Association between mental disorders with detectable viral load and poor adherence to antiretroviral therapy among adolescents infected with Human Immunodeficiency Virus on follow-up at Chantal Biya Foundation, Cameroon.

INTRODUCTION: Perinatally HIV-Infected Adolescents (HIVIA) are more likely to have mental health problems than their uninfected peers. In resource-limited settings, mental health disorders are rarely taken into account in the care offered to HIVIA and have an impact on their routine follow-up. The objective of this study was to assess the baseline socio-demographic factors and mental health conditions associated with detectable viral load or poor ART adherence in HIVIA on ART followed at the Mother and Child Centre of the Chantal Biya Foundation in Yaoundé (CME-FCB), Cameroon. METHODS: A cross-sectional study was conducted in HIVIA aged 10 to 19 years, followed at CME-FCB during the period from December 2021 to March 2022. Sociodemographic, clinical, and mental characteristics were collected using a structured questionnaire administered face-to-face by trained healthcare providers. The primary outcome was viral load ≥ 40 copies/mL in HIVIA on ART for at least six months. The secondary outcome was poor ART adherence, defined as ≥ 1 missed dose of antiretroviral therapy within the last past three days. The main exposure variables were mental health disorders, including the level of anxiety, depression and low self-esteem. RESULTS: In total, 302 adolescents were interviewed, 159 (52.7 %) were girls and median age was 15.2 years (IQR: 12.0-17.5). Having missed at least 1 dose of ART drugs during the last 3 days before screening concerned 53 (35.0 %) cases. Of the 247 adolescents with an available viral load (VL) in the last 12 months prior to screening, 33 (26.7 %) had a VL ≥ 40 copies/mL. Among participating adolescents, 29.1 % presented with high or very high anxiety, 26.5 % with severe depression, 36.4 % with history of suicidal ideation, and 20.5 % low self-esteem. Low self-esteem was strongly associated with a higher risk of poor ART adherence (adjusted odds ratio(aOR) (95 % confidence interval (95 %CI)): 2.2 (1.1-4.3); p = 0.022). Living with the father (aOR (95 %CI): 0.6 (0.3-1.1); p = 0.085) or in a household with a televisor (aOR (95 %CI): 0.5 (0.2-1.1); p = 0.069) were slightly associated with a lower risk of poor adherence to ART. Having both parents alive (aOR (95 %CI): 0.4 (0.2-0.9); p = 0.031) or receiving ART with efavirenz or dolutegravir (aOR (95 %CI): 0.5 (0.2-0.9); p = 0.047) was strongly associated with a lower likelihood of having a detectable VL. Moreover, detectable viral load was slightly less frequent in adolescents whose household was equipped with a television (p = 0.084) or who were completely disclosed for HIV status (p = 0.070). CONCLUSION: This study found that co-morbid low self-esteem had higher odds of poor ART adherence in HIVIA. Moreover, both poor ART adherence, and detectable viral load were associated with impaired life conditions in HIVIA.

Paediatric abacavir-lamivudine fixed-dose dispersible tablets and ritonavir-boosted lopinavir granules in neonates exposed to HIV (PETITE study): an open-label, two-stage, single-arm, phase 1/2, pharmacokinetic and safety trial.

BACKGROUND: Existing solid antiretroviral fixed-dose combination formulations are preferred over liquid formulations in children, but their suitability for neonates is unknown. We evaluated the pharmacokinetics and safety of paediatric abacavir-lamivudine fixed-dose dispersible tablets and ritonavir-boosted lopinavir granules in neonates. METHODS: In this open-label, two-stage, single-arm, phase 1/2, pharmacokinetic and safety trial, generic abacavir- lamivudine (120:60 mg) double-scored dispersible tablets and lopinavir boosted with ritonavir (40:10 mg) granules were studied. Neonates exposed to HIV (≥37 weeks gestational age) of no more than 3 days of age with birthweights of 2000-4000 g were identified through routine care in a tertiary hospital in Cape Town, South Africa. In stage 1, the pharmacokinetics and safety of two single doses were assessed to select the multidose strategy for stage 2. Neonates received a single dose of abacavir-lamivudine (30:15 mg, a quarter of a tablet) and lopinavir boosted with ritonavir (40:10 mg - one sachet) orally between 3 days and 14 days of age, and a second dose of a quarter tablet of abacavir-lamivudine and lopinavir boosted with ritonavir (80:20 mg, two sachets) 10-14 days later in stage 1. The multidose strategy selected in stage 2 was a quarter of the abacavir-lamivudine (30:15 mg) fixed-dose dispersible tablet once per day and two sachets of the lopinavir boosted with ritonavir (80:20 mg) granules twice per day from birth to age 28 days. In both stages two intensive pharmacokinetic visits were done, one at less than 14 days of life (pharmacokinetics 1) and another 10-14 days later (pharmacokinetics 2). Safety visits were done 1-2 weeks after each pharmacokinetic visit. Primary objectives were to assess pharmacokinetics and safety of abacavir, lamivudine, and lopinavir. Pharmacokinetic endpoints were area under the concentration time curve (AUC), maximum concentration, and concentration at end of dosing interval in all participants with at least one evaluable pharmacokinetic visit. Safety endpoints included grade 3 or worse adverse events, and grade 3 or worse treatment-related adverse events, occurring between study drug initiation and end of study. This completed trial is registered with the Pan African Clinical Trials Registry (PACTR202007806554538). FINDINGS: Between Aug 18, 2021, and Aug 18, 2022, 24 neonates were enrolled into the trial and received study drugs. Eight neonates completed stage 1, meeting interim pharmacokinetic and safety criteria. In stage 2, 16 neonates received study drugs. Geometric mean abacavir and lamivudine exposures (AUC0-24) were higher at 6-14 days (51·7 mg × h/L for abacavir and 17·2 mg × h/L for lamivudine) than at 19-24 days of age (25·0 mg × h/L and 11·3 mg × h/L), whereas they were similar for lopinavir over this period (AUC 0-12 58·5 mg × h/L vs 46·4 mg × h/L). Abacavir geometric mean AUC0-24 crossed the upper reference range at pharmacokinetics 1, but rapidly decreased. Lamivudine and lopinavir AUC0-tau were within range. No grade 2 or worse adverse events were related to study drugs. One neonate had a grade 1 prolonged corrected QT interval using the Fridericia method that spontaneously resolved. INTERPRETATION: Abacavir-lamivudine dispersible tablets and ritonavir-boosted lopinavir granules in neonates were safe and provided drug exposures similar to those in young infants. Although further safety data are needed, this regimen presents a new option for HIV prevention and treatment from birth. Accelerating neonatal pharmacokinetic studies of novel antiretroviral therapies is essential for neonates to also benefit from state-of-the-art treatments. FUNDING: Unitaid.

COVID-19 and MIS-C treatment in children-results from an international survey.

Children have been mostly excluded from COVID-19 clinical trials, and, as a result, most medicines approved for COVID-19 have no pediatric indication. In addition, access to COVID-19 therapeutics remains limited. Collecting physicians' experiences with off-label use of therapeutics is important to inform global prioritization processes and better target pediatric research and development. A standardized questionnaire was designed to explore the use of therapeutics used to treat COVID-19 and multisystem inflammatory syndrome in children (MIS-C) in pediatric patients globally. Seventy-three physicians from 29 countries participated. For COVID-19, steroids were used by 75.6% of respondents; remdesivir and monoclonal antibodies were prescribed by 48.6% and 27.1% of respondents, respectively. For MIS-C, steroids were prescribed by 79.1% of respondents and intravenous immunoglobulins by 69.6%. The use of these products depended on their pediatric approval and the limited availability of antivirals and most monoclonal antibodies in Africa, South America, Southeast Asia, and Eastern Europe. Off-label prescription resulted widespread due to the paucity of clinical trials in young children at the time of the survey; though, based on our survey results, it was generally safe and led to clinical benefits.  Conclusion: This survey provides a snapshot of current practice for treating pediatric COVID-19 worldwide, informing global prioritization efforts to better target pediatric research and development for COVID-19 therapeutics. Off-label use of such medicines is widespread for the paucity of clinical trials under 12 years and 40 kg, though appears to be safe and generally results in clinical benefits, even in young children. However, access to care, including medicine availability, differs widely globally. Clinical development of COVID-19 antivirals and monoclonal antibodies requires acceleration to ensure pediatric indication and allow worldwide availability of therapeutics that will enable more equitable access to COVID-19 treatment. What is Known: • Children have been mostly excluded from COVID-19 clinical trials, and, as a result, most medicines approved for COVID-19 have no pediatric indication. • Access to care differs widely globally, so because of the diversity of national healthcare systems; the unequal availability of medicines for COVID-19 treatment represents an obstacle to the pediatric population's universal right to health care. What is New: • Off-label COVID-19 drug prescription is widespread due to the lack of clinical trials in children younger than 12 years and weighing less than 40 kg, but relatively safe and generally leading to clinical benefit. • The application of the GAP-f framework to COVID-19 medicines is crucial, ensuring widespread access to all safe and effective drugs, enabling the rapid development of age-appropriate formulations, and developing specific access plans (including stability, storage, packaging, and labeling) for distribution in low- and middle-income countries (LMICs). Antivirals and monoclonal antibodies may benefit from the acceleration to reach widespread and equal diffusion.

Paediatric medicine issues and gaps from healthcare workers point of view: survey results and a narrative review from the global accelerator for paediatric formulations project.

The WHO Model List of Essential Medicines for Children (EMLc) has not been systematically revised in the last few years. We conducted a survey addressed to healthcare professionals prescribing, preparing, or administering medicines to children and a narrative review to identify problematic paediatric formulations or missing medicines in all therapeutic fields to inform the review of the EMLc in 2023. A total of 285 physicians (63%), 28 nurses (6%) and 142 pharmacists (31%), mostly working in the hospital setting, reported at least one problematic medicine. 290 medicines were reported as missing (completely or the child-appropriate formulation). The top three most mentioned were ciprofloxacin together with phenobarbital and omeprazole. 387 medicines were reported as problematic (34% were oral liquid formulations, 34% tablets, 18% parenteral preparations. Mostly of the products were antibacterials (27%), cardiovascular medicines (11%) and antivirals (11%). The obtained responses show the perspective of healthcare workers working around the world, particularly in the European region (25%), in the African region (24%), and in the Region of the Americas (19%), with limited representation from Northern Africa and the Middle East. Our results need to be analysed with the outputs of other ongoing works before specific products can enter the WHO-hosted Global Accelerator for Paediatric formulations network prioritisation process. Efforts to develop appropriate formulations for children should be accelerated so that the uncertainties associated with off-label drug preparation and use are minimised, and therapeutic benefits are optimised.

Mental health troubles among Cameroonian adolescents perinatally infected with Human Immunodeficiency Virus.

INTRODUCTION: Adolescents living with HIV are more likely to experience mental health challenges compared to their peers who do not have HIV. However, there is a lack of data regarding the mental health of adolescents living with HIV in Cameroon. Understanding risk factors and protective factors that influence mental health amongst adolescents is critical for effective programming. The purpose of this study was to estimate the prevalence and the factors associated with depression in adolescents infected with HIV and receiving ART in a Cameroonian referral hospital. METHODS: This was a cross-sectional study which enrolled adolescents perinatally infected with HIV, aged 10-19 years, on antiretroviral treatment and cared for at "Centre Mère et Enfant de la Fondation Chantal Biya", Yaounde, Cameroon. Structured questionnaires, including validated French versions of the Coopersmith Child Depression Inventory (CDI), the Multidimensional Anxiety Scale for Children (MASC) and the Coopersmith Self Esteem Inventory (SEI), were administered to the study participants by the healthcare providers. RESULTS: All in all, 302 adolescents were recruited in the study at a median age of 15.2 years (interquartile range : 12.0 - 17.5), including 159 (52.7 %) girls. Both parents had died for 57 (18.9 %) adolescents ; only the father was alive for 64 (21.2 %) ; only the mother was alive for 48 (15.9 %), both parents were alive for 133 (44.0 %). This study found prevalence of 26.5 % for severe depression, 36.4 % for suicidal ideation, 29.1 % for high/very high anxiety, and 20.5 % for low self-esteem. No factor was found significantly associated with severe depression but there was a trend towards decreased risk of severe depression among adolescents whose mother was alive [OR= 0.4 (0.1-1.0), p = 0.084]. CONCLUSION: This study found that elevated depression, anxiety, and low self-esteem symptoms were prevalent among Cameroonian adolescents perinatally infected with HIV. Services and systems should go beyond clinical management of HIV and address the psychosocial and mental health of adolescents. The indicators of mental health among adolescents infected with HIV should be included in HIV program reporting.

Systems Challenges in Accessing Medicines among Children under Thailand's Universal Health Coverage: A Qualitative Study of a Provincial Public Hospital Network.

Lack of access to child-appropriate medicines results in off-label use. This study aimed to explore medicine management for paediatric patients and to highlight the challenges of the healthcare system under the universal health coverage of Thailand. Semi-structured interviews were conducted with 35 healthcare practitioners working in the public hospital network of Chiang Mai province from February to September 2020. Participants were asked about their experiences in managing the medicine supply for children. Findings revealed that paediatric patients had limited access to age-appropriate medicines. Children's medicines are rarely selected for inclusion into hospital formularies because of constraining regulations and limited budgets. Additionally, child-appropriate formulations are unavailable on the market. Pharmaceutical compounding is unavoidable. Prepared products are provided weekly or monthly because of product stability concerns. Often, tablets are dispensed, and caregivers are instructed to cut up a tablet and disperse it in syrup in order to obtain a smaller dose in a dosage form appropriate for children to use at home. Without systematic support, access to safe and quality medicines for children is limited.

Gaps in Accessibility of Pediatric Formulations: A Cross-Sectional Observational Study of a Teaching Hospital in Northern Thailand.

The lack of appropriate medicines for children has a significant impact on health care practices in various countries around the world, including Thailand. The unavailability of pediatric medicines in hospital formularies causes issues regarding off-label use and extemporaneous preparation, resulting in safety and quality risks relating to the use of medicines among children. This research aimed to identify missing pediatric formulations based on the experience of healthcare professionals in a teaching hospital in northern Thailand. A cross-sectional survey was conducted to collect data on missing pediatric formulations, the reasons for their inaccessibility, their off-label uses, their reactions to the situation, and suggestions to improve access to these identified medications. The survey was distributed to all physicians, nurses, and pharmacists involved in prescribing, preparing, dispensing, and administering pediatric medicines. A total of 218 subjects responded to the survey. Omeprazole, sildenafil, and spironolactone suspension were most often identified as missing formulations for children by physicians and pharmacists. They are unavailable on the Thai market or in any hospital formulary. For nurses, sodium bicarbonate, potassium chloride, and chloral hydrate were the most problematic formulations in terms of preparation, acceptability, and administration. These medicines were difficult to swallow because of their taste or texture.

Abacavir pharmacokinetics in African children living with HIV: A pooled analysis describing the effects of age, malnutrition and common concomitant medications.

AIMS: Abacavir is part of WHO-recommended regimens to treat HIV in children under 15 years of age. In a pooled analysis across four studies, we describe abacavir population pharmacokinetics to investigate the influence of age, concomitant medications, malnutrition and formulation. METHODS: A total of 230 HIV-infected African children were included, with median (range) age of 2.1 (0.1-12.8) years and weight of 9.8 (2.5-30.0) kg. The population pharmacokinetics of abacavir was described using nonlinear mixed-effects modelling. RESULTS: Abacavir pharmacokinetics was best described by a two-compartment model with first-order elimination, and absorption described by transit compartments. Clearance was predicted around 54% of its mature value at birth and 90% at 10 months. The estimated typical clearance at steady state was 10.7 L/h in a child weighing 9.8 kg co-treated with lopinavir/ritonavir, and was 12% higher in children receiving efavirenz. During coadministration of rifampicin-based antituberculosis treatment and super-boosted lopinavir in a 1:1 ratio with ritonavir, abacavir exposure decreased by 29.4%. Malnourished children living with HIV had higher abacavir exposure initially, but this effect waned with nutritional rehabilitation. An additional 18.4% reduction in clearance after the first abacavir dose was described, suggesting induction of clearance with time on lopinavir/ritonavir-based therapy. Finally, absorption of the fixed dose combination tablet was 24% slower than the abacavir liquid formulation. CONCLUSION: In this pooled analysis we found that children on lopinavir/ritonavir or efavirenz had similar abacavir exposures, while concomitant TB treatment and super-boosted lopinavir gave significantly reduced abacavir concentrations.

Pediatric COVID-19 Therapeutics: Seizing the Right Research and Development Opportunities to Accelerate Access for Children.

Children, although at lower risk of poor outcomes from COVID-19 relative to adults, still stand to benefit from therapeutic interventions. Understanding of COVID-19 clinical presentation and prognosis in children is essential to optimize therapeutic trials design. This perspective illustrates how to collectively accelerate pediatric COVID-19 therapeutic research and development, based on the experience of the Global Accelerator for Paediatric Formulations.

Pharmacokinetics and Safety of the Abacavir/Lamivudine/Lopinavir/Ritonavir Fixed-Dose Granule Formulation (4-in-1) in Neonates: PETITE Study.

BACKGROUND: Antiretroviral options for neonates (younger than 28 days) should be expanded. We evaluated the pharmacokinetics, safety, and acceptability of the "4-in-1" fixed-dose pediatric granule formulation of abacavir/lamivudine/lopinavir/ritonavir (30/15/40/10 mg) in neonates. METHODS: The PETITE study is an ongoing phase I/II, open-label, single-arm, 2-stage trial conducted in South Africa. In stage 1, term neonates exposed to HIV on standard antiretroviral prophylaxis (nevirapine ± zidovudine) received single dose(s) of the 4-in-1 formulation, followed by intensive pharmacokinetic sampling and safety assessments. At each PK visit, blood was drawn after an observed dose at 1, 2, 4, 8, and 12 hours postdose. In this study, we have reported the planned interim pharmacokinetic and safety analysis after completion of the single-dose administration. RESULTS: Sixteen neonates, with a median (range) birth weight of 3130 g (2790-3590 g), completed 24 pharmacokinetic visits. The 4-in-1 formulation imposed relatively high doses of abacavir [8.6 mg/kg (6.6-11.4)] and lamivudine [4.3 mg/kg (3.3-5.7)] but lower doses of lopinavir [11.5 mg/kg (8.8-15.2)]. The geometric means (GM, 90% CI) AUC0-12 of abacavir, lamivudine, and lopinavir were 29.87 (26.29-33.93), 12.61 (10.72-14.83), and 3.49 (2.13-5.72) µg.h/mL, respectively. Lopinavir GM AUC0-12 was below the predefined target (20-100 µg.h/mL), and ritonavir concentrations were only detectable in 4 of the 120 (3%) samples. No adverse events were related to study drugs. No neonate had difficulty swallowing the 4-in-1 formulation. CONCLUSIONS: The high doses of abacavir and lamivudine (in mg/kg) and AUCs were safe, and the formulation was well tolerated; however, lopinavir/ritonavir exposures were extremely low, preventing its use in neonates use in neonates. Alternative pediatric solid antiretroviral formulations must be studied in neonates.

Outbreaks of COVID-19 in Nursing Homes: A Cross-Sectional Survey of 74 Nursing Homes in a French Area.

In this multi-centric cross-sectional survey conducted in nursing homes of the French Alps, from 1 March to 31 May 2020, we analyze the relationship between the occurrence of an outbreak of COVID 19 among residents and staff members. Out of 225 eligible nursing homes, 74 (32.8%) completed the survey. Among 5891 residents, the incidence of confirmed or probable COVID-19 was 8.2% (95CI, 7.5% to 8.9%), and 22 (29.7%) facilities had an outbreak with at least 3 cases. Among the 4652 staff members, the incidence of confirmed or probable COVID-19 was 6.3% (95CI, 5.6% to 7.1%). A strong positive correlation existed between residents and staff members for both numbers of cases (r2 = 0.77, p < 0.001) and the incidence (r2 = 0.76, p < 0.001). In univariate analyses, cases among the staff were the only factor associated with the occurrence of an outbreak among residents (OR = 11.2 (95CI, 2.25 to 53.6)). In bivariate analysis, this relationship was not influenced by any nursing home characteristics, nor the action they implemented to mitigate the COVID-19 crisis. Staff members were, therefore, likely to be a source of contamination and spread of COVID-19 among nursing home residents during the first wave of the pandemic.

Lack of Association between Adverse Pregnancy Outcomes and Zika Antibodies among Pregnant Women in Thailand between 1997 and 2015.

Data about Zika virus infection and adverse pregnancy outcomes in Southeast Asia are scarce. We conducted an unmatched case-control study of Zika virus (ZIKV) serology in pregnant women enrolled in human immunodeficiency virus (HIV) or hepatitis B virus (HBV) perinatal prevention trials between 1997 and 2015 in Thailand. Case and control groups included women with and without adverse pregnancy outcomes. Plasma samples collected during the last trimester of pregnancy were tested for ZIKV IgG/IgM and Dengue IgG/IgM (Euroimmun, AG, Germany). Case newborn plasma samples were tested for ZIKV IgM and ZIKV RNA (Viasure, Spain). The case group included women with stillbirth (n = 22) or whose infants had microcephaly (n = 4), a head circumference below the first percentile (n = 14), neurological disorders (n = 36), or had died within 10 days after birth (n = 11). No women in the case group were positive for ZIKV IgM, and none of their live-born neonates were positive for ZIKV IgM or ZIKV RNA. The overall ZIKV IgG prevalence was 29%, 24% in the case and 34% in the control groups (Fisher's exact test; p = 0.13), while the dengue IgG seroprevalence was 90%. Neither neonatal ZIKV infections nor ZIKV-related adverse pregnancy outcomes were observed in these women with HIV and/or HBV during the 18-year study period.

Effective and Safe Daclatasvir Drug Exposures Predicted in Children Using Adult Formulations.

BACKGROUND: Sofosbuvir (SOF)/daclatasvir (DCV) is the direct-acting antiviral regimen of choice in many low- and middle-income countries for curative treatment of chronic hepatitis C virus (HCV) infection in adults, but data on the use of DCV in children are lacking. We performed a population pharmacokinetic (PK) analysis to predict DCV exposure in children treated with available adult formulations. METHODS: DCV concentration data from HCV-infected adolescents receiving SOF/DCV [400/60 mg, once daily (OD)] who participated in a PK study in Egypt were used for model development. PK parameters were estimated using a population approach. Monte Carlo simulations were run for virtual children weighing 10 to <35 kg receiving 60 or 30 mg OD, and DCV exposures were compared with adults ranges. RESULTS: Seventeen HCV-infected adolescents (13 males) provided 151 DCV concentrations. Median (range) age was 14 (11-18) years and weight 50 (32-63) kg. In these adolescents receiving 60 mg DCV, median (interquartile range) DCV area under the concentration time curve 0 to 24 hours, maximum concentrations, and minimum concentrations were 11,130 (8140-14,690) ng·h/mL, 1030 (790-1220) ng/mL and 130 (110-220) ng/mL, respectively, compared with 10,343 (7661-14,095) ng·h/mL, 1132 (876-1518) ng/mL and 110 (55.7-192) ng/mL predicted in children 10 to <35 kg receiving 30 mg. The proportion of children with DCV exposures above the adult range rapidly increased for children <30 kg using 60 mg OD, similarly for children 10-14 kg using 30 mg. CONCLUSIONS: DCV 30 mg OD was predicted to achieve effective and safe exposures in children 14 to <35 kg, perhaps down to 10 kg. These results should be validated clinically. Low-cost available adult DCV formulations together with approved pediatric doses of SOF would expand global access to HCV treatment for children.

Risky injection practices and HCV awareness in Chiang Mai Province, Thailand: a respondent-driven sampling study of people who inject drugs.

BACKGROUND: People who inject drugs (PWID) are the most exposed to hepatitis C virus (HCV). In Thailand, drug use is highly criminalized, and harm reduction services are scarce. This study estimates risky injection practices and assesses the proportion of HCV awareness and screening in the PWID population in Northern Thailand. METHODS: We used respondent-driven sampling (RDS) to recruit PWID in Chiang Mai Province. Social and behavioural data were collected through face-to-face interviews at an addiction treatment facility. Weighted population estimates were calculated to limit biases related to the non-random sampling method. Univariate and multivariate analyses were performed to study factors associated with HCV awareness and screening. RESULTS: One hundred seventy-one PWID were recruited between April 2016 and January 2017. Median age was 33 (Interquartile range: 26-40) years, 12.2% were women, and 49.4% belonged to a minority ethnic group. Among participants, 76.8% injected heroin, 20.7% methadone, and 20.7% methamphetamine. We estimate that 22.1% [95% CI: 15.7-28.6] of the population had shared needles in the last 6 months and that 32.0% [95% CI: 23.6-40.4] had shared injection material. Only 26.6% [95% CI: 17.6-35.6] had heard of HCV. Factors independently associated with knowledge of HCV included belonging to a harm reduction organization (adjusted odds ratio (aOR) = 5.5 [95% CI: 2.0-15.3]) and voluntary participation in a drug rehabilitation programme (aOR = 4.3 [95% CI: 1.3-13.9]), while Lahu ethnicity was negatively associated (aOR = 0.3 [95% CI: 0.1-0.9]). We estimate that 5% of the PWID population were screened for HCV; the only factor independently associated with being screened was membership of a harm reduction organization (aOR = 5.7 [95% CI: 1.6-19.9]). CONCLUSION: Our study reveals that the PWID population is poorly informed and rarely screened for HCV, despite widespread risky injection practices. A public health approach aimed at reducing the incidence of HCV should target the PWID population and combine harm reduction measures with information and destigmatization campaigns. Civil society organizations working with PWID are a major asset for the success of such an approach, based on their current positive interventions promoting awareness of and screening for HCV.

Perinatal Antiretroviral Intensification to Prevent Intrapartum HIV Transmission When Antenatal Antiretroviral Therapy Is Initiated Less Than 8 Weeks Before Delivery.

INTRODUCTION: Infants born to women living with HIV initiating combination antiretroviral therapy (cART) late in pregnancy are at high risk of intrapartum infection. Mother/infant perinatal antiretroviral intensification may substantially reduce this risk. METHODS: In this single-arm Bayesian trial, pregnant women with HIV receiving standard of care antiretroviral prophylaxis in Thailand (maternal antenatal lopinavir-based cART; nonbreastfed infants 4 weeks' postnatal zidovudine) were offered "antiretroviral intensification" (labor single-dose nevirapine plus infant zidovudine-lamivudine-nevirapine for 2 weeks followed by zidovudine-lamivudine for 2 weeks) if their antenatal cART was initiated ≤8 weeks before delivery. A negative birth HIV-DNA polymerase chain reaction (PCR) followed by a confirmed positive PCR defined intrapartum transmission. Before study initiation, we modeled intrapartum transmission probabilities using data from 3738 mother/infant pairs enrolled in our previous trials in Thailand using a logistic model, with perinatal maternal/infant antiretroviral regimen and predicted viral load at delivery as main covariates. Using the characteristics of the women enrolled who received intensification, prior intrapartum transmission probabilities (credibility intervals) with/without intensification were estimated. After including the transmission data observed in the current study, the corresponding Bayesian posterior transmission probability was derived. RESULTS: No intrapartum transmission of HIV was observed among the 88 mother/infant pairs receiving intensification. The estimated intrapartum transmission probability was 2·2% (95% credibility interval 0·5-6·1) without intensification versus 0·3% (0·0-1·6) with intensification. The probability of superiority of intensification over standard of care was 94·4%. Antiretroviral intensification appeared safe. CONCLUSION: Mother/infant antiretroviral intensification was effective in preventing intrapartum transmission of HIV in pregnant women receiving ≤8 weeks antepartum cART.

Abacavir Exposure in Children Cotreated for Tuberculosis with Rifampin and Superboosted Lopinavir-Ritonavir.

In children requiring lopinavir coformulated with ritonavir in a 4:1 ratio (lopinavir-ritonavir-4:1) and rifampin, adding ritonavir to achieve a 4:4 ratio with lopinavir (LPV/r-4:4) overcomes the drug-drug interaction. Possible drug-drug interactions within this regimen may affect abacavir concentrations, but this has never been studied. Children weighing <15 kg needing rifampin and LPV/r-4:4 were enrolled in a pharmacokinetic study and underwent intensive pharmacokinetic sampling on 3 visits: (i) during the intensive and (ii) continuation phases of antituberculosis treatment with LPV/r-4:4 and (iii) 1 month after antituberculosis treatment completion on LPV/r-4:1. Pharmacometric modeling and simulation were used to compare exposures across weight bands with adult target exposures. Eighty-seven children with a median (interquartile range) age and weight of 19 (4 to 64) months and 8.7 (3.9 to 14.9) kg, respectively, were included in the abacavir analysis. Abacavir pharmacokinetics were best described by a two-compartment model with first-order elimination and transit compartment absorption. After allometric scaling adjusted for the effect of body size, maturation could be identified: clearance was predicted to be fully mature at about 2 years of age and to reach half of this mature value at about 2 months of age. Abacavir bioavailability decreased 36% during treatment with rifampin and LPV/r-4:4 but remained within the median adult recommended exposure, except for children in the 3- to 4.9-kg weight band, in which the exposures were higher. The observed predose morning trough concentrations were higher than the evening values. Though abacavir exposure significantly decreased during concomitant administration of rifampin and LPV/r-4:4, it remained within acceptable ranges. (This study is registered in ClinicalTrials.gov under identifier NCT02348177.).

Acceptability and Feasibility of Using Raltegravir Oral Granules for the Treatment of Neonates in a Low-resource Setting.

BACKGROUND: Raltegravir granules for oral suspension, now recommended by World Health Organization for use in neonates with HIV infection, may be challenging for caregivers because of the multistep preparation required. METHODS: We evaluated the acceptability and feasibility of preparing granules for oral suspension in a low-to-middle-income country setting. Thirty-four caregivers and 10 health-care workers were enrolled from an HIV clinic in Durban, South Africa. Health-care workers were provided with pictorial instruction booklet, demonstration kit and guidance on preparation of granules for oral suspension. The health-care workers then trained caregivers on the preparation of granules for oral suspension. Caregivers were evaluated during the preparation process and instructed to practice at home with a sample kit and return to the clinic for repeat evaluation 5-7 days later. Caregivers and health-care workers were interviewed and participated in a focus group discussion regarding their experiences. RESULTS: The median age of the caregivers was 31 years (interquartile range: 9.7); 70% had received secondary-level education, 37% were employed. The median preparation time was 7.95 minutes (interquartile range: 5.08 minutes) and 7.48 minutes (3.55 minutes) at initial and repeated observation, respectively. Major errors were insufficient mixing time and incorrect suspension volume. The average number of errors between the 2 observation time points was significantly reduced at the repeat session (2.5 vs. 0.87, P = 0.023). Most participants found the preparation difficult at first but gained confidence over time. CONCLUSION: Despite the complexity involved in the preparation of the granules for oral suspension, with practice, this formulation was found to be acceptable and feasible to majority of participants in this low-resource setting. As a result, this formulation was included in the 2018 World Health Organization recommendations for first line in neonates living with HIV.

Incidence and risk factors of loss to follow-up among HIV-infected children in an antiretroviral treatment program.

INTRODUCTION: The success of antiretroviral treatment (ART) programs can be compromised by high rates of patient loss to follow-up (LTFU). We assessed the incidence and risk factors of LTFU in a large cohort of HIV-infected children receiving ART in Thailand. METHODS: All children participating in a multicenter cohort (NCT00433030) between 1999 and 2014 were included. The date of LTFU was 9 months after the last contact date. ART interruption was defined as ART discontinuation for more than 7 days followed by resumption of treatment. Baseline and time-dependent risk factors associated with LTFU were identified using Fine and Gray competing risk regression models with death or referral to another hospital as competing events. RESULTS: Of 873 children who were followed during a median of 8.6 years (interquartile range 4.5-10.6), 196 were LTFU, 73 died, and 195 referred. The cumulative incidence of LTFU was 2.9% at 1 year, 7.3% at 5 years and 22.2% at 10 years. Children aged 13 years and more had a 3-fold higher risk (95% confidence interval 2.06-4.78) of LTFU than those younger. Children who had interrupted ART within the previous year had a 2.5-fold higher risk (1.12-5.91) than those who had not. The risk of LTFU was lower in children stunted (height-for-age Z-scores <-2 SD) (0.42-0.96) or underweight (weight-for-age Z-scores <-2 SD) (0.24-0.97). CONCLUSION: Adolescence, ART interruption and absence of growth deficit were associated with LTFU. These may be warnings that should draw clinicians' attention and possibly trigger specific interventions. Children with no significant growth retardation may also be at risk of LTFU.

Impact of antiretroviral treatment on height evolution of HIV infected children.

BACKGROUND: Antiretroviral treatment (ART) has been shown to have a beneficial effect on the weight evolution but its effect on height remains unclear. We described patterns of height evolution and identified predictors of catch-up growth in HIV-infected children on ART. METHODS: To describe the height evolution from birth to adulthood, we developed a nonlinear mixed effect model using data from perinatally HIV-infected children who initiated ART from 1999 to 2013 in a prospective cohort study in Thailand. The main covariates of interest were: sex, ART regimen (dual nucleoside reverse-transcriptase inhibitor, non-nucleoside reverse transcriptase inhibitor (NNRTI)-, or protease inhibitor (PI)-based), baseline CD4 percentage, HIV-RNA load and CDC HIV Classification stage and occurrence of AIDS-defining events. RESULTS: A total 477 children (43% boys) contributed 18,596 height measurements over a median duration of 6.3 years on ART (interquartile range, 3.0 to 8.3). At ART initiation, median age was 6.2 years (1.8 to 9.6), 16% of children were underweight (weight-for-age z-score < - 2), 49% presented stunting (height-for-age z-score < - 2), and 7% wasting (weight-for-height z-score < - 2). The most frequent regimen at ART initiation was NNRTI-based (79%). A model with 4 components, birth length and 3 exponential functions of age accounting for the 3 growth phases was developed and show that the height-growth velocity was inversely associated with the age at ART initiation, the adult height was significantly lower in those who had experienced at least one AIDS-defining event while, as expected, the model found that adult height in females was lower than in males. Age at ART initiation, type of ART regimen, CDC stage, CD4 percentages, and HIV-RNA load were not associated with the final height. CONCLUSIONS: The younger the children at ART initiation, the greater the effect on height-growth velocity, supporting the World Health Organization's recommendation to start ART as early as possible. However, final adult height was not linked to the age at ART initiation.