Browsing by Author "Gonzague Jourdain"

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    A comparison of 3 regimens to prevent nevirapine resistance mutations in HIV-infected pregnant women receiving a single intrapartum dose of nevirapine
    (2012-01-15) Russell B. Van Dyke; Nicole Ngo-Giang-Huong; David E. Shapiro; Lisa Frenkel; Paula Britto; Anuvat Roongpisuthipong; Ingrid A. Beck; Praparb Yuthavisuthi; Sinart Prommas; Thanyawee Puthanakit; Jullapong Achalapong; Nantasak Chotivanich; Wirawan Rasri; Tim R. Cressey; Robert Maupin; Mark Mirochnick; Gonzague Jourdain; Tulane University Health Sciences Center; LSU Health Sciences Center - New Orleans; Harvard School of Public Health; Center for Biostatistics in AIDS Research; Boston University School of Medicine; University of Washington, Seattle; Children's Hospital and Regional Medical Center; IRD Institut de Recherche pour le Developpement; Faculty of Associated Medical Sciences; Chiang Mai University; Mahidol University; Bhumibol Adulyadej Hospital; Prapokklao Hospital; Chiangrai Prachanukroh Hospital; Chonburi Regional Hospital; Phayao Hospital
    Background. Intrapartum single-dose (SD) nevirapine (NVP) reduces perinatal transmission of human immunodeficiency virus (HIV) infection but selects for NVP-resistant virus, which compromises subsequent NVP-based therapy. A 1-week "tail" of lamivudine and zidovudine after SD-NVP decreases the risk of resistance. We hypothesized that increasing the duration or potency of the tail would further reduce this risk to < 10%, using a sensitive assay to measure resistance.Methods.HIV-infected pregnant Thai women with a CD4 cell count > 250 cells/μL, most receiving zidovudine, were randomized at 28-38 weeks gestation to receive 1 of 3 intrapartum and postpartum regimens: (A) zidovudine plus enteric-coated didanosine plus lopinavir and ritonavir for 7 days, (B) zidovudine plus enteric-coated didanosine for 30 days, or (C) regimen 1 for 30 days. The incidence of NVP resistance mutations at day 10 or week 6 post partum in each arm was compared with that of a historical comparison group who received prenatal zidovudine and SD-NVP. NVP resistance was identified by consensus sequencing and a sensitive oligonucleotide ligation assay (OLA). Results. At entry, the 169 participants had a median CD4 cell count of 456 cells/μL and an HIV load of 3.49 log10 copies/mL. The incidence of mutations in each of the 3 P1032 arms was 0% by sequencing and 1.8%, 7.1%, and 5.3% by OLA in arms A, B, and C, respectively, compared with 13.4% by sequencing and 29.4% by OLA in the comparison group (P < . 001 for each study arm vs comparison group). Grade 4 anemia developed in 1 woman.Conclusions.A 7-day tail of highly active combination therapy or 1 month of dual therapy after SD-NVP prevents most NVP resistance to minimal toxicity.Clinical Trials Registration.The IMPAACT P1032 Clinical Trial is NCT00109590, and the PHPT-2 Clinical Trial is NCT00398684. © 2011 The Author.
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    High virologic response rate after second-line boosted protease inhibitor-based antiretroviral therapy regimens in children from a resource limited setting
    (2012-06-18) Thanyawee Puthanakit; Gonzague Jourdain; Piyarat Suntarattiwong; Kulkanya Chokephaibulkit; Umaporn Siangphoe; Tulathip Suwanlerk; Wasana Prasitsuebsai; Virat Sirisanthana; Pope Kosalaraksa; Witaya Petdachai; Rawiwan Hansudewechakul; Naris Waranawat; Jintanat Ananworanich; T. Bunupuradah; C. Phasomsap; P. Kaew-on; S. Kanjanavanit; T. Hinjiranandana; P. Layangool; N. Kamonpakorn; S. Buranabanjasatean; C. Ngampiyaskul; T. Chotpitayasunondh; S. Chanpradub; P. Leawsrisuk; S. Chearskul; N. Vanprapar; W. Phongsamart; K. Lapphra; P. Chearskul; O. Wittawatmongkol; W. Prasitsuebsai; K. Intalapaporn; N. Kongstan; N. Pannin; A. Maleesatharn; B. Khumcha; L. Aurpibul; N. Wongnum; R. Nadsasarn; P. Lumbiganon; P. Tharnprisan; T. Udompanich; M. Yentang; A. Khonponoi; N. Maneerat; S. Denjunta; WatanapornS.; C. Yodsuwan; W. Srisuk; S. Somsri; K. Surapanichadul; The HIV Netherlands Australia Thailand Research Collaboration; Chulalongkorn University; Chiang Mai University; Queen Sirikit National Institute of Child Health; Mahidol University; Khon Kaen University; Petchburi Hospital; Chiang Rai Regional Hospital; South East Asia Research Collaboration with Hawaii; Red Cross AIDS Research Centre; Nakornping Hospital; Bhumibol Adulyadej Hospital; Somdej Prapinklao Hospital; Mae Chan Hospital; Prapokklao Provincial Hospital
    Background: Limited data exist for the efficacy of second-line antiretroviral therapy among children in resource limited settings. We assessed the virologic response to protease inhibitor-based ART after failing first-line non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimens.Methods: A retrospective chart review was conducted at 8 Thai sites of children who switched to PI -based regimens due to failure of NNRTI -based regimens. Primary endpoints were HIV RNA < 400 copies/ml and CD4 change over 48 weeks.Results: Data from 241 children with median baseline values before starting PI-based regimens of 9.1 years for age, 10% for CD4%, and 4.8 log 10 copies/ml for HIV RNA were included; 104 (41%) received a single ritonavir-boosted PI (sbPI) with 2 NRTIs and 137 (59%) received double-boosted PI (dbPI) with/without NRTIs based on physician discretion. SbPI children had higher baseline CD4 (17% vs. 6%, p < 0.001), lower HIV RNA (4.5 vs. 4.9 log 10 copies/ml, p < 0.001), and less frequent high grade multi-NRTI resistance (12.4% vs 60.5%, p < 0.001) than the dbPI children. At week 48, 81% had HIV RNA < 400 copies/ml (sbPI 83.1% vs. dbPI 79.8%, p = 0.61) with a median CD4 rise of 9% (+7%vs. + 10%, p < 0.005). However, only 63% had HIV RNA < 50 copies/ml, with better viral suppression seen in sbPI (76.6% vs. 51.4%, p 0.002).Conclusion: Second-line PI therapy was effective for children failing first line NNRTI in a resource-limited setting. DbPI were used in patients with extensive drug resistance due to limited treatment options. Better access to antiretroviral drugs is needed. © 2012 Puthanakit et al.; licensee BioMed Central Ltd.
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    Incidence and clinical outcomes of diabetes mellitus in HIV-infected adults in Thailand: A retrospective cohort study
    (2018-08-30) Ninutcha Paengsai; Gonzague Jourdain; Romanee Chaiwarith; Apichat Tantraworasin; Chureeratana Bowonwatanuwong; Sorakij Bhakeecheep; Tim Roy Cressey; Jean Yves Mary; Nicolas Salvadori; Natapong Kosachunhanun; National Health Security Office; Institute of research for development, Thailand; Harvard School of Public Health; University of Liverpool; Mahidol University; Universite Paris 7- Denis Diderot; Chiang Mai University
    © 2018 The Author(s). Background: Since 2005, Thailand has scaled up one of the largest antiretroviral treatment (ART) programs in South East Asia. Although diabetes mellitus (DM) incidence is increasing in low and middle-income countries, its burden and contributing factors in the HIV infected population are not well known. Methods: Using the Thai National AIDS Program data over a period of 8-years, we identified patients diagnosed with DM based on the following records: 1) fasting plasma glucose equal to or greater than 126 mg/dl following the 2013 American Diabetes Association criteria or 2) diagnosis codes E11-E14 of the 2010 WHO International Classification of Diseases, or 3) anti-diabetic drugs. Incidence was the number of new cases divided by that of person-years of follow-up (PYFU). Competing risks survival regression, treating death without DM as a competing event, was used to identify factors associated with DM. The risk of death in patients diagnosed with DM was estimated using Cox regression models. Results: Data of 763,666 PYFU from 199,707 patients (54.2% male; median age 36.2 years at registration with the program) were available and 8383 cases were diagnosed with DM, resulting in an incidence rate of 11.0 per 1000 PYFU. New DM diagnosis was more likely in men (adjusted sub-distribution hazard ratio 1.2), older patients (compared to patients 18 to 34 years old: 1.8 for 35 to 44; 3.0 for 45 to 59; 3.8 for ≥60), and if ART was initiated (1.3). In 2014, 1313 (16.6%) of 7905 diabetic patients had DM complications (11.5% microvascular complications and 6.9% macrovascular complications). Patients diagnosed with DM were at higher risk of death compared to the others. Conclusions: DM incidence was higher in this Thailand cohort of HIV infected adults than in the general population. Risk factors were similar to those in the general population, in addition to starting ART.
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    Influence of CYP2B6 polymorphisms on the persistence of plasma nevirapine concentrations following a single intra-partum dose for the prevention of mother to child transmission in HIV-infected Thai women
    (2009-10-06) Soranun Chantarangsu; Tim R. Cressey; Surakameth Mahasirimongkol; Edmund Capparelli; Yardpiroon Tawon; Nicole Ngo-Giang-Huong; Gonzague Jourdain; Marc Lallemant; Wasun Chantratita; Mahidol University; Harvard School of Public Health; Chiang Mai University; Thailand Ministry of Public Health; University of California, San Diego
    Objectives: To investigate the association of single nucleotide polymorphisms (SNPs) with nevirapine concentrations following intra-partum single-dose nevirapine. Methods: Plasma and DNA samples were obtained from 330 HIV-infected Thai women who received intra-partum single-dose nevirapine in the PHPT-2 clinical trial to prevent perinatal HIV transmission. Nine SNPs within CYP2B6, CYP3A4 and ABCB1 were genotyped by real-time PCR. Nevirapine plasma concentrations were determined by HPLC and used in a population pharmacokinetic analysis. Results: Higher nevirapine exposure was observed in women carrying the CYP2B6 516G>T polymorphism, but this did not reach statistical significance (P = 0.054). The TGATC CYP2B6 haplotype (g.3003T, 516G, 785A, g.18492T and g.21563C) was associated with increased nevirapine clearance and lower exposure (P = 0.0029). The median time for nevirapine concentrations to reach 10 ng/mL post-partum (nevirapine IC50for HIV-1) was 14 days [interquartile range (IQR, 14-18)] for TGATC homozygotes, 16 days (14-20) for TGATC heterozygotes and 18 days (14-20) for non-TGATC homozygotes (P = 0.020). Conclusions: The CYP2B6 516G>T impact on nevirapine concentrations was less pronounced after intra-partum single-dose nevirapine than reported under steady-state conditions, perhaps due to lack of enzyme auto-induction at the time of dosing. Although the TGATC CYP2B6 haplotype may shorten the persistence of nevirapine post-partum, its practical implications for the prevention of HIV transmission or selection of resistance mutations are likely limited. © The Author 2009. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy.
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    Lack of association between adverse pregnancy outcomes and zika antibodies among pregnant women in thailand between 1997 and 2015
    (2021-08-01) Nicole Ngo-Giang-huong; Charline Leroi; Dahlene Fusco; Tim R. Cressey; Nantawan Wangsaeng; Nicolas Salvadori; Natedao Kongyai; Wasna Sirirungsi; Marc Lallemant; Prasert Auewarakul; Woottichai Khamduang; Gonzague Jourdain; Siriraj Hospital; Université de Montpellier; Tulane University School of Medicine; Chiang Mai University; Associated Medical Sciences (AMS)-CMU IRD Research Collaboration
    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.
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    Perinatal Antiretroviral Intensification to Prevent Intrapartum HIV Transmission When Antenatal Antiretroviral Therapy Is Initiated Less Than 8 Weeks Before Delivery
    (2020-07-01) Marc Lallemant; Billy Amzal; Patumrat Sripan; Saïk Urien; Tim R. Cressey; Nicole Ngo-Giang-Huong; Virat Klinbuayaem; Boonsong Rawangban; Prapan Sabsanong; Thitiporn Siriwachirachai; Tapnarong Jarupanich; Prateep Kanjanavikai; Phaiboon Wanasiri; Suporn Koetsawang; Gonzague Jourdain; Sophie Le Coeur; Université de Paris; INED Institut National d' Études Démographiques; Harvard T.H. Chan School of Public Health; Hatyai Hospital; Banglamung Hospital; Kasetsart University; Thailand Ministry of Public Health; Khon Kaen Regional Hospital; Mahidol University; Chiang Mai University; LASER Analytica; Paris Centre Descartes Necker Cochin; Institut de recherche pour le développement (IRD) UMI 174-PHPT
    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.
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    Randomized noninferiority trial of two maternal single-dose nevirapine-sparing regimens to prevent perinatal HIV in Thailand
    (2015-01-01) Marc Lallemant; Sophie Le Coeur; Wasna Sirirungsi; Tim R. Cressey; Nicole Ngo-Giang-Huong; Patrinee Traisathit; Virat Klinbuayaem; Prapan Sabsanong; Prateep Kanjanavikai; Gonzague Jourdain; Kenneth McIntosh; Suporn Koetsawang; Institute of research for development, Thailand; Harvard School of Public Health; Chiang Mai University; INED Institut National d' Etudes Demographiques; Thailand Ministry of Public Health; Banglamung Hospital; Children's Hospital Boston; Mahidol University
    © 2015 Wolters Kluwer Health, Inc. All rights reserved. Objectives: Perinatal single-dose nevirapine (sdNVP) selects for resistance mutations. The objective of this trial was to compare two maternal sdNVP-sparing regimens with standard zidovudine (ZDV)/sdNVP prophylaxis. Design: PHPT-5 was a randomized, partially double-blind placebo-controlled, noninferiority trial in Thailand (NCT00409591). Study participants were women with CD4+ of at least 250 cells/ml and their infants. Methods: All women received ZDV from 28 weeks' gestation and their newborn infants for one week. Women were also randomized to receive NVP-NVP (reference): maternal intrapartum sdNVP with a 7-day 'tail' of ZDV along with lamivudine, and infant NVP (one dose immediately, another 48 h later); infant-only NVP: maternal placebos for sdNVP and the 'tail', with infant NVP; LPV/r: maternal LPV/r starting at 28 weeks. Infants were formula-fed. HIV-diagnosis was determined by DNA-PCR. Results: Four-hundred and thirty-five women were randomized between January 2009 and September 2010. Accrual was terminated prematurely following a change in Thai guidelines recommending antiretroviral combination therapy for all pregnant women. Data on 405 mothers and 407 live-born children were analyzed. Baseline characteristics were similar between arms. Intent-to-treat transmission rates were 3.8% (95% confidence interval: 1.2-8.6) in NVP-NVP, 1.6% (0.2-5.6) in infant-only NVP, and 1.4% (0.4-5.1) in LPV/r arms. As-treated rates were 2.2% (0.5-6.4), 3.2% (0.9-7.9), and 1.5% (0.2-5.2), respectively. Factors independently associated with transmission were prophylaxis duration less than 8 weeks (adjusted odds ratio 15.5; 3.6-66.1) and viral load at baseline at least 4 log10copies/ml (adjusted odds ratio 10.9; 1.3-91.5). Regimens appeared well tolerated. Conclusion: Transmission rates in all arms were low but noninferiority was not proven. Antiretroviral prophylaxis for at least 8 weeks before delivery is necessary to minimize transmission risk.
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    Recommended First-Line Antiretroviral Therapy Regimens and Risk of Diabetes Mellitus in HIV-Infected Adults in Resource-Limited Settings
    (2019-09-30) Ninutcha Paengsai; Gonzague Jourdain; Nicolas Salvadori; Apichat Tantraworasin; Jean Yves Mary; Tim Roy Cressey; Romanee Chaiwarith; Chureeratana Bowonwatanuwong; Sorakij Bhakeecheep; Natapong Kosachunhanun; University of Phayao; National Health Security Office; Harvard T.H. Chan School of Public Health; IRD Institut de Recherche pour le Developpement; University of Liverpool; Mahidol University; Universite Paris 7- Denis Diderot; Chiang Mai University
    © 2019 The Author(s) 2019. Published by Oxford University Press on behalf of Infectious Diseases Society of America. Objective: The use of some antiretroviral drugs has been associated with a higher risk of diabetes mellitus (DM) in HIV-infected patients, but the risk associated with antiretroviral drug combinations remains unclear. We investigated the association between first-line antiretroviral therapy (ART) regimens, recommended by the World Health Organization (WHO) in 2016, and the risk of DM in adults. Method: We selected all HIV-infected adults within the Thai National AIDS Program who started a first-line ART regimen consisting the following between October 2006 and September 2013: zidovudine+lamivudine+nevirapine; tenofovir disoproxil fumarate (TDF)+lamivudine+nevirapine; zidovudine+lamivudine+efavirenz; TDF+lamivudine/emtricitabine+efavirenz; zidovudine+lamivudine+ritonavir-boosted lopinavir (LPV/r); or TDF+lamivudine+LPV/r. Diagnosis of DM was defined as having at least 2 of the following characteristics: fasting plasma glucose ≥126 mg/dl, 2010 WHO ICD-10 codes E11-E14, or prescription of antidiabetic drugs. To identify ART regimens associated with DM, we used competing risks regression models that considered mortality without DM as a competing event and adjusted for sex, age, pancreas disease, and stratified by groups defined by a score summarizing the propensity to receive a specific first-line ART regimen. Results: Data from 35 710 adults (49.1% male; median age, 35.0 years; median follow-up, 2.0 years) were included. In the multivariable analysis with zidovudine+lamivudine+nevirapine as the reference group, a higher risk of DM was observed with TDF+lamivudine/emtricitabine+efavirenz (adjusted sub-distribution hazard ratio [aSHR], 1.6; 95% confidence interval [CI], 1.3-1.9), zidovudine+lamivudine+efavirenz (aSHR, 2.0; 95% CI, 1.7-2.3), and TDF+lamivudine+LPV/r (aSHR, 2.7; 95% CI, 1.9-3.9). Conclusions: Several of the WHO recommended ART regimens, particularly tenofovir + lamivudine +LPV/r and regimens containing efavirenz, may be associated with an increased risk of DM.
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    Single-dose perinatal nevirapine plus standard zidovudine to prevent mother-to-child transmission of HIV-1 in Thailand
    (2004-07-15) Marc Lallemant; Gonzague Jourdain; Sophie Le Coeur; Jean Yves Mary; Nicole Ngo-Giang-Huong; Suporn Koetsawang; Siripon Kanshana; Kenneth McIntosh; Vallop Thaineua; IRD Institut de Recherche pour le Developpement; Harvard School of Public Health; INED Institut National d' Etudes Demographiques; Inserm; Mahidol University; Thailand Ministry of Public Health; Children's Hospital Boston; Harvard Medical School; Institute of research for development, Thailand
    BACKGROUND: Although zidovudine prophylaxis decreases the rate of transmission of the human immunodeficiency virus (HIV) type 1 substantially, a large number of infants still become infected. We hypothesized that the administration, in addition to zidovudine, of a single dose of oral nevirapine to mothers during labor and to neonates would further reduce transmission of HIV. METHODS: We conducted a randomized, double-blind trial of three treatment regimens in Thai women who were receiving zidovudine therapy during the third trimester of pregnancy. In one group, mothers and infants received a single dose of nevirapine (nevirapine-nevirapine regimen); in another, mothers and infants received nevirapine and placebo, respectively (nevirapine-placebo regimen); and in the last, mothers and infants received placebo (placebo-placebo regimen). The infants also received one week of zidovudine therapy and were formula-fed. The end point of the study was infection with HIV in the infants, established by virologic testing. RESULTS: Between January 15, 2001, and February 28, 2003, a total of 1844 Thai women were enrolled. At the first interim analysis, the independent data monitoring committee stopped enrollment in the placebo-placebo group. Among women who delivered before the interim analysis, the as-randomized Kaplan-Meier estimates of the transmission rates were 1.1 percent (95 percent confidence interval, 0.3 to 2.2) in the nevirapine-nevirapine group and 6.3 percent (95 percent confidence interval, 3.8 to 8.9) in the placebo-placebo group (P<0.001). The final per-protocol transmission rate in the nevirapine-nevirapine group, 1.9 percent (95 percent confidence interval, 0.9 to 3.0), was not significantly inferior to the rate in the nevirapine-placebo group (2.8 percent; 95 percent confidence interval, 1.5 to 4.1). Nevirapine had an effect within subgroups defined by known risk factors such as viral load and CD4 count. No serious adverse effects were associated with nevirapine therapy. CONCLUSIONS: A single dose of nevirapine to the mother, with or without a dose of nevirapine to the infant, added to oral zidovudine prophylaxis starting at 28 weeks' gestation, is highly effective in reducing mother-to-child transmission of HIV. Copyright © 2004 Massachusetts Medical Society.
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    Switching HIV Treatment in Adults Based on CD4 Count Versus Viral Load Monitoring: A Randomized, Non-Inferiority Trial in Thailand
    (2013-08-01) Gonzague Jourdain; Sophie Le Cœur; Nicole Ngo-Giang-Huong; Patrinee Traisathit; Tim R. Cressey; Federica Fregonese; Baptiste Leurent; Intira J. Collins; Malee Techapornroong; Sukit Banchongkit; Sudanee Buranabanjasatean; Guttiga Halue; Ampaipith Nilmanat; Nuananong Luekamlung; Virat Klinbuayaem; Apichat Chutanunta; Pacharee Kantipong; Chureeratana Bowonwatanuwong; Rittha Lertkoonalak; Prattana Leenasirimakul; Somboon Tansuphasawasdikul; Pensiriwan Sang-a-gad; Panita Pathipvanich; Srisuda Thongbuaban; Pakorn Wittayapraparat; Naree Eiamsirikit; Yuwadee Buranawanitchakorn; Naruepon Yutthakasemsunt; Narong Winiyakul; Luc Decker; Sylvaine Barbier; Suporn Koetsawang; Wasna Sirirungsi; Kenneth McIntosh; Sombat Thanprasertsuk; Marc Lallemant; A. Lautissier; S. Renaudin; E. Delacour; N. Chaiboonruang; T. Sriwised; T. Tritungtrakul; D. Punyatiam; P. Pirom; S. Jitharidkul; P. Palidta; S. Vorayutthanakarn; N. Rawanchaikul; S. Nupradit; T. Tankool; W. Champa; J. Krasaesuk; G. Ganjina; K. Thanin-at; R. Wongsang; M. Inta; N. Mungkhala; P. Saenchitta; K. Oopin; P. Wimolwattanasarn; S. Chalermpantmetagul; R. Peongjakta; C. Kanabkaew; J. Chaiwan; M. Y. Meynard; P. Sukrakanchana; B. Ratchanee; J. Thonglo; J. Khanmali; N. Kruenual; N. Krapunpongsakul; P. Krueduangkam; R. Kaewsai; R. Wongchai; S. Jinasa; T. Thimakam; W. Pongchaisit; W. Khamjakkaew; S. Thammajitsagul; J. Wallapachai; J. Chalasin; P. Kulchatchai; N. Thuenyeanyong; P. Thuraset; P. Pinklow; P. Chart; Institute of research for development, Thailand; Chiang Mai University; Harvard School of Public Health; Universite Paris Descartes; Prapokklao Hospital; Thailand Ministry of Public Health; Mae Chan Hospital; Phayao Provincial Hospital; Lamphun Hospital; Samutsakhon General Hospital; Chonburi Regional Hospital; Maharaj Nakhon Ratchasima Hospital; Nakornping Hospital; Buddhachinaraj Hospital; Ratchaburi Regional Hospital; Lampang Hospital; Mahidol University; Children's Hospital Boston
    Background:Viral load (VL) is recommended for monitoring the response to highly active antiretroviral therapy (HAART) but is not routinely available in most low- and middle-income countries. The purpose of the study was to determine whether a CD4-based monitoring and switching strategy would provide a similar clinical outcome compared to the standard VL-based strategy in Thailand.Methods and Findings:The Programs for HIV Prevention and Treatment (PHPT-3) non-inferiority randomized clinical trial compared a treatment switching strategy based on CD4-only (CD4) monitoring versus viral-load (VL). Consenting participants were antiretroviral-naïve HIV-infected adults (CD4 count 50-250/mm3) initiating non-nucleotide reverse transcriptase inhibitor (NNRTI)-based therapy. Randomization, stratified by site (21 public hospitals), was performed centrally after enrollment. Clinicians were unaware of the VL values of patients randomized to the CD4 arm. Participants switched to second-line combination with confirmed CD4 decline >30% from peak (within 200 cells from baseline) in the CD4 arm, or confirmed VL >400 copies/ml in the VL arm. Primary endpoint was clinical failure at 3 years, defined as death, new AIDS-defining event, or CD4 <50 cells/mm3. The 3-year Kaplan-Meier cumulative risks of clinical failure were compared for non-inferiority with a margin of 7.4%. In the intent to treat analysis, data were censored at the date of death or at last visit. The secondary endpoints were difference in future-drug-option (FDO) score, a measure of resistance profiles, virologic and immunologic responses, and the safety and tolerance of HAART. 716 participants were randomized, 356 to VL monitoring and 360 to CD4 monitoring. At 3 years, 319 participants (90%) in VL and 326 (91%) in CD4 were alive and on follow-up. The cumulative risk of clinical failure was 8.0% (95% CI 5.6-11.4) in VL versus 7.4% (5.1-10.7) in CD4, and the upper-limit of the one-sided 95% CI of the difference was 3.4%, meeting the pre-determined non-inferiority criterion. Probability of switch for study criteria was 5.2% (3.2-8.4) in VL versus 7.5% (5.0-11.1) in CD4 (p = 0.097). Median time from treatment initiation to switch was 11.7 months (7.7-19.4) in VL and 24.7 months (15.9-35.0) in CD4 (p = 0.001). The median duration of viremia >400 copies/ml at switch was 7.2 months (5.8-8.0) in VL versus 15.8 months (8.5-20.4) in CD4 (p = 0.002). FDO scores were not significantly different at time of switch. No adverse events related to the monitoring strategy were reported.Conclusions:The 3-year rates of clinical failure and loss of treatment options did not differ between strategies although the longer-term consequences of CD4 monitoring would need to be investigated. These results provide reassurance to treatment programs currently based on CD4 monitoring as VL measurement becomes more affordable and feasible in resource-limited settings.Trial registration:ClinicalTrials.gov NCT00162682 Please see later in the article for the Editors' Summary. © 2013 Jourdain et al.
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    A trial of shortened zidovudine regimens to prevent mother-to-child transmission of human immunodeficiency virus type 1
    (2000-10-05) Marc Lallemant; Gonzague Jourdain; Sophie Le Coeur; Kim Soyeon; Sporn Koetsawang; Anne Marie Comeau; Wiput Phoolcharoen; Max Essex; Kenneth McIntosh; Vicharn Vithayasai; IRD Institut de Recherche pour le Developpement; Harvard School of Public Health; INED Institut National d' Etudes Demographiques; Mahidol University; University of Massachusetts Medical School; Thailand Ministry of Public Health; Children's Hospital Boston; Chiang Mai University; PHPT
    Background: The optimal duration of zidovudine administration to prevent perinatal transmission of human immunodeficiency virus type 1 (HIV-1) should be determined to facilitate its use in areas where resources are limited. Methods: We conducted a randomized, double-blind equivalence trial of four regimens of zidovudine starting in the mother at 28 weeks' gestation, with 6 weeks of treatment in the infant (the long-long regimen), which is similar to protocol 076; zidovudine starting at 35 weeks' gestation, with 3 days of treatment in the infant (the short-short regimen); a long-short regimen; and a short-long regimen. The mothers received zidovudine orally during labor. The infants were fed formula and were tested for HIV DNA at 1, 45, 120, and 180 days. After the first interim analysis, the short-short regimen was stopped. Results: A total of 1437 women were enrolled. At the first interim analysis, the rates of HIV transmission were 4.1 percent for the long-long regimen and 10.5 percent for the short-short regimen (P=0.004); at this point the short-short regimen was stopped. For the entire study period, the transmission rates were 6.5 percent (95 percent confidence interval, 4.1 to 8.9 percent) for the long-long regimen, 4.7 percent (95 percent confidence interval, 2.4 to 7.0 percent) for the long-short regimen, and 8.6 percent (95 percent confidence interval, 5.6 to 11.6 percent) for the short-long regimen. The rate of in utero transmission was significantly higher with the two regimens with shorter maternal treatment (5.1 percent) than with the two with longer maternal treatment (1.6 percent). Conclusions: The short-short zidovudine regimen is inferior to the long-long regimen and leads to a higher rate of perinatal HIV transmission. The long-short, short-long, and long-long regimens had equivalent efficacy. However, the higher rate of in utero transmission with the short-long regimen suggests that longer treatment of the infant cannot substitute for longer treatment of the mother. (C) 2000, Massachusetts Medical Society.
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    Weight as predictors of clinical progression and treatment failure: Results from the TREAT Asia Pediatric HIV observational database
    (2014-09-01) Azar Kariminia; Nicolas Durier; Gonzague Jourdain; Suneeta Saghayam; Chau V. Do; Lam Van Nguyen; Rawiwan Hansudewechakul; Pagakrong Lumbiganon; Kulkanya Chokephaibulkit; Khanh Huu Truong; Virat Sirisanthana; Vibol Ung; Saphonn Vonthanak; Jintanat Ananworanich; Nik Khairulddin Nik Yusoff; Nia Kurniati; Kamarul Azahar Razali; Moy Siew Fong; Revathy Nallusamy; Dewi Kumara Wati; University of New South Wales (UNSW) Australia; TREAT Asia/amfAR-The Foundation for AIDS Research; IRD Institut de Recherche pour le Developpement; Chiang Mai University; YR Gaitonde Centre for AIDS Research and Education; Children's Hospital 2; National Hospital of Pediatrics Hanoi; Chiangrai Prachanukroh Hospital; Khon Kaen University; Mahidol University; Children's Hospital 1; National Pediatric Hospital; National Center for HIV/AIDS; The HIV Netherlands Australia Thailand Research Collaboration; Hospital Raja Perempuan Zainab II; University of Indonesia, RSUPN Dr. Cipto Mangunkusumo; Kuala Lumpur Hospital; Hospital Likas; Penang Hospital; Universitas Udayana
    Objective: To evaluate the value of time-updated weight and height in predicting clinical progression, and immunological and virological failure in children receiving combination antiretroviral therapy (cART). Methods: We used Cox regression to analyze data of a cohort of Asian children. Results: A total of 2608 children were included; median age at cART was 5.7 years. Time-updated weight for age z score <-3 was associated with mortality (P < 0.001) independent of CD4% and <-2 was associated with immunological failure (P ≤ 0.03) independent of age at cART. Conclusions: Weight monitoring provides useful data to inform clinical management of children on cART in resource-limited settings. © 2014 by Lippincott Williams & Wilkins.