Pediatric Antiretroviral Therapy Research Articles

Paediatric antiretroviral therapy challenges with emerging integrase resistance.

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. 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. 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.

Challenges with pediatric antiretroviral therapy administration: Qualitative perspectives from caregivers and HIV providers in Kenya.

Current formulations of pediatric antiretroviral therapy (ART) for children with HIV present significant barriers to adherence, leading to drug resistance, ART ineffectiveness, and preventable child morbidity and mortality. Understanding these challenges and how they contribute to suboptimal adherence is an important step in improving outcomes. This qualitative study describes how regimen-related challenges create barriers to adherence and impact families. We conducted key informant interviews (KIIs) with 30 healthcare providers and 9 focus group discussions (FGDs) with a total of 72 caregivers, across three public hospitals in Siaya and Mombasa Kenya. The KIIs and FGDs were audio recorded, translated, and transcribed verbatim. The transcripts were hand coded based on emergent and a-priori themes. Caregivers discussed major regimen-related challenges to adherence included poor palatability of current formulations, complex preparation, and administration (including measuring, crushing, dissolving, mixing), complex drug storage, and frequent refill appointments and how these regimen-related challenges contributed to individual and intrapersonal barriers to adherence. Caregivers discussed how poor taste led to child anxiety, refusal of medications, and the need for caregivers to use bribes or threats during administration. Complex preparation led to concerns and challenges about maintaining privacy and confidentiality, especially during times of travel. Providers corroborated this patient experience and described how these challenges with administration led to poor infant outcomes, including high viral load and preventable morbidity. Providers discussed how the frequency of refills could range from every 2 weeks to every 3 months, depending on the patient. Caregivers discussed how these refill frequencies interrupted work and school schedules, risked unwanted disclosure to peers, required use of financial resources for travel, and ultimately were a challenge to adherence. These findings highlight the need for improved formulations for pediatric ART to ease the daily burden on caregivers and children to increase adherence, improve child health, and overall quality of life of families.

The rollout of paediatric dolutegravir and virological outcomes among children living with HIV in Mozambique.

In 2022, Mozambique introduced Dolutegravir 10mg (pDTG), as part of paediatric antiretroviral therapy for children weighing < 20 kg. Understanding real-world challenges during national rollout can strengthen health systems in resource-limited settings. We described the transition rate to, and new initiation of, pDTG, viral load suppression (VLS) post-pDTG, and factors associated with VLS among children living with HIV. We conducted a retrospective cohort study involving children aged < 9 years and abstracted data from clinical sources. We used logistic regression to assess VLS and pDTG initiation predictors. Of 1353 children, 1146 initiated pDTG; 196 (14.5%) had no recorded weight. Post-pDTG switch, 98.9% (950/961) of children maintained the same nucleoside reverse transcriptase inhibitor backbone. After initiating Abacavir/Lamivudine+pDTG, 834 (72.8%) children remained on the regimen, 156 (13.6%) switched off (majority to Dolutegravir 50mg), 22 (1.9%) had ≥ 2 anchor drug switches; 134 (11.7%) had no documented follow-up regimen. Factors associated with pDTG initiation or switch were younger age (adjusted odds ratio [AOR] = 0.71 [0.63-0.80]) and a recorded weight (AOR = 55.58 [33.88-91.18]). VLS among the 294 children with a viral load (VL) test after ≥ 5 months post-pDTG was 75.5% (n = 222/294). Pre-pDTG VLS rate among treatment-experienced children was 56.5% (n = 130/230). Factors associated with VLS were older age (AOR = 1.18 [1.03-1.34]) and previous VLS (AOR = 2.27 [1.27-4.06]). Most eligible children initiated pDTG per guidelines, improving post-pDTG VLS. Challenges included unexplained switches off pDTG after initiation, low VL coverage and inadequate documentation in clinic records.

The Positive Impact of Foods Support on Loss to Follow Up Among Children and Adolescents on HIV Antiretroviral Therapy in a District Hospital in East Cameroon.

The pediatric HIV treatment coverage in Cameroon remains low at 35%. The high loss to follow up (LTFU) remains a major factor to this dismal performance which is related to the lack of implementation of effective interventions to improve retention in care. This study assessed the impact of foods support (FS) on LTFU among children and adolescents in a rural district hospital in eastern Cameroon. This was a retro-prospective study conducted in Abong Mbang District Hospital (ADH) in the East Region of Cameroon. We provided foods kits to children and adolescents initiated on antiretroviral therapy (ART) in this facility during the study and followed them up prospectively (prospective phase). On the other hand, using medical records, we collected retrospectively data for children and adolescents who enrolled on ART in the hospital prior to the study (retrospective phase). We then compared the proportions of children and adolescents LTFU before (no FS) and after (with FS) the study, using the Fisher's exact test, logistic regression, Kaplan-Meier survival curves and Cox proportional-hazards model at 5% significant level. We found that with FS, the proportion of children and adolescents LTFU was 11 times lower (2.4% vs 26.7%, p=0.014), the mean time of retention in care was 30% higher (17 months vs 12 months, p<0.001) and children and adolescents who did not receive FS were 10 times more likely to be LTFU [aHR=10.3 (4.0-26.2), p<0.001)]. Foods support is an effective intervention in reducing LTFU among children and adolescents on ART. This intervention should be adequately funded to enable a large-scale implementation in the field. This could help to improve the outcome of pediatric ART coverage in resource-limited settings.

Genotypic resistance testing improves antiretroviral treatment outcomes in a cohort of adolescents in Cameroon: Implications in the dolutegravir-era.

Acquired drug resistance (ADR) is common among adolescents living with perinatal HIV (APHI) in sub-Saharan Africa (SSA). Personalized management has the potential to improve pediatric antiretroviral therapy (ART), even in the presence of long-term treatment and HIV-1 subtype diversity. We sought to evaluate the effect of HIV-1 mutational profiling on immuno-virological response and ADR among APHI. A cohort-study was conducted from 2018-2020 among 311 APHI receiving ART in Cameroon. Clinical, immunological and virological responses were measured at enrolment (T1), 6-months (T2) and 12-months (T3). Immunological failure (IF: CD4 #x003C;250 cells/mm3), VF (viremia ≥1,000 copies/ml), and ADR were analyzed, with P#x003C;0.05 considered significant. Mean age was 15(±3) years; male-female ratio was 1:1; median [IQR] ART-duration was 36[21-81] months. At T1, T2, and T3 respectively, adherence-level was 66.4, 58.3 and 66.5%; 14 viral clades were found, driven by CRF02_AG (58.6%); ADR-mutations favored increased switch to second-line ART (16.1, 31.2, and 41.9%, P#x003C;0.0001). From T1-T3 respectively, there were declining rates of IF (25.5, 18.9, and 9.83%, P#x003C;0.0001), VF (39.7, 39.9, and 28.2%, P=0.007), and HIVDR (96.4, 91.7, and 85.0%, P=0.099). Predictors of ADR were being on first-line ART (P=0.045), high viremia at enrolment (AOR=12.56, P=0.059), and IF (AOR=5.86, P=0.010). Of note, optimized ART guided by mutational profile (AOR=0.05, P=0.002) was protective. Moreover, full Tenofovir+Lamivudine+Dolutegravir efficacy was predicted in 77 and 62% of APHI respectively after first- and second-line failure. Among APHI in this SSA setting, viral mutational profiling prompts the use of optimized Dolutegravir-based ART regimens, leading to improved immuno-virological response and declining ADR burdens. Thus, implementing personalized HIV medicine in this vulnerable population would substantially improve ART response and the achievement of the 95-95-95 goals in these underserved populations.

Incidence of switching to second-line antiretroviral therapy and its predictors among children on antiretroviral therapy at general hospitals, Northern Ethiopia: A survival analysis.

With expanding access to pediatric antiretroviral therapy, several patients in the developing world were switched to the second-line regimen, and some require third-line medications. A delay in a second-line switch is associated with an increased risk of mortality and other undesired therapeutic outcomes, drives up program costs, and challenges the pediatric antiretroviral therapy service. Nevertheless, there remain limited and often conflicting estimates on second-line antiretroviral therapy use during childhood, especially in resource-limited settings like Ethiopia. Thus, this study intended to determine the incidence and predictors of switching to second-line antiretroviral therapy among children. A retrospective cohort study was conducted by reviewing records of 424 randomly selected children on first-line antiretroviral therapy from January 2014 to December 2018 at public hospitals in the Central and Southern Zones of Tigray, Northern Ethiopia. Data were collected using extraction tool; entered into Epi-data; cleaned, and analyzed by STATA version-14. Kaplan-Meier curve, log-rank test, and life table were used for data description and adjusted hazard ratios and p-value for analysis by Cox proportional hazard regression. Variables at a P-value of ≤0.20 in the bi-variable analysis were taken to multivariable analysis. Finally, statistical significance was declared at a P-value of ≤0.05. Analysis was conducted on 424 charts with a total person-time observation of 11686.1 child-months and an incidence switch rate of 5.6 (95%CI: 4.36-7.09) per 1000 child-month-observations. Being orphan [AHR = 2.36; 95%CI: 1.10-5.07], suboptimal adherence [AHR = 2.10; 95% CI: 1.12-3.92], drug toxicity [AHR = 7.05; 95% CI: 3.61-13.75], advanced latest clinical stage [AHR = 2.75; 95%CI: 1.05-7.15], and tuberculosis co-infection at baseline [AHR = 3.08; 95%CI: 1.26-7.51] were significantly associated with switch to second-line antiretroviral therapy regimen. Moreover, a long duration of follow-up [AHR = 0.75; 95% CI: 0.71-0.81] was associated with decreased risk of switching. Hence, it is better to prioritize strengthening the focused evaluation of tuberculosis co-infection and treatment failure with continuous adherence monitoring. Further research is also needed to evaluate the effect of drug resistance.

High risk of virologic failure among HIV-infected children and adolescents routinely followed-up in Littoral region of Cameroon.

Virological response to antiretroviral therapy (ART) remains a challenge for HIV-infected children and adolescents due to non-optimization of pediatric ART for resource-limited settings. In this study, we aimed to investigate factors associated with virologic failure (VF) in HIV-infected-children and adolescents on ART in Cameroon. A prospective patient-based cohort study was conducted among HIV-infected children (0-9 years) and adolescents (10-19 years) followed-up between November 2018 and October 2019 in 38 healthcare centers located in the Littoral region of Cameroon. The 1st viral load (VL) was assessed after 6 months of ART initiation and the 2nd VL between 3 and 6 six months later in patients with VL ≥1000 copies/ml in accordance with the national algorithm using Abbott Real-Time HIV-1 Viral Load Assay. Multivariate analyses were performed to identify the determinants of higher risk of VF. Of 1,029 HIV-infected children and adolescents (393 children and 636 adolescents), 801 (77.8%) cumulatively presented with VL <1000 copies/mL within 12 months on ART. Adolescents were more likely to have VF than children (24.5% vs 18.3%, OR: 1.39; 95%CI: 1.00-1.93; p = 0.047). Patients followed-up in decentralized care units were significantly more likely to have VF compared to those attending the accredited treatment centers (26.1% vs 16.6%, OR: 1.88, 95%CI: 1.37-2.58; p<0.001). Our findings show a high rate of VL suppression (VLS, 77.8%) among HIV-infected children and adolescents, albeit lower than the established target of 90%. Being adolescent and patients followed in the decentralized care units are high risk factors for VF, thereby necessitating routine therapeutic education of patients and guardians in resource limited countries to improve VLS.

Pediatric Antiretroviral Therapy Coverage and AIDS Deaths in the "Treat All" Era.

In 2015, CD4-based clinical staging criteria for antiretroviral therapy (ART) initiation were removed, expanding ART eligibility ("Treat All") for children, who shoulder an outsized burden of HIV-related deaths. To quantify the impact of "Treat All" on pediatric HIV outcomes, we examined shifts in pediatric ART coverage and AIDS mortality before and after "Treat All" implementation. We abstracted country-level ART coverage (proportion of children <15 years on ART) and AIDS mortality (deaths per 100 000 population) estimates over 11 years. For 91 countries, we also abstracted the year "Treat All" was incorporated into national guidelines. We used multivariable 2-way fixed effects negative binomial regression to estimate changes in pediatric ART coverage and AIDS mortality potentially attributable to "Treat All" expansion, reported as adjusted incidence rate ratios (adj.IRR) with 95% confidence intervals (95% CI). From 2010 to 2020, pediatric ART coverage tripled (16% to 54%), and AIDS-related deaths were halved (240 000 to 99 000). Compared with the pre-implementation period, observed ART coverage continued increasing after "Treat All" adoption, but this rate of increase declined by 6% (adj.IRR = 0.94, 95% CI: 0.91-0.98). AIDS mortality continued declining after "Treat All" adoption, but this rate of decline decreased by 8% (adj.IRR = 1.08, 95% CI: 1.05-1.11) in the post-implementation period. Although "Treat All" called for increased HIV treatment equity, ART coverage continues lagging in children and comprehensive approaches that address structural issues, including family-based services and intensified case-finding, are needed to close pediatric HIV treatment gaps.

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

Antiretroviral treatment failure has emerged as a challenge in the management of pediatric human immunodeficiency virus (HIV) patients, especially in resource-limited countries despite accessibility to Highly Active Antiretroviral Therapy (HAART). A systematic review and meta-analysis was conducted to synthesize virological failure (VF) prevalence and ascertain its predictors in children in sub-Saharan Africa. An electronic database search strategy was conducted from January to September 2021 on PubMed, EMBASE, SCOPUS, HINARI, and CINAHL. Further, manual searching was conducted on non-indexed journals. Utilizing the JASP© version 0.17.2 (2023) statistical software, a meta-analysis of pooled prevalence of VF was estimated using the standardized mean differences. Further, selection models were used to assess the risk of bias and heterogeneity. The pooled odds ratios were estimated for the respective studies reporting on predictors of VF. The overall pooled estimate of the prevalence of VF in sub-Saharan Africa among the sampled population was 29% (95% CI: 27.0-32.0; p<0.001). Predictors of VF were drug resistance (OR: 1.68; 95% CI: 0.88-2.49; p < 0.001), poor adherence (OR: 5.35; 95% CI: 5.26-5.45; p < 0.001), nevirapine (NVP)-based regimen (OR: 5.11; 95% CI: 4.66-5.56; p < 0.001), non-usage of cotrimoxazole prophylaxis (OR: 4.30; 95% CI: 4.13-4.47; p < 0.001), higher viral load at the initiation of antiretroviral therapy (ART) (OR: 244.32; 95% CI: 244.2-244.47; p <0.001), exposure to the prevention of mother to child transmission (PMTCT) (OR: 8.02; 95%CI: 7.58-8.46; p < 0.001), increased age/older age (OR: 3.37; 95% CI: 2.70-4.04; p < 0.001), advanced World Health Organization (WHO) stage (OR: 6.57; 95% CI: 6.17-6.98; p < 0.001), not having both parents as primary caregivers (OR: 3.01; 95% CI: 2.50-3.53; p < 0.001), and tuberclosis (TB) treatment (OR: 4.22; 95% CI: 3.68-4.76; p <0.001). The mean VF prevalence documented is at variance with studies in other developing countries outside the sub-Saharan region. The high prevalence of HIV cases contrasting with the limited expertise in the management of pediatric ART patients could explain this variance.

Evaluation of the pediatric antiretroviral therapy service in Gondar city public health facilities-A case study design with mixed methods.

The pediatric antiretroviral therapy (ART) service is introduced to save lives, restore mental and physical functions, and improve the quality of life of children living with HIV/AIDS. This evaluation aimed to assess the implementation status of the pediatric ART service provision in Gondar city administration health facilities to promote evidence-based decision-making for program improvement. An institutional-based single case-study design with concurrent mixed methods were applied. The service was evaluated by the availability of essential resources, compliance of health providers with the standard guideline, and caregivers' satisfaction dimensions. Document review, key informant interviews, observations, and interviewer-administered exit-interview were conducted. The quantitative data were analyzed in descriptive and analytical, while the qualitative data were transcribed, translated, and thematically analyzed. A logistic regression analysis was performed to identify factors associated with caregivers' satisfaction. The overall implementation of pediatric ART service was 75.32%. The availability, compliance, and satisfaction were 68.96%, 74.44%, and 84.64%, respectively. Trained healthcare professionals, essential ART drugs, registers, and basic laboratory diagnostic equipment were reasonably available. However, the lack of opportunistic infection medications and adequate rooms were significant gaps in service provision. Respondents noted a shortage of drugs and rooms for consultation and service provision. Short travel distance (AOR = 2.87), low viral load (AOR = 3.15), and sex of caregivers (AOR = 4.98) were significantly associated with good satisfaction. The overall implementation of pediatric ART service is well based on the pre-determined judgment criteria. The health facilities and policymakers are advised to focus on availing medications to treat opportunistic infections and expanding the health facility to have enough space for consultation and service provision. Furthermore, particular emphasis should be given to caregivers who come from long distances and patients with a high viral load to increase caregivers' satisfaction.

Development and Evaluation of Dissolving Microarray Patches for Co-administered and Repeated Intradermal Delivery of Long-acting Rilpivirine and Cabotegravir Nanosuspensions for Paediatric HIV Antiretroviral Therapy

PurposeWhilst significant progress has been made to defeat HIV infection, the efficacy of antiretroviral (ARV) therapy in the paediatric population is often hindered by poor adherence. Currently, two long-acting (LA) intramuscular injectable nanosuspensions of rilpivirine (RPV) and cabotegravir (CAB) are in clinical development for paediatric populations. However, administration requires access to healthcare resources, is painful, and can result in needle-stick injuries to the end user. To overcome these barriers, this proof-of-concept study was developed to evaluate the intradermal delivery of RPV LA and CAB LA via self-disabling dissolving microarray patches (MAPs).MethodsDissolving MAPs of two conformations, a conventional pyramidal and a bilayer design, were formulated, with various nanosuspensions of RPV and CAB incorporated within the respective MAP matrix. MAPs were mechanically robust and were capable of penetrating ex vivo skin with intradermal ARV deposition.ResultsIn a single-dose in vivo study in rats, all ARV MAPs demonstrated sustained release profiles, with therapeutically relevant plasma concentrations of RPV and CAB detected to at least 63 and 28 d, respectively. In a multi-dose in vivo study, repeated MAP applications at 14-d intervals maintained therapeutically relevant plasma concentrations throughout the duration of the study.ConclusionsThese results illustrate the potential of the platform to repeatedly maintain plasma concentrations for RPV and CAB. As such, these MAPs could represent a viable option to improve adherence in the paediatric population, one that is capable of being painlessly administered in the comfort of the patient’s own home on a biweekly or less frequent basis.Graphical abstract

In-vivo pharmacokinetic studies of Dolutegravir loaded spray dried Chitosan nanoparticles as milk admixture for paediatrics infected with HIV

Dolutegravir (DTG) is an antiretroviral drug approved in the year 2013, and being categorized as a BCS-II molecule, it possesses solubility issues. In order to enhance the solubility and improve its bioavailability, DTG-loaded Chitosan nanoparticles (NPs) were synthesized utilizing spray drying technology. The developed nanoformulation was characterized for its physicochemical properties and investigated for the feasibility of its administration through an oral route along with milk/food as an admixture for paediatric antiretroviral therapy. The in vivo oral bioavailability studies were conducted in Balb-C mice, where the animals were treated with the selected formulation of DTG-loaded Chitosan NPs and compared to pure DTG. The NPs exhibited 2.5-fold increase in the Cmax (77.54 ± 7.93 μg/mL) when compared to the pure DTG (30.15 ± 8.06 μg/mL). This phenomenon was further reflected by the improved bioavailability of DTG (AUC: 678.3 ± 10.07 μg/h/mL) in the NPs administered to mice when compared to the AUC of animals administered with pure DTG (405.29 ± 7 μg/h/mL). Altogether, the research findings showed that Chitosan-based NPs were ideal carriers for oral administration of DTG along with milk and exhibited great potential to enhance the bioavailability of the drug and treatment adherence for paediatric HIV patients.

Rates and Determinants of Retention on ART Among Orphans and Vulnerable Children Living With HIV in Tanzania.

Despite the global progress in response to HIV and AIDS, notable challenges remain for children, especially identification, linkage, and retention in HIV care and treatment services. To succeed in pediatric HIV programming requires the linkage and retention of the children in those services over time. This study assessed the level of retention to antiretroviral therapy (ART) and its associated factors among orphans and vulnerable children living with HIV (OVCLHIV) in Tanzania. Data were obtained from the USAID Kizazi Kipya project that collected pediatric ART data from October 2017 to October 2019 in 81 district councils of Tanzania. Community-based volunteers supported the linkage and retention of the OVCLHIV on ART. Analysis of on-ART status was conducted in a cohort of OVCLHIV aged 0–20 years enrolled in the project and monitored for 24 months. OVCLHIV who remained on ART until the end of the follow-up period were referred to as “retained,” otherwise, “not retained”. Multivariable analysis was conducted using logistic regression, adjusting for baseline characteristics. Of the 5,304 OVCLHIV analyzed, the mean age was 13.1 years, 51.5% were female, and 72.2% were living with female caregivers. Their overall rate of retention on ART over the 24 months was 86.7%. Multivariable analysis showed that as the higher frequency of home visit by the project staff increased, the likelihood of retention increased by 8% [adjusted odds ratio (aOR) = 1.08, 95% CI 1.06–1.11, p < 0.001]. Membership in people living with HIV (PLHIV) support groups was associated with a higher likelihood of retention compared to nonmembership (aOR = 3.31, 95% CI 2.60–4.21, p < 0.001). Children in larger family size were 22% less likely to sustain ART (aOR = 0.78, 95% CI 0.72–0.84, p < 0.001). Urban OVCLHIV were 18% less likely to remain on ART than their rural counterparts (aOR = 0.82, 95% CI 0.69–0.98, p = 0.030). Remaining on ART was 49% more likely for OVC in economically better-off households than those in destitute households (aOR = 1.49, 95% CI 1.22–1.81, p < 0.001). Male OVC were 17% less likely to be retained on ART than their female counterparts (aOR = 0.83, 95% CI 0.71–0.99, p = 0.033). Community-based OVC support resulted in a high pediatric retention rate over the 24 months of follow-up. While key enablers of retention were higher frequency of home visits by the project volunteer, participation in PLHIV support groups, and better economic status, large family sizes, urban place of residence, and male gender of the OVC were barriers. This study brings useful evidence to inform strategies for advancing retention of OVCLHIV on ART for their better health outcomes and overall wellbeing.

Recent Trends in Adult and Pediatric Antiretroviral Therapy Monitoring and Failure.

To assess recent trends in the monitoring of antiretroviral therapy (ART) and detection of ART failure in adult and pediatric HIV clinics. We used data collected from 21 adult and 17 pediatric sites (across 13 and 6 countries/territories, respectively) in the International Epidemiology Databases to Evaluate AIDS - Asia-Pacific cohort. ART failure was defined as viral, immune, or clinical consistent with WHO guidelines. A total of 8567 adults and 6149 children contributed data. Frequency of CD4 count monitoring declined between 2010 and 2019 among adult sites (from 1.93 to 1.06 tests/person per year, a 45.1% decline) and pediatric sites (from 2.16 to 0.86 testsperson per year, a 60.2% decline), whereas rates of viral load monitoring remained relatively stable. The proportion of adult and pediatric treatment failure detected as immune failure declined (from 73.4% to 50.0% and from 45.8% to 23.1%, respectively), whereas the proportion of failure detected as viral failure increased (from 7.8% to 25.0% and from 45.8% to 76.9%, respectively). The proportion of ART failure detected as clinical failure remained stable among adult and pediatric sites. The largest shifts in ART monitoring and failure type occurred in lower middle-income countries. Although viral failure in our Asian cohort now comprises a larger portion of ART failure than in prior years, the diagnostic characteristics of immune and clinical failure, and recommendations on their management, remain important inclusions for regional ART guidelines.

Adapting strategies for effective and efficient pediatric HIV case finding in low prevalence countries: risk screening tool for testing children presenting at high-risk entry points in Ethiopia

BackgroundImplementing effective and efficient case-finding strategies is crucial to increasing pediatric antiretroviral therapy coverage. In Ethiopia, universal HIV testing is conducted for children presenting at high-risk entry points including malnutrition treatment, inpatient wards, tuberculosis (TB) clinics, index testing for children of positive adults, and referral of orphans and vulnerable children (OVC); however, low positivity rates observed at inpatient, malnutrition and OVC entry points warrant re-assessing current case-finding strategies. The aim of this study is to develop HIV risk screening tool applicable for testing children presenting at inpatient, malnutrition and OVC entry points in low-HIV prevalence settings.MethodsThe study was conducted from May 2017–March 2018 at 29 public health facilities in Amhara and Addis Ababa regions of Ethiopia. All children 2–14 years presenting to five high-risk entry points including malnutrition treatment, inpatient wards, tuberculosis (TB) clinics, index testing for children of positive adults, and referral of orphans and vulnerable children (OVC) were enrolled after consent. Data were collected from registers, medical records, and caregiver interviews. Screening tools were constructed using predictors of HIV positivity as screening items by applying both logistic regression and an unweighted method. Sensitivity, specificity and number needed to test (NNT) to identify one new child living with HIV (CLHIV) were estimated for each tool.ResultsThe screening tools had similar sensitivity of 95%. However, the specificities of tools produced by logistic regression methods (61.4 and 65.6%) which are practically applicable were higher than those achieved by the unweighted method (53.6). Applying these tools could result in 58‒63% reduction in the NNT compared to universal testing approach while maintaining the overall number of CLHIV identified.ConclusionThe screening tools developed using logistic regression method could significantly improve HIV testing efficiency among children presenting to malnutrition, inpatient, and OVC entry points in Ethiopia while maintaining case identification. These tools are simplified to practically implement and can potentially be validated for use at various entry points. HIV programs in low-prevalence countries can also further investigate and optimize these tools in their settings.

Where have we come from and where are we going? The paediatric HIV programme in Johannesburg, South Africa, from 2004 to 2018: A retrospective analysis of programme trends

Background. The paediatric HIV treatment programme in South Africa (SA) has grown since its inception in 2004. Despite this impressive scale-up of antiretroviral therapy (ART) in children, the proportion of children started on ART and retained in care remains unacceptably low, with only 47% of the 340 000 HIV-positive children in SA on ART in 2020. Johannesburg is one of the districts in SA with the largest number of children living with HIV who are not on ART, and is a priority district for paediatric case finding and retention. Objectives. To describe the dynamics of the paediatric HIV programme in Johannesburg, SA. Methods. A secondary analysis was conducted on patient-level HIV treatment data from TIER.Net, the nationally mandated HIV/ART database. Children aged &lt;15 years who received ART between January 2004 and June 2019 at public health facilities in Johannesburg were included. We reported the number of children on ART and the number who entered and exited the programme by age group over time, and analysed the trends of these indicators. Results. By December 2018, 7 630 children aged &lt;15 years remained in Johannesburg’s paediatric ART programme: 82.5% were aged 5 - &lt;15 years, with 54.1% of these being 10 - &lt;15 years old. During the study period, 19 850 children were newly initiated on ART. New initiations slowed from 2013, to range from 1 172 to 1 373 yearly. In 2018, 34.2% of initiators were aged &lt;1 year, 24.2% 1 - &lt;5 years and 41.6% 5 - &lt;15 years. Despite these initiations, the number of children on ART only grew by 97 in 2018, owing to programme losses. In 2018, 924 children (12.1%) aged out, 35 (0.5%) died and 983 (12.9%) were lost to follow-up (LTFU), the latter having increased from 10.7% in 2017. Of children who aged out of the paediatric ART programme, 56.3% remained in care at the same facility. Conclusion. Early in the SA ART roll-out, many children were found to be HIV infected and started on ART. This number started to slow in 2013, after which the growth rate of the paediatric HIV programme also began to slow. Scale-up of methods for identifying older children with HIV is needed. While ageing out of the paediatric programme is a consideration, the number of children LTFU remains unacceptably high. Further interrogation of barriers to paediatric retention is needed to help realise the Joint United Nations Programme on HIV and AIDS (UNAIDS) 90:90:90 goals for children in SA.

Challenges of antiretroviral therapy among children in Free State Province, South Africa

Background/Aim: Antiretroviral therapy (ART) is an important intervention for survival among children in Sub Saharan Africa where HIV infection rates are comparatively high. Only few studies have explored issues relating to paediatric ART initiation and maintenance. This study was conducted to explore the perceptions and experiences of trained professional nurses regarding paediatric ART. Methods: Six focus group discussions (FGDs) were conducted among trained professional nurses in selected health facilities in Free State Province, South Africa. Verbatim transcripts were analysed with a thematic approach. Results: The participants of this study reported counselling as an important component of paediatric ART in health facilities. The problem of non-disclosure, migration, incomplete records from referral health facilities, inadequate health workforce and difficulty in record keeping were cited as barriers against paediatric ART. Conclusion: This study showed that initiation and adherence to antiretroviral therapy among eligible children faces a significant challenge.

Time to switching to second-line antiretroviral therapy and its predictors among HIV/AIDS infected children, Northern Ethiopia, 2020

Background: With expanding access to pediatric antiretroviral therapy, a growing amount of patients in the developing world has switched to second-line therapy, and some requiring third-line medications. A delay in switch increases mortality and risk of developing opportunistic infections. There remain limited and often conflicting estimates on the use of second-line ART in children. Thus, this study intended to determine the incidence and predictors of switching to second-line antiretroviral therapy among children. Methods: Retrospective follow up study was conducted. Single population proportion formula was used to estimate the sample size and all charts were taken for review. Data were collected by extraction tool; entered using Epi-data manager; cleaned and analyzed by Stata V-14. Kaplan-Meier curve, log-rank test, life table, and crude hazard ratios were used for data description and adjusted hazard ratios and p-value for analysis by Cox proportional hazard regression. Any variable at P≤0.25 in the bi-variable analysis was taken to multivariate analysis and significance was declared at P≤0.05. Data were presented using texts, tables, and figures. Results: An overall 424 charts were incorporated for analysis. The total person-time observation was 11686.1 child-months with the incidence switch rate of 5.6 (95% CI 4.36-7.09) per 1000 child-months of observation. Being orphaned [AHR=2.36; 95%CI: 1.10-5.07], suboptimal ART adherence [AHR= 2.10; 95% CI: 1.12-3.92], drug toxicity [AHR= 7.05; 95% CI: 3.61-13.75], advanced recent WHO stage [AHR=2.75; 95%CI: 1.05-7.15], and initiating ART with TB co-infection [AHR=3.08; 95%CI: 1.26-7.51] were significantly associated with switch to second-line ART regimen. Moreover, long duration of ART follow up [AHR=0.75; 95% CI: 0.71-0.81] was found to be protective against switching. Conclusion and recommendation: A remarkable delay in switching to second-line ART drugs was observed. Having sub-optimal adherence, baseline TB infection, advanced WHO stage on follow-up, ART toxicity, being an orphan, and duration of follow up were independent predictors of switching. Hence, it is better to give priority for strengthening the focused evaluation of tuberculosis co-infection and treatment failure with continuous adherence monitoring. Further research is also needed to evaluate the effect of drug resistance.

Time to First-Line Antiretroviral Treatment Failure and Its Predictors among HIV-Positive Children in Shashemene Town Health Facilities, Oromia Region, Ethiopia, 2019.

With expanding pediatric antiretroviral therapy access, children will begin to experience treatment failure and require second-line therapy. In resource-limited settings, treatment failure is often diagnosed based on the clinical or immunological criteria which occur way after the occurrence of virological failure. Previous limited studies have evaluated immunological and clinical failure without considering virological failure in Ethiopia. The aim of this study was to investigate time to first-line antiretroviral treatment failure and its predictors in Shashamene town health facilities with a focus on virological criteria. Methods. A retrospective cohort study was conducted in three health facilities of Shashamene town, Oromia Regional State, from March 1 to 26, 2019. Children aged less than 15 years living with HIV/AIDS that were enrolled on ART between January 1, 2011, and December 30, 2015, in Shashamene town health facilities were the study population. Data were extracted using a checklist, entered into EpiData version 3.1, and exported to SPSS version 20 for data analysis. Cox proportional hazard regression was used to determine the predictors of time to first-line treatment failure. Result. The median survival time to virological failure was 30 months with IQR of 24.42 to 44.25. Baseline WHO stages 3 and 4 with AHR = 5.69 (95% CI: 2.07–15.66) and NVP-based NNRT at initial treatment with AHR = 2.72 (1.13–6.54) were the independent predictors of time to treatment failure. Conclusion. The median survival time of first-line antiretroviral treatment failure was moderate in the study area as compared to other studies. The incidence density of treatment failure in this study was low as compared to other studies. The finding also demonstrated that children treated with nevirapine-based nonnucleoside reverse transcriptase inhibitors at initial and advanced WHO clinical stages at baseline were at higher risk of treatment failure.

Three vs Four Dose Schedule of Double Strength Recombinant Hepatitis-B Vaccine in HIV-infected Children: A Randomized Controlled Trial

To compare seroprotection rates and the anti-HBs titers following primary immunization with double strength (20 µg) recombinant hepatitis B virus (rHBV) vaccine administered intramuscularly (IM) in a 3-dose (0, 1 and 6 months) vs 4-dose (0, 1, 2 and 6 months) schedule in HIV-infected children receiving antiretroviral therapy (ART). An accelerated 3-dose schedule (0, 1, 2 months) within the 4-dose group was also compared. Randomized controlled trial. Pediatric ART clinic of a tertiary hospital in Delhi from November, 2017 to April, 2019. Fifty (25 per group) HIV-infected children aged 18 months - 12 years receiving ART for at least 6 months who had not received any prior dose of HBV vaccine, and were anti-HBs negative. Group 1 received 20 µg of rHBV vaccine IM (in deltoid muscle) at 0, 1, and 6 months, and group 2 received 20 µg the same vaccine at 0, 1, 2 and 6 months. Anti-HBs titers and proportion of responders in 3-dose vs 4-dose group at seventh and twelfth month and at third month after an accelerated 3-dose schedule. Median (IQR) anti-HBs titers at the seventh month were significantly higher in group 2 [225.7 (151-300) IU/L] compared to group 1 [138.2 (35.2-250) IU/L], but were comparable at the 12th month. Seroprotection rates were comparable between group 2 and group 1 at 7th month (96% vs 80%; P=0.19) and 12th month (96% vs 88%; P=0.61). The proportion of good responders were also comparable between the groups at 7th month and 12th month (both P=0.29). Accelerated 3-dose schedule achieved comparable anti-HBs titers [179.9 (130.6-250) IU/L] and seroprotection rate (92%) one month after completion of schedule to the standard 3-dose + schedule. A 3-dose double strength recombinant HBV vaccine schedule offers comparable seroprotection to 4-dose schedule for HIV-infected children receiving ART.