Successful clinical outcomes following decentralization of tertiary paediatric HIV care to a community-based paediatric antiretroviral treatment network, Chiangrai, Thailand, 2002 to 2008

Introduction: Most paediatric antiretroviral treatments (ARTs) in Thailand are limited to tertiary care hospitals. To decentralize paediatric HIV treatment and care, Chiangrai Prachanukroh Hospital (CRH) strengthened a provincial paediatric HIV care network by training community hospital (CH) care teams to receive referrals of children for community follow-up. In this study, we assessed factors associated with death and clinical outcomes of HIV-infected children who received care at CRH and CHs after implementation of a community-based paediatric HIV care network. Methods: Clinical records were abstracted for all children who initiated ART at CRH. Paired Wilcoxon signed rank tests were used to assess CD4% and virological change among all children. Cox proportional hazard models were used to assess factors associated with death. Treatment outcomes (CD4%, viral load (VL) and weight-for-age Z-score (WAZ)) were compared between CRH and CH children who met the criteria for analysis. Results: Between February 2002 and April 2008, 423 HIV-infected children initiated ART and 410 included in the cohort analysis. Median follow-up for the cohort was 28 months (interquartile range (IQR)=12 to 42); 169 (41%) children were referred for follow-up at CH. As of 31 March 2008, 42 (10%) children had died. Baseline WAZ (<−2 (p=0.001)) and baseline CD4% (<5% (p=0.015)) were independently associated with death. At 48 months, 86% of ART-naïve children in follow-up had VL<400 copies/ml. For sub-group analysis, 133 children at CRH and 154 at CHs were included for comparison. Median baseline WAZ was lower in CH children than in CRH children (p=0.001); in both groups, WAZ, CD4% and VL improved after ART with no difference in rate of WAZ and CD4% gain (p=0.421 and 0.207, respectively). Conclusions: Children at CHs had more severe immunological suppression and low WAZ at baseline. Community- and tertiary care-based paediatric ART follow-ups result in equally beneficial outcomes with the strengthening of a provincial referral network between tertiary and community care. Nutrition interventions may benefit children in community-based HIV treatment and care

Height and timing of growth spurt during puberty in young people living with vertically acquired HIV in Europe and Thailand.

OBJECTIVE: The aim of this study was to describe growth during puberty in young people with vertically acquired HIV. DESIGN: Pooled data from 12 paediatric HIV cohorts in Europe and Thailand. METHODS: One thousand and ninety-four children initiating a nonnucleoside reverse transcriptase inhibitor or boosted protease inhibitor based regimen aged 1-10 years were included. Super Imposition by Translation And Rotation (SITAR) models described growth from age 8 years using three parameters (average height, timing and shape of the growth spurt), dependent on age and height-for-age z-score (HAZ) (WHO references) at antiretroviral therapy (ART) initiation. Multivariate regression explored characteristics associated with these three parameters. RESULTS: At ART initiation, median age and HAZ was 6.4 [interquartile range (IQR): 2.8, 9.0] years and -1.2 (IQR: -2.3 to -0.2), respectively. Median follow-up was 9.1 (IQR: 6.9, 11.4) years. In girls, older age and lower HAZ at ART initiation were independently associated with a growth spurt which occurred 0.41 (95% confidence interval 0.20-0.62) years later in children starting ART age 6 to 10 years compared with 1 to 2 years and 1.50 (1.21-1.78) years later in those starting with HAZ less than -3 compared with HAZ at least -1. Later growth spurts in girls resulted in continued height growth into later adolescence. In boys starting ART with HAZ less than -1, growth spurts were later in children starting ART in the oldest age group, but for HAZ at least -1, there was no association with age. Girls and boys who initiated ART with HAZ at least -1 maintained a similar height to the WHO reference mean. CONCLUSION: Stunting at ART initiation was associated with later growth spurts in girls. Children with HAZ at least -1 at ART initiation grew in height at the level expected in HIV negative children of a comparable age

Mortality and clinical outcomes in children treated with antiretroviral therapy in four African vertical programs during the first decade of paediatric HIV care, 2001-2010

Objective: To assess mortality and clinical outcomes in children treated with antiretroviral therapy (ART) in four African vertical programmes between 2001 and 2010. Methods: Cohort analysis of data from HIV-infected children (<15 years old) initiating ART in 4 sub-Saharan HIV programs in Kenya, Uganda and Malawi, between December 2001 and December 2010. Rates of mortality, program attrition and first-line clinico-immunological failure were calculated by age group (<2, 2-4 and 5-14 years), 1 or 2 years after ART initiation and risk factors were examined. Results: A total of 3,949 children, 22.7% aged <2 years, 32.2% 2-4 years, 45.1% aged 5-14 years, were included. At ART initiation 60.8% had clinical stage 3 or 4, and 46.5% severe immune-suppression. Overall mortality, attrition and 1-year failure rates were 5.1, 10.8 and 9.0 per 100 person-years, respectively. Immunosuppression, stage 3 or 4 and underweight were associated with increased rates of mortality, attrition and treatment failure. Adjusted estimates showed lower mortality hazard ratios (HR) among children aged 2-4 years (HR=0.57, 95%CI 0.42-0.77 compared to 5-14 years). One-year treatment failure incidence rate ratios (IRR) were similar regardless of age (IRR=0.91, 95%CI 0.67-1.25 for <2 years; 1.01, 95%CI 0.83-1.23 for 2-4 years, compared to 5-14 years). Conclusions: Good treatment outcomes were achieved during the first decade of HIV pediatric care despite the late start of therapy. Encouraging early HIV infant diagnosis in and outside prevention of mother-to-child-transmission programs, and linkage to care services for early ART initiation are needed to reduce mortality and delay treatment failure

Time of highest tuberculosis death risk and associated factors: an observation of 12 years in Northern Thailand

Saiyud Moolphate1,2, Myo Nyein Aung1,3, Oranuch Nampaisan1, Supalert Nedsuwan4, Pacharee Kantipong5, Narin Suriyon6, Chamnarn Hansudewechakul6, Hideki Yanai7, Norio Yamada2, Nobukatsu Ishikawa21TB/HIV Research Foundation, Chiang Rai, Thailand; 2Research Institute of Tuberculosis, Japan Anti-Tuberculosis Association (RIT-JATA), Tokyo, Japan; 3Department of Pharmacology, University of Medicine, Mandalay, Myanmar; 4Department of Preventive and Social Medicine, Chiang Rai Regional Hospital, Chiang Rai, Thailand; 5Department of Health Service System Development, Chiang Rai Regional Hospital, Chiang Rai, Thailand; 6Provincial Health Office, Chiang Rai, Thailand; 7Department of Clinical Laboratory, Fukujuji Hospital, Tokyo, JapanPurpose: Northern Thailand is a tuberculosis (TB) endemic area with a high TB death rate. We aimed to establish the time of highest death risk during TB treatment, and to identify the risk factors taking place during that period of high risk.Patients and methods: We explored the TB surveillance data of the Chiang Rai province, Northern Thailand, retrospectively for 12 years. A total of 19,174 TB patients (including 5,009 deaths) were investigated from 1997 to 2008, and the proportion of deaths in each month of TB treatment was compared. Furthermore, multiple logistic regression analysis was performed to identify the characteristics of patients who died in the first month of TB treatment. A total of 5,626 TB patients from 2005 to 2008 were included in this regression analysis.Result: The numbers of deaths in the first month of TB treatment were 38%, 39%, and 46% in the years 1997&amp;ndash;2000, 2001&amp;ndash;2004, and 2005&amp;ndash;2008, respectively. The first month of TB treatment is the time of the maximum number of deaths. Moreover, advancing age, HIV infection, and being a Thai citizen were significant factors contributing to these earlier deaths in the course of TB treatment.Conclusion: Our findings have pointed to the specific time period and patients at higher risk for TB death. These findings would be useful for prioritizing interventions in order to diminish TB-related deaths globally. Studies based on these findings are necessary for the introduction of newer intervention strategies.Keywords: tuberculosis, TB death, Thailand, time of deat

Risk Factors for Human Papillomavirus Infection and Abnormal Cervical Cytology Among Perinatally Human Immunodeficiency Virus-Infected and Uninfected Asian Youth.

BACKGROUND: Infection with high-risk human papillomavirus (HR-HPV) may be higher in perinatally human immunodeficiency virus (HIV)-infected (PHIV) than HIV-uninfected (HU) adolescents because of long-standing immune deficiency. METHODS: PHIV and HU females aged 12-24 years in Thailand and Vietnam were matched by age group and lifetime sexual partners. At enrollment, blood, cervical, vaginal, anal, and oral samples were obtained for HPV-related testing. The Wilcoxon and Fisher exact tests were used for univariate and logistic regression for multivariate analyses. RESULTS: Ninety-three PHIV and 99 HU adolescents (median age 19 [18-20] years) were enrolled (June 2013-July 2015). Among PHIV, 94% were currently receiving antiretroviral therapy, median CD4 count was 593 (392-808) cells/mm3, and 62% had a viral load &lt;40 copies/mL. Across anogenital compartments, PHIV had higher rates of any HPV detected (80% vs 60%; P = .003) and any HR-HPV (60% vs 43%, P = .02). Higher proportions of PHIV had abnormal Pap smears (eg, atypical squamous cells of unknown significance [ASC-US], 12% vs 14%; low-grade squamous intraepithelial neoplastic lesions, 19% vs 1%). After adjusting for ever being pregnant and asymptomatic sexually transmitted infections (STI) at enrollment, PHIV were more likely to have HR-HPV than HU (odds ratio, 2.02; 95% confidence interval, 1.09-3.77; P = .03). CONCLUSIONS: Perinatal HIV infection was associated with a higher risk of HR-HPV and abnormal cervical cytology. Our results underscore the need for HPV vaccination for PHIV adolescents and for prevention and screening programs for HPV and other STIs

Oral abstracts of the 21st International AIDS Conference 18-22 July 2016, Durban, South Africa

The rate at which HIV-1 infected individuals progress to AIDS is highly variable and impacted by T cell immunity. CD8 T cell inhibitory molecules are up-regulated in HIV-1 infection and associate with immune dysfunction. We evaluated participants (n=122) recruited to the SPARTAC randomised clinical trial to determine whether CD8 T cell exhaustion markers PD-1, Lag-3 and Tim-3 were associated with immune activation and disease progression.Expression of PD-1, Tim-3, Lag-3 and CD38 on CD8 T cells from the closest pre-therapy time-point to seroconversion was measured by flow cytometry, and correlated with surrogate markers of HIV-1 disease (HIV-1 plasma viral load (pVL) and CD4 T cell count) and the trial endpoint (time to CD4 count <350 cells/μl or initiation of antiretroviral therapy). To explore the functional significance of these markers, co-expression of Eomes, T-bet and CD39 was assessed.Expression of PD-1 on CD8 and CD38 CD8 T cells correlated with pVL and CD4 count at baseline, and predicted time to the trial endpoint. Lag-3 expression was associated with pVL but not CD4 count. For all exhaustion markers, expression of CD38 on CD8 T cells increased the strength of associations. In Cox models, progression to the trial endpoint was most marked for PD-1/CD38 co-expressing cells, with evidence for a stronger effect within 12 weeks from confirmed diagnosis of PHI. The effect of PD-1 and Lag-3 expression on CD8 T cells retained statistical significance in Cox proportional hazards models including antiretroviral therapy and CD4 count, but not pVL as co-variants.Expression of ‘exhaustion’ or ‘immune checkpoint’ markers in early HIV-1 infection is associated with clinical progression and is impacted by immune activation and the duration of infection. New markers to identify exhausted T cells and novel interventions to reverse exhaustion may inform the development of novel immunotherapeutic approaches

Time to Switch to Second-line Antiretroviral Therapy in Children With Human Immunodeficiency Virus in Europe and Thailand.

Background: Data on durability of first-line antiretroviral therapy (ART) in children with human immunodeficiency virus (HIV) are limited. We assessed time to switch to second-line therapy in 16 European countries and Thailand. Methods: Children aged <18 years initiating combination ART (≥2 nucleoside reverse transcriptase inhibitors [NRTIs] plus nonnucleoside reverse transcriptase inhibitor [NNRTI] or boosted protease inhibitor [PI]) were included. Switch to second-line was defined as (i) change across drug class (PI to NNRTI or vice versa) or within PI class plus change of ≥1 NRTI; (ii) change from single to dual PI; or (iii) addition of a new drug class. Cumulative incidence of switch was calculated with death and loss to follow-up as competing risks. Results: Of 3668 children included, median age at ART initiation was 6.1 (interquartile range (IQR), 1.7-10.5) years. Initial regimens were 32% PI based, 34% nevirapine (NVP) based, and 33% efavirenz based. Median duration of follow-up was 5.4 (IQR, 2.9-8.3) years. Cumulative incidence of switch at 5 years was 21% (95% confidence interval, 20%-23%), with significant regional variations. Median time to switch was 30 (IQR, 16-58) months; two-thirds of switches were related to treatment failure. In multivariable analysis, older age, severe immunosuppression and higher viral load (VL) at ART start, and NVP-based initial regimens were associated with increased risk of switch. Conclusions: One in 5 children switched to a second-line regimen by 5 years of ART, with two-thirds failure related. Advanced HIV, older age, and NVP-based regimens were associated with increased risk of switch

The Patient-Specific Implant Created with 3D Printing Technology in Treatment of the Irreparable Radial Head in Chronic Persistent Elbow Instability

Successful treatment of the chronic persistent elbow instability is a challenge for orthopedic surgeons. In this form, it is important to recognize and restore the osseous stabilizer in order to obtain the concentric reduction. In the present report, we describe a case of such injury with irreparable radial head treated with patient-specific radial head prosthesis which was created with 3D printing technology. To our knowledge, this is the first report in clinical use of this kind of prosthesis for the radial head fracture. At a 24-month follow-up visit, the patient was satisfied with the functional outcomes. The Mayo Elbow Performance Index (MEPI) increased from 20 points at the preoperative day to 85 points, and the patient-based Disabilities of the Arm, Shoulder, and Hand (DASH) was reduced from 88.33 points to 28.33 points. Due to the favorable result, replacement of the radial head with the patient-specific implant could be a useful treatment for the irreparable radial head in chronic persistent elbow instability