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.
Abstract In settings where plasma preparation and sample centralization are not feasible or inconvenient, dried blood spots (DBS) could be used as an alternative specimen to plasma to assess antiretroviral treatment response among HIV‐infected individuals. This study was aimed to (1) validate the recent QIAsymphony‐ artus assay for DBS HIV viral load (VL) and (2) assess the feasibility of measuring HIV VL on DBS using this assay in Thailand. Ethylenediaminetetraacetic acid‐blood samples from 99 HIV‐infected individuals were used to prepare paired DBS and plasma. Also, DBS samples were shipped to three distant hospitals in the northern region. After short‐term storage, DBS were returned by regular post to the AMS laboratory and were re‐tested for HIV VL using the same platform. HIV VL results were compared using Pearson's correlation and Bland‐Altman analysis. DBS HIV VL fairly correlated to plasma HIV VL (R = 0.62) with a mean difference of 0.02 log 10 IU/mL (SD = 1.06). A high correlation (R = 0.79) was observed between HIV VL in DBS before and after shipping (mean difference = 0.14 log 10 IU/mL, SD = 0.74), indicating good stability of HIV RNA in DBS. DBS can be used as an alternative specimen for HIV VL monitoring in Thailand. However, measurement of HIV VL with the QIAGEN QIAsymphony ‐artus assay should be improved, especially the DBS pre‐extraction process.
Background: In Thailand, hepatitis B surface antigen (HBsAg) testing is part of routine antenatal screening. We assessed the association between characteristics of pregnant women attending Samut Prakan Provincial Hospital antenatal care clinic (ANC) and their Hepatitis B virus (HBV) infection status. Methods: This is a cross-sectional study of pregnant women ≥ 18 yrs presenting at the ANC between August 1st, 2013 and June 30th, 2015. Data on socio-demographics, general physical examination, obstetrical and medical history and knowledge of HBV status were collected. Comparisons were performed using the Wilcoxon-Mann- Whitney test or Fisher’s exact test. Results: A total of 115 pregnant women, 18 HBsAg positive and 97 negative, participated. The women had a median age of 27.1 yrs (interquartile range (IQR): 22.4 to 31.5) at a median 28.0 weeks gestational age (IQR: 26.1 to 29.7). Forty-five (39%) reported being born abroad. Sixteen (14%) did not receive primary education. The women’s household contained a median of 3 persons (IQR: 2 to 4). None of these characteristics differed between HBsAg positive and negative women. HBsAg positive women were more likely to know their HBV status than HBsAg negative women [6 (33%)] vs. 12 [(12%), p=0.04] and their previous live offsprings’ HBV status [9 (60%)] vs. 21 [(26%), p=0.01]. In contrast, they were less likely to know their partner’s HBV status [3 (17%)] vs. 50 [(52%), p=0.009]. Conclusion: HBV chronic infection was not associated with any characteristics, which justifies systematic screening for HBsAg during antenatal care. The vast majority of women were not able to report their and their partner’s HBsAg status, underlining potential missed opportunities to be followed for their hepatitis B infection.
In a randomized, double-blind, placebo-controlled trial of tenofovir disoproxil fumarate (TDF) use from 28 weeks gestational age to 2 months postpartum to prevent mother-to-child transmission of hepatitis B virus, there was no significant effect of maternal TDF use on maternal or infant bone mineral density 1 year after delivery/birth. Clinical Trials Registration. NCT01745822.
Aims and Scope: For more than 50 years, clinical pharmacologists, clinical and pharmaceutical researchers, drug development specialists, physicians, nurses, and other medical professionals have relied on The Journal of Clinical Pharmacology (JCP) for original research, special reviews, commentaries, and case reports on all phases of drug development from absorption, disposition, metabolism, excretion interactions, and preferred uses through post-marketing evaluations.
Hepatitis B is a leading cause of morbidity and mortality worldwide. In view of the World Health Organization's 2030 targets, effective screening of chronic infection is crucial. We assessed the prevalence and risk factors of hepatitis B surface antigen in adults presenting for screening. Free-of-charge and anonymous services for simultaneous hepatitis B, hepatitis C, human immunodeficiency virus and syphilis screening and counseling were provided in four facilities in northern Thailand. Analyses were performed separately in clients born before integration in 1992 of hepatitis B vaccine in Thailand's Expanded Program on Immunization and in clients born after. Between October 2015 and August 2020, hepatitis B surface antigen prevalence was 7.2 % (185/2578) in clients born before 1992 (95 % confidence interval [CI] = 6.2%–8.2 %). In the multivariable analysis, characteristics independently associated with a higher risk of infection were being born male (adjusted odds ratio [aOR] = 1.49, 95 % CI = 1.10–2.01) and being part of a hill tribe (aOR = 1.65, 95 % CI = 1.01–2.70). 42 % were unaware of their infection. In clients born in 1992 or after, prevalence was 1.5 % (43/2933) (95 % CI = 1.1%–2.0 %) and characteristics independently associated with a higher risk were being born between 1992 and 1995 (aOR = 1.90, 95 % CI = 1.00–3.61), being born male (aOR = 2.60, 95 % CI = 1.34–5.07), being part of a hill tribe (aOR = 5.09, 95 % CI = 2.52–10.26) and having ever injected drugs (aOR = 4.33, 95 % CI = 1.23–15.24). Risk factor-based screening would miss many chronic hepatitis cases. Screening all adults once in their lifetime may be beneficial until the second generation of immunized infants have reached adult age.
Early diagnosis is key to achieving the goal of eliminating transmission of HIV and hepatitis B and C. We assessed the uptake, acceptability and interpretability of self-testing using a 3-in-1 rapid diagnostic test (RDT) in facility-based services. Stand-alone testing services were provided free of charge to consenting individuals aged ≥15 years in five facilities in northern Thailand. Clients were invited to choose between self-testing by fingerprick or venepuncture by a healthcare worker (HCW). In each facility, several clients could simultaneously self-test in separate private areas using TriQuik™ (Genlantis, San Diego, CA, USA), a single immunochromatographic cassette detecting HIV-1/2 antibody, hepatitis B surface antigen (HBsAg) and hepatitis C antibody (HCAb). An interactive program on a tablet computer was developed to collect socio-demographic, behavioural and satisfaction data and provide information to guide the self-test process, including video instructions, results interpretation and a picture of the cassette for immediate remote review by the HCW. When the HCW interpreted an HIV self-test as positive, the HCW collected blood by venepuncture for immediate confirmation. Between October 2020 and April 2022, 4119 clients presented for testing for the first time as part of the project. Of them, 3462 (84.0%) opted for self-testing. Among self-testers, 1801 (52.0%) were born female, the median age was 27 years (interquartile range, 22-36), 661 (19.1%) belonged to at least one key population and 2124 (61.4%) had never been tested for HIV; 3329 (99.8% of those who answered) reported being "very satisfied" or "satisfied" with the testing process. The proportions of test results interpreted as positive by self-testers among those interpreted as positive by HCWs were 95% for HIV-1/2 antibody, 95% for HBsAg and 78% for HCAb. These proportions were higher than those observed in a previous study evaluating another 3-in-1 RDT for HIV, HBsAg and HCAb, possibly due to the use of video instructions instead of paper-based instructions, lower prevalence and co-infection rates, or lower percentages of clients with low education level. Multiplex self-testing simplified and streamlined the service delivery process and was well accepted. HCW assistance proved to be essential in a limited number of cases.
In 188 HIV-infected children receiving efavirenz, a lower mid-dose (C12) was associated with a higher risk of HIV-1 viral load >400 copies/mL (P = 0.03). Simulations for a normalized population receiving US Food and Drug Administration weight-band dosing predicted that 15% of children would have a C12 below target threshold (<1.0 mg/L) with a 23% risk of viral replication.
Data evaluating the risk of proximal tubular dysfunction in women receiving tenofovir disoproxil fumarate for the prevention of mother-to-child transmission (PMTCT) of HBV are scarce. To assess the risk of proximal tubulopathy in pregnant women receiving tenofovir disoproxil fumarate for PMTCT of HBV. We used urine samples collected from HBV monoinfected pregnant women who participated in a Phase III, multicentre, randomized, double-blind, placebo-controlled clinical trial assessing a tenofovir disoproxil fumarate short course from 28 weeks gestational age (28-wk-GA) to 2 months post-partum (2-months-PP) for PMTCT of HBV in Thailand. Markers of tubular dysfunction, including retinol binding protein, kidney injury molecule-1, α1-microglobuin and β2-microglobulin, were assayed at 28- and 32-wk-GA and 2-months-PP visits. Proximal tubulopathy was defined as the presence of ≥2 of the following: tubular proteinuria, euglycaemic glycosuria and increased urinary phosphate. A total of 291 women participated in the study. No kidney-related adverse events were severe, and none led to tenofovir disoproxil fumarate discontinuation. At 2-months-PP, 3 of the 120 (3%) evaluated women in the tenofovir disoproxil fumarate group experienced proximal tubulopathy versus 3 of 125 (2%) in the placebo group (P = 1.00). None of the six women met the criteria for proximal tubulopathy at 12-months-PP but proteinuria persisted in three of them. No growth abnormalities were found at 1 year of age in infants born to mothers with proximal tubulopathy at 2-months-PP. In these HBV-infected pregnant and breastfeeding women, tenofovir disoproxil fumarate administered from 28-wk-GA to 2-months-PP was not associated with a higher risk of proximal tubulopathy.
Background: Dolutegravir dispersible tablets (DTG-DT) are approved for infants ≥4 weeks and ≥3 kg but their suitability for neonates remains unknown. Methods: PETITE-DTG is a Phase I/II, open-label, single center, two-stage trial in South Africa to evaluate the pharmacokinetics (PK) and safety of DTG in term neonates of pregnant individuals receiving DTG-based therapy. In Stage 1, neonates on standard antiretroviral prophylaxis received a single dose of 5 mg DTG-DT between ≥14 and <28 days of life (Cohort 1A); or <14 days of life (Cohort 1B), followed by PK and safety assessments. A population PK model was developed and multi-dose scenarios simulated [DTG targets: geometric mean (GM) C tau >0.67 µg/mL and C max <17.0 µg/mL]. Results: 16 neonates, 8 per cohort, completed Stage 1. Median (range) birth weight was 3.1 (2.6-4.2) kg and PK sampling was performed between 3-22 days of life. No Grade 3 or higher adverse events were observed. DTG clearance was influenced by body weight and postnatal age. Simulations predicted that >10% of neonates would have a C max >17.0 µg/mL with DTG once daily (q24) during the first 2 weeks of life. Administration of DTG every 48 hours (q48) from day 1-14 of life, followed by DTG every 24 hours through day 28, predicted a GM C tau between 0.86-4.35 µg/mL; 98% with a C max <17.0 µg/mL. Conclusions: Due to the slow postnatal DTG clearance after birth, a multi-dose strategy of 5 mg DTG-DT q48 for the first 2 weeks of life, followed by q24 through 28 days, was selected for assessment in Stage 2.
