13 research outputs found
HIV drug resistance profile of HIV-1 CRF 01_AE protease and integrase coding regions in HIV infected Cambodian patients failing LPV-based 2nd line antiretroviral regimen
Simplified Assessment of Antiretroviral Adherence and Prediction of Virological Efficacy in HIV-Infected Patients in Cambodia
Background. Adherence to antiviral therapy is important for HIV-infected people living in low- and middle-income countries, because of poor access to alternative regimens. Methods. We conducted a cross-sectional survey of adherence in Cambodian patients enrolled in the ESTHER program and treated with WHO first-line regimen for at least 6 months. The survey was based on a self-report questionnaire, drug assay, MCV measurement, visual analog scale, and viral load HIV RNA. Results. Two hundred fifty-nine patients treated for a median of 16 months participated in the survey. At inclusion in the program, 158 patients (61%) were ARV-naĂŻve. The virological success rate was 71% overall and 81% in previously ARV-naive patients. Considered individually, the measures suggested perfect adherence in 71% to 93% of patients. In multivariate analysis adjusted for sex and therapeutic status before HAART initiation, only the biological markers were associated with virological efficacy. Self-funded treatment before entry to the program was highly predictive of virological failure. Conclusion. Adherence was excellent in these Cambodian patients. Biological markers were predictive of virological efficacy. MCV might thus serve as a simple alternative for assessing adherence and predicting virological efficacy among patients receiving AZT- or d4T-based regimens
High efficacy of lopinavir/r-based second-line antiretroviral treatment after 24 months of follow up at ESTHER/Calmette Hospital in Phnom Penh, Cambodia
<p>Abstract</p> <p>Background</p> <p>The number of patients on second-line highly active antiretroviral therapy (HAART) regimens is increasing in resource-limited settings. We describe the outcomes after 24 months for patients on LPV/r-based second-line regimens followed up by the ESTHER programme in Phnom Penh, Cambodia.</p> <p>Methods</p> <p>Seventy patients who initiated second-line HAART regimens more than 24 months earlier were included, and immuno-virological data analyzed. HIV RNA viral load was determined by real-time RT-PCR. HIV-1 drug resistance was interpreted according to the ANRS algorithm.</p> <p>Results</p> <p>Of the 70 patients, two were lost to follow up, three died and 65 (92.8%) remained on second-line treatment after 24 months of follow up (median duration of treatment: 27.4 months). At switch to second-line, the median CD4 T cell count was 106 cells/mm<sup>3 </sup>and the median viral load was 4.7 Log<sub>10</sub>. Second-line regimens prescribed were ddI/3TC/LPV<sub>/r </sub>(65.7%), ddI/TDF/LPV<sub>/r </sub>(10.0%), ddI/AZT/LPV<sub>/r </sub>(8.6%) and TDF/3TC/LPV<sub>/r </sub>(7.1%). The median CD4 T cell gain was +258 cells/mm<sup>3 </sup>at 24 months (n = 63). After 24 months of follow up, 92.3% (60/65) of the patients presented undetectable viral loads, giving an overall treatment success rate of 85.7% (CI: 75.6- 92.0) in intent-to-treat analysis.</p> <p>Conclusions</p> <p>These data suggest that a LPV<sub>/r</sub>-based second-line regimen is associated with a high rate of virological suppression and immune reconstitution after 24 months of follow up in Cambodia.</p
StratĂ©gie alternative de prĂ©vention de la transmission mĂšre-enfant de lâhĂ©patite B au Cambodge : lâĂ©tude ANRS 12345 TA PROHM
Mother-to-child transmission (MTCT) of hepatitis B virus (HBV) infection is the cause of most chronic hepatitis B in countries with high HBV endemicity. Prevention is based on early vaccination of newborns at birth and, for HBsAg-positive women, on the administration of antiviral treatment in the third trimester of pregnancy if the HBV DNA viral load is > 5.3 log10 IU/mL and immunoglobulin (HBIg) to the newborn. In Cambodia, the prevalence of HBV infection among pregnant women, children aged 5 to 7 years, and those born to HBsAg-positive mothers was estimated at 4%, 0.6%, and 10%, respectively.The objective of this thesis was to design and evaluate a strategy to reduce HBV MTCT in Cambodia using tools available in the country.This work was structured around the ANRS 12345 TA PROHM study which objective was to evaluate the effectiveness of an HBIg-free alternative strategy to prevent HBV MTCT in Cambodia based on 1/ the use of HBsAg and HBeAg rapid diagnostic tests (RDT) for the screening and management of HBV infection in peripartum 2/a treatment with tenofovir from 24 weeks of amenorrhea of eligible women 3/an early vaccination for all infants at birth ( 5.3 log10 IU/mL. A new algorithm selecting HBeAg-positive women and HBeAg-negative women with ALT > 40 U/L increased sensitivity by 17% for this viral load threshold and was used in the study from January 2019.From 2017 to 2020, 21,251 women were screened in antenatal care. Of these, 1194 could be included in the study, of whom 338 (28%) were eligible for TDF. In the absence of HBIg, the rate of HBV MTCT was 1.48% [CI95%, 0.40-3.74] for women eligible for TDF and 0% [CI95%, 0-1.41] for those treated more than one month before delivery. In contrast, the rate of HBV MTCT was 8.33% [CI95%, 1.75-22.5] for those treated less than one month, highlighting the importance of HBV early detection during pregnancy. For women not eligible for TDF, the transmission rate was 1.06% [CI95%, 0.39-2.30], with transmission occurring in highly viremic women not identified by the algorithm. This work shows that an HBIg-free alternative strategy using maternal antiviral prophylaxis with TDF for at least one month before delivery combined with an early infant vaccination at birth can prevent HBV MTCT. This strategy is applicable in decentralized areas, which is essential for countries such as Cambodia where access to technical facilities is limited to the capital or major provincial cities. Such a strategy needs to be implemented in rural settings, including an analysis of the costs and supply chains of drugs and reagents, to initiate the political commitment necessary for a nationwide scaling-up.La transmission mĂšre-enfant (TME) de lâinfection par le virus de lâhĂ©patite B (VHB) est Ă lâorigine de la plupart des hĂ©patites B chroniques dans les pays Ă forte endĂ©mie pour le VHB. La prĂ©vention repose sur la vaccination prĂ©coce des nouveau-nĂ©s a la naissance et, pour les femmes positives pour lâAgHBs, sur lâadministration dâun traitement antiviral au troisiĂšme trimestre si la charge virale VHB est > 5.3 log10 UI/mL et dâimmunoglobulines (HBIg) au nouveau-nĂ©. Au Cambodge, les prĂ©valences du VHB chez les femmes enceintes, les enfants ĂągĂ©s de 5 Ă 7 ans et chez ceux nĂ©s de mĂšres positives pour lâAgHBs ont Ă©tĂ© estimĂ©es Ă 4%, 0.6% et 10%, respectivement.Lâobjectif de cette thĂšse Ă©tait de concevoir et Ă©valuer un programme de rĂ©duction de la TME du VHB au Cambodge en utilisant une stratĂ©gie basĂ©e sur les outils disponibles dans le pays. Ce travail sâest construit autour de lâĂ©tude ANRS 12345 TA PROHM dont lâobjectif Ă©tait dâĂ©valuer lâefficacitĂ© dâune stratĂ©gie alternative sans HBIg de prĂ©vention de la TME du VHB au Cambodge basĂ©e sur 1/lâutilisation de tests de diagnostic rapides (TDR) AgHBs et AgHBe pour le dĂ©pistage et la prise en charge de lâinfection VHB en peripartum 2/un traitement par Tenofovir (TDF) Ă partir de 24 semaines dâamĂ©norrhĂ©e des femmes Ă©ligibles 3/une vaccination prĂ©coce pour tous les enfants Ă la naissance ( 5,3 log10 UI/mL. Un nouvel algorithme sĂ©lectionnant les femmes AgHBe positives et celles AgHBe nĂ©gatives avec un taux dâALAT > 40 U/L a permis dâaugmenter la sensibilitĂ© de 17% pour ce seuil de charge virale et a Ă©tĂ© utilisĂ© dans lâĂ©tude Ă partir de Janvier 2019.De 2017 Ă 2020, 21 251 femmes ont Ă©tĂ© dĂ©pistĂ©es en consultation antĂ©natale dans 5 hopitaux cambodgiens. Parmi elles, 1194 ont pu ĂȘtre incluses dans lâĂ©tude dont 338 (28%) Ă©taient Ă©ligibles au TDF. En lâabsence dâHBIg, le taux de TME du VHB Ă©tait de 1.48% [IC95%, 0.40-3.74] pour les femmes Ă©ligibles au TDF et de 0% [IC95%, 0-1.41] pour celles traitĂ©es plus d'un mois avant l'accouchement. Ce taux Ă©tait de 8.33% [IC95%, 1.75â22.5] pour celles traitĂ©es moins dâun mois, soulignant lâimportance du dĂ©pistage prĂ©coce pendant la grossesse. Pour les femmes non Ă©ligibles au TDF, le taux de transmission Ă©tait de 1.06% [IC95%, 0.39-2.30], la transmission survenant chez des femmes hautement virĂ©miques non dĂ©pistĂ©es par lâalgorithme.Ce travail montre quâune stratĂ©gie alternative sans HBIg utilisant un traitement antiviral prophylactique maternel par TDF pendant au moins un mois avant lâaccouchement associĂ© Ă une vaccination prĂ©coce du nourrisson Ă la naissance permet de prĂ©venir la TME du VHB. Cette stratĂ©gie est applicable en zones dĂ©centralisĂ©es, ce qui est essentiel pour des pays comme le Cambodge oĂč lâaccĂšs au plateau technique est limitĂ© aux capitales ou aux grandes villes. Une telle stratĂ©gie doit maintenant ĂȘtre implantĂ©e en zones rurales en intĂ©grant une analyse des coĂ»ts et des circuits dâapprovisionnement en mĂ©dicaments et rĂ©actifs afin dâamorcer lâengagement politique nĂ©cessaire pour un passage Ă lâĂ©chelle sur lâensemble du pays
StratĂ©gie alternative de prĂ©vention de la transmission mĂšre-enfant de lâhĂ©patite B au Cambodge : lâĂ©tude ANRS 12345 TA PROHM
Mother-to-child transmission (MTCT) of hepatitis B virus (HBV) infection is the cause of most chronic hepatitis B in countries with high HBV endemicity. Prevention is based on early vaccination of newborns at birth and, for HBsAg-positive women, on the administration of antiviral treatment in the third trimester of pregnancy if the HBV DNA viral load is > 5.3 log10 IU/mL and immunoglobulin (HBIg) to the newborn. In Cambodia, the prevalence of HBV infection among pregnant women, children aged 5 to 7 years, and those born to HBsAg-positive mothers was estimated at 4%, 0.6%, and 10%, respectively.The objective of this thesis was to design and evaluate a strategy to reduce HBV MTCT in Cambodia using tools available in the country.This work was structured around the ANRS 12345 TA PROHM study which objective was to evaluate the effectiveness of an HBIg-free alternative strategy to prevent HBV MTCT in Cambodia based on 1/ the use of HBsAg and HBeAg rapid diagnostic tests (RDT) for the screening and management of HBV infection in peripartum 2/a treatment with tenofovir from 24 weeks of amenorrhea of eligible women 3/an early vaccination for all infants at birth ( 5.3 log10 IU/mL. A new algorithm selecting HBeAg-positive women and HBeAg-negative women with ALT > 40 U/L increased sensitivity by 17% for this viral load threshold and was used in the study from January 2019.From 2017 to 2020, 21,251 women were screened in antenatal care. Of these, 1194 could be included in the study, of whom 338 (28%) were eligible for TDF. In the absence of HBIg, the rate of HBV MTCT was 1.48% [CI95%, 0.40-3.74] for women eligible for TDF and 0% [CI95%, 0-1.41] for those treated more than one month before delivery. In contrast, the rate of HBV MTCT was 8.33% [CI95%, 1.75-22.5] for those treated less than one month, highlighting the importance of HBV early detection during pregnancy. For women not eligible for TDF, the transmission rate was 1.06% [CI95%, 0.39-2.30], with transmission occurring in highly viremic women not identified by the algorithm. This work shows that an HBIg-free alternative strategy using maternal antiviral prophylaxis with TDF for at least one month before delivery combined with an early infant vaccination at birth can prevent HBV MTCT. This strategy is applicable in decentralized areas, which is essential for countries such as Cambodia where access to technical facilities is limited to the capital or major provincial cities. Such a strategy needs to be implemented in rural settings, including an analysis of the costs and supply chains of drugs and reagents, to initiate the political commitment necessary for a nationwide scaling-up.La transmission mĂšre-enfant (TME) de lâinfection par le virus de lâhĂ©patite B (VHB) est Ă lâorigine de la plupart des hĂ©patites B chroniques dans les pays Ă forte endĂ©mie pour le VHB. La prĂ©vention repose sur la vaccination prĂ©coce des nouveau-nĂ©s a la naissance et, pour les femmes positives pour lâAgHBs, sur lâadministration dâun traitement antiviral au troisiĂšme trimestre si la charge virale VHB est > 5.3 log10 UI/mL et dâimmunoglobulines (HBIg) au nouveau-nĂ©. Au Cambodge, les prĂ©valences du VHB chez les femmes enceintes, les enfants ĂągĂ©s de 5 Ă 7 ans et chez ceux nĂ©s de mĂšres positives pour lâAgHBs ont Ă©tĂ© estimĂ©es Ă 4%, 0.6% et 10%, respectivement.Lâobjectif de cette thĂšse Ă©tait de concevoir et Ă©valuer un programme de rĂ©duction de la TME du VHB au Cambodge en utilisant une stratĂ©gie basĂ©e sur les outils disponibles dans le pays. Ce travail sâest construit autour de lâĂ©tude ANRS 12345 TA PROHM dont lâobjectif Ă©tait dâĂ©valuer lâefficacitĂ© dâune stratĂ©gie alternative sans HBIg de prĂ©vention de la TME du VHB au Cambodge basĂ©e sur 1/lâutilisation de tests de diagnostic rapides (TDR) AgHBs et AgHBe pour le dĂ©pistage et la prise en charge de lâinfection VHB en peripartum 2/un traitement par Tenofovir (TDF) Ă partir de 24 semaines dâamĂ©norrhĂ©e des femmes Ă©ligibles 3/une vaccination prĂ©coce pour tous les enfants Ă la naissance ( 5,3 log10 UI/mL. Un nouvel algorithme sĂ©lectionnant les femmes AgHBe positives et celles AgHBe nĂ©gatives avec un taux dâALAT > 40 U/L a permis dâaugmenter la sensibilitĂ© de 17% pour ce seuil de charge virale et a Ă©tĂ© utilisĂ© dans lâĂ©tude Ă partir de Janvier 2019.De 2017 Ă 2020, 21 251 femmes ont Ă©tĂ© dĂ©pistĂ©es en consultation antĂ©natale dans 5 hopitaux cambodgiens. Parmi elles, 1194 ont pu ĂȘtre incluses dans lâĂ©tude dont 338 (28%) Ă©taient Ă©ligibles au TDF. En lâabsence dâHBIg, le taux de TME du VHB Ă©tait de 1.48% [IC95%, 0.40-3.74] pour les femmes Ă©ligibles au TDF et de 0% [IC95%, 0-1.41] pour celles traitĂ©es plus d'un mois avant l'accouchement. Ce taux Ă©tait de 8.33% [IC95%, 1.75â22.5] pour celles traitĂ©es moins dâun mois, soulignant lâimportance du dĂ©pistage prĂ©coce pendant la grossesse. Pour les femmes non Ă©ligibles au TDF, le taux de transmission Ă©tait de 1.06% [IC95%, 0.39-2.30], la transmission survenant chez des femmes hautement virĂ©miques non dĂ©pistĂ©es par lâalgorithme.Ce travail montre quâune stratĂ©gie alternative sans HBIg utilisant un traitement antiviral prophylactique maternel par TDF pendant au moins un mois avant lâaccouchement associĂ© Ă une vaccination prĂ©coce du nourrisson Ă la naissance permet de prĂ©venir la TME du VHB. Cette stratĂ©gie est applicable en zones dĂ©centralisĂ©es, ce qui est essentiel pour des pays comme le Cambodge oĂč lâaccĂšs au plateau technique est limitĂ© aux capitales ou aux grandes villes. Une telle stratĂ©gie doit maintenant ĂȘtre implantĂ©e en zones rurales en intĂ©grant une analyse des coĂ»ts et des circuits dâapprovisionnement en mĂ©dicaments et rĂ©actifs afin dâamorcer lâengagement politique nĂ©cessaire pour un passage Ă lâĂ©chelle sur lâensemble du pays
Alternative strategy for the prevention of mother-to-child transmission of hepatitis B in Cambodia : the ANRS 12345 TA PROHM study
La transmission mĂšre-enfant (TME) de lâinfection par le virus de lâhĂ©patite B (VHB) est Ă lâorigine de la plupart des hĂ©patites B chroniques dans les pays Ă forte endĂ©mie pour le VHB. La prĂ©vention repose sur la vaccination prĂ©coce des nouveau-nĂ©s a la naissance et, pour les femmes positives pour lâAgHBs, sur lâadministration dâun traitement antiviral au troisiĂšme trimestre si la charge virale VHB est > 5.3 log10 UI/mL et dâimmunoglobulines (HBIg) au nouveau-nĂ©. Au Cambodge, les prĂ©valences du VHB chez les femmes enceintes, les enfants ĂągĂ©s de 5 Ă 7 ans et chez ceux nĂ©s de mĂšres positives pour lâAgHBs ont Ă©tĂ© estimĂ©es Ă 4%, 0.6% et 10%, respectivement.Lâobjectif de cette thĂšse Ă©tait de concevoir et Ă©valuer un programme de rĂ©duction de la TME du VHB au Cambodge en utilisant une stratĂ©gie basĂ©e sur les outils disponibles dans le pays. Ce travail sâest construit autour de lâĂ©tude ANRS 12345 TA PROHM dont lâobjectif Ă©tait dâĂ©valuer lâefficacitĂ© dâune stratĂ©gie alternative sans HBIg de prĂ©vention de la TME du VHB au Cambodge basĂ©e sur 1/lâutilisation de tests de diagnostic rapides (TDR) AgHBs et AgHBe pour le dĂ©pistage et la prise en charge de lâinfection VHB en peripartum 2/un traitement par Tenofovir (TDF) Ă partir de 24 semaines dâamĂ©norrhĂ©e des femmes Ă©ligibles 3/une vaccination prĂ©coce pour tous les enfants Ă la naissance ( 5,3 log10 UI/mL. Un nouvel algorithme sĂ©lectionnant les femmes AgHBe positives et celles AgHBe nĂ©gatives avec un taux dâALAT > 40 U/L a permis dâaugmenter la sensibilitĂ© de 17% pour ce seuil de charge virale et a Ă©tĂ© utilisĂ© dans lâĂ©tude Ă partir de Janvier 2019.De 2017 Ă 2020, 21 251 femmes ont Ă©tĂ© dĂ©pistĂ©es en consultation antĂ©natale dans 5 hopitaux cambodgiens. Parmi elles, 1194 ont pu ĂȘtre incluses dans lâĂ©tude dont 338 (28%) Ă©taient Ă©ligibles au TDF. En lâabsence dâHBIg, le taux de TME du VHB Ă©tait de 1.48% [IC95%, 0.40-3.74] pour les femmes Ă©ligibles au TDF et de 0% [IC95%, 0-1.41] pour celles traitĂ©es plus d'un mois avant l'accouchement. Ce taux Ă©tait de 8.33% [IC95%, 1.75â22.5] pour celles traitĂ©es moins dâun mois, soulignant lâimportance du dĂ©pistage prĂ©coce pendant la grossesse. Pour les femmes non Ă©ligibles au TDF, le taux de transmission Ă©tait de 1.06% [IC95%, 0.39-2.30], la transmission survenant chez des femmes hautement virĂ©miques non dĂ©pistĂ©es par lâalgorithme.Ce travail montre quâune stratĂ©gie alternative sans HBIg utilisant un traitement antiviral prophylactique maternel par TDF pendant au moins un mois avant lâaccouchement associĂ© Ă une vaccination prĂ©coce du nourrisson Ă la naissance permet de prĂ©venir la TME du VHB. Cette stratĂ©gie est applicable en zones dĂ©centralisĂ©es, ce qui est essentiel pour des pays comme le Cambodge oĂč lâaccĂšs au plateau technique est limitĂ© aux capitales ou aux grandes villes. Une telle stratĂ©gie doit maintenant ĂȘtre implantĂ©e en zones rurales en intĂ©grant une analyse des coĂ»ts et des circuits dâapprovisionnement en mĂ©dicaments et rĂ©actifs afin dâamorcer lâengagement politique nĂ©cessaire pour un passage Ă lâĂ©chelle sur lâensemble du pays.Mother-to-child transmission (MTCT) of hepatitis B virus (HBV) infection is the cause of most chronic hepatitis B in countries with high HBV endemicity. Prevention is based on early vaccination of newborns at birth and, for HBsAg-positive women, on the administration of antiviral treatment in the third trimester of pregnancy if the HBV DNA viral load is > 5.3 log10 IU/mL and immunoglobulin (HBIg) to the newborn. In Cambodia, the prevalence of HBV infection among pregnant women, children aged 5 to 7 years, and those born to HBsAg-positive mothers was estimated at 4%, 0.6%, and 10%, respectively.The objective of this thesis was to design and evaluate a strategy to reduce HBV MTCT in Cambodia using tools available in the country.This work was structured around the ANRS 12345 TA PROHM study which objective was to evaluate the effectiveness of an HBIg-free alternative strategy to prevent HBV MTCT in Cambodia based on 1/ the use of HBsAg and HBeAg rapid diagnostic tests (RDT) for the screening and management of HBV infection in peripartum 2/a treatment with tenofovir from 24 weeks of amenorrhea of eligible women 3/an early vaccination for all infants at birth ( 5.3 log10 IU/mL. A new algorithm selecting HBeAg-positive women and HBeAg-negative women with ALT > 40 U/L increased sensitivity by 17% for this viral load threshold and was used in the study from January 2019.From 2017 to 2020, 21,251 women were screened in antenatal care. Of these, 1194 could be included in the study, of whom 338 (28%) were eligible for TDF. In the absence of HBIg, the rate of HBV MTCT was 1.48% [CI95%, 0.40-3.74] for women eligible for TDF and 0% [CI95%, 0-1.41] for those treated more than one month before delivery. In contrast, the rate of HBV MTCT was 8.33% [CI95%, 1.75-22.5] for those treated less than one month, highlighting the importance of HBV early detection during pregnancy. For women not eligible for TDF, the transmission rate was 1.06% [CI95%, 0.39-2.30], with transmission occurring in highly viremic women not identified by the algorithm. This work shows that an HBIg-free alternative strategy using maternal antiviral prophylaxis with TDF for at least one month before delivery combined with an early infant vaccination at birth can prevent HBV MTCT. This strategy is applicable in decentralized areas, which is essential for countries such as Cambodia where access to technical facilities is limited to the capital or major provincial cities. Such a strategy needs to be implemented in rural settings, including an analysis of the costs and supply chains of drugs and reagents, to initiate the political commitment necessary for a nationwide scaling-up
StratĂ©gie alternative de prĂ©vention de la transmission mĂšre-enfant de lâhĂ©patite B au Cambodge : lâĂ©tude ANRS 12345 TA PROHM
Mother-to-child transmission (MTCT) of hepatitis B virus (HBV) infection is the cause of most chronic hepatitis B in countries with high HBV endemicity. Prevention is based on early vaccination of newborns at birth and, for HBsAg-positive women, on the administration of antiviral treatment in the third trimester of pregnancy if the HBV DNA viral load is > 5.3 log10 IU/mL and immunoglobulin (HBIg) to the newborn. In Cambodia, the prevalence of HBV infection among pregnant women, children aged 5 to 7 years, and those born to HBsAg-positive mothers was estimated at 4%, 0.6%, and 10%, respectively.The objective of this thesis was to design and evaluate a strategy to reduce HBV MTCT in Cambodia using tools available in the country.This work was structured around the ANRS 12345 TA PROHM study which objective was to evaluate the effectiveness of an HBIg-free alternative strategy to prevent HBV MTCT in Cambodia based on 1/ the use of HBsAg and HBeAg rapid diagnostic tests (RDT) for the screening and management of HBV infection in peripartum 2/a treatment with tenofovir from 24 weeks of amenorrhea of eligible women 3/an early vaccination for all infants at birth ( 5.3 log10 IU/mL. A new algorithm selecting HBeAg-positive women and HBeAg-negative women with ALT > 40 U/L increased sensitivity by 17% for this viral load threshold and was used in the study from January 2019.From 2017 to 2020, 21,251 women were screened in antenatal care. Of these, 1194 could be included in the study, of whom 338 (28%) were eligible for TDF. In the absence of HBIg, the rate of HBV MTCT was 1.48% [CI95%, 0.40-3.74] for women eligible for TDF and 0% [CI95%, 0-1.41] for those treated more than one month before delivery. In contrast, the rate of HBV MTCT was 8.33% [CI95%, 1.75-22.5] for those treated less than one month, highlighting the importance of HBV early detection during pregnancy. For women not eligible for TDF, the transmission rate was 1.06% [CI95%, 0.39-2.30], with transmission occurring in highly viremic women not identified by the algorithm. This work shows that an HBIg-free alternative strategy using maternal antiviral prophylaxis with TDF for at least one month before delivery combined with an early infant vaccination at birth can prevent HBV MTCT. This strategy is applicable in decentralized areas, which is essential for countries such as Cambodia where access to technical facilities is limited to the capital or major provincial cities. Such a strategy needs to be implemented in rural settings, including an analysis of the costs and supply chains of drugs and reagents, to initiate the political commitment necessary for a nationwide scaling-up.La transmission mĂšre-enfant (TME) de lâinfection par le virus de lâhĂ©patite B (VHB) est Ă lâorigine de la plupart des hĂ©patites B chroniques dans les pays Ă forte endĂ©mie pour le VHB. La prĂ©vention repose sur la vaccination prĂ©coce des nouveau-nĂ©s a la naissance et, pour les femmes positives pour lâAgHBs, sur lâadministration dâun traitement antiviral au troisiĂšme trimestre si la charge virale VHB est > 5.3 log10 UI/mL et dâimmunoglobulines (HBIg) au nouveau-nĂ©. Au Cambodge, les prĂ©valences du VHB chez les femmes enceintes, les enfants ĂągĂ©s de 5 Ă 7 ans et chez ceux nĂ©s de mĂšres positives pour lâAgHBs ont Ă©tĂ© estimĂ©es Ă 4%, 0.6% et 10%, respectivement.Lâobjectif de cette thĂšse Ă©tait de concevoir et Ă©valuer un programme de rĂ©duction de la TME du VHB au Cambodge en utilisant une stratĂ©gie basĂ©e sur les outils disponibles dans le pays. Ce travail sâest construit autour de lâĂ©tude ANRS 12345 TA PROHM dont lâobjectif Ă©tait dâĂ©valuer lâefficacitĂ© dâune stratĂ©gie alternative sans HBIg de prĂ©vention de la TME du VHB au Cambodge basĂ©e sur 1/lâutilisation de tests de diagnostic rapides (TDR) AgHBs et AgHBe pour le dĂ©pistage et la prise en charge de lâinfection VHB en peripartum 2/un traitement par Tenofovir (TDF) Ă partir de 24 semaines dâamĂ©norrhĂ©e des femmes Ă©ligibles 3/une vaccination prĂ©coce pour tous les enfants Ă la naissance ( 5,3 log10 UI/mL. Un nouvel algorithme sĂ©lectionnant les femmes AgHBe positives et celles AgHBe nĂ©gatives avec un taux dâALAT > 40 U/L a permis dâaugmenter la sensibilitĂ© de 17% pour ce seuil de charge virale et a Ă©tĂ© utilisĂ© dans lâĂ©tude Ă partir de Janvier 2019.De 2017 Ă 2020, 21 251 femmes ont Ă©tĂ© dĂ©pistĂ©es en consultation antĂ©natale dans 5 hopitaux cambodgiens. Parmi elles, 1194 ont pu ĂȘtre incluses dans lâĂ©tude dont 338 (28%) Ă©taient Ă©ligibles au TDF. En lâabsence dâHBIg, le taux de TME du VHB Ă©tait de 1.48% [IC95%, 0.40-3.74] pour les femmes Ă©ligibles au TDF et de 0% [IC95%, 0-1.41] pour celles traitĂ©es plus d'un mois avant l'accouchement. Ce taux Ă©tait de 8.33% [IC95%, 1.75â22.5] pour celles traitĂ©es moins dâun mois, soulignant lâimportance du dĂ©pistage prĂ©coce pendant la grossesse. Pour les femmes non Ă©ligibles au TDF, le taux de transmission Ă©tait de 1.06% [IC95%, 0.39-2.30], la transmission survenant chez des femmes hautement virĂ©miques non dĂ©pistĂ©es par lâalgorithme.Ce travail montre quâune stratĂ©gie alternative sans HBIg utilisant un traitement antiviral prophylactique maternel par TDF pendant au moins un mois avant lâaccouchement associĂ© Ă une vaccination prĂ©coce du nourrisson Ă la naissance permet de prĂ©venir la TME du VHB. Cette stratĂ©gie est applicable en zones dĂ©centralisĂ©es, ce qui est essentiel pour des pays comme le Cambodge oĂč lâaccĂšs au plateau technique est limitĂ© aux capitales ou aux grandes villes. Une telle stratĂ©gie doit maintenant ĂȘtre implantĂ©e en zones rurales en intĂ©grant une analyse des coĂ»ts et des circuits dâapprovisionnement en mĂ©dicaments et rĂ©actifs afin dâamorcer lâengagement politique nĂ©cessaire pour un passage Ă lâĂ©chelle sur lâensemble du pays
Population Pharmacokinetic-Pharmacogenetic Study of Nevirapine in HIV-Infected Cambodian Patients âż
The aims of this ANRS12154 open-label, single-center, multiple-dose pharmacokinetic study were to characterize nevirapine pharmacokinetics in a Cambodian population of HIV-infected patients and to identify environmental and genetic factors of variability, focusing on the CYP2B6, CYP3A5, and ABCB1 (MDR1) genes. A total of 170 Cambodian HIV-infected patients were included. Nevirapine trough concentrations were measured after 18 and 36 months of starting antiretroviral treatment and in samples drawn during a dosing interval in a subset of 10 patients. All data were analyzed by nonlinear mixed-effects modeling. The effect of covariates was investigated using the population pharmacokinetic model. Patients carrying homozygous loss-of-function alleles CYP3A5 6986A>G, CYP2B6 516G>T, CYP2B6 1459C>T, and ABCB1 3435C>T represent 42.4%, 9.2%, 0%, and 18% of the population, respectively. The median nevirapine trough concentrations did not differ after 18 and 36 months of treatment (5,705 ng/ml [range, â€50 to 13,871] and 5,709 ng/ml [range, â€50 to 15,422], respectively). Interpatient and intrapatient variabilities of nevirapine apparent clearance were 28% and 17%, respectively. CYP2B6 516G>T and creatinine clearance were found to significantly affect nevirapine apparent clearance. The estimated nevirapine apparent clearances were 2.95 liters/h, 2.62 liters/h, and 1.86 liters/h for CYP2B6 516GG, CYP2B6 516GT, and CYP2B6 516TT genotypes, respectively. The impact of creatinine clearance was small. This study demonstrates that 95% of the patients had sustained nevirapine exposure well above the 3,000-ng/ml threshold. Nevirapine clearance was shown to be affected by CYP2B6 516G>T genetic polymorphism and creatinine clearance, although this explained only part of the interpatient variability, which remains low compared to that for other antiretroviral drugs