Pediatric Antiretroviral Treatment Research Articles

Attrition Rates in HIV Viral Load Monitoring and Factors Associated With Overdue Testing Among Children Within South Africa's Antiretroviral Treatment Program: Retrospective Descriptive Analysis.

Numerous studies in South Africa have reported low HIV viral load (VL) suppression and high attrition rates within the pediatric HIV treatment program. Using routine laboratory data, we evaluated HIV VL monitoring, including mobility and overdue VL (OVL) testing, within 5 priority districts in South Africa. We performed a retrospective descriptive analysis of National Health Laboratory Service (NHLS) data for children and adolescents aged 1-15 years having undergone HIV VL testing between May 1, 2019, and April 30, 2020, from 152 facilities within the City of Johannesburg, City of Tshwane, eThekwini, uMgungundlovu, and Zululand. HIV VL test-level data were deduplicated to patient-level data using the NHLS CDW (Corporate Data Warehouse) probabilistic record-linking algorithm and then further manually deduplicated. An OVL was defined as no subsequent VL determined within 18 months of the last test. Variables associated with the last VL test, including age, sex, VL findings, district type, and facility type, are described. A multivariate logistic regression analysis was performed to identify variables associated with an OVL test. Among 21,338 children and adolescents aged 1-15 years who had an HIV VL test, 72.70% (n=15,512) had a follow-up VL test within 18 months. Furthermore, 13.33% (n=2194) of them were followed up at a different facility, of whom 3.79% (n=624) were in a different district and 1.71% (n=281) were in a different province. Among patients with a VL of ≥1000 RNA copies/mL of plasma, the median time to subsequent testing was 6 (IQR 4-10) months. The younger the age of the patient, the greater the proportion with an OVL, ranging from a peak of 52% among 1-year-olds to a trough of 21% among 14-year-olds. On multivariate analysis, 2 consecutive HIV VL findings of ≥1000 RNA copies/mL of plasma were associated with an increased adjusted odds ratio (AOR) of having an OVL (AOR 2.07, 95% CI 1.71-2.51). Conversely, patients examined at a hospital (AOR 0.86, 95% CI 0.77-0.96), those with ≥2 previous tests (AOR 0.78, 95% CI 0.70-0.86), those examined in a rural district (AOR 0.63, 95% CI 0.54-0.73), and older age groups of 5-9 years (AOR 0.56, 95% CI 0.47-0.65) and 10-14 years (AOR 0.51, 95% CI 0.44-0.59) compared to 1-4 years were associated with a significantly decreased odds of having an OVL test. Considerable attrition occurs within South Africa's pediatric HIV treatment program, with over one-fourth of children having an OVL test 18 months subsequent to their previous test. In particular, younger children and those with virological failure were found to be at increased risk of having an OVL test. Improved HIV VL monitoring is essential for improving outcomes within South Africa's pediatric antiretroviral treatment program.

Availability and stock-outs of paediatric antiretroviral treatment formulations at health facilities in Kenya and Uganda.

The large number of deaths among children with HIV is driven by poor antiretroviral treatment (ART) coverage among this cohort. The aim of the study was to assess the availability and stock-outs of paediatric and adult ART formulations in Kenya and Uganda across various regions and types of health facilities. A survey on availability and stock-outs of paediatric ART at health facilities was adapted from the standardized Health Action International-WHO Medicine Availability Monitoring Tool. All preferred and limited-use formulations, and three phased-out formulations according to the 2021 WHO optimal formulary list were included in the survey, as well as a selection of adult ART formulations suitable for older children, adolescents, and adults. Availability data were collected in June-July 2022 and stock-out data were obtained over the previous year from randomly selected public and private-not-for-profit (PNFP) facilities registered to dispense paediatric ART across six districts per country. All data were analysed descriptively. In total, 144 health facilities were included (72 per country); 110 were public and 34 PNFP facilities. Overall availabilities of preferred paediatric ART formulations were 52.2% and 63.5% in Kenya and Uganda, respectively, with dolutegravir (DTG) 10 mg dispersible tablets being available in 70.2% and 77.4% of facilities, respectively, and abacavir/lamivudine dispersible tablets in 89.8% and 98.2% of facilities. Of note, availability of both formulations was low (37.5% and 62.5%, respectively) in Kenyan PNFP facilities. Overall availabilities of paediatric limited-use products were 1.1% in Kenya and 1.9% in Uganda. At least one stock-out of a preferred paediatric ART formulation was reported in 40.0% of Kenyan and 74.7% of Ugandan facilities. Nevirapine solution stock-outs were reported in 43.1% of Ugandan facilities, while alternative formulations for postnatal HIV prophylaxis were not available. Recommended DTG-based first-line ART for children across all ages was reasonably available at health facilities in Kenya and Uganda, with the exception of Kenyan PNFP facilities. Availability of paediatric ART formulations on the limited-use list was extremely low across both countries. Stock-outs were reported regularly, with the high number of reported stock-outs of neonatal ART formulations in Uganda being most concerning.

High prevalence of impaired glucose metabolism among children and adolescents living with HIV in Ghana.

Antiretroviral therapy (ART)-associated metabolic abnormalities, including impairment of glucose metabolism, are prevalent in adults living with HIV. However, the prevalence and pathogenesis of impaired glucose metabolism in children and adolescents living with HIV, particularly in sub-Saharan Africa, are not well characterized. We investigated the prevalence of impaired glucose metabolism among children and adolescents living with perinatally infected HIV in Ghana. In this multicentre, cross-sectional study, we recruited participants from 10 paediatric antiretroviral treatment clinics from January to June 2022 in 10 facilities in Greater Accra and Eastern regions of Ghana. We determined impaired glucose metabolism in the study sample by assessing fasting blood sugar (FBS), insulin resistance as defined by the homeostatic model assessment for insulin resistance (HOMA-IR) index and glycated haemoglobin (HbA1c) levels. The prevalence of impaired glucose metabolism using each criterion was stratified by age and sex. The phenotypic correlates of glucose metabolism markers were also assessed among age, sex, body mass index (BMI) and waist-to-hip ratio (WHR). We analysed data from 393 children and adolescents living with HIV aged 6-18 years. A little over half (205/393 or 52.25%) of the children were female. The mean age of the participants was 11.60 years (SD = 3.50), with 122/393 (31.00%) aged 6-9 years, 207/393 (52.67%) aged 10-15 years, and 62/393 (15.78%) aged 16-18 years. The prevalence rates of glucose impairment in the study population were 15.52% [95% confidence interval (CI): 12.26-19.45], 22.39% (95% CI: 18.54-26.78), and 26.21% (95% CI: 22.10-30.78) using HbA1c, HOMA-IR, and FBS criteria, respectively. Impaired glucose metabolism detected by FBS and HOMA-IR was higher in the older age group, whereas the prevalence of abnormal HbA1c levels was highest among the youngest age group. Age and BMI were positively associated with FBS and HOMA-IR (p < 0.001). However, there was negative correlation of WHR with HOMA-IR (p < 0.01) and HbA1c (p = 0.01). The high prevalence of impaired glucose metabolism observed among the children and adolescents living with HIV in sub-Saharan Africa is of concern as this could contribute to the development of metabolic syndrome in adulthood.

Triangulation of Routine Antenatal HIV Prevalence Data and Adjusted HIV Estimates in Mozambique.

Routine health system data are central to monitoring HIV trends. In Mozambique, the reported number of women receiving antenatal care (ANC) and antiretroviral therapy for prevention of mother-to-child transmission (PMTCT) has exceeded the Spectrum-estimated number of pregnant women since 2017. In some provinces, reported HIV prevalence in pregnant women has declined faster than epidemiologically plausible. We hypothesized that these issues are linked and caused by programmatic overenumeration of HIV-negative pregnant women at ANC. We triangulated program-reported ANC client numbers with survey-based fertility estimates and facility birth data adjusted for the proportion of facility births. We used survey-reported ANC attendance to produce adjusted time series of HIV prevalence in pregnant women, adjusted for hypothesized program double counting. We calibrated the Spectrum HIV estimation models to adjusted HIV prevalence data to produce adjusted adult and pediatric HIV estimates. ANC client numbers were not consistent with facility birth data or modeled population estimates indicating ANC data quality issues in all provinces. Adjusted provincial ANC HIV prevalence in 2021 was median 45% [interquartile range 35%-52% or 2.3 percentage points (interquartile range 2.5-3.5)] higher than reported HIV prevalence. In 2021, calibrating to adjusted antenatal HIV prevalence lowered PMTCT coverage to less than 100% in most provinces and increased the modeled number of new child infections by 35%. The adjusted results better reconciled adult and pediatric antiretroviral treatment coverage and antenatal HIV prevalence with regional fertility estimates. Adjusting HIV prevalence in pregnant women using nationally representative household survey data on ANC attendance produced estimates more consistent with surveillance data. The number of children living with HIV in Mozambique has been substantially underestimated because of biased routine ANC prevalence. Renewed focus on HIV surveillance among pregnant women would improve PMTCT coverage and pediatric HIV estimates.

Rates of confirmatory HIV testing, linkage to HIV services, and rapid initiation of antiretroviral treatment among newly diagnosed children living with HIV in Ethiopia: perspectives from caregivers and healthcare workers

BackgroundSuccessful linkage to HIV services and initiation of antiretroviral treatment (ART) for children living with HIV (CLHIV) is critical to improve pediatric ART coverage. We aimed to assess confirmatory testing, linkage, and rapid ART initiation among newly diagnosed CLHIV in Ethiopia from the perspectives of caregivers and healthcare workers (HCWs).MethodsWe conducted standardized surveys with HCWs and caregivers of children 2–14 years who were diagnosed with HIV but not yet on ART who had been identified during a cross-sectional study in Ethiopia from May 2017–March 2018. Eight health facilities based on their HIV caseload and testing volume and 21 extension sites were included. Forty-one children, 34 care givers and 40 healthcare workers were included in this study. Three months after study enrollment, caregivers were surveyed about timing and experiences with HIV service enrollment, confirmatory testing, and ART initiation. Data collected from HCWs included perceptions of confirmatory testing in CLHIV before ART initiation. SPSS was used to conduct descriptive statistics.ResultsThe majority of the 41 CLHIV were enrolled to HIV services (n = 34, 83%) and initiated ART by three months (n = 32, 94%). Median time from diagnosis to ART initiation was 12 days (interquartile range 5–18). Five children died before the follow-up interview. Confirmatory HIV testing was conducted in 34 children and found no discordant results; the majority (n = 23, 68%) received it within one week of HIV diagnosis. Almost all HCWs (n = 39/40, 98%) and caregivers (n = 31/34, 91%) felt better/the same about test results after conducting confirmatory testing.ConclusionOpportunities remain to strengthen linkage for newly diagnosed CLHIV in Ethiopia through intensifying early follow-up to ensure prompt confirmatory testing and rapid ART initiation. Additional services could help caregivers with decision-making around treatment initiation for their children.

First line antiretroviral treatment failure and its association with drug substitution and sex among children in Ethiopia: systematic review and meta-analysis

Antiretroviral Treatment (ART) has significantly decreased HIV-related morbidity and mortality among children despite the issue of drug resistance and subsequent treatment failure appearing as a challenge. Different studies have been conducted in Ethiopia regarding the prevalence of first-line ART failure among children but the magnitudes of these studies were inconsistent and had great variability. This review aimed to estimate the pooled prevalence of first line ART failure among children and its association with drug substitution and sex of children among first-line ART users in Ethiopia. The review was conducted using both published and unpublished studies until September 2020 in Ethiopia. MEDLINE, PubMed, Hinari, Web of Science, Google Scholar, Africa journal online (AJOL), Open gray literature, and online repository articles were searched. The quality of individual studies was assessed by Joanna Briggs Institute's (JBI) critical appraisal checklist. The statistical analysis was done by STATA-14 software and a random effect model was used. Heterogeneity was assessed using forest plot Cochrane Q–test and I-squared statistic. Publication bias was checked by using a funnel plot and Egger’s and Begg’s statistical tests. The interpretation was made by an odds ratio and with their respective 95% confidence intervals. The heterogeneity rate was 90% and Begg’s and Egger’s for publication bias were insignificant with p-values of 0.89 and 0.11 respectively. The pooled prevalence of pediatric first line ART failure in Ethiopia was 14.98% (95% CI 11.74, 18.21). Subgroup analysis showed that the highest failure rate was virological (9.13%). Female children had 1.4 times more risk of first-line ART failure (OR = 1.42; 95% CI 1.08, 1.85). First-line ART failure among children in Ethiopia is considerably high. Being female increases the likelihood of facing first line ART failure. More attention should be given to female children.

Optimised paediatric antiretroviral treatment to achieve the 95-95-95 goals.

While the progress towards reaching the UNAIDS 95-95-95 targets in South African adults seems promising, the progress in the paediatric population is lagging far behind; only 79% percent of children living with HIV know their status. Of these, only 47% are on treatment, and a mere 34% of those are virally suppressed. Thus, virological suppression has been attained in only 13% of children living with HIV in South Africa. Multiple factors contribute to the high treatment failure rate, one of them being a lack of paediatric-friendly antiretroviral treatment (ART) formulations. For example, the Lopinavir/ritonavir syrup, which is the current mainstay of ART for young children, has an extremely unpleasant taste, contributing to the poor tolerability and lack of adherence by children using the formulation. Furthermore, the lack of appropriate formulations limits the optimisation of regimens, especially for young children and those who cannot swallow tablets. Switching from syrups to dispersible tablets will improve ease of administration and adherence and result in cost-saving. Despite the approval of simplified paediatric-friendly formulations internationally, including other sub-Saharan African countries, unnecessary delays are experienced in South Africa. Clinician groups and community organisations must speak up and demand that approvals be expedited to ensure the delivery of life-changing and life-saving formulations to our patients as a matter of urgency.

Virological Failure and Associated Risk Factors among HIV/AIDS Pediatric Patients at the ART Clinic of Jimma university Medical Center, Southwest Ethiopia

Background: Pediatric antiretroviral treatment failure is an under-recognized issue that receives inadequate attention in the field of pediatrics and within HIV treatment programs. Despite the reduction in morbidity and mortality, a considerable proportion of patients fail to achieve a sustained virologic response to therapy. Thus virological failure is an increasing concern globally. Objective: This study aimed to assess the virological failure and associated risk factors among HIV/AIDS pediatric patients at Antiretroviral Treatment (ART) follow up clinic of Jimma University Medical Center, southwest Ethiopia. Methods: An institution based cross-sectional study was conducted at the ART follow-up clinic of Jimma University Medical Center. A structured English version checklist was developed and used for data extraction from patients’ charts from April -May 2019. Then the data was coded and entered using epi data 4.2 and exported to statistical package for social science (SPSS version 22) for analysis. Descriptive analysis was conducted for categorical as well as continuous variables. Multivariable logistic regression was performed in a backward, step-wise manner until a best-fit model was found. Results: Of 140 HIV/AIDS pediatric patients enrolled in this study, 72(51.4%) were male and the mean age was 9.7±3.3 Years. ABC-3TC-NVP was the commonly used ART medication in this population, which was 37.1% followed by AZT-3TC-EFV(32.1%). The mean duration of antiretroviral treatment (ART) follow-up was 63.8±29.4 months. Among the study population, 11.0% of them had virological failure. Weight at ART initiation [OR=1.104, 95 CI% [1.013-1.203], p=0.024] and WHO clinical stage 3 [AOR=0.325, 95CI, 0.107-0.991,P=0.048] were the significant risk factors for the virological failure. Conclusion: A significant proportion of HIV/AIDS pediatric patients had virological failure. Weight at ART initiation and patients having WHO clinical stage 3 were risk factors associated with virological failure in this study. Governmental and non-governmental concerned bodies should invest their effort to devise strategies for the achievement of HIV/AIDS treatment targets.

Understanding acceptance of and adherence to a new formulation of paediatric antiretroviral treatment in the form of pellets (LPV/r)-A realist evaluation.

BackgroundImproving access to paediatric HIV treatment requires large-scale antiretroviral treatment programmes and medication adapted to infants and children’s needs. The World Health Organisation recommends lopinavir/ritonavir plus two nucleoside reverse transcriptase inhibitors as first-line treatment for all HIV-infected children younger than three years, usually given as a syrup. A pellet formulation (i.e. tiny cylinders of compressed medication put in capsules) was developed to overcome the syrup formulation’s disadvantages such as bitterness, toxicity and cold storage. This study assessed multi-level factors influencing caregivers’ acceptance of and adherence to lopinavir/ritonavir pellets as well as their underlying mechanisms.MethodsA realist evaluation (a theory-driven evaluation method considering the social context and mechanisms of change), embedded in a clinical trial was carried out in three hospital settings in Kenya. Data were collected through document review, observations (n = 34) in home and clinic settings and semi-structured interviews (n = 44) with caregivers and providers. Data analysis was based on realist principles.ResultsHigh levels of treatment initiation and adherence were observed. Taste masking, neutral packaging and easy storage made the new formulation highly acceptable. Caregivers developed individual strategies to deliver the treatment, particularly to overcome specific problems e.g. in case of just-weaned babies or food shortage. A refined program theory emerged from the triangulated findings showing that ease of administration combined with increased self-efficacy and competences of the caregivers, and effective provider support contributed to high levels of adherence.ConclusionsFormulating combined antiretroviral treatment in the form of pellets is clearly a more acceptable solution for infants and children and their caregivers compared to the syrup. Further research in non-trial settings may shed light on factors related to providers, services and the health system that contribute to better adherence of such formulations.

HIV positive status disclosure and associated factor among HIV infected children in pediatric ART clinics in Gondar town public health facilities, North West Ethiopia, 2018

BackgroundDue to the increasing availability of antiretroviral treatment, HIV infected children are living longer which points out the necessity of disclosure. And which is important to support the uptake and adherence to treatment. Disclosure is an important measure to prevent secondary transmission when children are sexually active. ObjectiveThe aim of this study was to determine the prevalence of HIV positive status disclosure and associated factors among human immune virus-infected children in pediatric antiretroviral treatment clinics in Gondar town public health facilities. MethodAn institution based cross-sectional study was conducted among 449 primary caregivers of children aged 6–15years in regular follow-up at pediatric ART clinics in Gondar town public health facilities between March 3, 2018, to April 25, 2018. All subjects in the study area were included in the study. Data was collected in 5 pediatric ART clinics in Gondar town by structured questionnaires through face to face interview and supplemented by chart review to obtain some clinical factors. The variables which have an association with disclosure were identified on the basis of AOR, with 95%CI and p-value <0. 05. Model fitness was checked using Hosmer and Lemeshow goodness of fit test. ResultOut of 449 participants, 418 were interviewed with response rate of 93%. The prevalence of HIV positive status disclosure found to be 44%. Age of child >10years [AOR=5.88, (95% CI: 3.52, 9.81)], duration on ART [AOR=2.67 (95% CI: 1.59, 4.51)], place of follow-up [AOR=2.23 (95% CI: 1.27, 5.01)] and educational status of caregiver [AOR=3.00 (95% CI: 1.62, 5.56)] were identified variables. ConclusionThe prevalence of disclosure found to be low. Therefore appropriate measure should be taken to promote disclosure.

Mortality among pediatric patients on HIV treatment in sub-Saharan African countries: a systematic review and meta-analysis

BackgroundDespite substantial improvements in accessibility of Anti-Retroviral Treatment (ART), death of children on ART remains a prevailing challenge in sub-Saharan African (SSA) countries. However, the pooled magnitude of mortality at different ART follow-up periods remains unknown for the region. We estimated the pooled proportion of all-cause mortality for pediatric patients receiving first-line ART at 3, 6, 12, and 24 months follow-up period in SSA.MethodsWe searched for relevant articles published between January 2014 and June 2018 on PubMed, Hinari and Google scholar databases. We searched for additional articles from reference lists and 2014–2018 abstracts archived by the Conference on Retroviruses and Opportunistic Infections (CROI) and the International AIDS Society Conference on HIV Science (IAS).ResultsWe reviewed 29 articles reporting mortality among pediatric ART patients at different follow-up periods in countries from 2001 to 2016. Among the 51,619 pediatric ART patients in these cohorts, studies reported 4061 (7.9%) all-cause cumulative death. The cumulative pooled proportion of mortality at 3, 6, 12 and 24 months of ART were 3% (95% CI: 3.0–4.0), 5% (95% CI: 4.0–6.0), 6% (95% CI: 5.0–7.0) and 7% (95% CI: 6.0–8.0), respectively.ConclusionsIn SSA, significant proportion of mortality among children occurs in the first 3–6 months of ART initiation. Western Africa has a little higher estimate of mortality among pediatric ART patients at 6 and 12 months of follow-up. Strategies to prevent early mortality including thorough screening and management of opportunistic infections before ART initiation are needed.

Viral Suppression in a Nationwide Sample of HIV-Infected Children on Antiretroviral Therapy in Rwanda.

Rwanda has made significant progress in expanding pediatric antiretroviral treatment coverage. This was a nationwide, cross-sectional study of pediatric HIV suppression rates. Of 292 children on antiretroviral treatment ≥12 months, 68.8% achieved viral suppression < 40 copies/ml, respectively. Rwanda achieved good pediatric viral suppression rates, comparable to those from other resource-limited settings, yet more efforts are needed to achieve the UNAIDS 90-90-90 target.

Performance of point-of-care birth HIV testing in primary health care clinics: An observational cohort study.

BackgroundFailure to timely diagnose HIV in infants is a major barrier for scaling-up paediatric antiretroviral treatment (ART). WHO recommends birth testing for earlier diagnosis and to improve test coverage, but current diagnosis takes 2–3 weeks to complete, thereby limiting the ability of care givers to provide follow-on care, especially in low-resource settings. We evaluated the benefit of implementing rapid diagnosis of HIV at birth in primary health care maternity wards in Mozambique.Methods and findingsInfants born to HIV-infected mothers delivering consecutively at eight primary health care clinics were tested within 24 hours of delivery using on-site POC (Alere q HIV1/2 Detect) and standard laboratory (Roche COBAS AmpliPrep/TaqMan HIV-1 qualitative assay v2.0) testing. Infants were also tested at 4–6 weeks of age with both assays. Of 2,350 HIV-exposed infants enrolled in this implementation research study, 33 tested HIV-positive at birth on both assays. Sensitivity and specificity of POC testing compared with laboratory testing at birth were 100% (95% CI 89·4–100·0) and 100% (95% CI 99·8–100·0), respectively. At 4–6 weeks of age, 61 infants were identified as HIV-positive; of these 29 (47·5%) had a positive test at birth. Testing at both birth and 4–6 weeks identified 71 HIV-positive infants compared with 61 infants by testing at 4–6 weeks alone, a 16% increase. Two infants tested positive at birth but tested HIV-negative during follow-up.ConclusionsAdding POC birth testing to the 4–6 week screen may increase access to HIV diagnosis and expedite ART initiation in primary health care settings within low resource settings. Guidance on appropriate confirmatory HIV testing algorithms for birth testing is needed.

Provision of antiretroviral therapy for children in Nelson Mandela Bay: Health care professionals’ challenges

BackgroundThe human immunodeficiency virus and/or acquired immune deficiency syndrome (HIV/AIDS) pandemic continues to increase in prevalence worldwide, particularly in South Africa, and includes the often overlooked paediatric population. The provision of paediatric antiretroviral treatment (ART) is as essential for children as for adults, and has numerous obstacles, not least of which is lack of decentralisation of facilities to provide essential treatment. Optimising ART, care and support for HIV-positive children, and their caregivers, at public sector primary health care (PHC) clinics is crucial to improve morbidity and mortality rates in children.AimTo explore the experiences of health care professionals regarding the provision of ART for children at PHC clinics.SettingThe study was conducted in six PHC clinics in Nelson Mandela Bay Health District, Eastern Cape, South Africa.MethodologyThe researchers used a qualitative, explorative, descriptive and contextual research design with in-depth interviews. We used non-probability purposive sampling. Data collected were thematically analysed using Creswell’s data analysis spiral. We used Lincoln and Guba’s model to ensure trustworthiness. Ethical standards were applied.ResultsHealth care professionals experienced numerous challenges, such as lack of resources, need for training, mentoring and debriefing, all related to providing decentralised ART for HIV-positive children at the PHC level.ConclusionCapacitation of the health care system, integration of services, competent management and visionary leadership to invoke a collaborative interdisciplinary team approach is required to ensure that HIV is treated as a chronic disease at the PHC clinic level.

Human Immunodeficiency Virus Type 1 in the Premature Infant

Prematurity and low birthweight are seen frequently in infants with human immunodeficiency virus (HIV) type 1 infection, adding significant comorbidities and complicating the approach to treatment. HIV disease progression accelerates in the setting of an immature immune system. Recent cases have underscored the unique opportunity to not only limit progression, but also limit the establishment of HIV reservoirs that impede viral clearance by starting antiretroviral treatment (ART) early in the neonatal period. Although pediatric ART alternatives are increasing, there are still only few available agents for the treatment of neonates, especially premature and low-birthweight infants. Zidovudine is the only agent for which there is sufficient experience in premature infants, while being an intravenous alternative for infants in whom enteric administration is not possible. Nevirapine has been studied for prophylactic dosing in preterm infants. It is imperative that resources are devoted to the study of the safety and efficacy of ARTs for use during the neonatal period.

Characteristics of Treatment-experienced HIV-infected African Children and Adolescents Initiating Darunavir and/or Etravirine-based Antiretroviral Treatment.

Data are limited on the selection and sequencing of second-line and third-line pediatric antiretroviral treatment (ART) in resource-limited settings. This study aimed to evaluate characteristics of African pediatric patients initiated on darunavir (DRV) and/or etravirine (ETR) through a specific drug donation program. This was a cross-sectional study of baseline immunologic, virologic and demographic characteristics of children and adolescents initiating DRV-based and/or ETR-based ART. Descriptive statistics were used. Study enrolled 48 patients (45.8% women; median age = 15 years [interquartile range 17.7-10.3]) at 9 clinical sites in Zambia, Swaziland, Kenya and Lesotho. The majority (87.5%; n = 42) had received ≥2 prior ART regimens; most (81.2%) had received lopinavir/ritonavir-based ART before switch. All patients had detectable HIV RNA (median = 56,653 copies/mL). Forty seven patients (98.9%) had HIV genotype results: 41 (87.2%) had ≥1 nucleos(t)ide reverse transcriptase inhibitor (NRTI)-resistance mutation (RM), predominantly M184V (76.6%; n = 36); 31 (65.9%) had ≥1 non-NRTI-RM, including 27 (57.4%) with ≥1 ETR-RM; 30 (63.8%) had ≥3 protease inhibitor RM, including 20 (42.6%) with ≥1 DRV-RM. For new ART regimens, DRV and raltegravir were most frequently prescribed (83.3%; n = 40 on DRV and raltegravir, each). Eighteen patients (37.5%) were initiated on the NRTI-sparing ART. In our study, a significant proportion of treatment-experienced African children and adolescents had one or more DRV-RM and ETR-RM. For the new regimen, more than a third of pediatric patients failing second-line ART were prescribed NRTI-sparing regimens. Better understanding of the current approaches to pediatric ART sequencing in resource-limited settings is needed.

Understanding the Influence of Socioeconomic Environment on Paediatric Antiretroviral Treatment Coverage: Towards Closing Treatment Gaps in Sub-Saharan Africa.

Many sub-Saharan African countries have massively scaled-up their antiretroviral treatment (ART) programmes, but many national programmes still show large gaps in paediatric ART coverage making it challenging to reduce AIDS-related deaths among HIV-infected children. We sought to identify enablers of paediatric ART coverage in Africa by examining the relationship between paediatric ART coverage and socioeconomic parameters measured at the population level so as to accelerate reaching the 90-90-90 targets. Ecological analyses of paediatric ART coverage and socioeconomic indicators were performed. The data were obtained from the United Nations agencies and Forum for a new World Governance reports for the 21 Global Plan priority countries in Africa with highest burden of mother-to-child HIV transmission. Spearman's correlation and median regression were utilized to explore possible enablers of paediatric ART coverage. Factors associated with paediatric ART coverage included adult literacy (r=0.6, p=0.004), effective governance (r=0.6, p=0.003), virology testing by 2 months of age (r=0.9, p=0.001), density of healthcare workers per 10,000 population (r=0.6, p=0.007), and government expenditure on health (r=0.5, p=0.046). The paediatric ART coverage had a significant inverse relationship with the national mother-to-child transmission (MTCT) rate (r=-0.9, p<0.001) and gender inequality index (r=-0.6, p=0.006). Paediatric ART coverage had no relationship with poverty and HIV stigma indices. Low paediatric ART coverage continues to hamper progress towards eliminating AIDS-related deaths in HIV-infected children. Achieving this requires full commitment to a broad range of socioeconomic development goals.

Understanding the acceptability and adherence to paediatric antiretroviral treatment in the new formulation of pellets (LPV/r): the protocol of a realist evaluation

BackgroundImproving access to paediatric HIV treatment requires both large-scale treatment programmes and medication that is adapted to infants and children's needs. The WHO recommends lopinavir/ritonavir as first-line antiretroviral therapy for...

Multicentre analysis of second-line antiretroviral treatment in HIV-infected children: adolescents at high risk of failure.

Introduction: The number of HIV-infected children and adolescents requiring second-line antiretroviral treatment (ART) is increasing in low- and middle-income countries (LMIC). However, the effectiveness of paediatric second-line ART and potential risk factors for virologic failure are poorly characterized. We performed an aggregate analysis of second-line ART outcomes for children and assessed the need for paediatric third-line ART. Methods: We performed a multicentre analysis by systematically reviewing the literature to identify cohorts of children and adolescents receiving second-line ART in LMIC, contacting the corresponding study groups and including patient-level data on virologic and clinical outcomes. Kaplan–Meier survival estimates and Cox proportional hazard models were used to describe cumulative rates and predictors of virologic failure. Virologic failure was defined as two consecutive viral load measurements >1000 copies/ml after at least six months of second-line treatment. Results: We included 12 cohorts representing 928 children on second-line protease inhibitor (PI)-based ART in 14 countries in Asia and sub-Saharan Africa. After 24 months, 16.4% (95% confidence interval (CI): 13.9–19.4) of children experienced virologic failure. Adolescents (10–18 years) had failure rates of 14.5 (95% CI 11.9–17.6) per 100 person-years compared to 4.5 (95% CI 3.4–5.8) for younger children (3–9 years). Risk factors for virologic failure were adolescence (adjusted hazard ratio [aHR] 3.93, p < 0.001) and short duration of first-line ART before treatment switch (aHR 0.64 and 0.53, p = 0.008, for 24–48 months and >48 months, respectively, compared to <24 months). Conclusions: In LMIC, paediatric PI-based second-line ART was associated with relatively low virologic failure rates. However, adolescents showed exceptionally poor virologic outcomes in LMIC, and optimizing their HIV care requires urgent attention. In addition, 16% of children and adolescents failed PI-based treatment and will require integrase inhibitors to construct salvage regimens. These drugs are currently not available in LMIC.

Survival Outcomes in a Pediatric Antiretroviral Treatment Cohort in Southern Malawi.

BackgroundPediatric uptake and outcomes in antiretroviral treatment (ART) programmes have lagged behind adult programmes. We describe outcomes from a population-based pediatric ART cohort in rural southern Malawi.MethodsData were analyzed on children who initiated ART from October/2003 –September/2011. Demographics and diagnoses were described and survival analyses conducted to assess the impact of age, presenting features at enrolment, and drug selection.ResultsThe cohort consisted of 2203 children <15 years of age. Age at entry was <1 year for 219 (10%), 1–1.9 years for 343 (16%), 2–4.9 years for 584 (27%), and 5–15 years for 1057 (48%) patients. Initial clinical diagnoses of tuberculosis and wasting were documented for 409 (19%) and 523 (24%) patients, respectively. Median follow-up time was 1.5 years (range 0–8 years), with 3900 patient-years of follow-up. Over the period of observation, 134 patients (6%) died, 1324 (60%) remained in the cohort, 345 (16%) transferred out, and 387 (18%) defaulted. Infants <1 year of age accounted for 19% of deaths, with a 2.7-fold adjusted mortality hazard ratio relative to 5–15 year olds; median time to death was also shorter for infants (60 days) than older children (108 days). Survival analysis demonstrated younger age at ART initiation, more advanced HIV stage, and presence of tuberculosis to each be associated with shorter survival time. Among children <5 years, severe wasting (weight-for-height z-score </ = -3.0) was also associated with reduced survival.ConclusionsCumulative incidence of mortality was 5.2%, 7.1% and 7.7% after 1, 3, and 5 years, respectively, with disproportionate mortality in infants <1 year of age and those presenting with tuberculosis. These findings reinforce the urgent need for early diagnosis and treatment in this population, but also demonstrate that provision of pediatric care in a rural setting can yield outcomes comparable to more resourced urban settings of poor countries.