Treatment Of HIV-infected Children Research Articles

Predictors of cardiac dysfunction in children with HIV/AIDS attending University of Nigeria Teaching Hospital Enugu

Cardiac dysfunction, though common as a primary effect of HIV infection or its treatment in HIV-infected children, is often clinically masked by pulmonary disease in patients with HIV infection and AIDS. The objective of the study was to determine the prevalence and predictors of cardiac dysfunction in children with HIV/AIDS infection. This was a cross-sectional comparative case - control study of clinical and echocardiographic findings in 90 pediatric HIV/AIDS children aged 18 months to 14years and their age and gender - matched HIV – negative controls attending the University of Nigeria Teaching Hospital, Enugu. Relevant clinical information including demographics, investigations including echocardiography and treatment, were captured using a datasheet designed for the study. Data analysis was done using SPSS version 20.0. A p value of <0.05 was considered significant. The majority of the subjects had cardiac abnormalities and was on HAART. The pattern of cardiac abnormalities in HIV – infected and AIDS groups were left ventricular diastolic dysfunction (33.8% and 36.4% in the HIV – infected and the AIDS groups respectively, followed by dilated cardiomyopathy (6.8%) seen only in AIDS group (p=0.03). A strong linear relationship between cardiac dysfunction and CD4+ counts (R2=0.8642) and age (R2=0.4203) among the patients were observed. Cardiac dysfunction is common in children with HIV/AIDS and predicted by CD4+ count and increasing age. Need exists to monitor the development of cardiac dysfunction using appropriate clinical details and echocardiography is recommended to improve their quality of life.

Determinants of Caretakers Acceptability of HIV Testing among Children Admitted at Lubango Provincial Pediatric Hospital, Angola

Early diagnosis and treatment of HIV infected children is particularly important since they face a very high mortality rate. With the recent availability of Antiretroviral Therapy (ART), routine HIV testing is now an essential component of HIV prevention and care. However, many HIV infected children are never identified or are lost from the health care system before they can be enrolled into care contributing to high mortality. Early diagnosis of HIV infected children is critical for optimal therapy and effective public health planning.

Weight-adapted fixed-dose combined adult antiretroviral tablets for HIV-infected children.

Therapeutic alternatives to simplify antiretroviral therapy (ART) in HIV-infected children are needed. We report our experience with abacavir(ABC)/lamivudine(3TC) individualized dose compounded capsules (IDCC). We present a prospective case series of HIV-infected children who did not weigh enough to receive the adult fixed-dose combination including ABC/3TC 600mg/300mg, and were treated with weight-adapted ABC/3TC IDCC in Barcelona, Spain. Thirteen patients (12 girls) received ABC/3TC IDCC for a median(IQR) time of 30(17-54) months. No significant changes were observed in CD4 cell counts, weight or height z-scores over time. Suppression of viral replication was maintained in 7 patients with undetectable viremia at baseline. Another 5 patients achieved viral suppression with ABC/3TC IDCC-based ART, while one non-adherent girl did not. No adverse events related to ABC/3TC IDCC were observed. Despite small numbers, the long-term use of ABC/3TC IDCC was feasible, safe, and effective in the treatment of HIV-infected children.

Abacavir versus Zidovudine-based regimens for treatment of HIV-infected children in resource limited settings: a retrospective cohort study

BackgroundAbacavir (ABC) and Zidovudine (AZT) based regimens are the preferred first line nucleoside reverse transcriptase (NRTIs) backbones being widely utilized for managing HIV infection in children. However, there is a dearth of data regarding the clinical outcomes and associated risk factors in Ethiopia. We compared the proportion of mortality and the rate of occurrence of Opportunistic Infections (OIs) with ABC versus AZT -based regimens in a cohort of HIV-infected children.MethodsA 42 months retrospective cohort study was conducted. A total of 179 records were reviewed by including data from October 2014 to April 2017. Data were collected on socio-demographic, clinical characteristics of patients and drug related variables. Data were analyzed using STATA13.1. Kaplan-Meier and Cox regression were used to compare survival experience and identify independent predictors. Propensity score matching analysis was conducted to elucidate the average treatment effects of each regimen over OIs.ResultOf 179 patients, 98 (54.7%) were females. The mean (+SD) age of the study subjects was 6.53 ± 2.83 years. Through 42 months analysis, a total of 4 patients (1 (1.14%) from ABC group and 3 (3.3%) from AZT group (p = 0.339)) were died. The incidence of opportunistic infections attributed to ABC group was 8.77/100,000 person years (py) and that of AZT was 6.9/100,000py. The incidence rate ratio (IRR) for OIs was (IRR = 0.87, 95% CI [0.49–1.53] (p = 0.304). Baseline CD4 count (AHR = 0.99, 95% CI [0.98–0.99]), Severe acute malnutrition (AHR = 15.92, 95% CI [5.34–47.50]), and exposure to tuberculosis treatment (AHR = 2.93, 95% CI [1.39–6.17]) were the independent predictors for the development of OIs.ConclusionABC and AZT based ART regimens seem to have comparable survival benefit among HIV-infected children in Ethiopia. Therefore, both regimens might be used as an alternative in resource limited settings.

Challenges and social support provisions in the treatment of HIV infected children in Indonesia

Latar belakang: Pengobatan pada anak yang terinfeksi HIV merupakan beban bagi para orang tua/pengasuh karena berbagai permasalahan menyangkut kesehatan mereka.
 Metode: Penelitian untuk mengeksplorasi pengalaman dan dukungan sosial pada pengobatan anak terinfeksi HIV dilakukan di 5 provinsi di Indonesia dengan prevalensi HIV tertinggi. Total sampel anak sebanyak 239 orang dari sejumlah 267 orang yang direncanakan. Data dikumpulkan dengan wawancara semi terstruktur dengan orang tua/pengasuhnya. Analisis dilakukan terhadap 16 anak berusia 2-14 tahun yang telah mendapatkan terapi obat antiretroviral.
 Hasil: Dari sejumlah 160 anak, sebanyak 62,5% anak mengkonsumsi 1-2 item obat dan 36,9% mengkonsumsi 3 5 item. Efek samping yang paling sering terjadi adalah kulit kemerahan, mual dan muntah. Kesulitan yang paling sering dihadapi adalah rasa bosan dan anak mempertanyakan minum obat. Orangtua/pengasuh berusaha melanjutkan pengobatan dengan mengingatkan jadwal minum obat, membujuk, memberikan penjelasan bahkan memaksa atau mengancam mereka untuk minum obat. Kesulitan tersebut makin bertambah seiring meningkatnya usia anak. Dukungan yang paling sering berasal dari orang tua dan keluarga besar seperti nenek atau paman, khususnya untuk anak yang sudah yatim.
 Kesimpulan: Pemahaman hambatan pengobatan pada anak terinfeksi HIV dapat membantu untuk menyediakan intervensi yang tepat untuk meningkatkan kepatuhan yang akan mendorong kesuksesan terapi mereka.
 Kata kunci: anak terinfeksi HIV, antiretroviral, dukungan social, pengobatan, kesulitan
 
 Abstract
 Background: The treatment of HIV infected children is a burden to their caregiver due to many existing problems related with their health.
 Methods: A research to explore the experience and social support on the treatment of HIV infected children was conducted in 5 provinces in Indonesia with highest prevalence of HIV. Total children sample was 239 out of previous 267 planned. Data was collected through semi structured interview with caregivers of the children. Analysis was conducted to 160 children aged 2-14 years old who were on antiretroviral therapy.
 Results: Among those 160 children, 62.5% took 1-2 items of medicines and 36.9% took 3-5 items. The most frequent adverse events were skin rash followed by nausea and vomiting. Boredom and questioning were the most frequent difficulties. The caregivers attempted to continue the treatment by reminding the children on schedule to take medicines, wheedling, explaining, forcing or even threatening them. The difficulties appeared more as the children grew older. The most frequent supports mainly came from parents, and extended family such as grandmother or uncle especially for orphaned children.
 Conclusion: Understanding obstacles in HIV infected children will help to do proper interventions to improve adherence that will lead to successful therapy.
 Keywords: HIV infected children, antiretroviral, social support, treatment, difficulties

Monocyte-to-Lymphocyte Ratio Is Associated With Tuberculosis Disease and Declines With Anti-TB Treatment in HIV-Infected Children.

The blood monocyte-to-lymphocyte ratio (MLR) is associated with active tuberculosis (TB) in adults but has not been evaluated as a TB diagnostic biomarker in HIV-infected children in whom respiratory sampling is difficult. In a cohort of HIV-infected hospitalized Kenyan children initiating antiretroviral therapy, absolute monocyte and lymphocyte counts were determined at enrollment and 4, 12, and 24 weeks thereafter. Children were classified as confirmed, unconfirmed, or unlikely pulmonary TB. Receiver operating characteristic curves of MLR cutoff values were generated to distinguish children with confirmed TB from those with unconfirmed and unlikely TB. General estimating equations were used to estimate change in the MLR over time by TB status. Of 160 children with median age 23 months, 13 (8.1%) had confirmed TB and 67 (41.9%) had unconfirmed TB. The median MLR among children with confirmed TB {0.407 [interquartile range (IQR) 0.378-0.675]} was higher than the MLR in children with unconfirmed [0.207 (IQR 0.148-0.348), P < 0.01] or unlikely [0.212 (IQR 0.138-0.391), P = 0.01] TB. The MLR above 0.378 identified children with confirmed TB with 77% sensitivity, 78% specificity, 24% positive predictive value, and 97% negative predictive value. After TB treatment, the median MLR declined in children with confirmed TB and levels were similar to children with unlikely TB after 12 weeks. The blood MLR distinguished HIV-infected children with confirmed TB from those with unlikely TB and declined with TB treatment. The MLR may be a useful diagnostic tool for TB in settings where respiratory-based microbiologic confirmation is inaccessible.

Predictors of treatment failure, time to switch and reasons for switching to second line antiretroviral therapy in HIV infected children receiving first line anti-retroviral therapy at a Tertiary Care Hospital in Ethiopia

BackgroundTreatment failure and delay in switching to second line regimen are major concerns in the treatment of HIV infected children in a resource limited setting. The aim of this study was to determine the prevalence and predictors of first line antiretroviral therapy (ART) regimen failure, reasons and time taken to switch to second line antiretroviral (ARV) medications after treatment failure among HIV-infected children.MethodsA retrospective cohort study was conducted February 2003 to May 2018 in HIV-clinic at Tikur Anbessa Specialized Hospital (TASH), Ethiopia. All HIV infected children ≤15 years of age and who were taking first line ART for at least 6 months were included. Data abstraction format was used to collect the data from patients’ chart and registry. Binary and multivariable logistic regression statistics were used.ResultsOut of 318 enrolled HIV-infected children, the prevalence of treatment failure was found to be 22.6% (72/318), among these 37 (51.4%) had only immunologic failure, 6 (8.3%) had only virologic failure and 24 (33.3%) had both clinical and immunological failure. The mean time taken to modify combination antiretroviral therapy (cART) regimen was 12.67 (4.96) weeks after treatment failure was confirmed. WHO Stage 3 and 4 [Adjusted Odds Ratio (AOR), 3.64, 95% CI 1.76–7.56], not having both parents as primary caretakers [AOR, 2.72 95% CI, 1.05–7.06], negative serology of care takers [AOR, 2.69 95% CI, 1.03–7.03], and cART initiation at 11 month or younger were predicting factors of treatment failure. Of the 141 (47.9%) children who had regimen switching or substitution, treatment failure (44.4%) and replacement of stavudine (d4T) (30.8%) were major reasons. Only 6.6% patients had received PMTCT service.ConclusionOne fifth of the patients had experienced treatment failure. Advanced WHO stage at baseline, not being taken care of by mother and father, negative sero-status caretakers, and younger age at initiation of cART were the predictors of treatment failure. PMTCT service uptake was very low. There was a significant time gap between detection of treatment failure and initiation of second line cART. Half of the patients encountered regimen switching or substitution of cART due to treatment failure and replacement of stavudine (d4T).

Utility of Mobile Communication Devices as a Tool to Improve Adherence to Antiretroviral Treatment in HIV-infected Children and Young Adults in Argentina.

Optimal adherence is critical to achieve the benefits of antiretroviral treatment (ART). The aim of the study is to evaluate the use of mobile devices as a strategy to improve adherence to ART, measured by viral load (VL) in HIV+ patients less than 25 years of age. A prospective study was conducted in a cohort of HIV+ patients less than 25 years of age. HIV+ patients, on ART, VL >1000 copies/mL, using mobile devices and suboptimal adherence were included. The intervention was based on a mobile generic contact twice a month using text message and Facebook during 32 weeks. Extended communications were generated by the patient. VL was performed before and after the intervention. Twenty-five patients were included. Three were excluded and 22 patients were enrolled. Mean age was 17.2 ± 6.1 years (range: 6-25); 15 (68%) were female; mean baseline VL was 25,100 copies/mL (range: 1020-500,000 copies/mL), mean log was 4.3 (range: 3-5.7 log). Each participant received a total of 16 contacts; 84% (296) were answered by the patient and 54% (189) of the contacts generated extended communications. After the strategy implementation, 20/22 VL results were available: 13/20 (65%) were undetectable, 14/20 (70%) had VL < 1000 copies/mL and 6/20 (30%) VLs had no changes. The use of mobile devices and social networks is a valid tool to improve ART adherence in HIV+ pediatric and young adults, evaluated through VL. The strategy is feasible. The reminder messages trigger additional communications between patients and health provider and better engagement with HIV care. Longer follow-up time is needed.

Pharmacokinetics and Drug-Drug Interactions of Lopinavir-Ritonavir Administered with First- and Second-Line Antituberculosis Drugs in HIV-Infected Children Treated for Multidrug-Resistant Tuberculosis.

Lopinavir-ritonavir forms the backbone of current first-line antiretroviral regimens in young HIV-infected children. As multidrug-resistant (MDR) tuberculosis (TB) frequently occurs in young children in high-burden TB settings, it is important to identify potential interactions between MDR-TB treatment and lopinavir-ritonavir. We describe the pharmacokinetics of and potential drug-drug interactions between lopinavir-ritonavir and drugs routinely used for MDR-TB treatment in HIV-infected children. A combined population pharmacokinetic model was developed to jointly describe the pharmacokinetics of lopinavir and ritonavir in 32 HIV-infected children (16 with MDR-TB receiving treatment with combinations of high-dose isoniazid, pyrazinamide, ethambutol, ethionamide, terizidone, a fluoroquinolone, and amikacin and 16 without TB) who were established on a lopinavir-ritonavir-containing antiretroviral regimen. One-compartment models with first-order absorption and elimination for both lopinavir and ritonavir were combined into an integrated model. The dynamic inhibitory effect of the ritonavir concentration on lopinavir clearance was described using a maximum inhibition model. Even after adjustment for the effect of body weight with allometric scaling, a large variability in lopinavir and ritonavir exposure, together with strong correlations between the pharmacokinetic parameters of lopinavir and ritonavir, was detected. MDR-TB treatment did not have a significant effect on the bioavailability, clearance, or absorption rate constants of lopinavir or ritonavir. Most children (81% of children with MDR-TB, 88% of controls) achieved therapeutic lopinavir trough concentrations (>1 mg/liter). The coadministration of lopinavir-ritonavir with drugs routinely used for the treatment of MDR-TB was found to have no significant effect on the key pharmacokinetic parameters of lopinavir or ritonavir. These findings should be considered in the context of the large interpatient variability found in the present study and the study's modest sample size.

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.

A prospective study of haematological changes after switching from stavudine to zidovudine-based antiretroviral treatment in HIV-infected children

Long-term use of stavudine is associated with a high incidence of lipodystrophy, warranting its substitution with zidovudine in first-line antiretroviral therapy (ART) regimens. In a prospective observational study, we determined the spectrum and severity of haematological changes after switching from stavudine- to zidovudine-based ART in Indian children aged 2-18 years who had received a stavudine-based ART regimen for at least 48 weeks. They were followed for 48 weeks for changes in haematological parameters and CD4 cell counts after switching to zidovudine. Of the 60 children analysed, 45 (75%) showed a significant fall in Hb (>1 g/dl). A majority developed grade 1 anaemia (14 [31%]) while only three (6%) developed grade 4 anaemia. The lowest Hb was recorded between 12 and 16 weeks with spontaneous improvement noticed after 28 weeks. A significant drop in absolute neutrophil count (5067 cells/mm3 to 3625 cells/mm3; p = 0.004) was also observed but none developed severe neutropenia. No significant changes were observed in platelet and CD4 cell counts. Since the incidence of severe drug toxicity was low with zidovudine and the majority of children recovered without intervention, drug toxicity should not preclude its routine use in poor countries.

Renal and Bone Adverse Effects of a Tenofovir-Based Regimen in the Treatment of HIV-Infected Children: A Systematic Review.

Tenofovir disoproxil fumarate (TDF)-containing regimens in the treatment of HIV-infected children have safety concerns with respect to renal and bone toxicity. The aim of this study was to systematically review and critically appraise the literature relating to the reported renal and bone adverse effects of TDF-based regimens in the treatment of HIV-infected children from 2 to 19years old. Searches were performed using the Cochrane Central Register of Controlled Trials (CENTRAL), Cumulative Index to Nursing and Allied Health Literature (CINAHL), MEDLINE, OvidSP, ScienceDirect and Web of Science databases and platforms. All primary studies involving tenofovir use in HIV-infected children were sought. Studies that involved the use of TDF for pre- and post-exposure prophylaxis, and treatment of chronic hepatitisB virus infection were excluded. Data on study characteristics, participant's characteristics, therapeutic intervention and adverse effects were extracted using a piloted tool. In addition, pharmacovigilance data from the WHO Adverse Reaction database were included. We identified 19 studies that reported the presence of renal and bone adverse effects of TDF and these included a total of 1100 study participants. The reports were in distinctly heterogeneous participant groups. A total of 287 renal and bone adverse effects were reported (250 renal and 37 bone adverse effects). Approximately 238 (21.6%) participants were affected by these adverse effects. Of these, 15 participants stopped their TDF-containing regimen due to these adverse effects. In addition, the pharmacovigilance data from the WHO Adverse Reaction database reported 101 renal and bone adverse effects for patients whose indication was HIV/AIDS. This systematic review summarises the reports of renal and bone adverse effects of a TDF-containing regimen in the treatment of HIV-infected children. Our findings suggest that the benefits of using TDF in children need to be balanced against the potential risk of toxicity.

Tuberculosis: opportunities and challenges for the 90-90-90 targets in HIV-infected children.

IntroductionIn 2014 the Joint United Nations Programme on HIV/AIDS defined the ambitious 90–90–90 targets for 2020, in which 90% of people living with HIV must be diagnosed, 90% of those diagnosed should be on sustained therapy and 90% of those on therapy should have an undetectable viral load. Children are considered to be a key focus population for these targets. This review will highlight key components of the epidemiology, prevention and treatment of tuberculosis (TB) in HIV-infected children in the era of increasing access to antiretroviral therapy (ART) and their relation to the 90–90–90 targets.DiscussionThe majority of HIV-infected children live in countries with a high burden of TB. In settings with a high burden of both diseases such as in sub-Saharan Africa, up to 57% of children diagnosed with and treated for TB are HIV-infected. TB results in substantial morbidity and mortality in HIV-infected children, so preventing TB and optimizing its treatment in HIV-infected children will be important to ensuring good long-term outcomes. Prevention of TB can be achieved by increasing access to ART to both children and adults, and appropriate provision of isoniazid preventative therapy. Co-treatment of HIV and TB is complicated by drug-drug interactions particularly due to the use of rifampicin; these may compromise virologic outcomes if appropriate corrective actions are not taken. There remain substantial operational challenges, and improved integration of paediatric TB and HIV services, including with antenatal and routine under-five care, is an important priority.ConclusionsTB may be an important barrier to achievement of the 90–90–90 targets, but specific attention to TB care in HIV-infected children may provide important opportunities to enhance the care of both TB and HIV in children.

Switching Nevirapine-Exposed, Virologically Suppressed Children to an Efavirenz-Based Antiretroviral Regimen

Lopinavir/ritonavir therapy is the currently recommended first-line treatment for HIV-infected children. Lopinavir/r syrup, which is administered twice

Efficacy and safety of abacavir-containing combination antiretroviral therapy as first-line treatment of HIV infected children and adolescents: a systematic review and meta-analysis

BackgroundAbacavir is one of the recommended nucleoside reverse transcriptase inhibitors (NRTIs) for the treatment of HIV infections among children and adolescents. However, there are concerns that the antiviral efficacy of abacavir might be low when compared to other NRTIs especially among children. There are also concerns that abacavir use may lead to serious adverse events such as hypersensitivity reactions and has potential predisposition to developing cardiovascular diseasesMethodsWe searched four electronic databases, four conference proceedings and two clinical trial registries in August 2014, without language restrictions. Experimental and observational studies with control groups that examined the efficacy and safety of abacavir-containing regimens in comparison with other NRTIs as first-line treatment for HIV-infected children and adolescents aged between one month and eighteen years were eligible. Two authors independently screened search results, extracted data and assessed the risk of bias of included studies using a pre-specified, standardised data extraction form and validated risk of bias tools. We also assessed the quality of evidence per outcome with the GRADE tool.ResultsWe included two randomised controlled trials (RCTs) and two analytical cohort studies with a total of 10,595 participants. Among the RCTs we detected no difference in virologic suppression after a mean duration of 48 weeks between abacavir- and stavudine-containing regimens (2 trials; n = 326: RR 1.28; 95 % CI 0.67–2.42) with significant heterogeneity (P = 0.02; I2 = 81 %). We also found no significant differences between the two groups for adverse events and death. After five years of follow-up, virologic suppression improved with abacavir (1 trial; n = 69: RR 1.96; 95 % CI 1.11–3.44). For cohort studies, we detected that the virologic suppression activity of abacavir was less effective than stavudine in both the lopinavir/ritonavir (1 study, n = 2165: RR 0.79, 95 % CI 0.67–0.92) and efavirenz sub-groups (1 study, n = 3204: RR 0.79, 95 % CI 0.67–0.92) respectively. The quality of evidence from RCTs was moderate for virologic suppression but low for death and adverse events, while that of cohort studies was low for all three these outcomes.ConclusionsAvailable evidence showed little or no difference between abacavir-containing regimen and other NRTIs regarding efficacy and safety when given to children and adolescents as a first-line antiretroviral therapy.Electronic supplementary materialThe online version of this article (doi:10.1186/s12879-015-1183-6) contains supplementary material, which is available to authorized users.

Ultrasensitive method to quantify intracellular zidovudine mono-, di- and triphosphate concentrations in peripheral blood mononuclear cells by liquid chromatography-tandem mass spectrometry.

Although zidovudine (AZT) is not the preferred antiretroviral drug for adult HIV-infected patients, it is still widely used in infants for both prevention of mother-to-infant HIV-1 transmission and treatment of HIV-infected children. However, it is difficult to measure intracellular concentrations of AZT metabolites in small blood samples due to their extremely low concentrations in peripheral blood mononuclear cells and interference by endogenous nucleotide triphosphates, residual plasma phosphates and electrolytes. We developed an ultrasensitive assay using liquid chromatography-tandem mass spectrometry (LC-MS/MS) for measurement of intracellular concentrations of zidovudine (AZT)-monophosphate (AZT-MP), -diphosphate (AZT-DP) and -triphosphate (AZT-TP). The high sensitivity was due to the improvement of peripheral blood mononuclear cells extraction for complete removal of plasma and electrolytes, alkalization of LC buffer and use of alkaline-stable high performance liquid chromatography column and tetrabutylammonium hydroxide as the ion pair. Using this method, the lower limits of quantification of AZT, AZT-MP, -DP and -TP were 6, 6, 10 and 10 fmol per sample, respectively. Accuracy ranged 89-115% and precision was lower than 15% in the quantification range of 6-6000 fmol/sample for plasma AZT and intracellular AZT-MP and 10-10 000 fmol/sample for AZT-DP and -TP. The validation parameters met the international requirements. Among nine AZT-treated HIV-infected adult patients, five had low AZT-TP levels (<10 fmol/10(6) cells). Our assay has high sensitivity and is advantageous for evaluation of AZT phosphates in children and infants based on minimum blood sampling requirement.

P001: Utility of mobile communication devices as a tool to improve adherence to antiretroviral treatment in HIV-infected children and adolescents in Argentina

P001: Utility of mobile communication devices as a tool to improve adherence to antiretroviral treatment in HIV-infected children and adolescents in Argentina

Clinical profile of hospitalized HIV-infected children in Bangladesh, a low-HIV-prevalence country

Background:Bangladesh has a low HIV prevalence and data on the risk factors and clinical presentation of HIV-infected children are lacking.Objective:To describe the clinical characteristics of hospitalized HIV-infected children in Bangladesh and determine the factors associated with a low CD4 count.Methods:An anonymous, retrospective review was undertaken of the medical records of all patients admitted to the HIV unit of the iccdr,b Dhaka Hospital between February 2009 and July 2012. Demographic, clinical and laboratory data were extracted from the electronic medical record system. HIV-infected children with a low absolute CD4 count (<200 cells/μl) were compared with HIV-infected children with a CD4 count ≧200 cells/μl.Results:Of 266 HIV-infected patients, 24 were children (9%), 13 (54%) of whom were male. Ages ranged from 2 to 17 years (median 7). Of the 21 (88%) children who acquired the infection by vertical transmission, median age at diagnosis was 5·2 years, and the parents of 19 (79%) reported a history of external migration. Children commonly presented with prolonged fever (n = 14, 58%), recurrent cough (n = 14, 58%), failure to thrive (n = 11, 46%) and recurrent diarrhoea (n = 4, 17%). Six (25%) patients had tuberculosis, four (16·7%) had herpes zoster and four (16·7%) were diagnosed with Pneumocystis jirovecii pneumonia. One child died during hospitalization. Children with a low CD4 count (<200 cells/μl) more often had severe wasting (95% CI 1·2–453·97) and severe under-nutrition (95% CI 1·39–196·25) than those with a higher CD4 count*.Conclusion:The majority of HIV-infected children presenting to an inpatient speciality ward in Dhaka acquired HIV through vertical transmission, and most of the parents had a history of external migration. Further studies are needed to determine the optimal strategy for preventing mother-to-child transmission and for early identification and treatment of HIV-infected children in this low-prevalence country.

The role of etravirine in the management of treatment-experienced pediatric patients with HIV.

Pediatric patients infected with human immunodeficiency virus (HIV) are now living longer, healthier lives due to the advent of combined antiretroviral (ARV) therapy, including regimens that often contain non-nucleoside reverse transcriptase inhibitors (NNRTIs). However, first-generation NNRTIs such as nevirapine (NVP) and efavirenz (EFV) have a low genetic barrier to resistance, and both drugs can become ineffective with a single viral point mutation. New agents with activity against resistant viral strains must be available to salvage children and adolescents with virologic failure after NNRTI use. One such drug, etravirine, an oral second-generation NNRTI approved for use in the US in heavily treatment-experienced HIV-1-infected adults in 2008, is accumulating data in this younger population. Etravirine became approved by the US Food and Drug Administration in early 2012 to be used in combination with other ARV medications in HIV-1-infected children aged 6 years to <18 years who are failing their regimens with HIV-1 strains resistant to NNRTIs and other ARVs. This approval was largely based on data from a prospective, open-label, phase II clinical trial in this age group prescribed etravirine at 5.2 mg/kg twice daily (up to the adult dose of 200 mg twice daily) in combination with an investigator-selected optimized background regimen. Currently available 48-week follow-up data show complete viral suppression (<50 copies/mL) in 56% of the patients, with relatively few serious adverse events attributed to the drug. Additional studies and case reports from the field suggest its utility in clinical practice. This review is designed to increase the background understanding of this drug in pediatric HIV providers, to lay out the current pediatric data to support its use, and to define its practical role in the treatment of HIV-infected children now and in the future.

Mitochondrial Evolution in HIV-Infected Children Receiving First- or Second-Generation Nucleoside Analogues

Highly active antiretroviral therapy (HAART) and HIV-related mitochondrial toxicity lead to several adverse effects and have become a major issue, especially in children. The main goal in the treatment of HIV-infected children is to maximize cost-effectiveness while minimizing toxicity. We aimed to study the evolution of mitochondrial parameters over time in children receiving different types antiretroviral regimens. We followed-up 28 HIV-infected children receiving HAART including either first-generation nucleoside reverse transcriptase inhibitors (1gNRTIs; didanosine, zidovudine, or stavudine; n = 15) or second-generation NRTIs (2gNRTIs; the remaining drugs; n = 13) for a period of 2 years for their immunovirological and mitochondrial status, and compared these subjects with a group of untreated HIV-infected patients (n = 10) and uninfected controls (n = 27). We measured T-lymphocyte CD4+ content (flow cytometry), viral load (real-time polymerase chain reaction), and lactate levels (spectrophotometry); we assessed mtDNA content (real-time polymerase chain reaction), mitochondrial protein levels (Western blot), oxidative stress, mitochondrial mass, and electron transport chain function (spectrophotometry) in peripheral blood mononuclear cells. At the second time point, lactate levels were significantly higher in children on 1gNRTIs compared with those receiving 2gNRTIs (1.28 ± 0.08 vs. 1.00 ± 0.07 mmol/L, respectively; P = 0.022). MtDNA content was similar among all HIV-infected groups and significantly lower than in healthy controls at baseline. Oxidative stress tended to increase over time in all the groups, with no differences among them. However, a significant decrease in cytochrome c oxidase activity was found over time in HIV-infected patients; this decline was greater in the 1gNRTIs group. HIV infection and the use of 1gNRTIs caused greater mitochondrial damage than 2gNRTIs over time. The higher lactate levels and the significant decrease observed in cytochrome c oxidase activity argue against the use of 1gNRTIs in HIV-infected children when an alternative is available, in accordance with international recommendations.