Thai HIV-infected Patients Research Articles

Pharmacogenetics-based population pharmacokinetic analysis for dose optimization of ritonavir-boosted atazanavir in Thai adult HIV-infected patients

ABSTRACT Background This population pharmacokinetic–pharmacogenetic study aimed to investigate the optimal dose of RTV-boosted ATV (ATV/RTV) for Thai adult HIV-infected patients. Methods A total of 1460 concentrations of ATV and RTV from 544 patients receiving an ATV/RTV-based regimen were analyzed. The CYP3A5 6986 A > G, ABCB1 3435 C > T, ABCB1 2677 G > T, SLCO1B1 521 T > C, and NR1I2 63396 C > T were genotyped. A population pharmacokinetic model was performed using a nonlinear mixed-effect model (NONMEM®). Monte Carlo simulations were conducted to compare the percentages of patients achieving the therapeutic range of ATV through concentrations (Ctrough). Results The apparent oral clearance of ATV (CL/FATV) without RTV was 7.69 L/h with interindividual variability (IIV) of 28.7%. Patients with CYP3A5 6986 GG had a 7.1% lower CL/FATV than those with AA or AG genotype. The CL/FATV decreased by 10.8% for females compared with males. Simulation results showed higher percentages (~70%) of patient receiving doses of 200/100 or 200/50 mg achieved the target ATV Ctrough, while more patients (~40%) receiving a standard dose (300/100 mg) had ATV Ctrough above this target. Conclusions Both CYP3A5 6986 A > G and female decreased CL/FATV in Thai HIV-infected patients. Simulations supported that the reduced dose of ATV/RTV was sufficient to achieve the target concentration for Thai population.

Characteristics of Graves Disease in HIV-Infected Patients on Antiretroviral Therapy

Objective: To demonstrate clinical and laboratory characteristics of Graves disease in human immunodeficiency virus (HIV)-infected patients on antiretroviral therapy (ART). Methods: This is a single-institution study. All HIV-infected Thai patients who were diagnosed with Graves disease following the initiation of ART between January, 2007, and June, 2018, were retrospectively enrolled. Results: Of the 24 subjects, the mean age was 39.6 ± 10 years at the time of Graves disease diagnosis. The male to female ratio was 1:1.2. Palpitation and weight loss were the most common clinical manifestations. Of the 6 patients (25%) with evidence of Graves orbitopathy, 1 had sight-threatening orbitopathy. Two patients also had other autoimmune diseases (vitiligo and psoriatic arthritis). The median CD4 cell counts at HIV and Graves disease diagnosis were 73.5 (interquartile range [IQR], 15.5 to 189.5) and 525 (IQR, 402.3 to 725) cells/μL, respectively. The median time from ART commencement of the last effective ART regimen to the development of Graves disease was 29.5 (IQR, 13.8 to 48) months with a mean CD4 cell count increment of 328.7 ± 174.9 cells/μL. The median duration of antithyroid therapy was 34.5 (IQR, 23.8 to 51.0) months. Thirteen patients (54.2%) received radioactive iodine ablation. Conclusion: Graves disease should be suspected in HIV-infected patients who present with palpitations and weight loss despite good immunologic response to ART. Awareness of this condition can lead to diagnosis and appropriate management. Unlike immune reconstitution disease associated with infection, Graves disease may develop many years after ART initiation. Abbreviations: AIDS = acquired immunodeficiency syndrome; ART = antiretroviral therapy; HIV = human immunodeficiency virus; IQR = interquartile range; IRD = immune restoration disease; T3 = triiodothyronine; T4 = thyroxine; TgAb = thyroglobulin antibody; TPOAb = thyroid peroxidase antibody; TRAb = thyrotropin receptor antibody; TSH = thyroid-stimulating hormone.

Dosage Optimization of Efavirenz Based on a Population Pharmacokinetic–Pharmacogenetic Model of HIV-infected Patients in Thailand

PurposeEfavirenz exhibits high interindividual variability in plasma concentrations, leading to unpredictable efficacy and toxicity. Polymorphism of CYP2B6 516G > T has been found to predominantly contribute to efavirenz variability. However, dosage recommendations incorporating CYP2B6 516G > T polymorphism have not been investigated in the Thai population. This study aimed to develop a population model of the pharmacokinetic properties of efavirenz, and to investigate the impact of patients' characteristics and CYP2B6 516G > T polymorphism on the pharmacokinetic properties of efavirenz. Model-based simulations were performed to provide genotype-based dosage optimization in a Thai population. MethodsPlasma efavirenz concentrations measured at 12 h post-dose in 360 Thai HIV-infected patients with and without tuberculosis were analyzed by the nonlinear mixed-effects modeling approach. A 1-compartment model with first-order absorption and elimination was used for describing the pharmacokinetic properties of efavirenz. FindingsThe allele frequency of CYP2B6 516G > T was 34.17%. The efavirenz oral clearance were 11.9, 8.0, and 2.8 L/h in patients weighing 57 kg and having the CYP2B6 516 GG, 516 GT, and 516 TT genotypes, respectively. The use of rifampicin increased efavirenz oral clearance by 28%. The results from the simulations suggest that efavirenz dosages of 400, 300, and 100 mg once daily in Thai HIV mono-infected patients, and 800, 600, and 200 mg once daily in HIV/tuberculosis co-infected patients carrying CYP2B6 516 GG, 516 GT, and 516 TT, respectively. ImplicationThe results from this study provide a rationale for efavirenz dose adjustment based on CYP2B6 516G > T polymorphism in Thai HIV-infected patients, which could help to improve treatment outcomes in this population. ClinicalTrials.gov identifier: NCT01138267.

Causes of Hospitalization and Death among Newly Diagnosed HIV-Infected Adults in Thailand.

More than half of newly diagnosed HIV-infected patients enter to care with a low CD4 count. A retrospective cohort study was conducted among newly diagnosed HIV-infected adults who were hospitalized. Of 148 patients, median (interquartile range [IQR]) age was 39.3 (30.5-47.1) years and 114 (77%) patients were male. Baseline median (IQR) CD4 count was 79 (24-218) cells/mm3. The median (IQR) length of hospital stay was 8 (4-16) days. Half of the patients were hospitalized with AIDS-defining illness (ADI). Common opportunistic infections were Pneumocystis jirovecii pneumonia (20.3%) and tuberculosis (18.9%). CD4 count was statistically significantly associated with hospitalization with ADI (odds ratio: 0.85, per 10 cells/mm3 increased; 95% confidence interval: 0.80-0.90). The mortality was 5.4%. In conclusion, half of newly diagnosed Thai HIV-infected patients were hospitalized with ADI. Early detection of HIV infection leading to early antiretroviral therapy initiation and prevention of serious complications is essential.

Immunogenicity and safety of 4 vs. 3 standard doses of HBV vaccination in HIV-infected adults with isolated anti-HBc antibody

BackgroundPresence of isolated anti-HBc antibody is common in HIV-infected patients in endemic areas and could be caused by prior HBV infection with loss of anti-HBs antibody. The role of vaccination in these patients remains controversial and is based largely on limited and low quality data. We, therefore, conducted this study to determine immunogenicity and safety of 4 vs. 3 standard doses of HBV vaccination in HIV-infected adults with isolated anti-HBc antibody.MethodsAn open-label, randomized controlled trial was conducted among HIV-infected patients visiting HIV clinic of the Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand between July and September 2017. Inclusion criteria included ≥ 18 years of age, currently on a stable antiretroviral regimen, CD4+ cell count ≥ 200 cells/mm3, plasma HIV-1 RNA < 20 copies/mL, and isolated anti-HBc antibody. The participants were randomized to receive either 3 standard doses (20 µg at month 0, 1, 6) or 4 standard-doses (20 µg at month 0, 1, 2, 6) of IM HBV vaccination, and were evaluated for anamnestic response at week 4 and vaccine response at week 28.ResultsOf the 97 patients screened, 54 (32 male, mean age of 46 years) were enrolled and 27 were allocated to each of the vaccination groups. Anamnestic response occurred in 25.9% vs. 33.3% in 3-dose group vs. 4-dose group, respectively (p = 0.551). The vaccine response rates at week 28 were 85.2% in 3-dose group vs. 88.9% in 4-dose group (p = 1.000); geometric mean titer of anti-HBs antibody at week 28 was 63.8 and 209.8 mIU/mL in 3-dose group and 4-dose group, respectively (p = 0.030). No adverse events were reported.ConclusionsAn anamnestic response occurred in one-third of Thai HIV-infected patients with isolated anti-HBc antibody who received one dose of HBV vaccination; however, the majority were still unprotected. The use of either 3 or 4 standard-doses of vaccination was highly effective and should be recommended in all HIV-infected individuals with isolated anti-HBc antibody.Trial registration ClinicalTrials.gov; NCT03212911. Registered 11 July 2019, https://clinicaltrials.gov/ct2/show/NCT03212911

Oral manifestations, salivary flow rates and Candida species in Thai HIV-infected patients.

BackgroundEffects of various Highly Active Antiretroviral Therapy (HAART) regimens on oral heath are unclear. Objectives: We aimed to evaluate effects of HAART on oral manifestations, salivary flow rates (SFR) and Candida species in HIV-infected patients who took mostly non-protease inhibitor-based HAART regimens.Material and MethodsA cross-sectional study was performed on HIV-infected patients taking and never taken HAART who attended Thai Red Cross AIDS Research Centre (n = 48). Non-HIV subjects were recruited as control (n = 20). Oral conditions and salivary flow rates were evaluated using oral examination and measurement of unstimulated and stimulated saliva. In addition, Candida colonization counts (colony forming units; CFUs) and Candida species from the collected saliva were evaluated using CHROMagar.ResultsThe most common oral manifestation in HIV-infected subjects taking HAART was hyperpigmentation. Unstimulated and stimulated SFR among the three groups were not statistically significant. Candida colonization was detected in 64%, 65% and 35% of HIV-infected subjects taking HAART, HAART-naïve, and non-HIV subjects, respectively. While 20% and 35% of HIV-infected subjects with and without HAART, respectively, had Candida CFUs higher than 500/ml, all non-HIV carriers had Candida CFUs lower than 500/ml. The most common Candida colonization species was C. albicans in HAART and non-HIV groups. Interestingly, HAART-naïve group was colonized more by non-albicans species.ConclusionsHAART has minimal effects on oral health. While HAART may not prevent Candida colonization, it might lead to reduction of non-albicans species. Because maintaining low Candida counts is important, HAART administration and antifungal sensitivity test should be considered in HIV-infected patients. Key words:HIV, Candida, HAART, Oral manifestation, Salivary flow rates.

2238. Immunogenicity and safety of four- vs. three-standard doses HBV vaccination in HIV-infected adults with isolated anti-HBc antibody

BackgroundHIV-infected patients have decreased serological response to HBV vaccination with faster decline of protective antibody (Ab) titer. In those with isolated anti-HBc Ab, the role of vaccination remains controversial. We, therefore, conducted this study aimed to determine immunogenicity and safety of four- vs. three-standard doses HBV vaccination in HIV-infected adults with isolated anti-HBc antibody.MethodsAn open-label randomized controlled trial with 1:1 allocation was conducted among HIV-infected patients attending the Infectious Diseases clinic of the Maharaj Nakorn Chiang Mai Hospital, Faculty of Medicine Chiang Mai University, Chiang Mai, Thailand between July and September 2017. Eligibility participants must be ≥18 years old, taking cART, CD4 ≥200 cells/mm3, HIV VL < 20 copies/mL, and positive isolated anti-HBc Ab. The participants were randomized to receive either three-standard-doses (20 µg at Months 0, 1, 6) or four-standard-doses (20 µg at Months 0, 1, 2, 6) IM HBV vaccination and were evaluated for anamnestic response at Week 4 after the first dose and response at Week 28. Predictive factors for anamnestic response and vaccine responders at Week 28 were analyzed.ResultsOf the total of 97 patients screened, 54 participants were enrolled and randomized. Thirty-two participants were male (59.3%) with the mean age of 46 years old. Anamnestic response occurred in 25.9% vs. 33.3% in three doses vs. four doses arm respectively (P = 0.551). After vaccination, the response rates at Week 28 were 85.2% in three doses arm vs. 88.9% in four doses arm (P = 1.000); with 44.4% vs. 63.0% being high-level responders, respectively (P = 0.172). GMT of anti-HBs Ab at Week 28 in three doses arm and four doses arm were 63.8 and 209.8 mIU/mL, respectively, P = 0.030. No adverse events were reported. A younger age (<45 years old) and higher nadir CD4 count (≥100 cells/mm3) were independently predictive factors of anamnestic response with the odd ratio (OR) of 17.4 (95% CI 3.0–102.0) and 21.6 (95% CI 2.7–170.4) respectively. No predictive factors of responders at Week 28 were found.ConclusionIn Thai HIV-infected patients with isolated anti-HBc Ab, anamnestic response occurred considerably with both regimens, but the majority was still unprotected. Hence, a single dose vaccination is insufficient. The usual three-standard-doses vaccination was highly effective with high response rate.Disclosures All authors: No reported disclosures.

558. Genotype-Guided vs. Standard First-line Antiretroviral Regimen for Treatment Naïve HIV-Infected Patients in Thailand: A Prospective Randomized Controlled Trial

BackgroundAn increase in the prevalence of pretreatment drug resistance (PDR) has been reported among HIV-infected individuals and PDR may be associated with poor treatment outcome of first-line antiretroviral therapy (ART). However, drug resistance testing prior to ART initiation is not routinely performed in resource-limited settings. We aimed to evaluate the prevalence of PDR in Thailand and whether genotype-guided first-line ART can improve treatment outcomes.MethodsA prospective, multicenter, randomized, controlled trial was conducted involving newly diagnosed HIV-infected adults. Participants who were going to initiate ART were randomly assigned to either genotype-guided (GG) group or standard of care (SC) group with 1:1 allocation as per a computer-generated randomization. Genotypic resistance assay was performed in all participants. The investigators in GG group were informed the results of genotypic resistance assays before selecting the ART regimen. In contrast, the results of SC group were blinded to the investigators. Factors associated with having PDR and undetectable HIV RNA were analyzed by logistic regression.ResultsA total of 153 participants were randomized to either GG group (78 participants) SC group (75 participants). Of all, median (IQR) age was 32 (26–42) years and 83% were male. Median (IQR) CD4 count was 190 (42–324) cells/mm3. Overall prevalence of PDR was 13.7% and NNRTIs PDR was 10.5%. The most common mutation was V179D (5.9%), T215Y (3.9%) and E138K (2.0%). No associated factor of having PDR was determined. At 24 weeks, 85.9% in GG group and 86.3% in SC group had undetectable HIV RNA (P = 0.940). By univariate logistic regression, having PDR was not associated with undetectable HIV RNA (OR 0.40; 95% CI 0.12–1.30, P = 0.122). By multiple logistic regression, factors associated with undetectable HIV RNA were adherence (OR 1.53 per 5% increment; 95% CI 1.15–2.05; P = 0.004) and no history of PJP (OR 6.24; 95% CI 1.62–24.08; P = 0.008).ConclusionIn Thailand, the prevalence of PDR is moderate and NNRTIs PDR is high according to the WHO category. Recommended first-line ART for Thai HIV-infected patients should be modified. Routine genotype-guided first-line ART is not now recommended in Thailand. Periodically PDR surveillance and cost-effectiveness study of genotype-guided first-line ART should be further studied. Disclosures All authors: No reported disclosures.

Genotype and allele frequencies of ABCB1 and SLCO1B1 polymorphisms in THAI HIV-infected patients

Genotype and allele frequencies of ABCB1 and SLCO1B1 polymorphisms in THAI HIV-infected patients

Chronic kidney disease incidence and survival of Thai HIV-infected patients

As data on chronic kidney disease (CKD) incidence among Asian HIV patients has been limited, the present study aimed to estimate the CKD incidence in HIV-infected patients who received standard antiretroviral therapy in Thailand and to compare baseline demographics and clinical characteristics of the patients who developed CKD with those who do not. A multicenter, observational prospective cohort of HIV patients with normal kidney functions who received standard antiretroviral therapy. CKD was diagnosed based on the KDIGO 2012 criteria, using Chronic Kidney Disease Epidemiology Collaboration based estimated glomerular filtration rate with and without urine protein. The cumulative probability of CKD incidence was analyzed using Kaplan-Meier estimation. Of 5552 patients, 96 patients with pre-existing CKD and 26 patients with incomplete data were excluded, and 5430 patients were analyzed. Their mean age was 39.87 years, 41.52% were women, and 49.45% were homosexual. They were followed up for 49.41 months on average, with 229 incident cases (4.22%) being identified during 22 035 person-years at risk. Overall CKD incidence rate was 10.39 per 1000 person-years. Average time to CKD was 26.4 months (95% confidence interval: 24.44-28.83). The adjusted relative hazard significantly increased by 8.6% and 10.3% for each additional year of patient age and each additional log10 copies/ml of HIV viral load, respectively. Patients with diabetes mellitus and hypercholesterolemia had significantly higher adjusted relative hazard (3.37 and 1.41; P < 0.001 and P = 0.014), respectively. CKD incidence among the Thai HIV-infected patients was lower than in white and non-Southeast Asian populations. Diabetes, hypercholesterolemia, age, and HIV viral load were the significant risk factors. ClinicalTrials.gov identifier: NCT01328275.

Impact of CYP3A5 and SLCO1B1 polymorphisms on atazanavir/ritonavir trough concentrations in Thai HIV-infected patients

Impact of CYP3A5 and SLCO1B1 polymorphisms on atazanavir/ritonavir trough concentrations in Thai HIV-infected patients

Pharmacogenetics-based population pharmacokinetic analysis of tenofovir in Thai HIV-infected patients.

To develop a population pharmacokinetic model and identify sources of variability, genetic and nongenetic factors, of tenofovir. The ABCC2 and ABCC4 polymorphisms were genotyped in 342patients. A nonlinear mixed effects model was used to develop the population pharmacokinetic model and investigate the influence of these polymorphisms and other patient specific covariates on the pharmacokinetics of tenofovir. The estimated glomerular filtration rate calculated by the Cockcroft and Gault equation, concomitant use of lopinavir/ritonavir and ABCC4 3463A>G polymorphism were associated with tenofovir apparent oral clearance (CL/F). The use of lopinavir/ritonavir decreased tenofovir CL/F by 25%. Patients carrying ABCC4 3463 AG or GG had a tenofovir CL/F 11% higher than those with genotype AA. Renal function, co-medication and genetic variation impact the pharmacokinetics of tenofovir. These factors should be taken into consideration to guide the individual tenofovir disoproxil fumarate dosage regimen in Thai HIV-infected patients.

A Prediction Model of Pretreatment HIV RNA Levels in Naïve Thai HIV-infected Patients: An Application for Resource-limited Settings

BackgroundThe use of abacavir (ABC) and rilpivirine (RPV) in the first-line regimen for naïve HIV-infected patients with pretreatment HIV RNA >100,000 copies/mL is not recommended due to a high rate of treatment failure. If a model could accurately predict pretreatment HIV RNA levels, it would be a useful tool for the selection ABC or RPV in the first-line regimen.MethodsThai HIV-infected adults enrolled in the TREAT Asia HIV Observational Database (TAHOD) and additional patients of Ramathibodi Hospital were eligible if they had an HIV RNA result at the time of antiretroviral therapy initiation. Factors associated with pretreatment HIV RNA <100,000 copies/mL were determined by logistic regression. Based on the results of the final model, a prediction model was created.ResultsA total of 1,223 patients were included in the analysis. Among those in the derivation data set, median [interquartile range (IQR)] age was 36.3 (30.5–42.9) years, median (IQR) CD4 count was 122 (39–216) cells/mm3, and pretreatment HIV RNA was 100,000 (32,449–229,777) copies/mL. Factors associated with pretreatment HIV RNA <100,000 copies/mL were anemia [odds ratio (OR) 2.05 vs. no anemia; 95% confidence interval (CI) 1.28–3.27], CD4 count >200 cells/mm3 (OR 3.00 vs. CD4 count <200 cells/mm3; 95% CI 2.08–4.33), and non-heterosexual HIV exposure (OR 1.61 vs. heterosexual HIV exposure; 95% CI 1.07–2.43). No AIDS-defining illness (11.5), no anemia (18.5), age <35 years (11), CD4 count >200 cells/mm3 (27), duration of HIV infection >1 year (9), and weight >50 years (11) were included in the clinical prediction tool scores. A score ≥45 yielded a sensitivity of 45.3%, specificity of 76.7%, positive predictive value of 68.1%, and negative predictive value of 56.1% among patients in the derivation. The area under the receiver-operator characteristic curve was 0.655 (95% CI 0.614- 0.696) and 0.600 (95% CI 0.533–0.667) in the derivation and validation patients, respectively.ConclusionOur final prediction model had poor sensitivity and specificity for predicting HIV RNA <100,000 copies/mL. Further study on a larger population with a greater diversity of data variables available is necessary to improve the model. Pretreatment HIV RNA remains necessary before ABC or RPV initiation for naïve Thai HIV-infected patients.Disclosures All authors: No reported disclosures.

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

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). 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. 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. 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.

New-onset diabetes in HIV-treated adults: predictors, long-term renal and cardiovascular outcomes.

To determine the incidence and risk factors for developing diabetes mellitus in a cohort of Thai HIV-infected patients on long-term combination antiretroviral therapy (cART). Prospective study conducted between July 1996 and 30 April 2015. A total of 1748 patients (60% men) who did not have diabetes mellitus prior to ART were assessed twice a year. Incident diabetes mellitus was defined as either having two consecutive fasting glucose levels more than 126 mg/dl, or reporting antidiabetes mellitus medication/diabetes mellitus diagnosis after starting cART. Incidence rates were calculated per 1000 person-year follow-up. Multivariate Cox regression was used to determine risk factors for the development of diabetes mellitus. During a median follow-up of 9 years (16 274 person-year of follow-up), 123 patients developed new-onset diabetes mellitus, resulting in an incidence rate of 7.6 (95% confidence interval 6.3-9) per 1000 person-year of follow-up. From the multivariate models, age more than 35 years, male sex, BMI at least 25 kg/m, family history of diabetes, abnormal waist circumference, lipodystrophy and exposure to didanosine were significantly associated with incident diabetes mellitus. The diabetes mellitus group had higher mortality rate (8.1 vs. 4.1%, P = 0.04). A significantly higher proportion diabetes vs. nondiabetes patients developed cardiovascular and cerebrovascular complications (8.9 vs. 3.6%, P = 0.008) or chronic kidney disease stage III (estimated glomerular filtration rate <60 ml/min/1.73 m) (15.3 vs. 1.9%, P < 0.001) over total follow-up. In addition to traditional risk factors, lipodystrophy and use of didanosine were strongly associated with development of incident diabetes. Given the higher rate of cardiovascular-cerebrovascular complications and chronic kidney disease among patients with diabetes mellitus, careful assessment and appropriate management of diabetes mellitus are essential.

Efficacy and safety of a once-daily single-tablet regimen of tenofovir, lamivudine, and efavirenz assessed at 144 weeks among antiretroviral-naïve and experienced HIV-1-infected Thai adults

ObjectiveTo assess the efficacy and safety of a new single-tablet regimen (STR) of tenofovir disoproxil fumarate (TDF) 300mg, lamivudine (3TC) 300mg, and efavirenz (EFV) 600mg in HIV-infected Thai patients. MethodsThis was a prospective study performed for 144 weeks among 51 treatment-naïve patients and 49 experienced patients on separate tablets of TDF, 3TC, and EFV with HIV RNA<50 copies/ml. CD4, HIV RNA, liver and renal function, and lipid profiles were assessed at baseline, weeks 12, 24, and 48, and then every 24 weeks. ResultsThe median baseline CD4 cell count was 512 cells/μl for treatment-experienced patients and 230 cells/μl for treatment-naïve patients. Median baseline log10 HIV-1 RNA for treatment-naïve subjects was 4.9 copies/ml. From the intention-to-treat (ITT) analysis, the proportion of subjects with HIV RNA <50 copies/ml at week 48, 96, and 144 was 95%, 94%, and 94%, respectively, for antiretroviral-experienced patients and 88%, 90%, and 80%, respectively, for antiretroviral-naïve patients. One virological failure at week 12 had primary drug resistance of K70R, T69D, V75L. Three serious adverse events occurred (tension headache, infective endocarditis, and cervical dysplasia) and another three discontinued the study drug due to EFV intolerance. ConclusionsThis generic STR TDF/3TC/EFV is effective and well-tolerated. These findings lend support to the use of this generic STR as first-line antiretroviral therapy in resource-limited settings.

CD4 count and risk of anti-tuberculosis drug-associated cutaneous reactions in HIV-infected Thai patients.

Tuberculosis (TB) is a major cause of morbidity and mortality in human immunodeficiency virus (HIV) infected patients. However, anti-tuberculosis drugs can cause cutaneous adverse drug reactions (CADRs). This study was conducted to evaluate differences in CADR incidence between low and high CD4 cell count in patients with low and high CD4 cell count and to identify other risk factors for CADR in HIV-TB co-infected patients. In a retrospective cohort of adult HIV-TB co-infected patients receiving standard anti-tuberculosis treatment between January 2008 and December 2015 at Vajira Hospital, Bangkok, Thailand, baseline demographic, clinical characteristics and factors associated with CADRs, including CD4 cell count status, were collected. Of 307 patients enrolled, CADRs occurred in 48 during the 6-month period of anti-tuberculosis treatment (incidence rate 0.41 events/person-year). Maculopapular rash was the most prevalent CADR. Low CD4 cell count was not associated with CADRs. Cox regression analysis revealed that moderate decrease in the glomerular filtration rate, history of drug hypersensitivity and concomitant cotrimoxazole use were all associated with CADRs. Concomitant antiretroviral therapy use was associated with lower risk of CADRs. No difference in the time to CADRs between patients with lower and higher CD4 cell count could be demonstrated. CADRs are common in HIV-TB co-infected patients. Early recognition and prompt withdrawal of the offending agent can prevent complications and improve TB care.

Population pharmacokinetics and dose optimisation of ritonavir-boosted atazanavir in Thai HIV-infected patients

There is evidence that Thai patients receiving standard doses of ritonavir (RTV)-boosted atazanavir (ATV/r) have high exposure to atazanavir (ATV) leading to a higher risk of toxicity. A lower dose of ATV/r may provide adequate exposure in this population. However, pharmacokinetic data on ATV/r in Thai patients required for dose adjustment are limited. This study aimed to develop a population pharmacokinetic model of ATV/r and to determine the influence of patient characteristics on ATV pharmacokinetics. Monte Carlo simulations were performed to estimate the proportion of patients achieving target ATV trough concentration (Ctrough) with the standard ATV/r dose of 300/100 mg and a low dose of 200/100 mg once daily (OD). A total of 127 Thai HIV-infected patients were included in this study. One random blood sample was collected to determine ATV and RTV concentrations at each clinic visit from 100 patients. Intensive data from 27 patients enrolled in previous studies were also included. Data were analysed using the non-linear mixed-effects modelling approach. A one-compartment model with first-order absorption and elimination and absorption lag time best described the data. The population mean clearance of ATV/r was 4.93 L/h in female patients and was 28.7% higher in male patients. Simulation results showed a higher proportion of patients achieving ATV Ctrough within the target range with ATV/r 200/100 mg compared with 300/100 mg. The 200/100 mg OD dose of ATV/r provides adequate ATV exposure in Thai HIV-infected patients. Therefore, a lower dose of ATV/r should be considered for Thai and Asian populations.

QuantiFERON-TB Gold In-Tube Test for Tuberculosis Prevention in HIV-Infected Patients.

Optimal testing strategies for diagnosing latent tuberculosis infection and the administration of isoniazid preventive therapy (IPT) remain uncertain among human immunodeficiency virus (HIV)-infected patients. A 4-year prospective study was conducted among Thai HIV-infected patients who underwent simultaneous tuberculin skin test (TST) and QuantiFERON-TB Gold In-Tube Test (QFT-IT) at care entry. Based on baseline test results, patients were categorized into the following 4 groups: i) QFT-IT-positive, TST-reactive; ii) QFT-IT-positive, TST-non-reactive; iii) QFT-IT-negative, TST-reactive; and iv) QFT-IT-negative, TST-non-reactive. The QFT-IT-positive patients were offered 9-month IPT and were QFT-IT tested annually. Of the 150 enrolled patients, 8, 12, 16, and 114 patients were assigned to groups 1, 2, 3, and 4, respectively. Sixteen of 19 QFT-IT-positive patients (84%) completed IPT. The incidence of tuberculosis was significantly higher in patients who declined IPT than in those underwent treatment (11.11 vs. 0 case/100 patient-year; P ＜ 0.001). Among the 16 patients completing IPT, 11 (69%) and 2 (12%) had QFT-IT reversion at 1 and 2 years after IPT, respectively. The remaining 3 (19%) did not demonstrate any reversion, and their baseline interferon-γ (IFN-γ) levels were above 1.2 IU/mL. Initial QFT-IT-guided IPT was effective in preventing tuberculosis. Serial QFT-IT for evaluating IPT effectiveness had limitations because of delayed or lack of reversion, especially for patients with high baseline IFN-γ levels.

Application of the WHOQOL-HIV-BREF Questionnaire in HIV-Infected Thai Patients: Reliability and Validity of the Instrument

Given the prolonged survival of HIV-infected individuals as a result of widespread availability of treatment, health-related quality of life (HRQOL) becomes a relevant endpoint for assessing the impacts of HIV interventions. We examined the reliability and validity of the World Health Organization Quality of Life in HIV-infected Persons instrument (WHOQOL-HIV-BREF) using data from 329 HIV-infected Thai patients who received outpatient care at seven public hospitals. Our findings revealed acceptable reliability, construct validity, and convergent validity of the WHOQOL-HIV-BREF. No significant difference in HRQOL was found between groups with different CD4+ Tcell counts. Conversely, the subgroup with a history of opportunistic infection appeared to have a higher HRQOL compared to those in the latency stage. Challenges to the interpretation of the questions related to culture are discussed. In conclusion, the WHOQOL-HIV-BREF can be added to the limited list of instruments for comprehensive outcome evaluation of HIV interventions in Thailand.