HIV-infected Children Research Articles

Genetic and non-genetic factors influencing efavirenz population pharmacokinetics among human immunodeficiency virus-1-infected children in Ethiopia.

Despite the potential for efavirenz (EFV) to be an effective alternative antiretroviral agent, its sources of wide inter- and intra-individual pharmacokinetic (PK) variability are not well-characterized in children. We investigated the effects of genetic and non-genetic factors, including demographic, treatment duration, baseline clinical, and biochemical characteristics, on the PKs of EFV through population-PK modeling. Antiretroviral therapy (ART) naïve HIV infected children, 3-16 years (n=100), were enrolled in Ethiopia and received EFV-based combination ART. EFV concentrations after the first dose and at steady-state collected over a span of 1 year were modeled using population-based methods. A one-compartment model with first-order absorption kinetics described the observed EFV data adequately. The CYP2B6*6 and ABCB1c.4036A>G genotypes were identified as major factors influencing EFV clearance. The typical estimates of oral clearance, volume of distribution, and absorption rate constant for typical 22 kg children with CYP2B6 *1/*1 and ABCB1c.4036G/G genotypes were 4.3L/h, 124 L, and 0.776/h, respectively. Clearance was reduced by 28% and 72% in CYP2B6*1/*6 and CYP2B6*6/*6 genotypes, respectively. Compared to week 1, clearance was higher from weeks 8 and 12 in CYP2B6*1/*6 and CYP2B6*1/*1 genotypes, respectively. Simulations indicated that EFV 12-h concentrations were comparable across weight bands, but more than 80% of subjects with CYP2B6*6/*6 had EFV concentrations greater than 4μg/mL. EFV PK variability among children is partly explained by body weight, treatment duration, CYP2B6*6, and ABCB1 rs3842 genotypes. Therefore, in addition to body weight, pediatric dosing of EFV should consider pharmacogenetic variability, duration of therapy, and individual treatment outcomes.

A Case Report of Achalasia in HIV-Tuberculosis Co-Infected Adolescent

Aims: To sensitize clinicians on the need to consider achalasia in HIV infected children presenting with dysphagia.
 Presentation of Case: A 14-year-old HIV-infected boy presented with 4years of difficulty and painful swallowing. It was initially to solid food and progressed to liquid diet and water. There were associated intermittent vomiting, weight loss, and recurrent fever. Examination revealed a stunted and chronically ill-looking boy, weighed 22.5Kg and measured 139cm in height, 48.3% and 86.3% of the expected for age respectively. He had generalized lymphadenopathy and whitish patches on the tongue. Initial differential diagnoses were oesophageal candidiasis and achalasia with pulmonary tuberculosis. Chest X-ray and stool gene Xpert confirmed Mycobacterium tuberculosis. The cluster of differentiation (CD) 4 count was 380 cells/ml. He had anti-Koch’s drugs and oral fluconazole for 6 months and 8 weeks respectively, and later highly active antiretroviral therapy. Despite the completion of the fluconazole, the presented symptoms got worsened and the patient could not even take his medications, and his weight dropped to 15kg. Barium swallow and upper GI endoscopy done later confirmed achalasia. He had a successfully modified Heller’s myotomy procedure after which he could eat, drink and take his medications. He was discharged and kept his regular clinic appointments with appreciable weight gain.
 Conclusion: Achalasia could occur in HIV-infected children when presented with dysphagia and therefore, a high index of suspicion is needed to make a timely diagnosis to avoid complications and death.

Prevalence and factors associated with pediatric HIV therapy failure in a tertiary hospital in Asmara, Eritrea: A 15-year retrospective cohort study.

Treatment failure (TF) in HIV infected children is a major concern in resource-constrained settings in Sub-Saharan Africa (SSA). This study investigated the prevalence, incidence, and factors associated with first-line cART failure using the virologic (plasma viral load), immunologic and clinical criteria among HIV-infected children. A retrospective cohort study of children (<18 years of age on treatment for a period of > 6 months) enrolled in the pediatric HIV/AIDs treatment program at Orotta National Pediatric Referral Hospital from January 2005 to December 2020 was conducted. Data were summarized using percentages, medians (± interquartile range (IQR)), or mean ± standard deviation (SD). Where appropriate, Pearson Chi-Squire (χ2) tests or Fishers exacts test, Kaplan-Meier (KM) estimates, and unadjusted and adjusted Cox-proportional hazard regression models were employed. Out of 724 children with at least 24 weeks' follow-up 279 experienced therapy failure (TF) making prevalence of 38.5% (95% CI 35-42.2) over a median follow-up of 72 months (IQR, 49-112 months), with a crude incidence of failure of 6.5 events per 100- person-years (95% CI 5.8-7.3). In the adjusted Cox proportional hazards model, independent factors of TF were suboptimal adherence (Adjusted Hazard Ratio (aHR) = 2.9, 95% CI 2.2-3.9, p < 0.001), cART backbone other than Zidovudine and Lamivudine (aHR = 1.6, 95% CI 1.1-2.2, p = 0.01), severe immunosuppression (aHR = 1.5, 95% CI 1-2.4, p = 0.04), wasting or weight for height z-score < -2 (aHR = 1.5, 95% CI 1.1-2.1, p = 0.02), late cART initiation calendar years (aHR = 1.15, 95% CI 1.1-1.3, p < 0.001), and older age at cART initiation (aHR = 1.01, 95% CI 1-1.02, p < 0.001). Seven in one hundred children on first-line cART are likely to develop TF every year. To address this problem, access to viral load tests, adherence support, integration nutritional care into the clinic, and research on factors associated with suboptimal adherence should be prioritized.

Doing more with less: The use of non-invasive ventilatory support in a resource-limited setting.

Bubble CPAP (bCPAP), a non-invasive ventilation modality, has emerged as an intervention that is able to reduce pneumonia-related mortality in children in low resourced settings. Our study primarily aimed to describe a cohort of children who were started on CPAP in the Medical Emergency Unit (MEU) of Red Cross War Memorial Children's Hospital 2016-2018. A retrospective review of a randomly selected sample of paper-based folders was conducted. Children started on bCPAP at MEU were eligible for inclusion. Demographic and clinical data, management, and outcomes regarding admission to PICU, need for invasive ventilation and mortality were documented. Descriptive statistical data were generated for all relevant variables. Percentages depicted frequencies of categorical data while medians with interquartile ranges (IQR) were used to summarise continuous data. Of 500 children started on bCPAP, 266 (53%) were male; their median age was 3.7 (IQR 1.7-11.3) months and 169 (34%) were moderately to severely underweight-for-age. There were 12 (2%) HIV-infected children; 403 (81%) had received appropriate immunisations for their age; and 119 (24%) were exposed to tobacco smoke at home. The five most common primary reasons for admission were acute respiratory illness, acute gastroenteritis, congestive cardiac failure, sepsis and seizures. Most children, 409 (82%), had no underlying medical condition. Most children, 411 (82%), were managed in high care areas of the general medical wards while 126 (25%) went to PICU. The median time on CPAP was 1.7 (IQR 0.9-2.8) days. The median hospitalisation time was 6 (IQR 4-9) days. Overall, 38 (8%) children required invasive ventilatory support. Overall, 12 (2%) children with a median age of 7.5 (IQR 0.7-14.5) months died, six of whom had an underlying medical condition. Seventy-five percent of children initiated on bCPAP did not require PICU admission. This form of non-invasive ventilatory support should be considered more widely in the context of limited access to paediatric intensive care units in other African settings.

Retention and Predictors of Attrition Among HIV-infected Children on Antiretroviral Therapy in Côte d'Ivoire Between 2012 and 2016.

An estimated 21,000 children 0-14 years of age were living with HIV in Côte d'Ivoire in 2020, of whom only 49% have been diagnosed and are receiving antiretroviral therapy (ART). Retention in HIV care and treatment is key to optimize clinical outcomes. We evaluated pediatric retention in select care and treatment centers (CTCs) in Côte d'Ivoire. We retrospectively reviewed medical records using 2-stage cluster sampling for children under 15 years initiated on ART between 2012 and 2016. Kaplan-Meier time-to-event analysis was done to estimate cumulative attrition rates per total person-years of observation. Cox proportional hazard regression was performed to identify factors associated with attrition. A total of 1198 patient records from 33 CTCs were reviewed. Retention at 12, 24, 36, 48 and 60 months after ART initiation was 91%, 84%, 74%, 72% and 70%, respectively. A total of 309 attrition events occurred over 3169 person-years of follow-up [266 children were lost to follow-up (LTFU), 29 transferred to another facility and 14 died]. LTFU determinants included attending a "public-private" CTC [adjusted hazard ratio (aHR) 6.05; 95% confidence interval (CI): 4.23-8.65], receiving care at a CTC without an on-site laboratory (aHR: 4.01; 95% CI: 1.70-9.46) or attending a CTC without an electronic medical record (EMR) system (aHR: 2.22; 95% CI: 1.59-3.12). In Cote d'Ivoire, patients attending a CTC that is public-private, does not have on-site laboratory or EMR system were likely to be LTFU. Decentralization of laboratory services and scaling use of EMR systems could help to improve pediatric retention.

Practical approaches to Bayesian sample size determination in non-inferiority trials with binary outcomes.

Bayesian analysis of a non-inferiority trial is advantageous in allowing direct probability statements to be made about the relative treatment difference rather than relying on an arbitrary and often poorly justified non-inferiority margin. When the primary analysis will be Bayesian, a Bayesian approach to sample size determination will often be appropriate for consistency with the analysis. We demonstrate three Bayesian approaches to choosing sample size for non-inferiority trials with binary outcomes and review their advantages and disadvantages. First, we present a predictive power approach for determining sample size using the probability that the trial will produce a convincing result in the final analysis. Next, we determine sample size by considering the expected posterior probability of non-inferiority in the trial. Finally, we demonstrate a precision-based approach. We apply these methods to a non-inferiority trial in antiretroviral therapy for treatment of HIV-infected children. A predictive power approach would be most accessible in practical settings, because it is analogous to the standard frequentist approach. Sample sizes are larger than with frequentist calculations unless an informative analysis prior is specified, because appropriate allowance is made for uncertainty in the assumed design parameters, ignored in frequentist calculations. An expected posterior probability approach will lead to a smaller sample size and is appropriate when the focus is on estimating posterior probability rather than on testing. A precision-based approach would be useful when sample size is restricted by limits on recruitment or costs, but it would be difficult to decide on sample size using this approach alone.

Dermatological manifestations during HIV infection in children in Dakar, Senegal

Background: Dermatological manifestations are frequent and often constitute a circumstance of HIV discovery in 70% of cases [1]. They are observed in 83% of patients with AIDS and at an early stage in 75% [2,3,4,5]. The objective of this study was to describe the epidemiological, clinical, therapeutic, and evolutionary aspects of skin manifestations during HIV infection in children. Materials and Methods: We conducted a cross-sectional, multicentric, descriptive study over a period of ten years in two dermatology departments and one pediatric department in Dakar, Senegal. We included all HIV-seropositive children aged 0–15 years with mucosal cutaneous manifestations. A dermatologist and a specialist in the medical care of HIV performed the diagnosis of cutaneous manifestations. Data entry and analysis were performed with the SPSS software, version 9.05. Results: We collected 206 cases of cutaneous manifestations in 454 children followed for HIV infection. The hospital frequency was 45.3%. The children were male in 115 cases (55.83%) and female in 91 cases (44.17%), giving a sex ratio of 1.26. The mean age of the patients was sixty months, with extremes of one month to fourteen years. A mycotic dermatosis origin was noted in 47.37%, ringworm in 22.37%, dermatophytosis in 8.58%, oral candidiasis in 6.58%, seborrheic dermatitis in 6.58%, and perleche in 3.29%. Bacterial skin diseases were represented by furunculosis in 1.97%, and impetigo in 7.24%. Viral dermatoses included molluscum contagiosum in 10.53%, shingles in 9.21%, warts in 9.87%, and chickenpox in 3.95%. As for parasitic dermatoses, scabies was noted in 8.55, followed by larva migrans in 0.66% and cutaneous leishmaniosis in 0.66%. Immuno-allergic dermatoses accounted for 25% and included prurigo in 94.3%, atopic dermatitis in 1.90%, and fixed pigmented erythema in 1.90%. Conclusion: Cutaneous manifestations are a common discovery during HIV infection in children. They are marked by a predominance of infectious dermatoses in sub-Saharan Africa. Key words: skin diseases; HIV; children; Dakar

Correlate of Left Ventricular Systolic Function in Children with Human Immunodeficiency Virus Infection on Combined Highly Active Antiretroviral Medications in Aminu Kano Teaching Hospital, Kano State.

Human immunodeficiency virus (HIV) affects many organ systems in the body including the cardiovascular system, often manifesting as a subclinical left ventricular (LV) systolic dysfunction that may progress to heart failure. This study assessed the prevalence of LV systolic dysfunction in children on highly active antiretroviral therapy (HAART) with established clinical stage 1 HIV-disease. The study was a cross-sectional comparative study conducted in Aminu Kano Teaching Hospital from April to August 2019 on 200. It involved study participants comprising 100 WHO clinical stage 1 HIV-infected children and 100 control subjects, aged between 1 and 18 years selected using systematic sampling method. Echocardiography was carried out on the study participants who had already completed a pretested questionnaire. Out of 100 HIV-infected children studied, 49 were males and 51 females (Male: Female ratio; 0.96:1.0). The mean age at diagnosis of HIV infection was 2.6 (±2.6 years) and the median viral load was 35 copies/ml. The mean ejection and shortening fractions in HIV-infected children were 59.0% and 31.0%, respectively, compared to 64.4% and 34.0% in control subjects, respectively, and were statistically significant (P = 0.000). The prevalence of LV systolic dysfunction was 8.0% (8 out of 100) in HIV-infected children while the control groups had zero prevalence (P = 0.002). The age at diagnosis correlated negatively with LV systolic dysfunction (r = 0.23, P = 0.02). This study found a subclinical LV systolic dysfunction in an HAART-established clinical stage 1 HIV-infected children. The age at diagnosis was negatively correlated with the LV systolic function. This study, therefore, support the inclusion of routine echocardiography into the evaluation of HIV-infected children.

Electrocardiographic Abnormalities in Children with Human Immunodeficiency Virus Infection Presenting to the Federal Medical Centre, Umuahia, South-east Nigeria

Background: With the availability of highly active anti-retroviral therapy and attendant increased lifespan of human immunodeficiency virus (HIV)-infected children, late complications of the disease, especially cardiovascular complications have become a growing problem for them. The cardiovascular complications of HIV infection start early in the course of the disease, although may remain asymptomatic until later in life, when they manifest with life-threatening symptoms. The electrocardiogram (ECG) is an invaluable tool in the early diagnosis of these abnormalities. Aim: This study assessed the prevalence and types of ECG abnormalities among HIV-infected children. Patients, Materials and Methods: It was a hospital-based, comparative, cross-sectional study involving randomly selected HIV-infected children (subjects) and age- and gender-matched HIV-uninfected children (controls). Relevant information was obtained through questionnaires, medical records, and physical examination. All participants underwent a 12-lead ECG assessment. Results: Electrocardiographic abnormalities were observed in 42.9% of subjects compared to 17.9% of controls (χ 2 = 8.28; P = 0.004). The participants were about three times more likely to have ECG abnormalities than controls (odds ratio = 3.45, 95% confidence interval = 1.45–8.19). Left ventricular hypertrophy (LVH) was the most common abnormality in the subjects (14.3%), and compared to controls (1.8%), this was significant (χ 2 = 0.032; P = 0.032). Other ECG abnormalities such as right ventricular hypertrophy, T-wave changes, and T-axis abnormalities were more prevalent among subjects (10.7%, 5.4%, and 10.7%, respectively) than controls (1.8%, 3.6%, and 14%, respectively), although not significant. Conclusion: Electrocardiographic abnormalities are quite prevalent among HIV-infected children, with LVH being predominant. It is recommended that routine ECG evaluations be done on HIV-infected children to enable the early detection and prompt management of these problems.

Clinicoepidemiological study of adverse cutaneous drug reactions among immunocompromised children at a tertiary care hospital.

Highly active antiretroviral therapy (HAART) is used to treat human immunodeficiency virus type 1 (HIV-1). Introduction of antiretroviral therapy (ART) has reduced the HIV/AIDS associated morbidity and mortality significantly. But 25% of all patients discontinue treatment because of adverse drug reactions (ADRs). Adverse cutaneous drug reactions (ACDR) are very common with ART regimens, which may range from mild pruritus, maculopapular rash to serious Steven Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN). ACDRs comprise 10%-30% of all reported ADRs. To assess the different types of cutaneous adverse drug reactions in immunocompromised children of less than 18years. This is a retrospective record-based study, conducted at department of Dermatology, Venereology and Leprosy, Government Medical College (GMC)/Government General Hospital (GGH), Suryapet, Telangana, India. Data was collected from the records available at ART centre, from November 2018 to October 2021 GGH, Suryapet. All the HIV infected children ≤18 years who were on ART, were included in this study. Patients of more than 18 years and on other medications were excluded. Demographic data, socio economic status, vaccination status, height, weight, complete blood analysis, complete urine analysis, erythrocyte sedimentation rate, liver and renal function tests and CD4 counts were recorded before initiation of ART. A total of 330 children of less than 18 years were initiated for ART, at ART centre, Government General Hospital, Suraypet. Out of 330 children, 27.8% (92) children developed ACDRs. 58.7% (54) were males and 41.3% (38) were females. Maculopapular rash was seen in 65.2% (60) cases, urticaria was seen in 15.3% (14) cases, Steven Johnson Syndrome (SJS) was seen in 9.8% (9) cases, SJS/TEN overlap was seen in 6.5% (6) cases and toxic epidermal necrolysis (TEN) was seen in 3.2% (3) case. CD4 count was below 300 in 65.3% (60) cases above 300 in 34.7% (32) cases. Gap between initiation of the treatment and onset of reaction was less than one month in 65.3% (60) cases, and more than one month in 34.7% (32) cases.

Development of retinal structure in perinatally HIV-infected children and adolescents: A longitudinal and cross-sectional assessment.

In perinatally HIV-infected (PHIV) children, cross-sectional studies reported on subtle structural retinal differences and found associations between the retina and structural brain changes. Our objective is to investigate whether neuroretinal development in PHIV children is similar to the development in healthy matched controls and to explore associations with the brain structure. We measured RT using optical coherence tomography (OCT) on two occasions in 21 PHIV children or adolescents and 23 matched controls-all with good visual acuity-with a mean interval of 4.6 years (SD 0.3). We also included 22 participants (11 PHIV children and 11 controls) together with the follow-up group for a cross-sectional assessment using a different OCT device. Magnetic resonance imaging (MRI) was used to assess the white matter microstructure. We used linear (mixed) models to assess changes in RT and its determinants (over time), adjusting for age and sex. The development of the retina was similar between the PHIV adolescents and controls. In our cohort, we found that changes in the peripapillary RNFL was significantly associated with changes in WM microstructural makers: fractional anisotropy (coefficient = 0.030, p = 0.022) and radial diffusivity (coefficient = -0.568, p = 0.025). We found comparable RT between groups. A thinner pRNFL was associated with lower WM volume (coefficient = 0.117, p = 0.030). PHIV children or adolescents appear to have a similar development of the retinal structure. In our cohort, the associations between RT and MRI biomarkers underscore the relation between retina and brain.

Zinc Levels in HIV-positive Children at the University of Nigeria Teaching Hospital

Background: Zinc is an abundant trace element in the body involved in many physiological processes. Its deficiency has been described in HIV-infected children, especially in advancing illness. This study, therefore, seeks to assess zinc levels in HIV-positive children attending the HIV clinic at University of Nigeria Teaching Hospital (UNTH). Materials and Methods: This was a descriptive, cross-sectional study among HIV-positive children aged 5–60 months attending the HIV clinic at UNTH. A 100 participants were enrolled from August 2013 to May 2014. Data were obtained using a pro forma developed by researchers, and blood samples were collected and analysed using an absorption spectrophotometer. Serum zinc level deficiency was defined as the values &lt;80 μg/dL. Data analysis was conducted using the SPSS version 26. Results: Most participants were males (53.0%). Their mean age was 47 months (standard deviation = 15.7). The median serum zinc level was 55.5 μg/dL (IQR = 35.0–84.8). The majority of the participant (72%) had zinc deficiency. There was a statistically significant relationship between serum zinc level and participants’ socioeconomic status (P &lt; 0.05) – higher socioeconomic status was associated with higher zinc levels. Conclusion: The study showed a high prevalence of zinc deficiency in children living with HIV, with a significant relationship between serum zinc level and the participants’ socioeconomic status. There is a need for zinc supplementation for HIV children, especially the indigent ones.

Anti-HIV drugs lopinavir/ritonavir activate bitter taste receptors.

Lopinavir and ritonavir (LPV/r) are the primary anti-human immunodeficiency virus (HIV) drugs recommended by the World Health Organization for treating children aged 3 years and above who are infected with the HIV. These drugs are typically available in liquid formulations to aid in dosing for children who cannot swallow tablets. However, the strong bitter taste associated with these medications can be a significant obstacle to adherence, particularly in young children, and can jeopardize the effectiveness of the treatment. Studies have shown that poor palatability can affect the survival rate of HIV-infected children. Therefore, developing more child-friendly protease inhibitor formulations, particularly those with improved taste, is critical for children with HIV. The molecular mechanism by which lopinavir and ritonavir activate bitter taste receptors, TAS2Rs, is not yet clear. In this study, we utilized a calcium mobilization assay to characterize the activation of bitter taste receptors by lopinavir and ritonavir. We discovered that lopinavir activates TAS2R1 and TAS2R13, while ritonavir activates TAS2R1, TAS2R8, TAS2R13, and TAS2R14. The development of bitter taste blockers that target these receptors with a safe profile would be highly desirable in eliminating the unpleasant bitter taste of these anti-HIV drugs.

Subnormal Immunity to Inactivated Poliovirus Vaccine (IPV) in Previously Vaccinated Human Immunodeficiency Virus (HIV) - Infected Children

Introduction: Minimal data exists regarding prevalence of immunity to inactivated poliovirus vaccine (IPV) in previously vaccinated HIV-infected children. Methods: Antibody titers to IPV against serotypes (ST) 1, 2 and 3 following 3-doses (primary series) and 4th and 5th doses (booster) were examined in 59 children who were born to HIV-infected mothers. Eight of those children tested negative for HIV by DNA PCR and served as the controls for the 3rd and 4th dose recipients. Anti-polio 1, 2, 3 antibody titers (1/dil) was measured by neutralization assay at Specialty Laboratory in New Jersey. Correlate of protective immunity (PI) was defined as antibody titer &gt;1:8 for all serotypes. ST specific PI was correlated with the T cell counts and clinical disease categories within the HIV-infected children. PI status was compared between the HIV- infected and HIV- uninfected children and between the numbers of vaccine dose recipients within the HIV-infected children. Results: Mean age of children at the time of vaccination was 6.6, 18.6 and 66.5 months in the 3rd, 4th and 5th dose recipients, respectively. The mean age of the HIV-infected and HIV- uninfected children was comparable in the 3-dose group. Among the 3rd and 4th dose recipients, prevalence of PI to all 3 ST was significantly (p= 0.002/ST1, 0.002/ST2 and 0.01/ST3) lower in the HIV-infected, compared to their uninfected counterparts; Within the HIVinfected children, prevalence of PI to ST 1 and 2 was around 7-10 percent for all dose recipients; and 28 percent to ST3 for the 5th dose vaccine recipients. The CD4 count was found to be significantly (p=0.009) lower (362/mm3) in the 5th dose compared to the 3rd dose vaccine recipients (1072 /mm3). Conclusion: A significantly high proportion of HIV- infected children may remain unprotected against all ST of IPV even after their booster doses and thus may remain at risk for infection with all 3 ST of poliovirus when exposed to recipients of the live oral polio vaccine worldwide. Global implementation of IPV over OPV may be considered to prevent resurgence of poliovirus disease in the growing population of immunocompromised patients. Extra vigilance in the maintenance of protective immunity to poliovirus serotypes and surveillance of disease in the immunocompromised host may be deemed necessary for prevention of disease occurrence and timely diagnosis and treatment.

Virological failure of antiretroviral therapy and associated social and clinical factors in children and adolescents living with HIV

According to the World Health Organization, sustained virological suppression of 90 % should be achieved among children and adolescents living with HIV / AIDS, which makes it important to assess the prevalence of virological failure of antiretroviral therapy. The aim of this study was to determine the prevalence of virological failure and the clinical factors associated with it, as well as therapeutic drug monitoring in groups divided by the viral load level among children and adolescents with HIV. Materials and Methods: A retrospective analysis of the medical records of 184 children and adolescents receiving antiretroviral therapy and registered at the Irkutsk Regional Center for the Prevention and Control of AIDS and Infectious Diseases, Irkutsk, was carried out. The study included 172 children aged 1-18 years with perinatal HIV infection. Patients were divided into groups depending on the level of viral load: group 1 – 21 patients with viral load &gt; 1000 copies/ml of plasma, group 2 – 42 patients with viral load 50– 1000 copies/ml of plasma, group 3 – 109 patients with undetectable viral load (&lt; 50 copies/ml). All patients underwent standard tests in accordance with clinical guidelines for the treatment of HIV infection in children, as well as therapeutic drug monitoring. Results. Against the background of ongoing antiretroviral therapy, a significant number of patients 21 / 172 (12,2 %) experienced virological failure. The proportion of children and adolescents with incomplete suppression of HIV replication is 42 / 172 (24,4 %). Statistically significant differences were obtained by changing the ART regimen (p = 0,031). In the first group, the proportion of patients who changed the therapy regimen is 7 / 21 (33,3 %), which is two times less than in the group with a zero viral load of 70 / 109 (64,2 %). There are differences in the proportion of children and adolescents with zero concentrations of ritonavir and lopinavir (p = 0,020 and p = 0,012) in the three compared groups. The distribution of patients with zero concentrations was as follows: for ritonavir in the first group 3 / 17 (17,6 %), in the second – 8/37 (21,6 %), in the third group – 4/80 (5 %); for lopinavir – 4/17 (23,5 %), 6/36 (16,7 %), 3/80 (3,8 %), respectively. Conclusion. This study demonstrates that the prevalence of virological failure among children and adolescents receiving ART remains high. To achieve sustained virological suppression in children and adolescents taking a protease inhibitor regimen, adherence to therapy must be increased. As one of the methods for assessing adherence, therapeutic drug monitoring can be used.

Prevalence of Co-infection of Hepatitis B and C with HIV in HIV-Positive Adolescents in Anambra State, South-East Nigeria

Purpose: HIV accelerates the progression of HBV-related liver disease which may be as a result of the effect of HAART on the liver. This study evaluated the frequency of hepatitis B and C co-infection, and the viral load suppression rate among children and adolescents receiving ART in six HIV program centers in Anambra State, Nigeria. Methods: A multi-facility cross-sectional study was conducted among HIV-infected children and adolescents currently receiving antiretroviral treatment (ART) in six selected HIV/AIDS program healthcare facilities in Anambra State between March 2018 and February 2020. The HBsAg and HCV antibody screening were done using LabACON (HangzhouBiotest Biotech C0, China). The HIV viral load of the patients was determined according to the national HIV program algorithm using the RocheCOBASAmpliPrep COBAS TaqMan (CAP/CTM) HIV-1 test, version 2.0. All the patients Data were analyzed using SPSS version 23 and test of significance set at p-value of 0.05. Results: Of the 308 children and adolescent HIV positive cohorts tested for hepatitis B and C, 156/308 (50.6%) were males. Fourteen of the 308 (4.5%) tested positive for HBV while 34/308 (11.0%) tested positive for HCV. The male participants were frequently infected with HBV 10/156 (6.4) than their female counterparts 4/152(2. 6%). Among the children and adolescents, 3/94 (3.2%) and 11/214 (5.1%) were positive for HBV respectively, while the HCV antibody was present in 9/94 (9.6%) of children and 25/214 (11.7%) of adolescents (p = 0.24 and p = 0.72). Conclusions: The estimated prevalence of HIV/HBV and HIV/HCV dual infections in this cohort of Anambra HIV-infected children and adolescents on ART was 15.5%. Keywords: Seroprevalence, HBV, HCV, HIV, Children, Adolescents, ART, Anambra State

Seroprevalence of hepatitis B and C virus among highly active antiretroviral therapy experienced children in Gondar, Ethiopia

BackgroundGlobally, chronic viral hepatitis is the cause of mortality alongside human immunodeficiency virus/acquired immunodeficiency syndrome and tuberculosis. Published reports on the seroprevalence of hepatitis B and C viruses among HIV-infected children are lacking in sub-Saharan Africa. Hence, this study aimed to determine the seroprevalence of hepatitis B and C viruses among highly active antiretroviral therapy (HAART)-experienced children at the University of Gondar Comprehensive Specialized Hospital.MethodsWe conducted a hospital-based cross-sectional study to determine the seroprevalence of hepatitis B and C viruses among HAART-experienced children from January to May 2020. We collected the socio-demographic characteristics of study participants with pretested questioners and clinical data from medical records. We performed enzyme-linked immunosorbent assay-based laboratory test for serum hepatitis B surface antigens and anti-hepatitis C virus antibodies. Finally, we analyzed the frequency of all variables, determined the association of independent variables with hepatitis B and C viruses by using univariable and then multivariable logistic regression.ResultsA total of 241 HAART-experienced children were enrolled, 49.8% of whom were girls. The median age of participants was 13 years (interquartile range 11–14). The seroprevalence of hepatitis B and C virus infection among HAART-experienced children were 9.5% and 2.9%, respectively. Being underweight was significantly associated with both hepatitis B virus (AOR = 3.87: 95% CI; 1.04–14.46, P = 0.044) and hepatitis C virus infections (AOR = 4.54: 95% CI; 1.21–17.04, P = 0.025).ConclusionsThis study showed that the magnitude of hepatitis B and C viruses was high among HIV-infected children who were under HAART and did not know their hepatitis B and C infection status before. Being underweight was associated with both hepatitis viruses. Therefore, screening for hepatitis B and C viruses should be a routine measure for all HIV-infected children.

Surgical implications of HIV infection

According to the joint United Nations Programme on HIV/AIDS (UNAIDS), 37.7 million adults and children worldwide were estimated to be living with HIV or acquired immune deficiency syndrome (AIDS) at the end of 2020 [UNAIDS. (2022). http://www.unaids.org . Accessed 30 May 2022]. Most reside in low- and middle-income countries, with approximately 67% in sub-Saharan Africa (SSA). At the end of 2020, the total number of children less than 15years of age living with HIV infection was 2.6 million, of whom 2.3 million (88%) were living in SSA. Aggressive interventions have reduced the annual number of incident (new) HIV infections among children to around 150,000 [UNAIDS. (2022). http://www.unaids.org . Accessed 30 May 2022]. However, paediatric HIV infection remains a pandemic affecting children predominantly in SSA but is also seen in Asia and sporadically elsewhere particularly in areas of civil strife such as is currently the case in Ukraine [War in Ukraine. (2022). https://www.unaids.org/en/War-Ukraine-special . Accessed Apr 2022]. New HIV infections among children declined by more than half (54%) from 2010 to 2020, due mainly to the increased provision of antiretroviral therapy to pregnant and breastfeeding women living with HIV [UNAIDS. (2022). http://www.unaids.org . Accessed 30 May 2022]. These programmes include early identification of HIV infection in pregnant or breastfeeding women through routine HIV testing, provision of antiretroviral therapy (ART) to all HIV-infected women who are pregnant or breastfeeding, provision of antiretroviral prophylaxis to their newborn infants during the first 6-12weeks of life, delivery by elective Caesarean section when indicated, promotion of exclusive breastfeeding, early infancy screening for HIV infection, and initiation of ART in infants with HIV infection. HIV-infected children may require surgery either as an emergency to deal with a life-threatening incidental condition unrelated to HIV infection or for a complication of the disease such as tuberculosis or an aggressive soft tissue infection like necrotising fasciitis. Non-emergency surgical procedures may be required to assist in the diagnosis of an HIV-related condition or to correct a routine surgical problem electively. Surgical conditions associated with HIV infection are described under categories of soft tissue or organ-specific infections requiring drainage or debridement; gastrointestinal tract disease and complications; infections in the perineal area; malignancies and HIV-associated vasculitis. Although surgical outcomes are less favourable in HIV-infected children, pre-operative treatment of coinfections, administration of cotrimoxazole prophylaxis, nutritional support and antiretroviral therapy, together with peri-operative antibiotic prophylaxis have resulted in excellent short-term outcomes [World Health Organization. Consolidated guidelines on the use of antiretroviral drugs for treating and preventing HIV infection: Recommendations for a public health approach, June 201 http://www.apps.who.int/iris/bitstream/10665/85321/1/9789241505727_eng.pdf?ua=1 ; World Health Organization Guideline on when to start antiretroviral therapy and on pre-exposure prophylaxis for HIV, September 2015. http://www.apps.who.int/iris/bitstream/10665/186275/1/9789241509565_eng.pdf?ua=1;Eley et al. in BMC Infect Dis 2:3, 2002;Karpelowsky et al. in Pediatr Surg Int 28:1007-1014, 2012;].

HIV-associated nephropathy in children: challenges in a resource-limited setting.

HIV infection remains one of the leading causes of morbidity and mortality worldwide, especially in children living in resource-limited settings. Although the World Health Organization (WHO) recently recommended antiretroviral therapy (ART) initiation upon diagnosis regardless of the number of CD4, ART access remains limited, especially in children living in sub-Saharan Africa (SSA). HIV-infected children who do not receive appropriate ART are at increased risk of developing HIV-associated nephropathy (HIVAN). Although due to genetic susceptibility, SSA is recognized to be the epicenter of HIVAN, limited information is available regarding the burden of HIVAN in children living in Africa. The present review discusses the information available to date on the prevalence, pathogenesis, risk factors, diagnosis, and management of HIVAN in children, focusing on related challenges in a resource-limited setting.

Some pharmacogenetic aspects of the &lt;i&gt;ABCB1&lt;/i&gt; gene in lopinavir / ritonavir concentration variability in children with HIV infection: A pilot study

Polymorphic variants of the multidrug resistance gene (ABCB1 or MDR1) are associated with changes in the absorption and transport of drugs in the body. One of the substrates of the ABCB1 transporter is an antiretroviral drug from the class of protease inhibitors, lopinavir. The aim. To research the effect of polymorphic variants C1236T and C3435T in the ABCB1 gene on the plasma concentration of lopinavir / ritonavir in children and adolescents living with HIV infection. Methods. The genotypes of polymorphic variants of the ABCB1 gene were identified in 136 HIV infected children and adolescents; median age – 10 [7–12] years. The plasma concentration of lopinavir / ritonavir was measured from blood taken during the next scheduled appointment as part of dispensary observation at the Irkutsk Regional AIDS Centre using high performance liquid chromatography. Results. The average duration of lopinavir/ritonavir use as part of an antiretroviral therapy was 55 months. Median viral load in patients was 1 [1–2.03] log 10 copies/ mL; the number of CD4 + T cells – 38.36 %. The frequency of occurrence of the 3435T and 1236T alleles of the ABCB1 gene was ~50 %. In carriers of the 3435TT genotype, the median lopinavir concentrations 2 and 12 hours after drug intake were 5050.8 [3615.8–5847.7] and 2665.5 [216–4896.3] ng/mL, respectively. In carriers of the 1236TT genotype, median lopinavir concentrations 2 and 12 hours after drug intake were 4913.5 [3355.1–5733.7] and 3290.6 [159.1–4972.5] ng/mL, respectively. Conclusions. The study did not reveal a significant relationship between the carriage of the C3435T and C1236T genotypes of the ABCB1 gene and the concentrations of lopinavir and ritonavir 2 and 12 hours after drug intake.