Effectiveness of first-line antiretroviral therapy and correlates of longitudinal changes in CD4 and viral load among HIV-infected children in Ghana

Barry, Oliver M.; Powell, Jonathan; Renner, Lorna; Bonney, Evelyn Yayra; Prin, Meghan; Ampofo, William; Kusah, Jonas Tettey; Goka, Bamenla; Sagoe, Kwamena W.; Shabanova, Veronika; Paintsil, Elijah

doi:10.1186/1471-2334-13-476

Cited by 47 publications

(48 citation statements)

References 34 publications

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“…As shown by the first derivative plot, the rate of CD4 increase in response of treatment was high during the first 10 months and stabilized later. This analysis also revealed that there was no difference in the trend of CD4 counts in the long-run among patients who initiated with EFV or NVP containing regimen which is inline with previous study conducted in Ghana [18]. Considering only the NRTI backbones, there was difference in the evolution of log CD4 cell counts which is consistent with the study in Italy [45].…”

Section: Discussionsupporting

confidence: 89%

Modeling Outcomes of First-Line Antiretroviral Therapy and Rate of CD4 Counts Change among a Cohort of HIV/AIDS Patients in Ethiopia: A Retrospective Cohort Study

et al. 2016

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BackgroundAntiretroviral therapy has shown to be effective in reducing morbidity and mortality in patients infected with HIV for the past couples of decades. However, there remains a need to better understand the characteristics of long-term treatment outcomes in resource poor settings. The main aim of this study was to determine and compare the long-term response of patients on nevirapine and efavirenz based first line antiretroviral therapy regimen in Ethiopia.MethodsHospital based retrospective cohort study was conducted from January 2009 to December 2013 at University hospital located in Northwest Ethiopia. Human subject research approval for this study was received from University of Gondar Research Ethics Committee and the medical director of the hospital. Cox-proportional hazards model was used to assess the effect of baseline covariates on composite outcome and a semi-parametric mixed effect model was used to investigate CD4 counts response to treatments.ResultsA total of 2386 HIV/AIDS naive patients were included in this study. Nearly one-in-four patients experienced the events, of which death, lost to follow up, treatment substitution and discontinuation of Non-Nucleoside Reverse Transcriptase Inhibitors(NNRTI) accounted: 99 (26.8%), 122 (33.0%), 137 (37.0%) and 12 (3.2%), respectively. The hazard of composite outcome on nevirapine compared with efavirenz was 1.02(95%CI: 0.52-1.99) with p-value = 0.96. Similarly, the hazard of composite outcome on tenofovir and stavudine compared with zidovudine were 1.87 (95%CI: 1.52-2.32), p-value < 0.0001 and 1.72(95% CI: 1.22-2.32), p-value = 0.002, respectively. The rate of CD4 increase in response to treatment was high during the first 10 months and stabilized later.ConclusionsThis study revealed that treatment responses were comparable whether nevirapine or efavirenz was chosen to initiate antiretroviral therapy for HIV/AIDS patients in Ethiopia. There was significant difference on risk of composite outcome between patients who were initiated with Tenofovir containing ART regimen compared with zidovudine after controlling for NNRTI drug combinations.

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Section: Discussionsupporting

confidence: 89%

Modeling Outcomes of First-Line Antiretroviral Therapy and Rate of CD4 Counts Change among a Cohort of HIV/AIDS Patients in Ethiopia: A Retrospective Cohort Study

et al. 2016

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“…The results do however support the need for virologic monitoring as a better strategy for early detection of virologic failure especially with increased duration of ART exposure, since immunologic monitoring is a poor predictor of treatment failure. Our ndings are in agreement with previous Sub-Saharan Africa studies which have shown that clinical and immunologic monitoring is not su cient to detect virologic failure in a timely manner [32][33][34], which further supports the need for viral load testing as a strategy to monitor response to treatment in children. This is similar to ndings from a study done in Uganda and Zimbabwe, the ARROW TRIAL which highlighted the importance of con rming virological failure before switching to second-line ART, since some children with detectable low-level viraemia spontaneously resuppressed [35].…”

Section: Discussionsupporting

confidence: 91%

Virologic Response of Treatment Experienced HIV-Infected Ugandan Children and Adolescents on NNRTI Based First-Line Regimen, Previously Monitored Without Viral Load

Ssemambo

Nalubega-Mboowa

Owora

et al. 2020

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Background: Many HIV-infected African children gained access to antiretroviral treatment (ART) through expansion of PEPFAR programs since 2004 and introduction of “Test and Treat” WHO guidelines in 2015. As ART access increases and children transition from adolescence to adulthood, treatment failure is inevitable. Viral load (VL) monitoring in Uganda was introduced in 2016 replacing clinical monitoring. However, there’s limited data on the comparative effectiveness of these two strategies among HIV-infected children in resource-limited settings (RLS).Methods: HIV-infected Ugandan children aged 1-12 years from HIV-care programs with >1 year of first-line ART using only immunologic and clinical criteria to monitor response to treatment were screened in 2010. Eligible children were stratified by VL ≤ 400 and >400 copies/ml randomized to clinical and immunological (control) versus clinical, immunological and VL monitoring to determine treatment failure with follow-up at 12, 24, 36, and 48 weeks. Plasma VL was analyzed retrospectively for controls. Mixed-effects logistic regression models were used to compare the prevalence of viral suppression between study arms and identify factors associated with viral suppression. Results: At baseline all children (n=142) were on NNRTI based ART (75% Nevirapine, 25% efavirenz). One third of ART-experienced children had detectable VL at baseline despite high CD4%. Median age was 6 years (interquartile range [IQR]: 5-9) and 43% were female. Overall, the odds of viral suppression were not different between study arms: (arm by week interaction, p=0.63), adjusted odds ratio [aOR]: 1.07; 95%CI: 0.53, 2.17, p=0.57) and did not change over time (aOR: 0 vs 24 week: 1.15; 95% CI: 0.91, 1.46, p=0.24 and 0 vs 48 weeks: 1.26; 95%CI: 0.92, 1.74, p=0.15). Longer duration of a child’s ART exposure was associated with lower odds of viral suppression (aOR: 0.61; 95% CI: 0.42, 0.87, p<.01). Only 13% (9/71) of children with virologic failure were switched to second-line ART, in spite of access to real-time VL.Conclusion: With increasing ART exposure, viral load monitoring is critical for early detection of treatment failure in RLS. Clinicians need to make timely informed decisions to switch failing children to second-line ART. Trial Registration: ClinicalTrials.gov NCT04489953, 28 Jul 2020. Retrospectively registered.

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“…From our finding, this cutoff may be too high, thereby leading to high prevalence of virologic failure and subsequent CD4+ T-cell decline. Moreover, early virologic failure may be missed, resulting in evolution of drug resistant HIV variants in HIV-infected children in sub-Saharan Africa [37,38]. Further studies on the clinical significance of frequency of episodes of detectable viremia in HIV-infected children are needed to inform appropriate cutoffs for virologic failure.…”

Section: Discussionmentioning

confidence: 99%

Frequent Episodes of Detectable Viremia in HIV Treatment-Experienced Children is Associated with a Decline in CD4+ T-cells Over Time

et al. 2016

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Background The clinical consequences of the magnitude and the duration of detectable viremia in HIV-infected children have not been well characterized. We examined the predictors and immunologic consequences over time of frequent episodes of detectable viremia in HIV-infected children followed at Yale-New Haven Hospital. Methods We analyzed the CD4+ T-cell and HIV viral load over a 19-year period (1996 to 2013) of 104 HIV-infected children enrolled in the Yale Prospective Longitudinal Pediatric HIV Cohort. Both CD4+ T-lymphocytes and HIV viral load were measured at clinic visits every 3 to 4 months. Longitudinal data analyses using polynomial random coefficients models were conducted to examine overtime changes in CD4+ T-cell counts by frequency of episodes of detectable viremia. Moreover, regression analyses using logistic regression models were used to assess the predictors of frequent episodes of detectable viremia. Results One hundred and four (104) HIV-infected children with more than one HIV viral load measurement between 1996 and November 2013 were included in the analysis. Over 80% (N=86) of the children had detectable viral load (HIV RNA viral load ≥50 copies/ml) during more than 50% of their clinic visits. Children with infrequent episodes of detectable viremia had significantly higher CD4+ T-cell counts overtime compared to those with frequent episodes of detectable viremia (P<0.0001). Conclusions Both frequency and magnitude of episodes of detectable viremia had effect on CD4+ T-cells. Strict adherence to a treatment goal of undetectable HIV viremia in children is likely to be beneficial.

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Effectiveness of first-line antiretroviral therapy and correlates of longitudinal changes in CD4 and viral load among HIV-infected children in Ghana

Cited by 47 publications

References 34 publications

Modeling Outcomes of First-Line Antiretroviral Therapy and Rate of CD4 Counts Change among a Cohort of HIV/AIDS Patients in Ethiopia: A Retrospective Cohort Study

Modeling Outcomes of First-Line Antiretroviral Therapy and Rate of CD4 Counts Change among a Cohort of HIV/AIDS Patients in Ethiopia: A Retrospective Cohort Study

Virologic Response of Treatment Experienced HIV-Infected Ugandan Children and Adolescents on NNRTI Based First-Line Regimen, Previously Monitored Without Viral Load

Frequent Episodes of Detectable Viremia in HIV Treatment-Experienced Children is Associated with a Decline in CD4+ T-cells Over Time

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