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 followup. Median CD4(+) T-cell count was 109 cells/mm(3) 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/mm(3) 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 Asi

Incidence and clinical outcomes of diabetes mellitus in HIV-infected adults in Thailand: a retrospective cohort study

Abstract 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

A Population Pharmacokinetic/Pharmacodynamic Model Predicts Favorable HDL Cholesterol Changes Over the First 5 Years in Children Treated with Current Efavirenz-Based Regimens

Efavirenz use is associated with changes in cholesterol concentrations but it is unclear whether this effect is related to drug concentrations. Using efavirenz and cholesterol plasma concentrations measured in 87 antiretroviral naive children in Thailand, we assessed indirect response models to describe the evolution of high- and low-density lipoprotein cholesterol (HDL, LDL) concentrations in relation to efavirenz plasma concentrations over time where efavirenz was assumed to either stimulate cholesterol production or inhibit its elimination. Simulations of cholesterol evolution for children with different average efavirenz concentrations (Cav ) according to their assumed status of 'fast' or 'slow' metabolizers of efavirenz were performed. At treatment initiation, children's median (interquartile range, IQR) age was 8 years (5 to 10), body mass index z-score 0.01 (-1.05 to 1.44), HDL 31 mg/dL (24 to 44) and LDL 83 mg/dL (69 to 100). Median (IQR) efavirenz Cav was 1.7 mg/L (1.3 to 2.1) during the period of observation. The best model describing the evolution of HDL and LDL cholesterol concentrations over time assumed that efavirenz inhibited their elimination. HDL concentrations increase over 5 years while LDL concentrations only increased during the first 4 months and then returned to baseline levels afterwards. Simulations predicted that, after 3 years, HDL would increase to 63 mg/dL in 'fast' metabolizers and 97 mg/dL in 'slow' metabolizers of efavirenz. The population pharmacokinetic-pharmacodynamic (PK-PD) model shows that favorable HDL cholesterol changes can be expected in children with current efavirenz dosing guidelines over 5 years of treatment. This article is protected by copyright. All rights reserved

Neurocognitive impairment in patients randomized to second-line lopinavir/ritonavir-based antiretroviral therapy vs. lopinavir/ritonavir monotherapy.

We compared rates of neurocognitive impairment (NCI) among 93 Thai adults failing non-nucleoside reverse transcriptase inhibitor (NNRTI)-based combination antiretroviral therapy (cART) before and after switching to lopinavir/ritonavir monotherapy (mLPV/r) vs. tenofovir/lamivudine/LPV/r (TDF/3TC/LPV/r). Participants completed the Color Trails 1 and 2, Digit Symbol, and Grooved Pegboard at weeks 0, 24, and 48. We calculated z-scores using normative data from 451 healthy HIV-negative Thais. We defined NCI as performance of <-1 SD on ≥2 tests. The Thai depression inventory was used to capture depressive symptoms. Lumbar puncture was optional at week 0 and 48. At baseline, median (IQR) age was 36.9 (32.8-40.5) years, and 46 % had primary school education or lower. The median CD4 count was 196 (107-292) cells/mm(3), and plasma HIV RNA was 4.1 (3.6-4.5) log(10) copies/ml. Almost all (97 %) had circulating recombinant CRF01_AE. At baseline, 20 (47 %) of the mLPV/r vs. 22 (44 %) of TDF/3TC/LPV/r arms met NCI criteria (p = 0.89). The frequency of NCI at week 48 was 30 vs. 32 % (p = 0.85) with 6 vs. 7 % (p = 0.85) developing NCI in the mLPV/r vs. TDF/3TC/LPV/r arms, respectively. Having NCI at baseline and lower education each predicted NCI at week 48. Depression scores at week 48 did not differ between arms (p = 0.47). Cerebrospinal fluid HIV RNA of <50 copies/ml at 48 weeks was observed in five out of seven in mLPV/r vs. three out of four in TDF/3TC/LPV/r arm. The rates of NCI and depression did not differ among cases failing NNRTI-based cART who received mLPV/r compared to LPV/r triple therapy

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

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. 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. 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). 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. The National Health Security Office and Kirby Institute for Infection and Immunity in Societ