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1.
PLoS One ; 19(6): e0303085, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38941315

RESUMO

BACKGROUND: The study of non-communicable diseases (NCDs) in a developing country like Thailand has rarely been conducted in long-term cohorts, especially among the working-age population. We aim to assess the prevalence and incidence of risk factors and their associations underlying NCDs, especially type-2 diabetes mellitus (T2DM) among healthcare workers enrolled in the Siriraj Health (SIH) study cohort. METHODS: The SIH study was designed as a longitudinal cohort and conducted at Siriraj hospital, Thailand. A total of 5,011 participants (77% women) were recruited and follow-up. Physical examinations, blood biochemical analyses, family history assessments, behavior evaluations, and genetics factors were assessed. RESULTS: The average age was 35.44±8.24 years and 51% of participants were overweight and obese. We observed that men were more likely to have a prevalence of T2DM and dyslipidemia (DLP) compared to women. Aging was significantly associated with pre-diabetes and T2DM (P<0.001). Additionally, aging, metabolic syndrome, and elevated triglycerides were associated with the development of pre-diabetes and T2DM. The minor T allele of the rs7903146(C/T) and rs4506565 (A/T) were associated with a high risk of developing pre-diabetes with odds ratios of 2.74 (95% confidence interval [CI]: 0.32-23.3) and 2.71 (95% CI: 0.32-23.07), respectively; however, these associations were statistically insignificant (P>0.05). CONCLUSION: The findings of the SIH study provide a comprehensive understanding of the health status, risk factors, and genetic factors related to T2DM in a specific working population and highlight areas for further research and intervention to address the growing burden of T2DM and NCDs.


Assuntos
Diabetes Mellitus Tipo 2 , Pessoal de Saúde , Estado Pré-Diabético , Humanos , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/epidemiologia , Masculino , Feminino , Tailândia/epidemiologia , Adulto , Fatores de Risco , Pessoa de Meia-Idade , Estado Pré-Diabético/epidemiologia , Estado Pré-Diabético/genética , Estudos Longitudinais , Prevalência , Predisposição Genética para Doença , Estudos de Coortes , Síndrome Metabólica/epidemiologia , Síndrome Metabólica/genética , Polimorfismo de Nucleotídeo Único , População do Sudeste Asiático
2.
Lancet HIV ; 10(8): e497-e505, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37451297

RESUMO

BACKGROUND: Lenacapavir, a first-in-class HIV-1 capsid inhibitor, is in development as a long-acting agent for treating and preventing HIV-1. We aimed to evaluate the efficacy and safety of lenacapavir with an optimised background regimen in adults living with multidrug-resistant HIV-1 up to 52 weeks. METHODS: This ongoing, international, phase 2/3 trial at 42 sites included adults living with multidrug-resistant HIV-1. In cohort 1, 36 participants were randomly assigned (2:1) to add oral lenacapavir (600 mg, days 1 and 2; 300 mg, day 8) or placebo to an existing failing regimen. At day 15, those on oral lenacapavir received subcutaneous lenacapavir 927 mg every 26 weeks; those on placebo started lenacapavir (2-week oral lead-in then subcutaneous). Cohort 1 started an optimised background regimen on day 15. In cohort 2 (non-randomised), 36 participants started an optimised background regimen concurrent with lenacapavir (oral to subcutaneous). Here we report the secondary endpoints of plasma HIV-1 RNA of less than 50 copies per mL or less than 200 copies per mL at week 52 (US Food and Drug Administration snapshot algorithm) in cohort 1 along with results for cohorts 1 and 2 combined. This trial is registered with ClinicalTrials.gov, NCT04150068, and clinicaltrialregister.eu, EudraCT 2019-003814-16 and is ongoing. FINDINGS: Of 72 participants, 46 (64%) had CD4 counts of less than 200 cells per µL and 38 (53%) had no more than one fully active antiretroviral drug at baseline. In cohort 1, 30 of 36 participants (83%, 95% CI 67-94) had less than 50 HIV-1 RNA copies per mL and 31 of 36 participants (86%, 71-95) had less than 200 HIV RNA copies per mL, at week 52. In all, nine participants (four in cohort 1, five in cohort 2) had emergent lenacapavir resistance; four resuppressed (HIV-1 RNA <50 copies per mL) while maintaining lenacapavir use. One participant discontinued study drug owing to injection site reaction. INTERPRETATION: In participants with multidrug-resistant HIV-1, subcutaneous lenacapavir in combination with an optimised background regimen resulted in a high rate of virological suppression up to 52 weeks. FUNDING: Gilead Sciences.


Assuntos
Fármacos Anti-HIV , Infecções por HIV , HIV-1 , Adulto , Humanos , Infecções por HIV/tratamento farmacológico , Capsídeo , Piridonas/efeitos adversos , Fármacos Anti-HIV/efeitos adversos , RNA/uso terapêutico , Carga Viral
3.
HIV Med ; 24(3): 290-300, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36912172

RESUMO

OBJECTIVES: Data on switching to bictegravir, emtricitabine, and tenofovir alafenamide (B/F/TAF) in virologically suppressed Asian people living with HIV are limited. We performed a pooled analysis of virologically suppressed Asian participants from three international phase III trials to evaluate the efficacy and safety of switching to B/F/TAF. METHODS: Virologically suppressed people living with HIV were randomized to switch to B/F/TAF or to stay on baseline regimens. The primary endpoint was the proportion of participants with plasma HIV-1 RNA ≥50 copies/ml at week 48. We analysed the incidence of adverse events (AEs), laboratory abnormalities, and changes in relevant tolerability parameters through 48 weeks. RESULTS: Overall, 136 Asian participants were included. The proportions of participants with plasma HIV-1 RNA ≥50 copies/ml at week 48 were low in both arms (0% for B/F/TAF vs 1.4% for those who stayed on baseline regimens). Those who switched to B/F/TAF had virological suppression rates similar to those who stayed on baseline regimens (100% vs 95.9%, p = 0.2485), with no treatment-emergent resistance. Drug-related AEs occurred in three participants in each arm; none were serious. No participants discontinued the study drug because of AEs, and no deaths were observed. No significant differences were observed between the arms in the median changes in estimated glomerular filtration rate, body weight, and most lipid parameters. Switching from tenofovir disoproxil fumarate-containing regimens to B/F/TAF resulted in a significant decrease in tubular proteinuria compared with those who stayed on baseline regimens (p < 0.01). CONCLUSIONS: Virologically suppressed Asian people living with HIV who switched to B/F/TAF maintained 100% virological suppression at week 48, with no treatment-emergent drug resistance and safety profiles comparable to those seen in people who stayed on baseline regimens. CLINICAL TRIAL NUMBER: ClinicalTrials.gov (NCT02603120, NCT02652624, and NCT02603107).


Assuntos
Fármacos Anti-HIV , Infecções por HIV , Adulto , Humanos , Emtricitabina/uso terapêutico , Infecções por HIV/tratamento farmacológico , Fármacos Anti-HIV/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Adenina/efeitos adversos , Compostos Heterocíclicos de 4 ou mais Anéis/efeitos adversos , RNA/uso terapêutico
4.
Trop Med Infect Dis ; 7(9)2022 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-36136659

RESUMO

Hospital workers are at high risk of contact with COVID-19 patients. Currently, there is no evidence-based, comprehensive risk assessment tool for healthcare-related exposure; so, we aimed to identify independent factors related to COVID-19 infection in hospital workers following workplace exposure(s) and construct a risk prediction model. We analyzed the COVID-19 contact tracing dataset from 15 July to 31 December 2021 using multiple logistic regression analysis, considering exposure details, demographics, and vaccination history. Of 7146 included exposures to confirmed COVID-19 patients, 229 (4.2%) had subsequently tested positive via RT-PCR. Independent risk factors for a positive test were having symptoms (adjusted odds ratio 4.94, 95%CI 3.83−6.39), participating in an unprotected aerosol-generating procedure (aOR 2.87, 1.66−4.96), duration of exposure >15 min (aOR 2.52, 1.82−3.49), personnel who did not wear a mask (aOR 2.49, 1.75−3.54), exposure to aerodigestive secretion (aOR 1.5, 1.03−2.17), index patient not wearing a mask (aOR 1.44, 1.01−2.07), and exposure distance <1 m without eye protection (aOR 1.39, 1.02−1.89). High-potency vaccines and high levels of education protected against infection. A risk model and scoring system with good discrimination power were built. Having symptoms, unprotected exposure, lower education level, and receiving low potency vaccines increased the risk of laboratory-confirmed COVID-19 following healthcare-related exposure events.

5.
Trop Med Infect Dis ; 7(7)2022 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-35878140

RESUMO

It is important to focus on adherence to antiretroviral therapy (ART) and health problems of travellers living with HIV (TLWHIV) during travel. This study was conducted to investigate factors related to adherence and health problems among TLWHIV. This multicentre, cross-sectional observational study was conducted among TLWHIV in university hospitals from August 2019 to July 2020. Factors associated with adherence to ART were evaluated using a logistic regression model. Health problems and risk exposure were also examined among participants during travel. Of 321 TLWHIV, 20 (6.23%) showed moderate-to-poor adherence, among whom 3 (15%) had viral rebound after travelling. Travellers frequently missed ART during the first 3 days of their trip. International destination was associated with moderate-to-poor adherence. In total, 237 (73.8%) travellers reported health problems during travel, among whom 36 required medical attention. Sexual or sharp exposure was found in <5% of travellers during travel. Approximately 95% of Thai TLWHIV had good ART adherence. International destination was the major factor determining adherence. TLWHIV should be encouraged to seek pretravel consultation. Healthcare providers should discuss health risk prevention and teach about ART dosing during travel to enhance adherence and minimise toxicity.

6.
AIDS ; 36(3): 373-382, 2022 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-34750291

RESUMO

OBJECTIVES: To evaluate safety and immunogenicity of V114 [15-valent pneumococcal conjugate vaccine (PCV) containing serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 22F, 23F, and 33F], followed by 23-valent pneumococcal polysaccharide vaccine (PPSV23) 8 weeks later, in adults living with HIV. DESIGN: In this phase 3 study (V114-018; NCT03480802), pneumococcal vaccine-naive adults with HIV (CD4+ cell count ≥50 cells/µl, plasma HIV RNA <50 000 copies/ml, receiving antiretroviral therapy) were randomized 1 : 1 to receive one dose of V114 or licensed 13-valent PCV (PCV13) on day 1; participants received PPSV23 at week 8. METHODS: Adverse events and serotype-specific opsonophagocytic activity (OPA) and immunoglobulin G (IgG) antibodies were evaluated after each vaccination. RESULTS: Of 302 participants enrolled, 292 (96.7%) completed the study. Proportions of participants experiencing at least one adverse event were 73.0 and 62.7% in the V114 and PCV13 groups following PCV and 60.7 and 71.6% following PPSV23. Most solicited adverse events were of mild or moderate severity and short duration. OPA geometric mean titers (GMTs) and IgG geometric mean concentrations (GMCs) were generally comparable between groups for shared serotypes at day 30 and maintained at week 12. OPA and IgG responses for additional serotypes in V114 (22F, 33F) were higher following V114 than PCV13 at day 30 but comparable at week 12, 30 days post-PPSV23. CONCLUSION: In pneumococcal vaccine-naive adults living with HIV, V114 was well tolerated and induced immune responses for all 15 pneumococcal serotypes. V114 can be followed by PPSV23 8 weeks later to broaden serotype coverage.


Assuntos
Infecções por HIV , Infecções Pneumocócicas , Adulto , Anticorpos Antibacterianos , Infecções por HIV/tratamento farmacológico , Humanos , Imunoglobulina G , Infecções Pneumocócicas/prevenção & controle , Vacinas Pneumocócicas , Streptococcus pneumoniae , Vacinas Conjugadas/efeitos adversos
7.
HIV Res Clin Pract ; 20(3): 73-81, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31303140

RESUMO

Background: The efficacy and safety of a single tablet regimen (STR) of elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) was analyzed in Phase 3 clinical trials in antiretroviral therapy (ART)-naive and ART-experienced Asian participants infected with human immunodeficiency virus (HIV)-1 through 96 or 144 weeks.Objective: In Asian population requiring treatment, it is imperative to have data specific to this group, particularly as there is a general concern that Asians with lower body weight have increased risk of tenofovir disoproxil fumarate (TDF)-related renal dysfunction.Methods: Studies -104 and 111 were randomized, double-blind, placebo-controlled, 144-week studies conducted in ART-naive participants, comparing E/C/F/TAF versus E/C/F/TDF. Study 109 was a randomized, open-label, 96-week study conducted in virologically suppressed, ART-experienced participants, who switched to E/C/F/TAF from ritonavir/cobicistat-boosted atazanavir ATV+(RTV or COBI) + F/TDF regimens, from non-nucleoside reverse transcriptase inhibitors (NNRTI) + F/TDF regimens, or from E/C/F/TDF. Study 112 was a single arm, open-label, 144-week study conducted in HIV suppressed, ART-experienced participants with mild-moderate renal impairment, who switched to E/C/F/TAF.Results: Asian participants in these studies had sustained efficacy safety and tolerability. In Study 104/111, Asian participants achieved 93% virologic suppression on TAF vs 88% on TDF at week 144. At baseline, there were numerically more Asians with median CD4 counts < 200 cells/uL and VL > 100,000 c/mL. In Study 109, 95% of Asians on TAF vs 86% on TDF maintained virologic suppression at week 96. Lastly, in Study 112, 91% maintained virologic suppression at week 144. There were no discontinuations due to renal AE, no cases of PRT or Fanconi syndrome in any of the studies.

8.
J Int AIDS Soc ; 22(3): e25264, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30924281

RESUMO

INTRODUCTION: Cotrimoxazole (CTX) is recommended as prophylaxis against Pneumocystis jiroveci pneumonia, malaria and other serious bacterial infections in HIV-infected patients. Despite its in vitro activity against Mycobacterium tuberculosis, the effects of CTX preventive therapy on tuberculosis (TB) remain unclear. METHODS: Adults living with HIV enrolled in a regional observational cohort in Asia who had initiated combination antiretroviral therapy (cART) were included in the analysis. Factors associated with new TB diagnoses after cohort entry and survival after cART initiation were analysed using Cox regression, stratified by site. RESULTS: A total of 7355 patients from 12 countries enrolled into the cohort between 2003 and 2016 were included in the study. There were 368 reported cases of TB after cohort entry with an incidence rate of 0.99 per 100 person-years (/100 pys). Multivariate analyses adjusted for viral load (VL), CD4 count, body mass index (BMI) and cART duration showed that CTX reduced the hazard for new TB infection by 28% (HR 0.72, 95% CI l 0.56, 0.93). Mortality after cART initiation was 0.85/100 pys, with a median follow-up time of 4.63 years. Predictors of survival included age, female sex, hepatitis C co-infection, TB diagnosis, HIV VL, CD4 count and BMI. CONCLUSIONS: CTX was associated with a reduction in the hazard for new TB infection but did not impact survival in our Asian cohort. The potential preventive effect of CTX against TB during periods of severe immunosuppression should be further explored.


Assuntos
Infecções por HIV/complicações , Combinação Trimetoprima e Sulfametoxazol/uso terapêutico , Tuberculose/prevenção & controle , Adulto , Fármacos Anti-HIV/uso terapêutico , Antirretrovirais/uso terapêutico , Ásia/epidemiologia , Estudos de Coortes , Feminino , Infecções por HIV/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Tuberculose/epidemiologia , Tuberculose/etiologia , Tuberculose/mortalidade , Carga Viral
9.
J Int AIDS Soc ; 22(2): e25228, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30803162

RESUMO

INTRODUCTION: Multiple comorbidities among HIV-positive individuals may increase the potential for polypharmacy causing drug-to-drug interactions and older individuals with comorbidities, particularly those with cognitive impairment, may have difficulty in adhering to complex medications. However, the effects of age-associated comorbidities on the treatment outcomes of combination antiretroviral therapy (cART) are not well known. In this study, we investigated the effects of age-associated comorbidities on therapeutic outcomes of cART in HIV-positive adults in Asian countries. METHODS: Patients enrolled in the TREAT Asia HIV Observational Database cohort and on cART for more than six months were analysed. Comorbidities included hypertension, diabetes, dyslipidaemia and impaired renal function. Treatment outcomes of patients ≥50 years of age with comorbidities were compared with those <50 years and those ≥50 years without comorbidities. We analysed 5411 patients with virological failure and 5621 with immunologic failure. Our failure outcomes were defined to be in-line with the World Health Organization 2016 guidelines. Cox regression analysis was used to analyse time to first virological and immunological failure. RESULTS: The incidence of virologic failure was 7.72/100 person-years. Virological failure was less likely in patients with better adherence and higher CD4 count at cART initiation. Those acquiring HIV through intravenous drug use were more likely to have virological failure compared to those infected through heterosexual contact. On univariate analysis, patients aged <50 years without comorbidities were more likely to experience virological failure than those aged ≥50 years with comorbidities (hazard ratio 1.75, 95% confidence interval (CI) 1.31 to 2.33, p < 0.001). However, the multivariate model showed that age-related comorbidities were not significant factors for virological failure (hazard ratio 1.31, 95% CI 0.98 to 1.74, p = 0.07). There were 391 immunological failures, with an incidence of 2.75/100 person-years. On multivariate analysis, those aged <50 years without comorbidities (p = 0.025) and age <50 years with comorbidities (p = 0.001) were less likely to develop immunological failure compared to those aged ≥50 years with comorbidities. CONCLUSIONS: In our Asia regional cohort, age-associated comorbidities did not affect virologic outcomes of cART. Among those with comorbidities, patients <50 years old showed a better CD4 response.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/tratamento farmacológico , Adulto , Fatores Etários , Idoso , Antirretrovirais/uso terapêutico , Ásia/epidemiologia , Contagem de Linfócito CD4 , Comorbidade , Bases de Dados Factuais , Feminino , Infecções por HIV/epidemiologia , Infecções por HIV/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Resultado do Tratamento , Adulto Jovem
10.
J Acquir Immune Defic Syndr ; 78(5): 589-598, 2018 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-29771789

RESUMO

BACKGROUND: Raltegravir 1200mg (2×600mg tablets) once daily (QD) demonstrated noninferior efficacy and similar safety to raltegravir 400mg twice daily (BID) at week 48 of the ONCEMRK trial. Here, we report the week 96 results from this study. METHODS: ONCEMRK is a phase 3, multicenter, double-blind, noninferiority trial comparing raltegravir 1200mg QD with raltegravir 400mg BID in treatment-naive HIV-1-infected adults. Participants were assigned (2:1) to raltegravir 2×600mg QD or 400mg BID, both with emtricitabine and tenofovir disoproxil fumarate (FTC/TDF) for 96 weeks. Randomization was stratified by screening HIV-1 RNA and hepatitis B/C status. Efficacy was assessed as the proportion of participants with HIV-1 RNA <40 copies per milliliter (Food and Drug Administration Snapshot approach); the noninferiority margin was 10 percentage points. RESULTS: Of the 797 participants who received study therapy (84.6% were men, 59.3% were white, and mean age was 35.9 years), 694 completed 96 weeks of treatment (87.6% QD; 84.4% BID), with few discontinuations because of lack of efficacy (1.1% for both groups) or adverse events (1.3% QD; 2.3% BID). At week 96, 81.5% (433/531) of QD recipients and 80.1% (213/266) of BID recipients achieved HIV-1 RNA <40 copies per milliliter (difference 1.4%, 95% confidence interval: -4.4 to 7.3). CD4 T-cell counts increased >260 cells/mm from baseline in both groups. Resistance to raltegravir was infrequent, occurring in 0.8% of each treatment group through week 96. Adverse event rates were similar for the 2 regimens. CONCLUSIONS: In HIV-1-infected treatment-naive adults receiving FTC/TDF, raltegravir 1200mg QD demonstrated noninferior efficacy to raltegravir 400mg BID that was durable to week 96, with a safety profile similar to raltegravir 400mg BID.


Assuntos
Adenina/análogos & derivados , Fármacos Anti-HIV/uso terapêutico , Emtricitabina/uso terapêutico , Infecções por HIV/tratamento farmacológico , Ácidos Fosforosos/uso terapêutico , Raltegravir Potássico/uso terapêutico , Adenina/administração & dosagem , Adenina/uso terapêutico , Adulto , Fármacos Anti-HIV/administração & dosagem , Relação Dose-Resposta a Droga , Método Duplo-Cego , Esquema de Medicação , Quimioterapia Combinada , Emtricitabina/administração & dosagem , Feminino , HIV-1/genética , HIV-1/isolamento & purificação , Humanos , Masculino , Ácidos Fosforosos/administração & dosagem , Placebos , RNA Viral/sangue , Raltegravir Potássico/administração & dosagem
11.
Lancet HIV ; 4(11): e486-e494, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28918877

RESUMO

BACKGROUND: Once daily regimens are preferred for HIV-1 treatment, to facilitate adherence and improve quality of life. We compared a new once daily formulation of raltegravir to the currently marketed twice daily formulation. METHODS: In this randomised, double-blind, parallel-group, phase 3, non-inferiority study, we enrolled participants aged 18 years or older with HIV-1 RNA of 1000 or more copies per mL and no previous antiretroviral treatment at 139 sites worldwide. We randomly assigned participants (2:1) via an interactive voice and web response system to raltegravir 1200 mg (two 600 mg tablets) orally once daily or raltegravir 400 mg (one tablet) orally twice daily, each with tenofovir disoproxil fumarate and emtricitabine orally once daily, for up to 96 weeks. A computer-generated allocation schedule stratified randomisation by screening HIV-1 RNA value and co-infection with hepatitis B or C. Participants, sponsor personnel, investigators, and study site personnel involved in the treatment or evaluation of the participants were unaware of the treatment group assignments. The primary endpoint was the proportion of participants with HIV-1 RNA less than 40 copies per mL at week 48 assessed with the US Food and Drug Administration Snapshot algorithm. Non-inferiority was concluded if the lower bound of the two-sided 95% CI was greater than -10%. We assessed efficacy and safety in all participants who received one dose or more of study treatment. This study is registered with ClinicalTrials.gov, number NCT02131233. FINDINGS: Between May 26, 2014, and Dec 5, 2014, 802 participants were enrolled and randomly assigned, 533 to once daily treatment and 269 to twice daily; 797 received study therapy, 531 once daily and 266 twice daily. At week 48, 472 (89%) of 531 once daily recipients and 235 (88%) of 266 twice daily recipients achieved HIV-1 RNA less than 40 copies per mL (treatment difference 0·5%, 95% CI -4·2 to 5·2). Drug-related adverse events occurred in 130 (24%) of 531 participants in the once daily group (one of which was serious; none led to treatment discontinuation) and 68 (26%) of 266 participants in the twice daily group (two of which were serious; two led to treatment discontinuation). The most common drug-related adverse events were nausea (39 [7%] vs 18 [7%]), headache (16 [3%] vs 12 [5%]), and dizziness (12 [2%] vs eight [3%]). No treatment-related deaths were reported. INTERPRETATION: A once daily raltegravir 1200 mg regimen was non-inferior compared with raltegravir 400 mg twice daily for initial treatment of HIV-1 infection. These results support the use of raltegravir 1200 mg once daily for first-line therapy. FUNDING: Merck & Co, Inc.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Emtricitabina/uso terapêutico , Infecções por HIV/tratamento farmacológico , HIV-1/efeitos dos fármacos , Raltegravir Potássico/administração & dosagem , Tenofovir/administração & dosagem , Administração Oral , Adulto , Fármacos Anti-HIV/administração & dosagem , Fármacos Anti-HIV/efeitos adversos , Disponibilidade Biológica , Coinfecção/virologia , Método Duplo-Cego , Emtricitabina/administração & dosagem , Emtricitabina/efeitos adversos , Emtricitabina/farmacocinética , Feminino , Infecções por HIV/virologia , HIV-1/fisiologia , Hepatite B/virologia , Hepatite C/virologia , Humanos , Masculino , Qualidade de Vida , RNA Viral/sangue , RNA Viral/efeitos dos fármacos , Raltegravir Potássico/efeitos adversos , Raltegravir Potássico/farmacocinética , Raltegravir Potássico/uso terapêutico , Tenofovir/efeitos adversos , Tenofovir/farmacocinética , Tenofovir/uso terapêutico , Carga Viral/efeitos dos fármacos
12.
AIDS Res Ther ; 14: 27, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28484509

RESUMO

BACKGROUND: Abacavir and rilpivirine are alternative antiretroviral drugs for treatment-naïve HIV-infected patients. However, both drugs are only recommended for the patients who have pre-treatment HIV RNA <100,000 copies/mL. In resource-limited settings, pre-treatment HIV RNA is not routinely performed and not widely available. The aims of this study are to determine factors associated with pre-treatment HIV RNA <100,000 copies/mL and to construct a model to predict this outcome. METHODS: HIV-infected adults enrolled in the TREAT Asia HIV Observational Database were eligible if they had an HIV RNA measurement documented at the time of ART initiation. The dataset was randomly split into a derivation data set (75% of patients) and a validation data set (25%). Factors associated with pre-treatment HIV RNA <100,000 copies/mL were evaluated by logistic regression adjusted for study site. A prediction model and prediction scores were created. RESULTS: A total of 2592 patients were enrolled for the analysis. Median [interquartile range (IQR)] age was 35.8 (29.9-42.5) years; CD4 count was 147 (50-248) cells/mm3; and pre-treatment HIV RNA was 100,000 (34,045-301,075) copies/mL. Factors associated with pre-treatment HIV RNA <100,000 copies/mL were age <30 years [OR 1.40 vs. 41-50 years; 95% confidence interval (CI) 1.10-1.80, p = 0.01], body mass index >30 kg/m2 (OR 2.4 vs. <18.5 kg/m2; 95% CI 1.1-5.1, p = 0.02), anemia (OR 1.70; 95% CI 1.40-2.10, p < 0.01), CD4 count >350 cells/mm3 (OR 3.9 vs. <100 cells/mm3; 95% CI 2.0-4.1, p < 0.01), total lymphocyte count >2000 cells/mm3 (OR 1.7 vs. <1000 cells/mm3; 95% CI 1.3-2.3, p < 0.01), and no prior AIDS-defining illness (OR 1.8; 95% CI 1.5-2.3, p < 0.01). Receiver-operator characteristic (ROC) analysis yielded area under the curve of 0.70 (95% CI 0.67-0.72) among derivation patients and 0.69 (95% CI 0.65-0.74) among validation patients. A cut off score >25 yielded the sensitivity of 46.7%, specificity of 79.1%, positive predictive value of 67.7%, and negative predictive value of 61.2% for prediction of pre-treatment HIV RNA <100,000 copies/mL among derivation patients. CONCLUSION: A model prediction for pre-treatment HIV RNA <100,000 copies/mL produced an area under the ROC curve of 0.70. A larger sample size for prediction model development as well as for model validation is warranted.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Terapia Antirretroviral de Alta Atividade/métodos , Técnicas de Apoio para a Decisão , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , RNA Viral/sangue , Carga Viral , Adulto , Ásia , Países em Desenvolvimento , Didesoxinucleosídeos/uso terapêutico , Feminino , Humanos , Masculino , Estudos Prospectivos , Rilpivirina/uso terapêutico
13.
PLoS One ; 11(8): e0161562, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27560968

RESUMO

BACKGROUND: In resource-limited settings, routine monitoring of renal function during antiretroviral therapy (ART) has not been recommended. However, concerns for tenofovir disoproxil fumarate (TDF)-related nephrotoxicity persist with increased use. METHODS: We investigated serum creatinine (S-Cr) monitoring rates before and during ART and the incidence and prevalence of renal dysfunction after starting TDF by using data from a regional cohort of HIV-infected individuals in the Asia-Pacific. Time to renal dysfunction was defined as time from TDF initiation to the decline in estimated glomerular filtration rate (eGFR) to <60 ml/min/1.73m2 with >30% reduction from baseline using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation or the decision to stop TDF for reported TDF-nephrotoxicity. Predictors of S-Cr monitoring rates were assessed by Poisson regression and risk factors for developing renal dysfunction were assessed by Cox regression. RESULTS: Among 2,425 patients who received TDF, S-Cr monitoring rates increased from 1.01 to 1.84 per person per year after starting TDF (incidence rate ratio 1.68, 95%CI 1.62-1.74, p <0.001). Renal dysfunction on TDF occurred in 103 patients over 5,368 person-years of TDF use (4.2%; incidence 1.75 per 100 person-years). Risk factors for developing renal dysfunction included older age (>50 vs. ≤30, hazard ratio [HR] 5.39, 95%CI 2.52-11.50, p <0.001; and using PI-based regimen (HR 1.93, 95%CI 1.22-3.07, p = 0.005). Having an eGFR prior to TDF (pre-TDF eGFR) of ≥60 ml/min/1.73m2 showed a protective effect (HR 0.38, 95%CI, 0.17-0.85, p = 0.018). CONCLUSIONS: Renal dysfunction on commencing TDF use was not common, however, older age, lower baseline eGFR and PI-based ART were associated with higher risk of renal dysfunction during TDF use in adult HIV-infected individuals in the Asia-Pacific region.


Assuntos
Fármacos Anti-HIV/efeitos adversos , Infecções por HIV/tratamento farmacológico , Nefropatias/induzido quimicamente , Rim/efeitos dos fármacos , Rim/fisiopatologia , Tenofovir/efeitos adversos , Adulto , Fármacos Anti-HIV/uso terapêutico , Creatinina/sangue , Bases de Dados Factuais , Feminino , Taxa de Filtração Glomerular , Humanos , Masculino , Pessoa de Meia-Idade , Distribuição de Poisson , Modelos de Riscos Proporcionais , Estudos Prospectivos , Fatores de Risco , Tenofovir/uso terapêutico
14.
PLoS One ; 11(3): e0150512, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26933963

RESUMO

BACKGROUND: We assessed the effects of hepatitis B (HBV) or hepatitis C (HCV) co-infection on outcomes of antiretroviral therapy (ART) in HIV-infected patients enrolled in the TREAT Asia HIV Observational Database (TAHOD), a multi-center cohort of HIV-infected patients in the Asia-Pacific region. METHODS: Patients testing HBs antigen (Ag) or HCV antibody (Ab) positive within enrollment into TAHOD were considered HBV or HCV co-infected. Factors associated with HBV and/or HCV co-infection were assessed by logistic regression models. Factors associated with post-ART HIV immunological response (CD4 change after six months) and virological response (HIV RNA <400 copies/ml after 12 months) were also determined. Survival was assessed by the Kaplan-Meier method and log rank test. RESULTS: A total of 7,455 subjects were recruited by December 2012. Of patients tested, 591/5656 (10.4%) were HBsAg positive, 794/5215 (15.2%) were HCVAb positive, and 88/4966 (1.8%) were positive for both markers. In multivariate analysis, HCV co-infection, age, route of HIV infection, baseline CD4 count, baseline HIV RNA, and HIV-1 subtype were associated with immunological recovery. Age, route of HIV infection, baseline CD4 count, baseline HIV RNA, ART regimen, prior ART and HIV-1 subtype, but not HBV or HCV co-infection, affected HIV RNA suppression. Risk factors affecting mortality included HCV co-infection, age, CDC stage, baseline CD4 count, baseline HIV RNA and prior mono/dual ART. Shortest survival was seen in subjects who were both HBV- and HCV-positive. CONCLUSION: In this Asian cohort of HIV-infected patients, HCV co-infection, but not HBV co-infection, was associated with lower CD4 cell recovery after ART and increased mortality.


Assuntos
Antirretrovirais/uso terapêutico , Coinfecção/complicações , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Hepatite B/complicações , Hepatite C/complicações , Adulto , Terapia Antirretroviral de Alta Atividade , Ásia/epidemiologia , Contagem de Linfócito CD4 , Estudos de Coortes , Coinfecção/epidemiologia , Feminino , Infecções por HIV/epidemiologia , HIV-1/efeitos dos fármacos , HIV-1/isolamento & purificação , Hepatite B/epidemiologia , Hepatite C/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Análise de Sobrevida , Resultado do Tratamento
15.
Trop Med Int Health ; 21(5): 662-74, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26950901

RESUMO

OBJECTIVES: Treatment interruptions (TIs) of combination antiretroviral therapy (cART) are known to lead to unfavourable treatment outcomes but do still occur in resource-limited settings. We investigated the effects of TI associated with adverse events (AEs) and non-AE-related reasons, including their durations, on treatment failure after cART resumption in HIV-infected individuals in Asia. METHODS: Patients initiating cART between 2006 and 2013 were included. TI was defined as stopping cART for >1 day. Treatment failure was defined as confirmed virological, immunological or clinical failure. Time to treatment failure during cART was analysed using Cox regression, not including periods off treatment. Covariables with P < 0.10 in univariable analyses were included in multivariable analyses, where P < 0.05 was considered statistically significant. RESULTS: Of 4549 patients from 13 countries in Asia, 3176 (69.8%) were male and the median age was 34 years. A total of 111 (2.4%) had TIs due to AEs and 135 (3.0%) had TIs for other reasons. Median interruption times were 22 days for AE and 148 days for non-AE TIs. In multivariable analyses, interruptions >30 days were associated with failure (31-180 days HR = 2.66, 95%CI (1.70-4.16); 181-365 days HR = 6.22, 95%CI (3.26-11.86); and >365 days HR = 9.10, 95% CI (4.27-19.38), all P < 0.001, compared to 0-14 days). Reasons for previous TI were not statistically significant (P = 0.158). CONCLUSIONS: Duration of interruptions of more than 30 days was the key factor associated with large increases in subsequent risk of treatment failure. If TI is unavoidable, its duration should be minimised to reduce the risk of failure after treatment resumption.


Assuntos
Fármacos Anti-HIV/administração & dosagem , Fármacos Anti-HIV/efeitos adversos , Infecções por HIV/tratamento farmacológico , Adesão à Medicação/estatística & dados numéricos , Adulto , Fármacos Anti-HIV/uso terapêutico , Ásia , Contagem de Linfócito CD4 , Progressão da Doença , Esquema de Medicação , Quimioterapia Combinada , Feminino , Humanos , Masculino , Adesão à Medicação/psicologia , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Prospectivos , Fatores de Risco , Fatores de Tempo , Falha de Tratamento , Resultado do Tratamento , Carga Viral
16.
AIDS Res Hum Retroviruses ; 32(3): 255-61, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26414065

RESUMO

Many HIV-infected individuals do not enter health care until late in the infection course. Despite encouraging earlier testing, this situation has continued for several years. We investigated the prevalence of late presenters and factors associated with late presentation among HIV-infected patients in an Asian regional cohort. This cohort study included HIV-infected patients with their first positive HIV test during 2003-2012 and CD4 count and clinical status data within 3 months of that test. Factors associated with late presentation into care (CD4 count <200 cells/µl or an AIDS-defining event within ±3 months of first positive HIV test) were analyzed in a random effects logistic regression model. Among 3,744 patients, 2,681 (72%) were late presenters. In the multivariable model, older patients were more likely to be late presenters than younger (≤30 years) patients [31-40, 41-50, and ≥51 years: odds ratio (OR) = 1.57, 95% confidence interval (CI) 1.31-1.88; OR = 2.01, 95% CI 1.58-2.56; and OR = 1.69, 95% CI 1.23-2.31, respectively; all p ≤ 0.001]. Injecting drug users (IDU) were more likely (OR = 2.15, 95% CI 1.42-3.27, p < 0.001) and those with homosexual HIV exposure were less likely (OR = 0.45, 95% CI 0.35-0.58, p < 0.001) to be late presenters compared to those with heterosexual HIV exposure. Females were less likely to be late presenters (OR = 0.44, 95% CI 0.36-0.53, p < 0.001). The year of first positive HIV test was not associated with late presentation. Efforts to reduce the patients who first seek HIV care at the late stage are needed. The identified risk factors associated with late presentation should be utilized in formulating targeted public health intervention to improve earlier entry into HIV care.


Assuntos
Diagnóstico Tardio , Infecções por HIV/diagnóstico , Adulto , Fatores Etários , Ásia/epidemiologia , Contagem de Linfócito CD4 , Feminino , Infecções por HIV/epidemiologia , Infecções por HIV/patologia , Infecções por HIV/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Prospectivos , Fatores Sexuais , Comportamento Sexual , Abuso de Substâncias por Via Intravenosa
17.
J Antimicrob Chemother ; 71(3): 731-8, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26620101

RESUMO

OBJECTIVES: BIT225 (N-carbamimidoyl-5-(1-methyl-1H-pyrazol-4-yl)-2-naphthamide), a novel acyl-guanidine, is a novel antiviral drug that blocks Vpu ion channel activity and has anti-HIV-1 activity in vitro. The antiviral effect of BIT225 is most pronounced in cells of the myeloid lineage. With infected circulating monocytes and tissue-resident macrophages representing a key cellular reservoir of HIV-1, BIT225 has a potential role in the eradication of the virus from the host. PATIENTS AND METHODS: BIT225-004 is a Phase 1b/2a, placebo-controlled, randomized study of the safety, pharmacokinetics and antiviral activity of BIT225 in 21 HIV-1-infected, ART-naive subjects. Twenty-one subjects were enrolled and received BIT225 (400 mg twice daily) or placebo treatment for 10 days (randomized 2:1). The anti-HIV-1 effect of BIT225 in the monocyte reservoir was measured in CD14+ monocytes isolated from the peripheral blood on days 1 (pre-dose), 5, 10 and 20; isolated monocytes were co-cultured ex vivo with MT4 T cells. De novo HIV-1 replication was measured by p24 activity of released virus into the culture supernatant to day 25 of co-culture. In addition, monocyte samples were collected for analysis by RT-PCR total HIV-1 DNA single-copy assay. RESULTS: Measurement of HIV-1 directly within the patient's monocyte population indicated that BIT225 treatment significantly reduced the viral burden in myeloid lineage cells, which was more evident in those individuals with the highest viral loads. In addition, BIT225-treated subjects demonstrated a significantly reduced level of monocyte activation (sCD163) compared with the placebo controls. CONCLUSIONS: This study's unique design demonstrates that BIT225 can significantly reduce the dissemination of HIV-1 from infected monocytes. This has important ramifications for diminishing the seeding/re-seeding of the viral reservoir.


Assuntos
Fármacos Anti-HIV/farmacologia , Fármacos Anti-HIV/farmacocinética , Guanidinas/farmacologia , Guanidinas/farmacocinética , Infecções por HIV/tratamento farmacológico , Pirazóis/farmacologia , Pirazóis/farmacocinética , Adolescente , Adulto , Idoso , Fármacos Anti-HIV/efeitos adversos , Feminino , Guanidinas/efeitos adversos , Proteína do Núcleo p24 do HIV/análise , Infecções por HIV/virologia , HIV-1/isolamento & purificação , Humanos , Masculino , Pessoa de Meia-Idade , Monócitos/virologia , Placebos/administração & dosagem , Pirazóis/efeitos adversos , Resultado do Tratamento , Carga Viral , Adulto Jovem
18.
J Med Virol ; 88(2): 234-43, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26147742

RESUMO

HIV drug resistance assessments and interpretations can be obtained from genotyping (GT), virtual phenotyping (VP) and laboratory-based phenotyping (PT). We compared resistance calls obtained from GT and VP with those from PT (GT-PT and VP-PT) among CRF01_AE and subtype B HIV-1 infected patients. GT predictions were obtained from the Stanford HIV database. VP and PT were obtained from Janssen Diagnostics BVBA's vircoType(TM) HIV-1 and Antivirogram®, respectively. With PT assumed as the "gold standard," the area under the curve (AUC) and the Bland-Altman plot were used to assess the level of agreement in resistance interpretations. A total of 80 CRF01_AE samples from Asia and 100 subtype B from Janssen Diagnostics BVBA's database were analysed. CRF01_AE showed discordances ranging from 3 to 27 samples for GT-PT and 1 to 20 samples for VP-PT. The GT-PT and VP-PT AUCs were 0.76-0.97 and 0.81-0.99, respectively. Subtype B showed 3-61 discordances for GT-PT and 2-75 discordances for VP-PT. The AUCs ranged from 0.55 to 0.95 for GT-PT and 0.55 to 0.97 for VP-PT. Didanosine had the highest proportion of discordances and/or AUC in all comparisons. The patient with the largest didanosine FC difference in each subtype harboured Q151M mutation. Overall, GT and VP predictions for CRF01_AE performed significantly better than subtype B for three NRTIs. Although discrepancies exist, GT and VP resistance interpretations in HIV-1 CRF01_AE strains were highly robust in comparison with the gold-standard PT.


Assuntos
Fármacos Anti-HIV/farmacologia , Farmacorresistência Viral , Genótipo , Infecções por HIV/virologia , HIV-1/efeitos dos fármacos , HIV-1/genética , Fenótipo , Ásia , Técnicas de Genotipagem/métodos , HIV-1/isolamento & purificação , Humanos , Testes de Sensibilidade Microbiana/métodos
19.
Antivir Ther ; 21(1): 27-35, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26069150

RESUMO

BACKGROUND: The World Health Organization recommends HBV-HIV-coinfected individuals start antiretroviral therapy containing tenofovir. Here we describe first-line tenofovir use and treatment outcomes in coinfected patients in Asia. METHODS: HBV surface antigen positive patients enrolled in the TREAT Asia HIV Observational Database who started first-line antiretroviral therapy were included. Logistic regression adjusted for period of treatment initiation was used to determine factors associated with tenofovir use. Generalized estimating equations were used to evaluate factors associated with alanine transaminase levels and CD4(+) T-cell count on treatment. RESULTS: There were 548 eligible patients, of whom 149 (27.2%) started tenofovir. Patients treated in high/high-middle income countries (odds ratio 4.4 versus low/low-middle, 95% CI 2.6, 7.4; P<0.001) and those with elevated baseline alanine transaminase (odds ratio 4.2 versus normal, 95% CI 2.4, 7.2; P<0.001) were more likely to receive tenofovir. Hepatitis C antibody positive patients (odds ratio 0.4 versus negative, 95% CI 0.2, 0.8; P=0.008) were less likely. In those starting antiretroviral therapy with elevated alanine transaminase, mean reduction after tenofovir initiation was 11.2 IU/l (95% CI 0.9, 21.6; P=0.034) lower compared with those using a non-tenofovir-based regimen although this did not significantly increase the chance of alanine transaminase normalization. Tenofovir use was not associated with a superior CD4(+) T-cell response. CONCLUSIONS: HBV-HIV-coinfected patients in Asia are most likely to receive tenofovir if they are treated in a high/high-middle income country, have elevated alanine transaminase levels and are hepatitis C antibody negative. Compared to other antiretroviral therapies, tenofovir-based regimens more effectively reduce liver inflammation in HBV-HIV-coinfection but do not result in superior CD4(+) T-cell recovery.


Assuntos
Antivirais/uso terapêutico , Coinfecção , Infecções por HIV/tratamento farmacológico , Hepatite B/tratamento farmacológico , Inibidores da Transcriptase Reversa/uso terapêutico , Tenofovir/uso terapêutico , Terapia Antirretroviral de Alta Atividade , Antivirais/farmacologia , Biomarcadores , Contagem de Linfócito CD4 , Estudos de Coortes , Bases de Dados Factuais , Quimioterapia Combinada , Feminino , Infecções por HIV/mortalidade , Infecções por HIV/virologia , HIV-1 , Hepatite B/mortalidade , Hepatite B/virologia , Vírus da Hepatite B , Humanos , Testes de Função Renal , Testes de Função Hepática , Masculino , Mortalidade , Inibidores da Transcriptase Reversa/farmacologia , Fatores de Risco , Tenofovir/farmacologia , Resultado do Tratamento
20.
J Acquir Immune Defic Syndr ; 69(3): e85-92, 2015 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-25850606

RESUMO

BACKGROUND: Current treatment guidelines for HIV infection recommend routine CD4 lymphocyte (CD4) count monitoring in patients with viral suppression. This may have a limited impact on influencing care as clinically meaningful CD4 decline rarely occurs during viral suppression. METHODS: In a regional HIV observational cohort in the Asia-Pacific region, patients with viral suppression (2 consecutive viral loads <400 copies/mL) and a CD4 count ≥200 cells per microliter who had CD4 testing 6 monthly were analyzed. Main study end points were occurrence of 1 CD4 count <200 cells per microliter (single CD4 <200) and 2 CD4 counts <200 cells per microliter within a 6-month period (confirmed CD4 <200). A comparison of time with single and confirmed CD4 <200 with biannual or annual CD4 assessment was performed by generating a hypothetical group comprising the same patients with annual CD4 testing by removing every second CD4 count. RESULTS: Among 1538 patients, the rate of single CD4 <200 was 3.45/100 patient-years and of confirmed CD4 <200 was 0.77/100 patient-years. During 5 years of viral suppression, patients with baseline CD4 200-249 cells per microliter were significantly more likely to experience confirmed CD4 <200 compared with patients with higher baseline CD4 [hazard ratio, 55.47 (95% confidence interval: 7.36 to 418.20), P < 0.001 versus baseline CD4 ≥500 cells/µL]. Cumulative probabilities of confirmed CD4 <200 was also higher in patients with baseline CD4 200-249 cells per microliter compared with patients with higher baseline CD4. There was no significant difference in time to confirmed CD4 <200 between biannual and annual CD4 measurement (P = 0.336). CONCLUSIONS: Annual CD4 monitoring in virally suppressed HIV patients with a baseline CD4 ≥250 cells per microliter may be sufficient for clinical management.


Assuntos
Fármacos Anti-HIV/administração & dosagem , Contagem de Linfócito CD4 , Infecções por HIV/tratamento farmacológico , HIV-1/efeitos dos fármacos , Adulto , Fármacos Anti-HIV/farmacologia , Fármacos Anti-HIV/uso terapêutico , Estudos de Coortes , Feminino , Infecções por HIV/imunologia , Infecções por HIV/virologia , HIV-1/imunologia , Humanos , Masculino , Pessoa de Meia-Idade
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