Prevalence and predictors of virological failure in pediatric patients on HAART in sub-Saharan Africa: a systematic review and meta-analysis

Machila, Nchimunya; Libonda, Liyali; Habineza, Paul; Velu, Rachel Milomba; Kamboyi, Harvey Kakoma; Ndhlovu, Jacob; Wamunyima, Inonge; Sinadambwe, Monahani; Mudenda, Steward; Sianantu, Cosmas Zyambo; Bumbangi, Flavien Nsoni

doi:10.11604/pamj.2023.45.98.37017

Cited by 3 publications

(1 citation statement)

References 56 publications

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“…The incidence density of virologic failure in our cohort was 4.3 per 100 person-years, including both ART-naïve and ART-experienced children. This rate is notably lower than what has been reported in recent literature, particularly in sub-Saharan Africa, where a systematic review and meta-analysis indicated a virological failure rate of 29% (23), and a retrospective study in South Africa documented a failure rate of 18.7 per 100 person-years (24).…”

Section: Discussioncontrasting

confidence: 58%

Thirteen-year viral suppression and immunologic recovery of LPV/r-based regimens in pediatric HIV treatment: a multicenter cohort study in resource-constrained settings of China

Lao,

Zhang,

Yan

et al. 2023

Front. Med.

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BackgroundAntiretroviral Therapy (ART) in children remains challenging due to resource-constrained settings. We conducted a 13-year, prospective, multicenter cohort study on the effectiveness and safety of LPV/r-based regimens in ART-naive and ART-experienced children.MethodsFrom January 2008 to May 2021, children living with HIV-1 were recruited with LPV/r-based regimens from 8 clinical research sites in 6 provinces in China. Effectiveness outcomes were virologic failure (defined as at least two consecutive measurements of VL > 200 copies/mL after 6 months of ART) and immune response (defined as CD4% recovered to more than 25% after 12 months of treatment). The safety outcomes were treatment-related grade 2–4 adverse events and abnormal laboratory test results.ResultsA total of 345 ART-naïve children and 113 ART-experienced children were included in this cohort study. The median follow-up time was 7.3 (IQR 5.5–10.5) years. The incidence density of virologic failure was 4.1 (95% CI 3.3–4.9) per 100 person-years in ART-naïve children and 5.0 (95% CI 3.5–6.5) per 100 person-years in ART-experienced children. Kaplan Meyer (KM) curve analysis showed children with ART experience were at a higher risk of virologic failure (p < 0.05). The risk factors of virologic failure in ART-naïve children were clinic setting in rural hospitals (aHR = 2.251, 1.108–4.575), annual missed dose times >5 days of LPV intake (aHR = 1.889, 1.004–3.554); The risk factor of virologic failure in ART-experienced children was missed dose times >5 days (aHR = 2.689, 1.299–5.604) and mother as caregivers for ART administration (aHR = 0.475, 0.238–0.948). However, during long-term treatment, viral suppression rates between ART-naïve and ART-experienced children remained similar. No significant differences were observed in the immune response, treatment-related grade 2–4 events, and abnormal laboratory test results between ART-naïve children and ART-experienced children.ConclusionOur research underscores that with consistent, long-term treatment of LPV/r-based regimens, ART-experienced children can achieve therapeutic outcomes comparable to ART-naïve children. It provides crucial insights on LPV/r-based regimens in pediatric HIV treatment, especially in resource-limited settings where high-cost Integrase Strand Transfer Inhibitors (INSTs) are inaccessible. This evidence-based understanding provides an essential addition to the global therapeutic strategies for pediatric HIV treatment.

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Section: Discussioncontrasting

confidence: 58%

Thirteen-year viral suppression and immunologic recovery of LPV/r-based regimens in pediatric HIV treatment: a multicenter cohort study in resource-constrained settings of China

Lao,

Zhang,

Yan

et al. 2023

Front. Med.

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Paediatric antiretroviral therapy challenges with emerging integrase resistance

Bamford,

Hamzah,

Turkova

2024

Current Opinion in HIV and AIDS

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Purpose of review Universal antiretroviral (ART) coverage and virological suppression are fundamental to ending AIDS in children by 2030. Availability of new paediatric dolutegravir (DTG)-based ART formulations is a major breakthrough and will undoubtedly help achieve this goal, but treatment challenges still remain. Recent findings Paediatric formulations remain limited compared to those for adults, especially for young children, those unable to tolerate DTG or with DTG-based first-line ART failure. Tenofovir alafenamide is virologically superior to standard-of-care backbone drugs in second-line, but paediatric formulations are not widely available. The roles of resistance testing and recycling of backbone drugs following first-line ART failure remain to be determined. Results of trials of novel treatment strategies including dual therapy and long-acting agents are awaited. Although numbers are currently small, safe and effective ART options are urgently required for children developing DTG resistance. Summary The antiretroviral treatment gap between adults and children persists. The potential benefits from rollout of new paediatric DTG-based fixed-dose combination ART for first-line treatment are considerable. However, children remain disadvantaged when DTG-based first-line ART fails or cannot be used. Research efforts to address this inequity require prioritisation in order to ensure health outcomes are optimised for all ages in all settings.

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Disparities in dolutegravir utilisation in children, adolescents and young adults (0-24 years) living with HIV. An analysis of the IeDEA Paediatric West African cohort

Desmonde,

Dame,

Malateste

et al. 2024

Preprint

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Introduction: We describe the incidence of Dolutegravir (DTG)-containing antiretroviral treatment (ART) initiation since its introduction in 2019 in pediatric West African IeDEA cohorts. Methods: We included all patients aged 0-24 years on ART, from nine clinics in Cote d\'Ivoire (n=4), Ghana, Nigeria, Mali, Benin, and Burkina Faso. Baseline varied by site and was defined as date of first DTG prescription; patients were followed-up until database closure/death/loss to follow-up (LTFU, no visit ≥7 months), whichever came first. We computed the cumulative incidence function for DTG initiation; associated factors were explored in a shared frailty model, accounting for clinic heterogeneity. Results: Since 2019, 3,350 patients were included; 49% were female;79% had been on ART ≥12 months. Median baseline age was 12.9 years (IQR: 9-17). Median follow-up was 14 months (IQR: 7-22). Overall, 1496 (48%) initiated DTG. The overall cumulative incidence of DTG initiation reached 23.6% (95% CI: 21.6-25.6) and 41.3% (95% CI: 39.0-43.6) at 6 and 12 months respectively. Adjusted ART line and available viral load (VL) at baseline, among patients >5 years, DTG-initiation was associated with being male (aHR among 5-9 years: 1.39, 95% CI: 1.06-1.84; among 10-14 years: 1.78, 95% CI: 1.52-2.01; among ≥15 years: 2.46, 95% CI: 2.08-2.91). After 12 months of DTG-implementation, those with detectable VL were less likely to initiate DTG compared to those in viral suppression (aHR: 0.86, 95% CI: 0.76-0.97) and those on NNRTIs were three times more likely to initiate DTG compared to those on PIs (aHR: 3.30, 95% CI: 1.91-5.69). Conclusion: Children and adolescent males ≥5 years, on NNRTIs, with access to VL were the most likely to switch to DTG. As DTG access scales up, updated documentation of treatment practices is required to better ensure universal and equal access.

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Prevalence and predictors of virological failure in pediatric patients on HAART in sub-Saharan Africa: a systematic review and meta-analysis

Cited by 3 publications

References 56 publications

Thirteen-year viral suppression and immunologic recovery of LPV/r-based regimens in pediatric HIV treatment: a multicenter cohort study in resource-constrained settings of China

Thirteen-year viral suppression and immunologic recovery of LPV/r-based regimens in pediatric HIV treatment: a multicenter cohort study in resource-constrained settings of China

Paediatric antiretroviral therapy challenges with emerging integrase resistance

Disparities in dolutegravir utilisation in children, adolescents and young adults (0-24 years) living with HIV. An analysis of the IeDEA Paediatric West African cohort

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