Non-inferiority study of purified Vero rabies vaccine - serum free in three-dose and two-dose pre-exposure prophylaxis regimens in comparison with licensed rabies vaccines.

Background: A next-generation, serum-free, highly purified Vero cell rabies vaccine, PVRV-NG2, is in development.

Methods: This multicenter, observer-blind, phase 3 study evaluated the immunogenicity and safety of PVRV-NG2, compared with two licensed rabies vaccines (purified Vero cell rabies vaccine [PVRV] and human diploid cell vaccine [HDCV]), as a pre-exposure prophylaxis (PrEP) regimen. Participants were randomized 3:1:1 to PVRV-NG2, PVRV, or HDCV, as a three-dose (Cohort 1; children and adults; day [D] 0, D7, and D28) or two-dose (Cohort 2; adults; D0 and D7) PrEP regimen.

Randomized Controlled Trial of the Immunogenicity and Safety of a Serum-Free Purified Vero Rabies Vaccine (PVRV-NG2) Using a Simulated Postexposure Zagreb Regimen With Human Rabies Immunoglobulin in Adults in Thailand.

Background: A serum-free, highly purified Vero rabies vaccine-next generation (PVRV-NG2) is under development. We conducted a phase III trial to describe the safety and immunogenicity profile of PVRV-NG2 compared with those of licensed purified Vero rabies vaccine (PVRV) in a simulated rabies postexposure prophylaxis (PEP) Zagreb regimen in Thailand.

Methods: Healthy adults aged ≥18 years (n = 201) were randomized in a 2:1 ratio to receive PVRV-NG2 or PVRV in a rabies PEP Zagreb (days 0, 7, 21 [2-1-1]) regimen, with concomitant human rabies immunoglobulin (HRIG) at day 0.

Metabolic and genetic risk factors associated with pre-diabetes and type 2 diabetes in Thai healthcare employees: A long-term study from the Siriraj Health (SIH) cohort study.

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.

Efficacy and safety of the novel capsid inhibitor lenacapavir to treat multidrug-resistant HIV: week 52 results of a phase 2/3 trial.

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.

Efficacy and safety of switching to bictegravir, emtricitabine, and tenofovir alafenamide in virologically suppressed Asian adults living with HIV: A pooled analysis from three international phase III randomized trials.

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.

A Risk Prediction Model and Risk Score of SARS-CoV-2 Infection Following Healthcare-Related Exposure.

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.

Adherence and Health Problems in Thai Travellers Living with HIV.

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.

Safety and immunogenicity of V114, a 15-valent pneumococcal conjugate vaccine, in adults living with HIV.

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.

Efficacy and safety of elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide in Asian participants with human immunodeficiency virus 1 infection: A sub-analysis of phase 3 clinical trials.

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. 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. 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.

Cotrimoxazole prophylaxis decreases tuberculosis risk among Asian patients with HIV.

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.

The influence of age-associated comorbidities on responses to combination antiretroviral therapy in older people living with HIV.

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.

Raltegravir 1200 mg Once Daily vs 400 mg Twice Daily, With Emtricitabine and Tenofovir Disoproxil Fumarate, for Previously Untreated HIV-1 Infection: Week 96 Results From ONCEMRK, a Randomized, Double-Blind, Noninferiority Trial.

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.

Raltegravir 1200 mg once daily versus raltegravir 400 mg twice daily, with tenofovir disoproxil fumarate and emtricitabine, for previously untreated HIV-1 infection: a randomised, double-blind, parallel-group, phase 3, non-inferiority trial.

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.

Safety, Pharmacokinetics, and Antiviral Activity of a Novel HIV Antiviral, ABX464, in Treatment-Naive HIV-Infected Subjects in a Phase 2 Randomized, Controlled Study.

We investigated the safety and antiviral effects of an anti-HIV compound (ABX464) with a unique mechanism of viral replication inhibition. This was a randomized, double-blind, placebo-controlled, dose-ranging study in treatment-naive HIV-infected patients. Participants were assigned to eight groups; each group included eight subjects receiving either the study compound, ABX464 ( = 6), or the corresponding placebo ( = 2), according to a randomization code.

Factors associated with pre-treatment HIV RNA: application for the use of abacavir and rilpivirine as the first-line regimen for HIV-infected patients in resource-limited settings.

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.

Renal Dysfunction during Tenofovir Use in a Regional Cohort of HIV-Infected Individuals in the Asia-Pacific.

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.

Effects of unplanned treatment interruptions on HIV treatment failure - results from TAHOD.

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.

Hepatitis B and C Co-Infection in HIV Patients from the TREAT Asia HIV Observational Database: Analysis of Risk Factors and Survival.

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.

A Phase 1b/2a study of the safety, pharmacokinetics and antiviral activity of BIT225 in patients with HIV-1 infection.

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.

Late Presentation into Care of HIV Disease and Its Associated Factors in Asia: Results of TAHOD.

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.

Comparison of genotypic and virtual phenotypic drug resistance interpretations with laboratory-based phenotypes among CRF01_AE and subtype B HIV-infected individuals.

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.

Tenofovir-based antiretroviral therapy in HBV-HIV coinfection: results from the TREAT Asia HIV Observational Database.

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.

Guidelines for antiretroviral therapy in HIV-1 infected adults and adolescents 2014, Thailand.

New evidence has emerged regarding when to commence antiretroviral therapy (ART), optimal treatment regimens, management of HIV co-infection with opportunistic infections, and management of ART failure. The 2014 guidelines were developed by the collaborations of the Department of Disease Control, Ministry of Public Health (MOPH) and the Thai AIDS Society (TAS). One of the major changes in the guidelines included recommending to initiating ART irrespective of CD4 cell count.

Implementation and Operational Research: Effects of CD4 Monitoring Frequency on Clinical End Points in Clinically Stable HIV-Infected Patients With Viral Suppression.

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.