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Long-Term Post-Transition Outcomes of Adolescents and Young Adults Living With Perinatally and Non-perinatally Acquired HIV in Southeast Asia

Sohn AH, Singtoroj T, Chokephaibulkit K, Lumbiganon P, Hansudewechakul R, Gani YM, et al.

J Adolesc Health, 2023 Mar;72(3):471-479.
PMID: 36535867 DOI: 10.1016/j.jadohealth.2022.10.021

PURPOSE: We assessed factors associated with clinical, social, and behavioral outcomes of adolescents and young adults with HIV (AYHIV) in Southeast Asia after transition from pediatric to adult HIV care.
METHODS: AYHIV in Malaysia, Thailand, and Vietnam were prospectively followed through annual clinical assessments and laboratory testing. Data were described descriptively and a generalized estimating equation was used to calculate independent predictors for HIV viremia (>40 copies/mL).
RESULTS: A total of 93 AYHIV were followed until February 2019: 60% female, 94% acquired HIV perinatally, 81% Thai, median age 20 (interquartile range, 18-21) years. The median follow-up time was 94 (91-100) weeks; 88% completed the study. At week 96, median CD4 was 557 cells/mm3 (interquartile range, 337-786), 77% had suppressed HIV viral load, 39% reported recent alcohol use, 49% had been sexually active, 53% of females and 36% of males intended to have children, and 23% screened positive for moderate depression (Patient Health Questionnaire-9 score ≥9) or reported suicidal ideation. HIV viremia was associated with <90% adherence to HIV treatment (adjusted incidence rate ratio [aIRR] 2.2 [1.28-3.78]), CD4 count ≤500 cells/mm3 (aIRR 4.75 [2.11-10.69]), and being on a nonnucleoside reverse transcriptase inhibitor regimen (vs. protease inhibitor aIRR 2.71 [1.13-6.49]). Having a trusted person to talk with about their feelings was protective (vs. never; usually or always, aIRR 0.41 [0.18-0.92]).
DISCUSSION: After transition to adult HIV care, there were indications of social isolation and mental health problems that could prevent these AYHIV from maintaining control over their HIV infection and hinder progress toward social independence.
Fulltext Short Communication: Impact of Viral Load Use on Treatment Switch in Perinatally HIV-Infected Children in Asia

Jamal Mohamed T, Teeraananchai S, Kerr S, Phongsamart W, Nik Yusoff NK, Hansudewechakul R, et al.

AIDS Res Hum Retroviruses, 2017 03;33(3):230-233.
PMID: 27758114 DOI: 10.1089/AID.2016.0039

We sought to assess the impact of routine HIV viral load (VL) monitoring on the incidence of switching from a first- to a second-line antiretroviral therapy (ART) regimen, and to describe factors associated with switch. Data from a regional cohort of 16 clinical programs in six Asian countries were analyzed. Second-line switch was defined as a change from a non-nucleoside reverse transcriptase inhibitor (NNRTI) to a protease inhibitor (PI) or vice versa, and ≥1 of the following: (1) reported treatment failure by local criteria, (2) switch of ≥1 additional drug, or (3) a preceding HIV VL ≥1,000 copies/ml. Routine VL was having ≥1 test after ≥24 weeks of ART and ≥1 time/year thereafter. Factors associated with time to switch were evaluated with death and loss to follow-up as competing risks. A total of 2,398 children were included in this analysis. At ART initiation, the median (interquartile range) age was 6.0 (3.3-8.9) years, more than half had WHO stage 3 or 4, the median CD4 was 189 (47-456) cells/mm3, 93% were on NNRTI-based first-line ART, and 34% had routine VL monitoring. Treatment switch occurred in 17.6% of patients, at a median of 35 (22-49) months. After adjusting for country, sex, first ART regimen, and CD4% at ART initiation, children with routine VL monitoring were 1.46 (95% confidence interval 1.11-1.93) times more likely to be switched (p = .007). Scale-up of VL testing will lead to earlier identification of treatment failure, and it can help guide earlier switches to prevent resistance.
Safety and immunogenicity of a prefusion non-stabilized spike protein mRNA COVID-19 vaccine: a phase I trial

Gatechompol S, Kittanamongkolchai W, Ketloy C, Prompetchara E, Thitithanyanont A, Jongkaewwattana A, et al.

Nat Microbiol, 2022 Dec;7(12):1987-1995.
PMID: 36376393 DOI: 10.1038/s41564-022-01271-0

Effective mRNA SARS-CoV-2 vaccines are available but need to be stored in freezers, limiting their use to countries that have appropriate storage capacity. ChulaCov19 is a prefusion non-stabilized SARS-CoV-2 spike-protein-encoding, nucleoside-modified mRNA, lipid nanoparticle encapsulated vaccine that we report to be stable when stored at 2-8 °C for up to 3 months. Here we report safety and immunogenicity data from a phase I open-label, dose escalation, first-in-human trial of the ChulaCov19 vaccine (NCT04566276). Seventy-two eligible volunteers, 36 of whom were aged 18-55 (adults) and 36 aged 56-75 (elderly), were enroled. Two doses of vaccine were administered 21 d apart at 10, 25 or 50 μg per dose (12 per group). The primary outcome was safety and the secondary outcome was immunogenicity. All three dosages of ChulaCov19 were well tolerated and elicited robust dose-dependent and age-dependent B- and T-cell responses. Transient mild/moderate injection site pain, fever, chills, fatigue and headache were more common after the second dose. Four weeks after the second dose, in the adult cohort, MicroVNT-50 geometric mean titre against wild-type SARS-CoV-2 was 848 (95% CI, 483-1,489), 736 (459-1,183) and 1,140 (854-1,522) IU ml-1 at 10, 25 and 50 μg doses, respectively, versus 285 (196-413) IU ml-1 for human convalescent sera. All dose levels elicited 100% seroconversion, with geometric mean titre ratios 4-8-fold higher than for human convalescent sera (P
Fulltext Trends in first-line antiretroviral therapy in Asia: results from the TREAT Asia HIV observational database

Boettiger DC, Kerr S, Ditangco R, Merati TP, Pham TT, Chaiwarith R, et al.

PLoS One, 2014;9(9):e106525.
PMID: 25184314 DOI: 10.1371/journal.pone.0106525

Antiretroviral therapy (ART) has evolved rapidly since its beginnings. This analysis describes trends in first-line ART use in Asia and their impact on treatment outcomes.
Fulltext Changes in renal function with long-term exposure to antiretroviral therapy in HIV-infected adults in Asia

Joshi K, Boettiger D, Kerr S, Nishijima T, Van Nguyen K, Ly PS, et al.

Pharmacoepidemiol Drug Saf, 2018 Nov;27(11):1209-1216.
PMID: 30246898 DOI: 10.1002/pds.4657

PURPOSE: Renal disease is common among people living with human immunodeficiency virus (HIV). However, there is limited information on the incidence and risk factors associated with renal dysfunction among this population in Asia.
METHODS: We used data from the TREAT Asia HIV Observational Database. Patients were included if they started antiretroviral therapy during or after 2003, had a serum creatinine measurement at antiretroviral therapy initiation (baseline), and had at least 2 follow-up creatinine measurements taken ≥3 months apart. Patients with a baseline estimated glomerular filtration rate (eGFR) ≤60 mL/min/1.73 m2 were excluded. Chronic kidney disease was defined as 2 consecutive eGFR values ≤60 mL/min/1.73 m2 taken ≥3 months apart. Generalized estimating equations were used to identify factors associated with eGFR change. Competing risk regression adjusted for study site, age and sex, and cumulative incidence plots were used to evaluate factors associated with chronic kidney disease (CKD).
RESULTS: Of 2547 patients eligible for this analysis, tenofovir was being used by 703 (27.6%) at baseline. Tenofovir use, high baseline eGFR, advanced HIV disease stage, and low nadir CD4 were associated with a decrease in eGFR during follow-up. Chronic kidney disease occurred at a rate of 3.4 per 1000 patient/years. Factors associated with CKD were tenofovir use, old age, low baseline eGFR, low nadir CD4, and protease inhibitor use.
CONCLUSIONS: There is an urgent need to enhance renal monitoring and management capacity among at-risk groups in Asia and improve access to less nephrotoxic antiretrovirals.