a median of 5.9 y (IQR 3.3–8.6). At 36 weeks, 22/40 (55%) participants in the switch versus 10/40 (25%) in the control group achieved viral suppression (adjusted difference 29%, 95% CI 8%–50%, p = 0.009). The switch group had significantly higher probability of viral suppression across different VL thresholds (<20, <100, <200, <400, and <600 copies/mL) but not for <1,000 copies/mL. Thirty-four (85%) participants in switch group and 21 (53%) in control group experienced at least one adverse event (AE) ( p = 0.002). No hospitalization or death or other serious adverse events were observed. Study limitations include a follow-up period too short to observe differences in clinical outcomes, missing values in CD4 cell counts due to national stockout of reagents during the study, and limited generalizability of findings to other than NNRTI-based first-line ART regimens. Conclusions In this study, switching to second-line ART among patients with sustained low-level HIV-1 viremia resulted in a higher proportion of participants with viral suppression. These results endorse lowering the threshold for virologic failure in future WHO guidelines. Trial registration The trial is registered at ClinicalTrials.gov, NCT03088241 .

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“…HIV viral load was measured in the Sichuan Center for Disease Control and Prevention. Virological failure in ART was defined as HIV RNA level ≥ 1000 copies/ml [20,21] after receiving ART for more than 6 months.…”

Section: Laboratory Testsmentioning

confidence: 99%

Prevalence and determinants of virological failure, genetic diversity and drug resistance among people living with HIV in a minority area in China: a population-based study

et al. 2020

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Background: Liangshan Yi Autonomous Prefecture is one of the areas that most severely affected by human immunodeficiency virus (HIV) in China, and virological failure on antiretroviral therapy (ART) is serious in this area. Analyses of prevalence and determinants of ART failure, the genetic diversity and drug resistance among people living with HIV (PLWH) helps improve HIV treatment efficiency and prevent HIV transmission. Methods: A total of 5157 PLWH were recruited from 2016 to 2017. The venous blood samples were subjected to RT-PCR, followed by sequencing of the HIV-1 pol gene, targeting the protease and reverse transcriptase fragments. HIV-1 diversity was analyzed using the DNAStar software and drug resistance mutations were analyzed using the Stanford University HIV Drug Resistance Database.

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Cited by 8 publications

References 27 publications

Predictors of treatment failure, time to switch and reasons for switching to second line antiretroviral therapy in HIV infected children receiving first line anti-retroviral therapy at a Tertiary Care Hospital in Ethiopia

Predictors of treatment failure, time to switch and reasons for switching to second line antiretroviral therapy in HIV infected children receiving first line anti-retroviral therapy at a Tertiary Care Hospital in Ethiopia

Switch to second-line versus continued first-line antiretroviral therapy for patients with low-level HIV-1 viremia: An open-label randomized controlled trial in Lesotho

Prevalence and determinants of virological failure, genetic diversity and drug resistance among people living with HIV in a minority area in China: a population-based study

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