Displaying publications 1 - 20 of 99 in total

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  1. Chaudhary S, Nair AB, Shah J, Gorain B, Jacob S, Shah H, et al.
    AAPS PharmSciTech, 2021 Apr 09;22(3):127.
    PMID: 33835317 DOI: 10.1208/s12249-021-01995-y
    Being a candidate of BCS class II, dolutegravir (DTG), a recently approved antiretroviral drug, possesses solubility issues. The current research was aimed to improve the solubility of the DTG and thereby enhance its efficacy using the solid dispersion technique. In due course, the miscibility study of the drug was performed with different polymers, where Poloxamer 407 (P407) was found suitable to move forward. The solid dispersion of DTG and P407 was formulated using solvent evaporation technique with a 1:1 proportion of drug and polymer, where the solid-state characterization was performed using differential scanning calorimetry, Fourier transform infrared spectroscopy and X-ray diffraction. No physicochemical interaction was found between the DTG and P407 in the fabricated solid dispersion; however, crystalline state of the drug was changed to amorphous as evident from the X-ray diffractogram. A rapid release of DTG was observed from the solid dispersion (>95%), which is highly significant (p<0.05) as compared to pure drug (11.40%), physical mixture (20.07%) and marketed preparation of DTG (35.30%). The drug release from the formulated solid dispersion followed Weibull model kinetics. Finally, the rapid drug release from the solid dispersion formulation revealed increased Cmax (14.56 μg/mL) when compared to the physical mixture (4.12 μg/mL) and pure drug (3.45 μg/mL). This was further reflected by improved bioavailability of DTG (AUC: 105.99±10.07 μg/h/mL) in the experimental Wistar rats when compared to the AUC of animals administered with physical mixture (54.45±6.58 μg/h/mL) and pure drug (49.27±6.16 μg/h/mL). Therefore, it could be concluded that the dissolution profile and simultaneously the bioavailability of DTG could be enhanced by means of the solid dispersion platform using the hydrophilic polymer, P407, which could be projected towards improved efficacy of the drug in HIV/AIDS.
    Matched MeSH terms: Anti-HIV Agents/administration & dosage*; Anti-HIV Agents/pharmacokinetics*; Anti-HIV Agents/therapeutic use
  2. Kharkwal H, Kumar BK, Murugesan S, Singhvi G, Avasthi P, Goyal A, et al.
    Future Med Chem, 2021 02;13(3):269-286.
    PMID: 33399497 DOI: 10.4155/fmc-2020-0257
    Reverse transcriptase and integrase are key enzymes that play a pivotal role in HIV-1 viral maturation and replication. Reverse transcriptase consists of two active sites: RNA-dependent DNA polymerase and RNase H. The catalytic domains of integrase and RNase H share striking similarity, comprising two aspartates and one glutamate residue, also known as the catalytic DDE triad, and a Mg2+ pair. The simultaneous inhibition of reverse transcriptase and integrase can be a rational drug discovery approach for combating the emerging drug resistance problem. In the present review, the dual inhibition of RNase H and integrase is systematically discussed, including rationality of design, journey of development, advancement and future perspective.
    Matched MeSH terms: Anti-HIV Agents/metabolism; Anti-HIV Agents/therapeutic use; Anti-HIV Agents/chemistry*
  3. Ching SZ, Wong LP, Said MAB, Lim SH
    AIDS Educ Prev, 2020 10;32(5):416-431.
    PMID: 33112675 DOI: 10.1521/aeap.2020.32.5.416
    The aim of the study was to consolidate evidence on barriers and facilitators to PrEP adherence among men who have sex with men. PubMed, Science Direct, and EBSCO host were utilized to search for relevant articles. Six articles from PubMed, published between 2010 and 2018, were reviewed. Thematic analysis was employed to synthesize findings. At the individual level, HIV susceptibility, knowledge of PrEP, and individual lifestyle affected PrEP adherence. At the organizational level, cost of PrEP and quality of PrEP services influenced adherence to PrEP. At the societal level, social stigma, financial assistance or medical insurance, and family and peer support were determinants of PrEP adherence. Facilitators included perceived high risk of HIV infection and payment assistance, while barriers included social stigma and high cost of PrEP. Social stigma and structural level factors such as payment assistance and cost of PrEP need to be examined to ensure optimal adherence to PrEP.
    Matched MeSH terms: Anti-HIV Agents/administration & dosage*; Anti-HIV Agents/therapeutic use
  4. Qin Y, Huang X, Chen H, Liu X, Li Y, Hou J, et al.
    BMC Infect Dis, 2020 Jul 29;20(1):551.
    PMID: 32727383 DOI: 10.1186/s12879-020-05260-8
    BACKGROUND: Talaromyces marneffei (TM) is a dimorphic fungus mainly prevalent in Southeast Asian countries, which often causes disseminated life-threatening infection. TM infection often occurs in HIV/AIDS patients even in the antiretroviral therapy (ART) era. However, there has as yet, not been a systematic analysis of the prevalence of TM infection in HIV-infected populations in Asia.

    METHODS: In this study, we searched Pubmed, Embase, Web of Science, China National Knowledge Infrastructure (CNKI), and WanFang from inception to 21 November 2018 for studies reporting TM infection in people living with HIV/AIDS (PLWHA). Our meta-analysis included studies investigating the prevalence of TM infection in PLWHA. Reviews, duplicate studies, and animal studies were excluded. A random effects model was used to estimate pooled prevalence, and meta-regression analysis was conducted to explore potential factors for heterogeneity.

    RESULTS: 159,064 patients with HIV infection in 33 eligible studies were included in our meta-analysis. The pooled prevalence of TM infection in PLWHA was 3.6%. Vietnam had the highest prevalence (6.4%), followed by Thailand (3.9%), China (3.3%), India (3.2%) and Malaysia (2.1%). In China, TM infection was most prevalent in South China (15.0%), while the burden in Southwest China was not very heavy (0.3%). CD4+ T-cell counts below 200 cells/mm3 contributed to the increased risk of TM infection in PLWHA (OR 12.68, 95%CI: 9.58-16.77). However, access to ART did not significantly decrease the risk of TM infection in PLWHA.

    CONCLUSIONS: The burden of TM infection in Asia is heavy, and varies from region to region. PLWHA in lower latitude areas are more likely to suffer from TM infection. Optimization of diagnostic tools and universal screening for TM in vulnerable people to ensure early case detection and prompt antifungal treatment should be considered.

    Matched MeSH terms: Anti-HIV Agents/therapeutic use*
  5. Han WM, Bijker R, Chandrasekaran E, Pujari S, Ng OT, Ly PS, et al.
    PMID: 32740369 DOI: 10.1097/QAI.0000000000002464
    BACKGROUND: We validated the Data collection on Adverse events of anti-HIV Drugs (D:A:D) full- and short-risk score models for CKD in the Asian HIV cohorts.

    SETTINGS: A validation study among people living with HIV(PLHIV) aged ≥18 years among the cohorts in the Asia-Pacific region.

    METHODS: PLHIV with baseline eGFR>60 mL/min/1.73m were included for validation of the D:A:D CKD full version and the short version without cardiovascular risk factors. Those with <3 eGFR measurements from baseline or previous exposure to potentially nephrotoxic antiretrovirals were excluded. Kaplan-Meier methods were used to estimate the probability of CKD development. Area Under the Receiver Operating Characteristics (AUROC) was also used to validate the risk score.

    RESULTS: We included 5,701 participants in full model(median 8.1 [IQR 4.8-10.9] years follow-up) and 9,791 in short model validation(median 4.9 [IQR 2.5-7.3] years follow-up). The crude incidence rate of CKD was 8.1 (95%CI 7.3-8.9) per 1,000 person-years(PYS) in the full model cohort and 10.5 (95%CI 9.6-11.4) per 1,000 PYS in the short model cohort. The progression rates for CKD at 10 years in the full model cohort were 2.7%, 8.9% and 26.1% for low-, medium- and high-risk groups, and 3.5%, 11.7% and 32.4% in the short model cohort. The AUROC for the full and short risk score was 0.81 (95%CI 0.79-0.83) and 0.83 (95%CI 0.81-0.85), respectively.

    CONCLUSION: The D:A:D CKD full- and short-risk score performed well in predicting CKD events among Asian PLHIV. These risk prediction models may be useful to assist clinicians in identifying individuals at high risk of developing CKD.

    Matched MeSH terms: Anti-HIV Agents
  6. Rupasinghe D, Kiertiburanakul S, Kamarulzaman A, Zhang F, Kumarasamy N, Chaiwarith R, et al.
    HIV Med, 2020 07;21(6):397-402.
    PMID: 31852025 DOI: 10.1111/hiv.12836
    OBJECTIVES: Early mortality among those still initiating antiretroviral therapy (ART) with advanced stages of HIV infection in resource-limited settings remains high despite recommendations for universal HIV treatment. We investigated risk factors associated with early mortality in people living with HIV (PLHIV) starting ART at low CD4 levels in the Asia-Pacific.

    METHODS: PLHIV enrolled in the Therapeutics, Research, Education and AIDS Training in Asia (TREAT Asia) HIV Observational Database (TAHOD) who initiated ART with a CD4 count  1 year were censored at 12 months. Competing risk regression was used to analyse risk factors with loss to follow-up as a competing risk.

    RESULTS: A total of 1813 PLHIV were included in the study, of whom 74% were male. With 73 (4%) deaths, the overall first-year mortality rate was 4.27 per 100 person-years (PY). Thirty-eight deaths (52%) were AIDS-related, 10 (14%) were immune reconstituted inflammatory syndrome (IRIS)-related, 13 (18%) were non-AIDS-related and 12 (16%) had an unknown cause. Risk factors included having a body mass index (BMI)  100 cells/μL: SHR 0.12; 95% CI 0.05-0.26) was associated with reduced hazard for mortality compared to CD4 count ≤ 25 cells/μL.

    CONCLUSIONS: Fifty-two per cent of early deaths were AIDS-related. Efforts to initiate ART at CD4 counts > 50 cell/μL are associated with improved short-term survival rates, even in those with late stages of HIV disease.

    Matched MeSH terms: Anti-HIV Agents/therapeutic use*
  7. Sudjaritruk T, Teeraananchai S, Kariminia A, Lapphra K, Kumarasamy N, Fong MS, et al.
    J Int AIDS Soc, 2020 07;23(7):e25550.
    PMID: 32628816 DOI: 10.1002/jia2.25550
    INTRODUCTION: The clinical relevance of low-level viraemia (LLV) and virological outcomes among children living with HIV (CLHIV) remains controversial. This study aimed to determine the impact of LLV on virological failure (VF) among Asian CLHIV on first-line combination antiretroviral therapy (cART).

    METHODS: CLHIV aged <18 years, who were on first-line cART for ≥12 months, and had virological suppression (two consecutive plasma viral load [pVL] <50 copies/mL) were included. Those who started treatment with mono/dual antiretroviral therapy, had a history of treatment interruption >14 days, or received treatment and care at sites with a pVL lower limit of detection >50 copies/mL were excluded. LLV was defined as a pVL 50 to 1000 copies/mL, and VF as a single pVL >1000 copies/mL. Baseline was the time of the second pVL 

    Matched MeSH terms: Anti-HIV Agents/therapeutic use*
  8. Mohd Salleh NA, Van Draanen J, Nosova E, Barrios R, Milloy MJ, Richardson L
    AIDS, 2020 06 01;34(7):1037-1045.
    PMID: 32073444 DOI: 10.1097/QAD.0000000000002501
    OBJECTIVE: To examine the relationship between poverty, operationalized using a novel material security measure, and adherence to antiretroviral therapy (ART) among people who use illicit drugs (PWUD) in a context of universal access to HIV care.

    DESIGN: We analyzed data from a community-recruited prospective cohort in Vancouver, Canada (n = 623), from 2014 to 2017.

    METHODS: We used multivariable generalized mixed-effects analyses to estimate longitudinal factors associated with mean material security score. We then estimated the association between achieving at least 95% adherence to ART and overall mean material score, as well as mean score for three factors derived from a factor analysis. The three-factor structure, employed in the current analyses, were factor 1 (basic needs); factor 2 (housing-related variables) and factor 3 (economic resources).

    RESULTS: Recent incarceration [β-coefficient (β) = -0.176, 95% confidence interval (95% CI): -0.288 to -0.063], unmet health needs [β = -0.110, 95% CI: -0.178 to -0.042), unmet social service needs (β = -0.264, 95% CI: -0.336 to -0.193) and having access to social services (β= -0.102, 95% CI: -0.1586 to -0.0465) were among the factors associated with lower material security scores. Contrary to expectations that low levels of material security in this population would lead to poor ART adherence, we did not observe a significant relationship between adherence and overall material security score, or for each factor individually.

    CONCLUSION: Our findings highlight the potentially important role of no-cost, universal access to HIV prevention and treatment, in mitigating the impact of socioeconomic disadvantage on ART adherence.

    Matched MeSH terms: Anti-HIV Agents/therapeutic use*
  9. Bórquez A, Rich K, Farrell M, Degenhardt L, McKetin R, Tran LT, et al.
    J Int AIDS Soc, 2020 Jun;23 Suppl 1(Suppl 1):e25495.
    PMID: 32562365 DOI: 10.1002/jia2.25495
    INTRODUCTION: Among men who have sex with men (MSM) and transgender women (TW), stimulant use is high and has been associated with an increased risk of HIV infection, suicide and cardiovascular disease (CVD) mortality. We used epidemic modelling to investigate these intersecting health harms among MSM/TW in Lima, Peru and assess whether they could be mitigated by prioritizing HIV pre-exposure prophylaxis (PrEP) and harm reduction interventions among MSM/TW who use stimulants.

    METHODS: We adapted a dynamic model of HIV transmission among MSM/TW in Lima to incorporate stimulant use and increased HIV risk, suicide and CVD mortality. Among 6% to 24% of MSM/TW using stimulants (mostly cocaine), we modelled an increased risk of unprotected anal sex (RR = 1.35 [95%CI: 1.17 to 1.57]) obtained from local data, and increased risk of suicide (SMR = 6.26 [95%CI: 2.84 to 13.80]) and CVD (SMR = 1.83 [95%CI: 0.39 to 8.57]) mortality associated with cocaine use based on a global systematic review. We estimated the proportion of health harms occurring among MSM/TW who use stimulants in the next year (01-2020/01-2021). We also investigated the 10-year impact (01-2020/01-2030) of: (1) PrEP prioritization for stimulant-using MSM/TW compared to random allocation, and (2) integrating PrEP with a theoretical intervention halving stimulant-associated risk.

    RESULTS: MSM/TW in Lima will experience high HIV incidence, suicide mortality and CVD mortality (1.6/100 py, and 0.018/100 py, 0.13/100 py respectively) in 2020. Despite stimulant using MSM/TW comprising an estimated 9.5% (95%CI: 7.8 to 11.5) of all MSM/TW, in the next year, 11% 95%CI (i.e. 2.5% to 97.5% percentile) 10% to 13%) of new HIV infections, 39% (95%CI: 18% to 60%) of suicides and 15% (95%CI: 3% to 44%) of CVD deaths could occur among this group. Scaling up PrEP among all stimulant using MSM/TW could prevent 19% (95%CI: 11% to 31%) more HIV infections over 10 years compared to random allocation. Integrating PrEP and an intervention to halve stimulant-associated risks could reduce new HIV infections by 20% (95%CI: 10% to 37%), suicide deaths by 14% (95%CI: 5% to 27%) and CVD deaths by 3% (95%CI: 0% to 16%) over a decade.

    CONCLUSIONS: MSM/TW who use stimulants experience a disproportionate burden of health harms. Prioritizing PrEP based on stimulant use, in addition to sexual behaviour/gender identity criteria, could increase its impact. Integrated substance use, harm reduction, mental health and HIV care among MSM/TW is needed.

    Matched MeSH terms: Anti-HIV Agents/therapeutic use*
  10. Nabih MF, Puteh SEW, Nur AM
    Sci Rep, 2019 12 27;9(1):19923.
    PMID: 31882645 DOI: 10.1038/s41598-019-56314-0
    In 2007, HIV treatment services were established in five main governorates out of twenty-two which resulted in low access to services and poor treatment outcomes. The main goal of this study was to evaluate and analyse the selected treatment outcomes of eight cohorts of PLHIV who were treated with cART during 2007-2014. The method used was a retrospective descriptive study of 1,703 PLHIV who initiated cART at five public health facilities. The results: Retention rate was less than 80%, male: female ratio 1.661, with a mean age of 35 years (±9.2 SD), 85% had been infected with HIV via heterosexual contact. 65% of patients presented with clinical stages 3 and 4, and 52% of them were initiated cART at a CD4 T-cell count ≤200 cells/mm. 61% of cART included Tenofovir and Efavirenz. TB treatment started for 5% of PLHIV, and 22% developed HIV-related clinical manifestations after cART initiation. 67% of PLHIV had experienced cART substitution. The mean AIDS-mortality rate was 15% and the mean LTFU rate was 16%. Conclusion: Although cART showed effectiveness in public health, mobilization of resources and formulation of better health policies are important steps toward improving access to cART and achieving the desired treatment outcomes.
    Matched MeSH terms: Anti-HIV Agents/therapeutic use*
  11. Bartlett AW, Lumbiganon P, Kurniati N, Sudjaritruk T, Mohamed TJ, Hansudewechakul R, et al.
    J Adolesc Health, 2019 11;65(5):651-659.
    PMID: 31395514 DOI: 10.1016/j.jadohealth.2019.05.025
    PURPOSE: Antiretroviral monotherapy and treatment interruption are potential strategies for perinatally HIV-infected adolescents (PHIVA) who face challenges maintaining effective combination antiretroviral therapy (ART). We assessed the use and outcomes for adolescents receiving monotherapy or undergoing treatment interruption in a regional Asian cohort.

    METHODS: Regional Asian data (2001-2016) were analyzed to describe PHIVA who experienced ≥2 weeks of lamivudine or emtricitabine monotherapy or treatment interruption and trends in CD4 count and HIV viral load during and after episodes. Survival analyses were used for World Health Organization (WHO) stage III/IV clinical and immunologic event-free survival during monotherapy or treatment interruption, and a Poisson regression to determine factors associated with monotherapy or treatment interruption.

    RESULTS: Of 3,448 PHIVA, 84 (2.4%) experienced 94 monotherapy episodes, and 147 (4.3%) experienced 174 treatment interruptions. Monotherapy was associated with older age, HIV RNA >400 copies/mL, younger age at ART initiation, and exposure to ≥2 combination ART regimens. Treatment interruption was associated with CD4 count <350 cells/μL, HIV RNA ≥1,000 copies/mL, ART adverse event, and commencing ART age ≥10 years compared with age <3 years. WHO clinical stage III/IV 1-year event-free survival was 96% and 85% for monotherapy and treatment interruption cohorts, respectively. WHO immunologic stage III/IV 1-year event-free survival was 52% for both cohorts. Those who experienced monotherapy or treatment interruption for more than 6 months had worse immunologic and virologic outcomes.

    CONCLUSIONS: Until challenges of treatment adherence, engagement in care, and combination ART durability/tolerability are met, monotherapy and treatment interruption will lead to poor long-term outcomes.

    Matched MeSH terms: Anti-HIV Agents/therapeutic use*
  12. Gill MSA, Hassan SS, Ahemad N
    Eur J Med Chem, 2019 Oct 01;179:423-448.
    PMID: 31265935 DOI: 10.1016/j.ejmech.2019.06.058
    HIV infection is a major challenge to mankind and a definitive cure or a viable vaccine for HIV is still elusive. HIV-1 is constantly evolving and developing resistant against clinically used anti-HIV drugs thus posing serious hurdles in the treatment of HIV infection. This prompts the need to developed new anti-HIV drugs; preferentially adopting intelligent ways to counteract an evolving virus. Highly Active Anti-Retroviral Therapy (HAART): a strategy involving multiple targeting through various drugs has proven beneficial in the management of AIDS. However, it is a complex regimen with high drug load, increased risk of drug interactions and adverse effects, which lead to poor patient compliance. Reverse transcriptase (RT) and Integrase (IN) are two pivotal enzymes in HIV-1 lifecycle with high structural and functional analogy to be perceived as drug-able targets for novel dual-purpose inhibitors. Designed multi-functional ligand (DML) is a modern strategy by which multiple targets can be exploited using a single chemical entity. A single chemical entity acting on multiple targets can be much more effective than a complex multi-drug regimen. The development of such multifunctional ligands is highly valued in anti-HIV drug discovery with the proposed advantage of being able to stop two or more stages of viral replication cycle. This review will encompass the evolution of the RT-IN dual inhibitory scaffolds reported so far and the contribution made by the leading research groups over the years in this field.
    Matched MeSH terms: Anti-HIV Agents/pharmacology*; Anti-HIV Agents/chemistry
  13. Mohd Salleh NA, Fairbairn N, Nolan S, Barrios R, Shoveller J, Richardson L, et al.
    HIV Med, 2019 10;20(9):606-614.
    PMID: 31359615 DOI: 10.1111/hiv.12777
    OBJECTIVES: We sought to examine the association between dispensation of methadone maintenance therapy (MMT) and antiretroviral therapy (ART) at the same facility, across multiple low-barrier dispensing outlets, and achieving optimal adherence to ART among people who use illicit drugs (PWUD).

    METHODS: We used data from the AIDS Care Cohort to Evaluate Exposure to Survival Services (ACCESS) study, a long-running study of a community-recruited cohort of HIV-positive PWUD, linked to comprehensive HIV clinical records in Vancouver, Canada, a setting of no-cost, universal access to HIV care. The longitudinal relationship between MMT-ART dispensation at the same facility and the odds of ≥ 95% ART adherence was analysed using multivariable generalized linear mixed-effects modelling. We conducted a further analysis using a marginal structural mode with inverse probability of treatment weights as a sensitivity analysis.

    RESULTS: This study included data on 1690 interviews of 345 ART- and MMT-exposed participants carried out between June 2012 and December 2017. In the final multivariable model, MMT-ART dispensation, compared with nondispensation at the same facility, was associated with greater odds of achieving ≥ 95% adherence [adjusted odds ratio (AOR) 1.56; 95% confidence interval (CI) 1.26-1.96]. A marginal structural model estimated a 1.48 (95% CI 1.15-1.80) greater odds of ≥ 95% adherence among participants who reported MMT-ART dispensation at the same facility compared with those who did not.

    CONCLUSIONS: The odds of achieving optimal adherence to ART were 56% higher during periods in which MMT and ART medications were dispensed at the same facility, in a low-barrier setting. Our findings highlight the need to consider a simpler integrated approach with medication dispensation at the same facility in low-threshold settings.

    Matched MeSH terms: Anti-HIV Agents/therapeutic use*
  14. Yap PK, Loo Xin GL, Tan YY, Chellian J, Gupta G, Liew YK, et al.
    J Pharm Pharmacol, 2019 Sep;71(9):1339-1352.
    PMID: 31144296 DOI: 10.1111/jphp.13107
    OBJECTIVES: Antiretroviral agents (ARVs) have been the most promising line of therapy in the management of human immunodeficiency virus (HIV) infections. Some of these ARVs are used in the pre-exposure prophylaxis (PrEP) to suppress the transmission of HIV. Prophylaxis is primarily used in uninfected people, before exposure, to effectively prevent HIV infection. Several studies have shown that ART PrEP prevents HIV acquisition from sexual, blood and mother-to-child transmissions. However, there are also several challenges and limitations to PrEP. This review focuses on the current antiretroviral therapies used in PrEP.

    KEY FINDINGS: Among ARVs, the most common drugs employed from the class of entry inhibitors are maraviroc (MVC), which is a CCR5 receptor antagonist. Other entry inhibitors like emtricitabine (FTC) and tenofovir (TFV) are also used. Rilpivirine (RPV) and dapivirine (DPV) are the most common drugs employed from the Non-nucleoside reverse transcriptase inhibitor (NNRTIs) class, whereas, tenofovir disoproxil fumarate (TDF) is primarily used in the Nucleoside Reverse Transcriptase Inhibitor (NRTIs) class. Cabotegravir (CAB) is an analog of dolutegravir, and it is an integrase inhibitor. Some of these drugs are also used in combination with other drugs from the same class.

    SUMMARY: Some of the most common pre-exposure prophylactic strategies employed currently are the use of inhibitors, namely entry inhibitors, non-nucleoside reverse transcriptase inhibitors, nucleoside reverse transcriptase inhibitors, integrase and protease inhibitors. In addition, we have also discussed on the adverse effects caused by ART in PrEP, pharmacoeconomics factors and the use of antiretroviral prophylaxis in serodiscordant couples.

    Matched MeSH terms: Anti-HIV Agents/therapeutic use*
  15. Sudjaritruk T, Boettiger DC, Nguyen LV, Mohamed TJ, Wati DK, Bunupuradah T, et al.
    J Int AIDS Soc, 2019 Jun;22(6):e25312.
    PMID: 31179641 DOI: 10.1002/jia2.25312
    INTRODUCTION: Recommendations on the optimal frequency of plasma viral load (pVL) monitoring in children living with HIV (CLWH) who are stable on combination antiretroviral therapy (cART) are inconsistent. This study aimed to determine the impact of annual versus semi-annual pVL monitoring on treatment outcomes in Asian CLWH.

    METHODS: Data on children with perinatally acquired HIV aged <18 years on first-line, non-nucleoside reverse transcriptase inhibitor-based cART with viral suppression (two consecutive pVL <400 copies/mL over a six-month period) were included from a regional cohort study; those exposed to prior mono- or dual antiretroviral treatment were excluded. Frequency of pVL monitoring was determined at the site-level based on the median rate of pVL measurement: annual 0.75 to 1.5, and semi-annual >1.5 tests/patient/year. Treatment failure was defined as virologic failure (two consecutive pVL >1000 copies/mL), change of antiretroviral drug class, or death. Baseline was the date of the second consecutive pVL <400 copies/mL. Competing risk regression models were used to identify predictors of treatment failure.

    RESULTS: During January 2008 to March 2015, there were 1220 eligible children from 10 sites that performed at least annual pVL monitoring, 1042 (85%) and 178 (15%) were from sites performing annual (n = 6) and semi-annual pVL monitoring (n = 4) respectively. Pre-cART, 675 children (55%) had World Health Organization clinical stage 3 or 4, the median nadir CD4 percentage was 9%, and the median pVL was 5.2 log10 copies/mL. At baseline, the median age was 9.2 years, 64% were on nevirapine-based regimens, the median cART duration was 1.6 years, and the median CD4 percentage was 26%. Over the follow-up period, 258 (25%) CLWH with annual and 40 (23%) with semi-annual pVL monitoring developed treatment failure, corresponding to incidence rates of 5.4 (95% CI: 4.8 to 6.1) and 4.3 (95% CI: 3.1 to 5.8) per 100 patient-years of follow-up respectively (p = 0.27). In multivariable analyses, the frequency of pVL monitoring was not associated with treatment failure (adjusted hazard ratio: 1.12; 95% CI: 0.80 to 1.59).

    CONCLUSIONS: Annual compared to semi-annual pVL monitoring was not associated with an increased risk of treatment failure in our cohort of virally suppressed children with perinatally acquired HIV on first-line NNRTI-based cART.

    Matched MeSH terms: Anti-HIV Agents/therapeutic use*
  16. Mu W, Bartlett AW, Bunupuradah T, Chokephaibulkit K, Kumarasamy N, Ly PS, et al.
    J Acquir Immune Defic Syndr, 2019 03 01;80(3):308-315.
    PMID: 30531299 DOI: 10.1097/QAI.0000000000001921
    BACKGROUND: Virologic failure is a major threat to maintaining effective combination antiretroviral therapy, especially for children in need of lifelong treatment. With efforts to expand access to HIV viral load testing, our understanding of pediatric virologic failure is evolving.

    SETTING: An Asian cohort in 16 pediatric HIV services across 6 countries.

    METHODS: From 2005 to 2014, patients younger than 20 years who achieved virologic suppression and had subsequent viral load testing were included. Early virologic failure was defined as a HIV RNA ≥1000 copies per milliliter within 12 months of virologic suppression, and late virologic as a HIV RNA ≥1000 copies per milliliter after 12 months following virologic suppression. Characteristics at combination antiretroviral therapy initiation and virologic suppression were described, and a competing risk time-to-event analysis was used to determine cumulative incidence of virologic failure and factors at virologic suppression associated with early and late virologic failure.

    RESULTS: Of 1105 included in the analysis, 182 (17.9%) experienced virologic failure. The median age at virologic suppression was 6.9 years, and the median time to virologic failure was 24.6 months after virologic suppression. The incidence rate for a first virologic failure event was 3.3 per 100 person-years. Factors at virologic suppression associated with late virologic failure included older age, mostly rural clinic setting, tuberculosis, protease inhibitor-based regimens, and early virologic failure. No risk factors were identified for early virologic failure.

    CONCLUSIONS: Around 1 in 5 experienced virologic failure in our cohort after achieving virologic suppression. Targeted interventions to manage complex treatment scenarios, including adolescents, tuberculosis coinfection, and those with poor virologic control are required.

    Matched MeSH terms: Anti-HIV Agents/therapeutic use
  17. Ku SW, Jiamsakul A, Joshi K, Pasayan MKU, Widhani A, Chaiwarith R, et al.
    J Int AIDS Soc, 2019 Mar;22(3):e25264.
    PMID: 30924281 DOI: 10.1002/jia2.25264
    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.

    Matched MeSH terms: Anti-HIV Agents/therapeutic use
  18. Han WM, Jiamsakul A, Kiertiburanakul S, Ng OT, Sim BL, Sun LP, et al.
    J Int AIDS Soc, 2019 Jan;22(1):e25236.
    PMID: 30697944 DOI: 10.1002/jia2.25236
    INTRODUCTION: Comorbidities including diabetes mellitus (DM) among people living with HIV (PLHIV) are of increasing clinical concerns in combination antiretroviral therapy (cART) era. We aimed to determine the incidence and risk factors of new-onset DM among PLHIV in Asian settings.

    METHODS: PLHIV from a regional observational cohort without DM prior to antiretroviral therapy (ART) initiation were included in the analysis. DM was defined as having a fasting blood glucose ≥126 mg/dL, glycated haemoglobin ≥6.5%, a two-hour plasma glucose ≥200 mg/dL, or a random plasma glucose ≥200 mg/dL. A Cox regression model, stratified by site, was used to identify risk factors associated with DM.

    RESULTS AND DISCUSSION: Of the 1927 participants included, 127 were diagnosed with DM after ART initiation. Median follow-up time from ART initiation to DM diagnosis was 5.9 years (interquartile range (IQR): 2.8 to 8.9 years). The crude incidence rate of DM was 1.08 per 100 person-years (100 PYS), 95% confidence interval (CI) (0.9 to 1.3). In the multivariate analysis, later years of follow-up (2011 to 2013: HR = 2.34, 95% CI 1.14 to 4.79, p = 0.02; and 2014 to 2017: HR = 7.20, 95% CI 3.27 to 15.87, p 50 years: HR = 4.19, 95% CI 2.12 to 8.28, p 30 kg/m2 (HR = 4.3, 95% CI 1.53 to 12.09, p = 0.006) compared to BMI <18.5 kg/m2 , and high blood pressure (HR = 2.05, 95% CI 1.16 to 3.63, p = 0.013) compared to those without high blood pressure, were associated with developing DM. The hazard was reduced for females (HR = 0.47, 95% CI 0.28 to 0.80, p = 0.006).

    CONCLUSIONS: Type 2 DM in HIV-infected Asians was associated with later years of follow-up, high blood pressure, obesity and older age. This highlights the importance of monitoring and routine screening for non-communicable diseases including DM as PLHIV age.

    Matched MeSH terms: Anti-HIV Agents/therapeutic use
  19. Jung IY, Rupasinghe D, Woolley I, O'Connor CC, Giles M, Azwa RI, et al.
    J Int AIDS Soc, 2019 Jan;22(1):e25219.
    PMID: 30615271 DOI: 10.1002/jia2.25219
    INTRODUCTION: AIDS-related deaths in people living with HIV/AIDS have been decreasing in number since the introduction of combination antiretroviral treatment (cART). However, data on recent causes of death in the Asia-Pacific region are limited. Hence, we analysed and compared AIDS-related and non-AIDS-related mortality in high- and low-income settings in the region.

    METHODS: Patients from the TREAT Asia HIV Observational Database (TAHOD) and Australian HIV Observational Database (AHOD) receiving cART between 1999 and 2017 were included. Causes of death verification were based on review of the standardized Cause of Death (CoDe) form designed by the D:A:D group. Cohorts were grouped as AHOD (all high-income sites), TAHOD-high (high/upper-middle income countries) and TAHOD-low (lower-middle income countries). TAHOD sites were split into high/upper-middle income and lower-middle income country settings based on World Bank classifications. Competing risk regression was used to analyse factors associated with AIDS and non-AIDS-related mortality.

    RESULTS: Of 10,386 patients, 522 died; 187 from AIDS-related and 335 from non-AIDS-related causes. The overall incidence rate of deaths during follow-up was 0.28 per 100 person-years (/100 PYS) for AIDS and 0.51/100 PYS for non-AIDS. Analysis indicated that the incidence rate of non-AIDS mortality decreased from 0.78/100 PYS to 0.37/100 PYS from year groups 2003 to 2007 to 2013 to 2017 (p 

    Matched MeSH terms: Anti-HIV Agents/therapeutic use*
  20. Jiamsakul A, Kerr SJ, Kiertiburanakul S, Azwa I, Zhang F, Chaiwarith R, et al.
    AIDS Care, 2018 12;30(12):1560-1566.
    PMID: 30021450 DOI: 10.1080/09540121.2018.1499859
    Missed clinic visits can lead to poorer treatment outcomes in HIV-infected patients. Suboptimal antiretroviral therapy (ART) adherence has been linked to subsequent missed visits. Knowing the determinants of missed visits in Asian patients will allow for appropriate counselling and intervention strategies to ensure continuous engagement in care. A missed visit was defined as having no assessments within six months. Repeated measures logistic regression was used to analyse factors associated with missed visits. A total of 7100 patients were included from 12 countries in Asia with 2676 (37.7%) having at least one missed visit. Patients with early suboptimal self-reported adherence <95% were more likely to have a missed visit compared to those with adherence ≥95% (OR = 2.55, 95% CI(1.81-3.61)). Other factors associated with having a missed visit were homosexual (OR = 1.45, 95%CI(1.27-1.66)) and other modes of HIV exposure (OR = 1.48, 95%CI(1.27-1.74)) compared to heterosexual exposure; using PI-based (OR = 1.33, 95%CI(1.15-1.53) and other ART combinations (OR = 1.79, 95%CI(1.39-2.32)) compared to NRTI+NNRTI combinations; and being hepatitis C co-infected (OR = 1.27, 95%CI(1.06-1.52)). Patients aged >30 years (31-40 years OR = 0.81, 95%CI(0.73-0.89); 41-50 years OR = 0.73, 95%CI(0.64-0.83); and >50 years OR = 0.77, 95%CI(0.64-0.93)); female sex (OR = 0.81, 95%CI(0.72-0.90)); and being from upper middle (OR = 0.78, 95%CI(0.70-0.80)) or high-income countries (OR = 0.42, 95%CI(0.35-0.51)), were less likely to have missed visits. Almost 40% of our patients had a missed clinic visit. Early ART adherence was an indicator of subsequent clinic visits. Intensive counselling and adherence support should be provided at ART initiation in order to optimise long-term clinic attendance and maximise treatment outcomes.
    Matched MeSH terms: Anti-HIV Agents/therapeutic use*
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