Attrition and Mortality of Children Receiving Antiretroviral Treatment through the Universal Coverage Health Program in Thailand.

OBJECTIVE: To assess mortality and loss to follow-up of children with HIV infection who started antiretroviral therapy (ART) through the Universal Coverage Health Program (UC) in Thailand. STUDY DESIGN: Children with HIV infection who initiated ART at age <15 years through the UC between 2008 and 2013 were included in the analysis. Death was ascertained through linkage with the National Death Registry. A competing-risks method was used to calculate subdistribution hazard ratios (SHRs) of predictors for loss to follow-up. Death was considered a competing risk. Cox proportional hazards models were used to assess predictors of mortality. RESULTS: A total of 4618 children from 497 hospitals in Thailand were included in the study. Median age at ART initiation was 9 years (IQR, 6-12 years), and the median duration of tracking was 4.1 years (a total of 18 817 person-years). Three hundred and ninety-five children (9%) died, for a mortality rate of 2.1 (95% CI, 1.9-2.3) per 100 person-years, and 525 children (11%) were lost to follow-up, for a lost to follow-up rate of 2.9 (95% CI, 2.7-3.2) per 100 person-years. The cumulative incidence of loss to follow-up increased from 4% at 1 year to 8.8% at 3 years. Children who started ART at age ≥12 years were at the greatest risk of loss to follow-up. The probability of death was 3.2% at 6 months and 6.4% at 3 years. Age ≥12 years at ART initiation, lower baseline CD4%, advanced HIV staging, and loss to follow-up were associated with mortality. CONCLUSION: The Thai national HIV treatment program has been very effective in treating children with HIV infection, with low mortality and modest rates of loss to follow-up.

Elimination of Mother-to-Child Transmission of HIV - Thailand.

Thailand experienced a generalized human immunodeficiency virus (HIV) epidemic during the 1990s. HIV prevalence among pregnant women was 2.0% and the mother-to-child transmission (MTCT) rate was >20% (1-3). In June 2016, Thailand became the first country in Asia to validate the elimination of MTCT by meeting World Health Organization (WHO) targets. Because Thailand's experience implementing a successful prevention of MTCT program might be instructive for other countries, Thailand's prevention of MTCT interventions, outcomes, factors that contributed to success, and challenges that remain were reviewed. Thailand's national prevention of MTCT program has evolved with prevention science from national implementation of short course zidovudine (AZT) in 2000 to lifelong highly active antiretroviral therapy regardless of CD4 count (WHO option B+) in 2014 (1). By 2015, HIV prevalence among pregnant women had decreased to 0.6% and the MTCT rate to 1.9% (the elimination of MTCT target is <2% for nonbreastfeeding populations) (4). A strong public health infrastructure, committed political leadership, government funding, engagement of multiple partners, and a robust monitoring system allowed Thailand to achieve this important public health milestone.

Attrition and treatment outcomes among adolescents and youths living with HIV in the Thai National AIDS Program.

BACKGROUND: There are limited data describing the care outcome of youth living with HIV in Asia. We assessed attrition and treatment outcomes among youths with behaviourly acquired HIV (BIY) and adolescents with perinatally acquired HIV (PIY) who initiated antiretroviral treatment (ART) through the National AIDS Program (NAP) in Thailand. METHODS: People living with HIV aged 10-24 years who initiated antiretroviral therapy (ART) from 2008 to 2013 through the Thai NAP and who were followed up until 2014 were included in the analysis. We assessed youths initiating ART: BIY aged 15-19 years (BIY1) and BIY aged 20-24 (BIY2) compared against PIY aged 10-14 years. Attrition rates (mortality and loss to follow-up [LTFU]) were calculated and potential associations were assessed using Cox regression. Logistic regression was used to assess associations with treatment failure. RESULTS: Of 11,954 individuals, 9909 (83%) were BIY with a median follow-up of 2.1 years and 17% were PIY with 4.2 years of follow-up. The median baseline CD4 cell count in BIY was higher (190 vs 154 cells/mm3) compared to PIY. Mortality rates were not significantly different among PIY (2.5 per 100 person years [PY], BIY1 3.1/100 PY and BIY2 2.9/100 PY, P=0.46). Compared to PIY with a crude LTFU rate of 2.9/100 PY, LTFU was higher in BIY1 (13.9/100 PY) and BIY2 (9.5/100 PY), P<0.001 and P<0.001, respectively. At 1 year after initiating ART, 16% experienced virological failure (viral load above 1000 copies/mL). Combined treatment failure and LTFU rates at 1 year after ART were higher among BIY1 (45.0%) and BIY2 (34.4%) compared to PIY (29.9%), P<0.001 and 0.001, respectively. CONCLUSION: Youth with behaviourally acquired HIV aged 15-19 years had poorer retention rates than older BIY and PIY. Targeted interventions for youth are urgently needed to improve overall treatment outcomes.

Loss to follow-up and associated factors of patients in the National AIDS Program in Thailand.

BACKGROUND: Loss to follow-up (LTFU) is a crucial indicator to evaluate the effectiveness of HIV care and treatment programmes. We assessed the LTFU rate and associated factors of Thai HIV-infected patients who enrolled in the National AIDS Program (NAP) for two periods: prior to (pre-ART) and after starting ART (ART-patients). METHODS: Thai HIV patients aged ≥15 years enrolled in NAP from 2008 to 2014. Vital status was ascertained by linkage with the National Death Registry. Competing risk models were used to calculate the adjusted sub-distribution hazards (aSHR) for LTFU for pre-ART and ART-patients, with death considered as a competing risk. RESULTS: A total of 157,026 patients registered in care and were included in analyses. The cumulative incidence of LTFU in pre-ART patients at 1 year was 10.2%, whereas in ART-patients it was 12.8%. Among pre-ART patients, younger age (<30 versus ≥45 years, aSHR 1.60, 95% CI 1.49, 1.72), less advanced HIV stage (aSHR 1.29, 95% CI 1.21, 1.37) and higher CD4+ T-cell count (≥350 versus <100, aSHR 6.31, 95% CI 5.74, 6.95) had a higher chance of LTFU. ART-patients with high baseline CD4+ T-cell count (CD4 ≥350 versus CD4 <50, aSHR 2.06, 95% CI 1.97, 2.15) and non-advanced HIV stage had increased risk of LTFU. CONCLUSIONS: Our findings provide new evidence of the LTFU rate in Thai HIV-infected patients in NAP. Emphasis needs to be placed on improving follow-up in all patients with higher CD4+ T-cell counts. LTFU will be important to monitor as programmes move to commence ART regardless of CD4+ T-cell count.

First-Line Antiretroviral Treatment Outcomes and Durability in HIV-Infected Children Treated Through the Universal Coverage Health Program in Thailand.

BACKGROUND: We assessed the treatment outcomes on first-line antiretroviral therapy (ART), and factors associated with switching regimen in HIV-infected children treated through the universal coverage health program (UC) in Thailand. METHODS: Children aged <15 years at ART initiation who had been receiving ART for at least 6 months between 2008 and 2014 through UC were included in the analysis. The Kaplan-Meier method was used to estimate immunological recovery (IMR), immunological failure, and virological failure (VF). Cox models were used to assess predictors of IMR and VF. Competing risk models were used to assess factors associated with switching to a second-line regimen, with death considered as a competing risk. RESULTS: A total of 4120 children initiated ART at a median (interquartile range) age of 9.3 (5.8-12.0) years. The median duration of ART was 3.7 years with 17,950 person-years of follow-up. Two thousand eight hundred five children achieved IMR, and the probability of IMR increased to 76% by 3 years after ART initiation. Among 1054 children switched to second-line regimens, 84% had VF and 19% had immunological failure. The cumulative rate of switching regimen increased from 4% to 20% from 1 to 3 years after treatment. Children aged ≥12 years at ART initiation, starting with nonnucleoside reverse-transcriptase inhibitors, and baseline CD4% <10% had an increased risk of switching to second-line regimens. CONCLUSIONS: Children receiving ART through UC had good treatment outcomes, although a fifth required switching regimen by 3 years. Earlier treatment initiation and avoiding nonnucleoside reverse-transcriptase inhibitor first-line regimens in high-risk children may prevent treatment failure.

Life expectancy after initiation of combination antiretroviral therapy in Thailand.

BACKGROUND: Access to combination antiretroviral therapy (cART) has decreased mortality in HIV-positive people. We aimed to estimate the expected additional years of life in HIV-positive Thai people after starting cART through the National AIDS Program (NAP), administered by the Thai National Health Security Office (NHSO). METHODS: The NHSO database collects characteristics of all Thai HIV-infected patients through the National AIDS Program, including linkage with the National Death Registry for vital status. This study included patients aged ≥15 years at cART initiation between 2008 and 2014. The abridged life table method was used to construct life tables stratified by sex and baseline CD4+ T-cell count. Life expectancy was defined as the additional years of life from age at starting cART. RESULTS: 201,688 eligible patients were included in analyses, contributing 618,837 person-years of follow-up. Median CD4+ T-cell count was 109 cells/mm3 and median age 37 years. The overall life expectancy after cART initiation at age 20 was 25.4 (95% CI, 25.3, 25.6) years and 20.6 (95% CI, 20.5, 20.7) at age 35 years. Life expectancy at baseline CD4+ T-cell count ≥350 cells/mm3 was 51.9 (95% CI, 51.0, 52.9) years for age 20 years and 43.2 (95% CI, 42.4, 44.1) years for age 35 years, close to life expectancy in the general Thai population. CONCLUSIONS: Increasing life expectancy with higher baseline CD4+ T-cell counts supports the guideline recommendations to start cART irrespective of CD4+ T-cell count. These results are beneficial to forecast the treatment cost and develop health policies for people living with HIV in Thailand and Asia.

The challenges of ending AIDS in Asia: outcomes of the Thai National AIDS Universal Coverage Programme, 2000-2014.

OBJECTIVES: We sought to determine Thai National AIDS Program (NAP) outcomes and gaps, and success in reaching the WHO 90:90:90 goals. METHODS: Retrospective study of treatment outcomes, mortality and loss to follow-up (LTFU), of all individuals aged >15 years who registered to the NAP from 2000 to 2014. We focused outcomes on data from 2008 when the NAP was linked to the death registry. RESULTS: A total of 429,294 patients registered to the NAP up to November 2014, and 309,313 patients aged >15 years started ART. Median (IQR) age was 37 (31-43) years; 51% were male. From 2008 to 2014, long-term follow-up rates per 100 person-years were 3.2 in those who started ART vs 3.5 in those who did not (P<0.001) and mortality rates per 100 person-years were 3.5 in those who started ART vs 4.9 in those who did not (P<0.001). Mortality reduced from 16% in 2008 to 3% in 2014 for those who started ART. For patients starting treatment since 2000, 87% of those alive and with a recent viral load (VL) result had <50 copies/mL, and 6% had VL ≥1000 copies/mL. In a continuum-of-care analysis from 2008 to 2014, 68% were living and retained on ART, and 46% of diagnosed individuals were virally suppressed at <50 copies/mL. CONCLUSIONS: In the Thai NAP, death and LTFU are major factors disrupting the care-continuum, and many patients initiate ART with low CD4 cell counts. Rolling out systems for early detection and treatment for all, regardless of CD4 cell count, are essential and under way.

Early infant HIV diagnosis and entry to HIV care cascade in Thailand: an observational study.

BACKGROUND: Early infant diagnosis of HIV is crucial for timely initiation of antiretroviral therapy (ART) in infected children who are at high risk of mortality. Early infant diagnosis with dried blood spot testing was provided by the National AIDS Programme in Thailand from 2007. We report ART initiation and vital status in children with HIV after 7 years of rollout in Thailand. METHODS: Dried blood spot samples were collected from HIV-exposed children in hospitals in Thailand and mailed to the Faculty of Associated Medical Sciences, Chiang Mai University, where HIV DNA was assessed with real-time PCR to establish HIV infection. We linked data from children with an HIV infection to the National AIDS Programme database to ascertain ART and vital status. FINDINGS: Between April 5, 2007, and Oct 1, 2014, 16 046 dried blood spot samples were sent from 8859 children in 364 hospitals in Thailand. Median age at first dried blood spot test was 2·1 (IQR 1·8-2·5) months. Of 7174 (81%) children with two or more samples, 223 (3%) were HIV positive (including five unconfirmed). Of 1685 (19%) children with one sample, 70 (4%) were unconfirmed positive. Of 293 (3%) children who were HIV positive, 220 (75%) registered for HIV care and 170 (58%) initiated ART. Median age at ART initiation decreased from 14·2 months (IQR 10·2-25·6) in 2007 to 6·1 months (4·2-9·2) in 2013, and the number of children initiating ART aged younger than 1 year increased from five (33%) of 15 children initiating ART in 2007 to ten (83%) of 12 initiating ART in 2013. 15 (9%) of 170 children who initiated ART died and 16 (32%) of 50 who had no ART record died. INTERPRETATION: Early infant diagnosis with dried blood spot testing had high uptake in primary care settings. Further improvement of linkage to HIV care is needed to ensure timely treatment of all children with an HIV infection. FUNDING: None.

Low-dose versus standard-dose ritonavir-boosted atazanavir in virologically suppressed Thai adults with HIV (LASA): a randomised, open-label, non-inferiority trial.

BACKGROUND: Thai patients with HIV have higher exposure to HIV protease inhibitors than do white people and dose reduction might be possible. We compared the efficacy of low-dose with standard-dose ritonavir-boosted atazanavir in virologically suppressed Thai patients with HIV. METHODS: In this randomised, open-label, non-inferiority trial, we recruited patients aged 18 years or older who were receiving ritonavir-boosted protease-inhibitor-based antiretroviral therapy (ART) with HIV plasma viral loads of less than 50 copies per mL, an alanine aminotransferase concentration of less than 200 IU/L, and a creatinine clearance of at least 60 mL/min from 14 hospitals in Thailand. We excluded patients who had active AIDS-defining disease or opportunistic infections, had a history of an HIV viral load of 1000 copies per mL or more after 24 weeks of any ritonavir-boosted protease-inhibitor-based ART, used concomitant medications that could interact with the study drugs, were pregnant or lactating, had illnesses that might change the effect of the study drugs, or had a history of sensitivity to the study drugs. A biostatistician at the study coordinating centre randomly allocated patients (1:1) to switch the protease inhibitor for oral atazanavir 200 mg and ritonavir 100 mg or for atazanavir 300 mg and ritonavir 100 mg once daily, both with two nucleoside or nucleotide reverse transcriptase inhibitors at recommended doses. Randomisation was done with a minimisation schedule, stratified by recruiting centre, use of tenofovir, and use of indinavir as a component of the preswitch regimen. The primary endpoint was the proportion of patients with viral loads of less than 200 copies per mL at week 48, and we followed up patients every 12 weeks. Treatments were open label, the non-inferiority margin was -10%, and all patients who received at least one dose of study medication were analysed. This trial is registered with ClinicalTrials.gov, number NCT01159223. FINDINGS: Between July 6, 2011, and Dec 23, 2013, we randomly assigned 559 patients: 279 to receive atazanavir 200 mg and ritonavir 100 mg (low dose) and 280 to atazanavir 300 mg and ritonavir 100 mg (standard dose). At week 48, 265 (97·1%) of 273 in the low-dose group and 267 (96·4%) of 277 in the standard-dose group had viral loads of less than 200 copies per mL (difference 0·68; 95% CI -2·29 to 3·65). Seven (3%) of 273 in the low-dose group and 21 (8%) of 277 in the standard-dose group discontinued their assigned treatment (p=0·01). 46 (17%) of 273 participants in the low-dose group and 97 (35%) of 277 in the standard-dose group had total bilirubin grade 3 or higher toxicity (≥3·12 mg/dL; p<0·0001). INTERPRETATION: A switch to low-dose atazanavir should be recommended for Thai patients with well controlled HIV viraemia while on regimens based on boosted protease inhibitors. FUNDING: The National Health Security Office and Kirby Institute for Infection and Immunity in Society.