Analyse du mécanisme et moment de la transmission mère-enfant du VIH par des approches fondées sur des modèles intégrant des données historiques

Grâce aux combinaison d’antirétroviraux (ART), le taux de transmission mère-enfant (TME) du Virus de l’Immunodéficience Humaine VIH est maintenant réduit à moins de 1%. Des progrès restent néanmoins à faire, en particuliers chez les femmes débutant tardivement leurs consultations prénatales. Mais l’évaluation de nouvelles stratégies ART pour la prévention de la TME (PTME) devient de plus en plus complexe à cause des exigences statistiques liées au fait que les transmissions sont rares. Dés lors, il devient crucial de modéliser l’efficacité des ART sur la charge virale (CV) et la transmission. Dans cette thèse, nous modélisons les mécanismes et le moment de la TME du VIH en utilisant des modèles mixtes. Les données proviennent de 4 études de prévention périnatales du VIH en Thaïlande (PHPT-1, PHPT-2, PHPT-5 1st phase et PHPT-5 2nd phase), une base de données historiques de qualité, collectées de 1996 à 2015, où différentes prophylaxies ART ont été prescrites à plus de 4000 femmes enceintes pendant des durées variables: Zidovudine (ZDV) seule; ZDV + une dose unique de nevirapine périnatale (sdNVP); ZDV+lopinavir/ritonavir (LPV/r) ou ZDV+LPV/r+lamivudine (3TC). Les modèles développés apportent un éclairage sur les mécanismes et le moment de la PTME ainsi que sur le rôle respectif de différents ART sur la réduction de la CV et sur leur contribution à la prophylaxie pre/post exposition. Partant de ces connaissances, une approche bayésienne est appliquée à une étude de cas (essai de supériorité dans le contexte d’un événement rare comme la TME du VIH) afin d’améliorer la puissance statistique tout en limitant la taille de l’échantillon, et comparée à une approche fréquentiste.Nowadays, with the use of highly efficacious antiretroviral (ART) combination, the rate of mother-to-child transmission (MTCT) of Human Immunodeficiency Virus (HIV) is reduced to less than 1%. However, there are still some gaps to be filled, especially in women who initiate antenatal prophylaxis late. The evaluation of new ART strategies or drug combinations for the prevention of MTCT (PMTCT) of HIV becomes more difficult in view of the statistical requirements in case of rare outcomes. Therefore modeling the impact of ART on maternal viral load (VL) and transmission rate is increasingly important. In this thesis, the mechanisms and timing of MTCT of HIV were investigated using mixed model approaches. Data were derived from four perinatal HIV prevention studies in Thailand (PHPT-1, PHPT-2, PHPT-5 1st phase and PHPT-5 2nd phase), a unique set of quality historical data, consistently collected from 1996 to 2015, in which different ART prophylaxis regimens were provided to more than 4000 HIV-infected pregnant women for varying durations: Zidovudine (ZDV) alone; ZDV plus perinatal single dose nevirapine; ZDV+lopinavir/ritonavir (LPV/r) or ZDV+LPV/r+lamivudine. The developed models provide insights on the mechanisms and timing of PMTCT as well as on the respective role of different ARTs on the maternal VL reduction and in turn on their contribution to pre/post-exposure prophylaxis in MTCT of HIV. With this prior knowledge, a Bayesian design is applied to a case study, a trial aimed at evaluating treatment superiority in the context of rare outcomes such as MTCT of HIV, to improve the statistical power –while limiting sample size— and compared to a frequentist design

Association between Sociodemographic Factors and Condom Use among Migrant Sex Workers in Chiang Mai, Northern Thailand

Thailand has the highest HIV burden in the Asia-Pacific region, with the majority of cases occurring in specific populations. Migrant Sex Workers (MSWs) in Thailand are an important population for HIV risk, yet there has been limited literature on this group and their protective sexual behavior. A cross-sectional study was conducted among 396 MSWs 18–49 years old from 23 sex work-identified venues in Chiang Mai. Participants were surveyed on their own sociodemographic information, health behavior, sexual risk behavior, quality of life, and depression. Male respondents were significantly younger than females (p = 0.003). Most respondents were from Myanmar and were ethnic Shan. In the month preceding the survey, 17.0% of MSWs had consistent condom use with regular partners, 53.7% with casual partners, and 87.9% with clients. Condom use was least practiced with regular partners and most practiced with clients (17% and 87.9%, respectively; p < 0.001). There was a significant positive association between condom use and starting high school (χ2 = 8.08, p = 0.018). Education was the only variable that was significantly correlated with condom use with any sexual partner (OR = 0.41; 95%CI 0.20–0.82). Findings of the study indicate that further efforts are needed to promote condom use among migrant sex workers and their sexual partners in Thailand

Characteristics, clinical outcomes, and mortality of older adults living with HIV receiving antiretroviral treatment in the sub-urban and rural areas of northern Thailand

Since the introduction of antiretroviral treatment (ART), people living with HIV worldwide live into older age. This observational study described the characteristics, clinical outcomes, and mortality of older adults living with HIV (OALHIV) receiving ART from the National AIDS program in northern Thailand. Participants aged ≥ 50 years were recruited from the HIV clinics in 12 community hospitals. Data were obtained from medical records and face-to-face interviews. In 2015, 362 OALHIV were enrolled; their median (interquartile range) age and ART duration were 57 years (54–61), and 8.8 years (6.4–11.2), respectively. At study entry, 174 (48.1%) had CD4 counts ≥ 500 cells/mm3; 357 of 358 (99.6%) with available HIV RNA results were virologic-suppressed. At the year 5 follow-up, 39 died, 11 were transferred to other hospitals, 3 were lost to follow-up, and 40 did not contribute data for this analysis, but remained in care. Among the 269 who appeared, 149 (55%) had CD4 counts ≥ 500 cells/mm3, and 227/229 tested (99%) were virologic-suppressed. The probability of 5-year overall survival was 89.2% (95% confidence interval, CI 85.4–92.1%). A significantly low 5-year overall survival (66%) was observed in OALHIV with CD4 counts < 200 cells/mm3 at study entry. The most common cause of death was organ failure in 11 (28%), followed by malignancies in 8 (21%), infections in 5 (13%), mental health-related conditions in 2 (5%), and unknown in 13 (33%). In OALHIV with stable HIV treatment outcomes, mortality from non-infectious causes was observed. Monitoring of organ function, cancer surveillance, and mental health screening are warranted

Characteristics, clinical outcomes, and mortality of older adults living with HIV receiving antiretroviral treatment in the sub-urban and rural areas of northern Thailand.

Since the introduction of antiretroviral treatment (ART), people living with HIV worldwide live into older age. This observational study described the characteristics, clinical outcomes, and mortality of older adults living with HIV (OALHIV) receiving ART from the National AIDS program in northern Thailand. Participants aged ≥ 50 years were recruited from the HIV clinics in 12 community hospitals. Data were obtained from medical records and face-to-face interviews. In 2015, 362 OALHIV were enrolled; their median (interquartile range) age and ART duration were 57 years (54-61), and 8.8 years (6.4-11.2), respectively. At study entry, 174 (48.1%) had CD4 counts ≥ 500 cells/mm3; 357 of 358 (99.6%) with available HIV RNA results were virologic-suppressed. At the year 5 follow-up, 39 died, 11 were transferred to other hospitals, 3 were lost to follow-up, and 40 did not contribute data for this analysis, but remained in care. Among the 269 who appeared, 149 (55%) had CD4 counts ≥ 500 cells/mm3, and 227/229 tested (99%) were virologic-suppressed. The probability of 5-year overall survival was 89.2% (95% confidence interval, CI 85.4-92.1%). A significantly low 5-year overall survival (66%) was observed in OALHIV with CD4 counts < 200 cells/mm3 at study entry. The most common cause of death was organ failure in 11 (28%), followed by malignancies in 8 (21%), infections in 5 (13%), mental health-related conditions in 2 (5%), and unknown in 13 (33%). In OALHIV with stable HIV treatment outcomes, mortality from non-infectious causes was observed. Monitoring of organ function, cancer surveillance, and mental health screening are warranted

A comparison of performance between a deep learning model with residents for localization and classification of intracranial hemorrhage

Abstract Intracranial hemorrhage (ICH) from traumatic brain injury (TBI) requires prompt radiological investigation and recognition by physicians. Computed tomography (CT) scanning is the investigation of choice for TBI and has become increasingly utilized under the shortage of trained radiology personnel. It is anticipated that deep learning models will be a promising solution for the generation of timely and accurate radiology reports. Our study examines the diagnostic performance of a deep learning model and compares the performance of that with detection, localization and classification of traumatic ICHs involving radiology, emergency medicine, and neurosurgery residents. Our results demonstrate that the high level of accuracy achieved by the deep learning model, (0.89), outperforms the residents with regard to sensitivity (0.82) but still lacks behind in specificity (0.90). Overall, our study suggests that the deep learning model may serve as a potential screening tool aiding the interpretation of head CT scans among traumatic brain injury patients

Comparison of antibody responses following natural infection with Severe Acute Respiratory Syndrome Coronavirus 2 or receipt of CoronaVac or ChAdOx1 (AZD1222) vaccination in Chiang Mai, Thailand

Background: In Thailand, early vaccination initiatives for SARS-CoV-2 relied on CoronaVac (Sinovac Life Sciences) and ChAdOx1 (Oxford–AstraZeneca) vaccines. However, the data of immunogenicity of these two vaccines in Thai populations is limited. This real time, head-to-head comparative study was conducted to investigate antibody (Ab) responses to SARS-CoV-2 following infection or receipt of either CoronaVac or ChAdOx1 vaccination in Chiang Mai, Thailand. Methods: Sera was collected within two months from participants having a history of documented SARS-CoV-2 infection or at one month after the second dose of CoronaVac vaccine. Sera from participants with a history of receiving one dose of ChAdOx1 vaccination was collected twice, at one month following each vaccine dose. Neutralizing antibodies (NAbs) were assessed using the surrogate neutralization test and anti-spike protein antibodies were assessed using an in-house enzyme-linked immunosorbent assay. Results: The prevalence of NAbs against SARS-CoV-2 was 92.1 %, 95.7 %, 64.1 % and 100 % in the infection group, CoronaVac group, ChAdOx1 group after 1st dose, and ChAdOx1 group after 2nd dose, respectively. The inhibition rate in individuals receiving two doses of ChAdOx1 vaccine (90.8%) was significantly higher than individuals who had recovered from natural infection (71.7%) or individuals who had received two doses of CoronaVac vaccine (66.7%). The prevalence of anti-spike Abs was 97.4 %, 97.8 %, 97.4 % and 100 % in the infection group, CoronaVac group, ChAdOx1 group after 1st dose, and ChAdOx1 group after 2nd dose, respectively. Significantly higher levels of anti-spike Abs were observed in the ChAdOx1 group after two doses of vaccination (1975 AU/mL) compared to those who had recovered from natural infection (468.5 AU/mL) and individuals who had received CoronaVac (554.4 AU/mL). Neutralizing activity had a statistically significant positive correlation with levels of anti-spike Abs. Conclusions: ChAdOx1 vaccine may provide superior immunogenicity than CoronaVac and natural infection

Clinical outcomes and dosimetric study of hypofractionated Helical TomoTherapy in breast cancer patients.

We present a single center's experience of treatment outcomes and dosimetric parameters for breast cancer patients treated with hypofractionated Helical TomoTherapy (HT). This is a retrospective study of one hundred and thirty-six patients with invasive breast cancer treated between March 2012 and October 2016. Dosimetric parameters and 3-year loco-regional failure free survival (LRFFS) were analyzed. Dose to ipsilateral lung, heart and contralateral breast as well as acute and late toxicities were recorded. The median follow-up time is 45 months (range: 5-83). Two patients had loco-regional failure. The 3-year LRFFS was 99%. Acute grade 1 and 2 skin toxicities occurred in 95% and 1%, respectively. Coverage of the target volumes was achieved with the mean ± standard deviation (SD) of homogeneity and conformity index being 0.1 ± 0.04, and 0.8 ± 0.07, respectively. Dose to ipsilateral lung, contralateral breast, and heart was also within the limited constraints regardless of the complexity of target volumes. Only two percent of patients experienced late grade 2 skin toxicity. No late grade 2 subcutaneous tissue toxicity was found. Nine percent of patients developed late grade 1 lung toxicity. Hypofractionated radiotherapy using Helical TomoTherapy in breast irradiation provides excellent 3-year LRFFS and minimal acute and late toxicities. A careful, longer follow-up of healthy tissue effects to lung, heart, and contralateral breast is warranted

Caesarean delivery is associated with increased blood pressure in young adult offspring

We examined the associations between caesarean section (CS) delivery and cardiovascular risk factors in young adults in Thailand. Participants were 632 offspring from a birth cohort in Chiang Mai (Northern Thailand), born in 1989-1990 and assessed in 2010 at a mean age of 20.6 years, including 57 individuals (9.0%) born by CS and 575 born vaginally. Clinical assessments included anthropometry, blood pressure (BP), carotid intima-media thickness, and fasting blood glucose, insulin, and lipid profile. Young adults born by CS had systolic BP (SBP) 6.2 mmHg higher (p&lt;0.001), diastolic BP 3.2 mmHg higher (p=0.029), and mean arterial pressure (MAP) 4.1 mmHg higher (p=0.003) than those born vaginally. After covariate adjustments, SBP and MAP remained 4.1 mmHg (p=0.006) and 2.9 mmHg (p=0.021) higher, respectively, in the CS group. The prevalence of abnormal SBP (i.e., pre-hypertension or hypertension) in the CS group was 2.5 times that of those born vaginally (25.0% vs 10.3%; p=0.003), with an adjusted relative risk of abnormal SBP 1.9 times higher (95% CI 1.15, 2.98; p=0.011). There were no differences in anthropometry (including obesity risk) or other metabolic parameters. In this birth cohort in Thailand, CS delivery was associated with increased blood pressure in young adulthood

The outcome of the first 100 nasopharyngeal cancer patients in thailand treated by helical tomotherapy

The aim of the study was to analyse of two-year loco-regional failure free survival (LRFFS), distant metastasis free survival (DMFS), overall survival (OS), and toxicity outcomes of the first 100 nasopharyngeal carcinoma patients in Thailand treated by helical tomotherapy