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Ngo-Giang-Huong N.,Institute Of Recherche Pour Le Developpement Ird Umi 174 Phpt | Ngo-Giang-Huong N.,Chiang Mai University | Ngo-Giang-Huong N.,Harvard University | Jourdain G.,Institute Of Recherche Pour Le Developpement Ird Umi 174 Phpt | And 16 more authors.
PLoS ONE | Year: 2011

Background: WHO recommends starting therapy with a non-nucleoside reverse transcriptase inhibitor (NNRTI) and two nucleoside reverse transcriptase inhibitors (NRTIs), i.e. nevirapine or efavirenz, with lamivudine or emtricitabine, plus zidovudine or tenofovir. Few studies have compared resistance patterns induced by efavirenz and nevirapine in patients infected with the CRF01_AE Southeast Asian HIV-subtype. We compared patterns of NNRTI- and NRTI-associated mutations in Thai adults failing first-line nevirapine- and efavirenz -based combinations, using Bayesian statistics to optimize use of data. Methods and Findings: In a treatment cohort of HIV-infected adults on NNRTI-based regimens, 119 experienced virologic failure (>500 copies/mL), with resistance mutations detected by consensus sequencing. Mutations were analyzed in relation to demographic, clinical, and laboratory variables at time of genotyping. The Geno2Pheno system was used to evaluate second-line drug options. Eighty-nine subjects were on nevirapine and 30 on efavirenz. The NRTI backbone consisted of lamivudine or emtricitabine plus either zidovudine (37), stavudine (65), or tenofovir (19). The K103N mutation was detected in 83% of patients on efavirenz vs. 28% on nevirapine, whereas Y181C was detected in 56% on nevirapine vs. 20% efavirenz. M184V was more common with nevirapine (87%) than efavirenz (63%). Nevirapine favored TAM-2 resistance pathways whereas efavirenz selected both TAM-2 and TAM-1 pathways. Emergence of TAM-2 mutations increased with the duration of virologic replication (OR 1.25-1.87 per month increment). In zidovudine-containing regimens, the overall risk of resistance across all drugs was lower with nevirapine than with efavirenz, whereas in tenofovir-containing regimen the opposite was true. Conclusions: TAM-2 was the major NRTI resistance pathway for CRF01_AE, particularly with nevirapine; it appeared late after virological failure. In patients who failed, there appeared to be more second-line drug options when zidovudine was combined with nevirapine or tenofovir with efavirenz than with alternative combinations. © 2011 Ngo-Giang-Huong et al.


Sripan P.,Kasetsart University | Sripan P.,Institute Of Recherche Pour Le Developpement Ird Umi 174 Phpt | Sripan P.,University Paris Saclay | Le Coeur S.,Institute Of Recherche Pour Le Developpement Ird Umi 174 Phpt | And 25 more authors.
Antiviral Therapy | Year: 2016

Background: Antiretroviral (ARV) regimens used for the prevention of mother-to-child transmission of HIV have evolved over time. We evaluated the contribution of different ARV regimens on the reduction of the plasma HIV RNA viral load (VL) during pregnancy. Methods: A total of 1,833 VL measurements from ARVnaive pregnant women participating in perinatal prevention trials in Thailand were included. Women received either zidovudine (ZDV) monotherapy, ZDV plus lopinavir/ ritonavir (LPV/r), or ZDV plus lamivudine (3TC) plus LPV/r. VL time-course during pregnancy was described as a function of pretreatment VL and treatment duration using an Emax non-linear mixed-effect model. VL reduction and median time to achieve a VL<50 copies/ml were estimated for each regimen. Results: Among 745 women, 279 (37%), 145 (20%) and 321 (43%) received ZDV monotherapy, ZDV+LPV/r and ZDV+3TC+LPV/r, respectively. The predicted VL reduction from baseline to delivery after a median of 10 weeks of treatment were 0.5, 2.7 and 2.9 log10 copies/ml with ZDV monotherapy, ZDV+LPV/r and ZDV+3TC+LPV/r, respectively. At delivery, 1%, 57% and 63% of women receiving ZDV monotherapy, ZDV+LPV/r or ZDV+3TC+LPV/r had a VL<50 copies/ml. The addition of 3TC to ZDV+LPV/r reduced the time to achieve a VL<50 copies/ml and the higher the pretreatment VL, the larger the effect 3TC had on reducing the time to VL<50 copies/ml. Conclusions: The addition of 3TC to ZDV+LPV/r was associated with a slight further VL reduction but the time to reach a VL<50 copies/ml was shorter. This beneicial effect of 3TC is crucial for prevention of motherto-child transmission in women who receive ARVs late and with high pretreatment VL. © 2016 International Medical Press.


Homkham N.,Institute Of Recherche Pour Le Developpement Ird Umi 174 Phpt | Homkham N.,Chiang Mai University | Homkham N.,Kasetsart University | Homkham N.,University Paris Saclay | And 24 more authors.
Pediatric Infectious Disease Journal | Year: 2015

In 188 HIV-infected children receiving efavirenz, a lower middose (C12) was associated with a higher risk of HIV-1 viral load >400 copies/ mL (P = 0.03). Simulations for a normalized population receiving US Food and Drug Administration weight-band dosing predicted that 15% of children would have a C12 below target threshold (<1.0 mg/L) with a 23% risk of viral replication. Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.


PubMed | Banglamung Hospital, Institute Of Recherche Pour Le Developpement Ird Umi 174 Phpt, Chiang Mai University, University Paris - Sud and 6 more.
Type: Journal Article | Journal: PloS one | Year: 2015

Antiretroviral treatments decrease HIV mother-to-child transmission through pre/post exposure prophylaxis and reduction of maternal viral load. We modeled in-utero and intra-partum HIV transmissions to investigate the preventive role of various antiretroviral treatments interventions.We analysed data from 3,759 women-infant pairs enrolled in 3 randomized clinical trials evaluating (1) zidovudine monotherapy, (2) zidovudine plus perinatal single-dose nevirapine or (3) zidovudine plus lopinavir/ritonavir for the prevention of mother-to-child transmission of HIV in Thailand. All infants were formula-fed. Non-linear mixed effect modeling was used to express the viral load evolution under antiretroviral treatments and the probability of transmission.Median viral load was 4 log10 copies/mL (Interquartile range: 3.36-4.56) before antiretroviral treatments initiation. An Emax model described the viral load time-course during pregnancy. Half of the maximum effect of zidovudine (28% decrease) and lopinavir/ritonavir (72% decrease) were achieved after 98 and 12 days, respectively. Adjusted on viral load at baseline (Odds ratio = 1.50 [95% confidence interval: 1.34, 1.68] per log10 copies/mL increment), antiretroviral treatments duration (OR = 0.80 [0.75, 0.84] per week increment) but not the nature of antiretroviral treatments were associated with in-utero transmission. Adjusted on gestational age at delivery (<37 weeks, OR = 2.37 [1.37, 4.10]), baseline CD4 (Odds ratio = 0.79 [0.72, 0.88] per 100 cells/mm3 increment) and predicted viral load at delivery (OR = 1.47 [1.25, 1.64] per log10 copies/mL increment), single-dose nevirapine considerably reduced intra-partum transmission (OR = 0.32 [0.2, 0.51]).These models determined the respective contributions of various antiretroviral strategies on prevention of mother-to-child transmission. This can help predict the efficacy of new antiretroviral treatments and/or prevention of mother-to-child transmission strategies particularly for women with no or late antenatal care who are at high risk of transmitting HIV to their offspring.This analysis is based on secondary data obtained from three clinical trials. ClinicalTrials.gov. NCT00386230, NCT00398684, NCT00409591.


Collins I.,Institute Of Recherche Pour Le Developpement Ird Umi 174 Phpt | Collins I.,Chiang Mai University | Collins I.,Harvard University | Collins I.,London School of Hygiene and Tropical Medicine | And 17 more authors.
Journal of Acquired Immune Deficiency Syndromes | Year: 2013

BACKGROUND: As antiretroviral treatment (ART) programs mature, data on drug utilization and costs are needed to assess durability of treatments and inform program planning. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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. Copyright © 2013 by Lippincott Williams & Wilkins.


Riyaten P.,Chiang Mai University | Riyaten P.,Institute Of Recherche Pour Le Developpement Ird Umi 174 Phpt | Salvadori N.,Institute Of Recherche Pour Le Developpement Ird Umi 174 Phpt | Salvadori N.,Chiang Mai University | And 29 more authors.
Journal of Acquired Immune Deficiency Syndromes | Year: 2015

Background: Use of several antiretrovirals (ARVs) has been shown to be associated with a higher risk of diabetes in HIV-infected adults. We estimated the incidence of new-onset diabetes and assessed the association between individual ARVs and ARV combinations, and diabetes in a large cohort in Thailand. Methods: We selected all HIV-1-infected, nondiabetic, antiretroviral-naive adults enrolled in the Program for HIV Prevention and Treatment cohort (NCT00433030) between January 2000 and December 2011. Diabetes was defined as confirmed fasting plasma glucose ≤126 mg/dL or random plasma glucose ≤200 mg/dL. Incidence was the number of cases divided by the total number of person-years of follow-up. Association between ARVs and ARV combinations, and new-onset diabetes was assessed using Cox proportional hazards models. Results: Overall, 1594 HIV-infected patients (76% female) were included. Median age at antiretroviral therapy initiation was 32.5 years. The incidence rate of diabetes was 5.0 per 1000 person-years of followup (95% confidence interval: 3.8 to 6.6) (53 cases). In analyses adjusted for potential confounders, exposure to stavudine + didanosine [adjusted hazard ratio (aHR) = 3.9; P = 0.001] and cumulative exposure ≤1 year to zidovudine (aHR = 2.3 vs. no exposure; P = 0.009) were associated with a higher risk of diabetes. Conversely, cumulative exposure≤1 year to tenofovir (aHR = 0.4 vs. no exposure; P = 0.02) and emtricitabine (aHR = 0.4 vs. no exposure; P = 0.03) were associated with a lower risk. Conclusions: The incidence of diabetes in this predominantly female, young, lean population was relatively low. Although stavudine and didanosine have now been phased out in most antiretroviral therapy programs, our analysis suggests a higher risk of diabetes with zidovudine, frequently prescribed today in resource-limited settings. Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.


Leroi C.,Institute Of Recherche Pour Le Developpement Ird Umi 174 Phpt | Leroi C.,Chiang Mai University | Adam P.,Institute Of Recherche Pour Le Developpement Ird Umi 174 Phpt | Adam P.,Chiang Mai University | And 12 more authors.
International Journal of Infectious Diseases | Year: 2016

Objective To estimate the number of people living in Thailand with chronic hepatitis B (CHB), a major cause of liver cirrhosis and cancer, in view of the implementation of programs to prevent CHB complications. Methods Using PubMed/Medline and ScienceDirect, all studies reporting hepatitis B surface antigen (HBsAg) seroprevalence estimates conducted in Thailand and published between 1975 and 2015 were reviewed systematically. Pooled prevalence estimates and their 95% confidence intervals (CIs) were calculated, and potential sources of heterogeneity investigated. Results A high heterogeneity was observed between prevalence estimates. There was a significant decrease in the 150 estimates of HBsAg prevalence with more recent decades of birth (p < 0.001), even before the implementation of the national universal immunization program in 1992. When restricted to the general population, the pooled prevalence estimate was 5.1% (95% CI 4.3–6.0%), which would translate to an estimated number of individuals with CHB living in Thailand in 2015 as high as three million. Conclusions The high burden of CHB in Asian countries is a major challenge for the incorporation of national programs to prevent CHB complications within health care systems. © 2016 The Author(s)


PubMed | Institute Of Recherche Pour Le Developpement Ird Umi 174 Phpt
Type: Journal Article | Journal: Journal of acquired immune deficiency syndromes (1999) | Year: 2013

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.

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