Objectives
The aim of the study was to explore factors associated with CD4 percentage (CD4%) reconstitution following treatment interruptions (TIs) of antiretroviral therapy (ART).
Methods
Data from ...paediatric HIV‐infected cohorts across 17 countries in Europe and Thailand were pooled. Children on combination ART (cART; at least three drugs from at least two classes) for > 6 months before TI of ≥ 30 days while aged < 18 years were included. CD4% at restart of ART (r‐ART) and in the long term (up to 24 months after r‐ART) following the first TI was modelled using asymptotic regression.
Results
In 779 children with at least one TI, the median age at first TI was 10.1 interquartile range (IQR) 6.4, 13.6 years and the mean CD4% was 27.3% standard deviation (SD) 11.0%; the median TI duration was 9.0 (IQR 3.5, 22.5) months. In regression analysis, the mean CD4% was 19.2% 95% confidence interval (CI) 18.3, 20.1% at r‐ART, and 27.1% (26.2, 27.9%) in the long term, with half this increase in the first 6 months. r‐ART and long‐term CD4% values were highest in female patients and in children aged < 3 years at the start of TI. Long‐term CD4% was highest in those with a TI lasting 1 to <3 months, those with r‐ART after year 2000 and those with a CD4% nadir ≥ 25% (all P < 0.001). The effect of CD4% nadir during the TI differed significantly (P = 0.038) by viral suppression at the start of the TI; in children with CD4% nadir < 15% during TI, recovery was better in those virally suppressed prior to the TI; viral suppression was not associated with recovery in children with CD4% nadir ≥ 25%.
Conclusions
After restart of ART following TI, most children reconstituted well immunologically. Nevertheless, several factors predicted better immunological reconstitution, including younger age and higher nadir CD4% during TI.
As antiretroviral treatment (ART) programs mature, data on drug utilization and costs are needed to assess durability of treatments and inform program planning.
Children initiating ART were followed ...up in an observational cohort in Thailand. Treatment histories from 1999 to 2009 were reviewed. Treatment changes were categorized as: drug substitution (within class), switch across drug class (non nucleoside reverse-transcriptase inhibitors (NNRTI) to/from protease inhibitor (PI)), and to salvage therapy (dual PI or PI and NNRTI). Antiretroviral drug costs were calculated in 6-month cycles (US$ 2009 prices). Predictors of high drug cost including characteristics at start of ART (baseline), initial regimen, treatment change, and duration on ART were assessed using mixed-effects regression models.
Five hundred seven children initiated ART with a median 54 (interquartile range, 36-72) months of follow-up. Fifty-two percent had a drug substitution, 21% switched across class, and 2% to salvage therapy. When allowing for drug substitution, 78% remained on their initial regimen. Mean drug cost increased from $251 to $428 per child per year in the first and fifth year of therapy, respectively. PI-based and salvage regimens accounted for 16% and 2% of treatments prescribed and 33% and 5% of total costs, respectively. Predictors of high cost include baseline age ≥ 8 years, non nevirapine-based initial regimen, switch across drug class, and to salvage regimen (P < 0.005).
At 5 years, 21% of children switched across drug class and 2% received salvage therapy. The mean drug cost increased by 70%. Access to affordable second- and third-line drugs is essential for the sustainability of treatment programs.
A trial to compare the reactogenicity and immunogenicity of a reduced antigen content diphtheria–tetanus–acellular pertussis (dTpa) vaccine with diphtheria–tetanus–whole-cell pertussis (DTPw) vaccine ...was conducted in Thailand. Three hundred and thirty children aged 4–6 years, primed with four doses of DTPw, received a single injection of either dTpa or DTPw. There was a significantly lower incidence of local and general reactions following dTpa than DTPw (
P<0.001). One month after vaccination, 99.4 and 100% of all subjects had protective anti-diphtheria and -tetanus titers, respectively. The vaccine response rate to pertussis antigens was similar in both groups, with 96.9% versus 92.5% for anti-pertussis toxin (PT), 96.9% versus 97.5% for anti-filamentous hemagglutinin (FHA) and 95.1% versus 90.8% for anti-pertactin (PRN) in the dTpa and DTPw groups, respectively. For anti-BPT, the vaccine response in the dTpa group was 29.6% versus 94.4% for DTPw. In conclusion, the dTpa vaccine was as immunogenic and significantly better tolerated than DTPw. The new dTpa vaccine could improve coverage for routine booster vaccination in children and provide a good replacement for DTP vaccines at 4–6 years of age.
To access the long term relationship between efavirenz plasma concentrations and evolution of HIV RNA loads and CD4 cell counts in children.
Retrospective analysis of data from HIV-infected children ...on first line efavirenz-containing regimen. A population pharmacokinetic-pharmacodynamic (PK-PD) model was developed to describe the evolution of HIV RNA load and CD4 cell count (efficacy outcomes) in relation to efavirenz plasma concentration. Individual CYP2B6 516 G>T genotype data were not available for this analysis. A score (ISEFV) quantifying the effect of efavirenz concentrations on the long-term HIV replication was calculated from efavirenz concentrations and PD parameters and, a value of ISEFV below which HIV replication is likely not suppressed was determined. Cox proportional hazards regression models were used to assess the association of the risk of viral replication with ISEFV, and with efavirenz mid-dose concentration(C12).
At treatment initiation, median (interquartile range, IQR) age was 8 years (5 to 10), body weight 17 kg (14 to 23), HIV RNA load 5.1 log10 copies/mL (4.6 to 5.4), and CD4 cell count 71 cells/mm3. A model of PK-PD viral dynamics assuming that efavirenz decreases the rate of infected host cells adequately described the relationship of interest. After adjusting for age, baseline HIV RNA load and CD4 cell counts an ISEFV <85% was significantly associated with a higher risk of viral replication (p-value <0.001) while no significant association was observed with C12 <1.0 mg/L.
The ISEFV score was a good predictor of viral replication in children on efavirenz-based treatment.
Previous studies have shown low frequencies of seroreactivity to HIV diagnostic assays for infected infants treated with antiretroviral therapy (ART) early in infection.
Fifty-eight HIV-infected ...infants treated with ART at a median age of 1.9 months (range: 0.2-5.4) for up to 4 years of life were assessed for seroreactivity to 4 routinely used HIV clinical immunoassays (IA): Second-generation (2ndG) IA and 2 rapid diagnostic tests (RDT), based on third-generation principles, measuring antibody only and a fourth-generation (4thG) antigen/antibody IA. HIV Western blot assay was also performed to assess HIV-specific antibodies.
The 2ndG IA demonstrated the highest frequency of seroreactivity in children (69%) followed by the 4thG IA (40%) and the RDT (26%) after one year of ART. Infants initiating ART during ages 3-6 months (N = 15) showed a greater frequency (range: 53%-93%) and breadth (median and range: 3 1-4) of reactivity across the assays compared with those treated within 3 months (N = 43):16%-61% and breadth (1 0-4). The 4thG IA showed significantly reduced reactivity relative to the 2ndG IA at one (P = 0.016) and 3 (P = 0.004) years of ART. Western blot profiles following 3 years of ART showed the highest frequency of reactivity to HIV Gag p24 (76%) and lowest reactivity to Env gp120 and gp41, with only 24% of children confirmed positive by the assay.
These results suggest that the use of 4thG IA and RDT test combination algorithms with limited HIV antigen breadth may not be adequate for diagnosis of HIV-infected children following early treatment.
Introduction
Early initiation of antiretroviral therapy (ART) can reduce HIV‐related morbidity and mortality in HIV‐positive infants. We implemented an Active Case Management Network to promote early ...ART initiation Aiming for Cure (ACC) in August 2014. We describe ACC implementation, early infant diagnosis (EID) coverage and ART initiation during August 2014 to July 2018 compared with a national EID survey during October 2007 to September 2011 (pre‐ACC).
Methods
Thailand's 2014 HIV Treatment Guidelines recommend that HIV‐exposed infants have HIV polymerase chain reaction (PCR) testing at birth, one month and at two to four months. Testing is done at 14 national HIV PCR laboratories. When an HIV‐positive infant (HIV PCR+) is identified, PCR laboratory staff send the result to the hospital staff responsible for the infant's care and to the national laboratory case manager (CM). As part of ACC, the national laboratory CM alerts a regional CM who contacts the hospital staff caring for the infant to offer technical support with ART initiation and ART adherence. CMs enter clinical, demographic and laboratory data into the national ACC database. We analysed the ACC data from August 2014 to July 2018 to assess the ACC's impact on EID coverage, ART initiation and time‐to‐ART initiation.
Results
The uptake of EID increased from 64% (pre‐ACC) to >95% in 2018 (ACC). The number of HIV‐positive infants born declined from 429 cases (pre‐ACC) to 267 cases (ACC). Median age at the first‐positive PCR declined from 75 days (pre‐ACC) to 60 days (ACC); P < 0.001. Among 429 infants diagnosed before ACC was started, 241 (56%) received ART; during ACC, 235 (88%) of 267 HIV‐positive infants received ART. The median age at ART initiation declined from 282 days before ACC to 83 days during ACC (P < 0.001) and the median time from blood collection to ART initiation declined from 168 days before ACC to 23 days during ACC (P < 0.001).
Conclusions
An innovative case management network (ACC) has been established in Thailand and results suggest that the network is promoting EID and early ART initiation. The ACC model, using case‐managed PCR notification and follow‐up, may speed ART initiation in other settings.
Nevirapine (NVP) is a key component of antiretroviral prophylaxis and treatment for neonates. We evaluated current World Health Organization (WHO) weight-band NVP prophylactic dosing recommendations ...and investigated optimal therapeutic NVP dosing for neonates.
The PHPT-5 study in Thailand assessed the efficacy of "Perinatal Antiretroviral Intensification" to prevent mother-to-child transmission of HIV in women with <8 weeks of antiretroviral treatment before delivery (NCT01511237). Infants received a 2-week course of zidovudine/lamivudine/NVP (NVP syrup/once daily: 2 mg/kg for 7 days; then 4 mg/kg for 7 days). Infant samples were assessed during the first 2 weeks of life. NVP population pharmacokinetics (PK) parameters were estimated using nonlinear mixed-effects models. Simulations were performed to estimate the probability of achieving target NVP trough concentrations for prophylaxis (>0.10 mg/L) and for therapeutic efficacy (>3.0 mg/L) using different infant dosing strategies.
Sixty infants (55% male) were included. At birth, median (range) weight was 2.9 (2.3-3.6) kg. NVP concentrations were best described by a 1-compartment PK model. Infant weight and postnatal age influenced NVP PK parameters. Based on simulations for a 3-kg infant, ≥92% would have an NVP trough >0.1 mg/L after 48 hours through 2 weeks using the PHPT-5 and WHO-dosing regimens. For NVP-based therapy, a 6-mg/kg twice daily dose produced a trough >3.0 mg/L in 87% of infants at 48 hours and 80% at 2 weeks.
WHO weight-band prophylactic guidelines achieved target concentrations. Starting NVP 6 mg/kg twice daily from birth is expected to achieve therapeutic concentrations during the first 2 weeks of life.
Our objective was to analyze, in formula-fed infants, correlates of HIV mother-to-child transmission, including cytomegalovirus (CMV) infection. HIV-infected infants were matched with HIV uninfected ...by maternal HIV RNA in a case-control design. Infant CMV infection was determined by CMV IgG at 18 months and timed by earlier CMV IgM or CMV DNA. Correlations were assessed using logistic regression. In utero HIV infection was independently associated with congenital CMV infection (P = 0.01), intrapartum HIV infection with congenital-plus-intrapartum/neonatal CMV infection (P = 0.01), and overall HIV with overall CMV infection (P = 0.001), and prematurity (P = 0.004). Congenital and acquired CMV infections are strong independent correlates of mother-to-child HIV transmission.
Abstract Background Despite implementation of universal infant hepatitis B (HB) vaccination, mother-to-child transmission (MTCT) of hepatitis B virus (HBV) still occurs. Limited data are available on ...the residual MTCT of HBV in human immunodeficiency virus (HIV)-HBV co-infected women. Objectives We assessed the prevalence of HBV infection among HIV-infected pregnant women and the rate of residual MTCT of HBV from HIV-HBV co-infected women and analyzed the viral determinants in mothers and their HBV-infected children. Study design HIV-1 infected pregnant women enrolled in two nationwide perinatal HIV prevention trials in Thailand were screened for HB surface antigen (HBsAg) and tested for HBeAg and HBV DNA load. Infants born to HBsAg-positive women had HBsAg and HBV DNA tested at 4–6 months. HBV diversity within each HBV-infected mother–infant pair was analyzed by direct sequencing of amplified HBsAg-encoding gene and cloning of amplified products. Results Among 3312 HIV-1 infected pregnant women, 245 (7.4%) were HBsAg-positive, of whom 125 were HBeAg-positive. Of 230 evaluable infants born to HBsAg-positive women, 11 (4.8%) were found HBsAg and HBV DNA positive at 4–6 months; 8 were born to HBeAg-positive mothers. HBV genetic analysis was performed in 9 mother–infant pairs and showed that 5 infants were infected with maternal HBV variants harboring mutations within the HBsAg “a” determinant, and four were infected with wild-type HBV present in highly viremic mothers. Conclusions HBV-MTCT still occurs when women have high HBV DNA load and/or are infected with HBV variants. Additional interventions targeting highly viremic women are thus needed to reduce further HBV-MTCT.
Whipple procedure is the most complex abdominal surgical procedure to treat periampullary carcinoma. With the benefit of minimally invasive approach, many institutes attempt to do Whipple procedure ...laparoscopically. However, only 146 cases of laparoscopic Whipple procedure have yet been reported in the literature worldwide between 1994 and 2008. The authors reported the first laparoscopic Whipple procedure at Hat Yai Hospital in December 2009. The patient was a 40-year-old, Thai-Muslim female, with the diagnosis of ampullary carcinoma. The operating time was 685 minutes. The patient was discharged on postoperative day 14 without serious complication. The surgical technique and postoperative progress of the patient were described.
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