Displaying publications 141 - 160 of 164 in total

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  1. Kamarulzaman A, Altice FL
    Curr. Opin. Infect. Dis., 2015 Feb;28(1):10-6.
    PMID: 25490106 DOI: 10.1097/QCO.0000000000000125
    HIV management in people who use drugs (PWUD) is typically complex and challenging due to the presence of multiple medical and psychiatric comorbidities as well as social, physical, economic and legal factors that often disrupt the HIV continuum of care. In this review, we describe the individual, health systems and societal barriers to HIV treatment access and care retention for PWUD. In addition, the clinical management of HIV-infected PWUD is often complicated by the presence of multiple infectious and noninfectious comorbidities.
    Matched MeSH terms: HIV Infections/drug therapy*
  2. 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.
    Matched MeSH terms: HIV Infections/drug therapy*
  3. Moy FS, Fahey P, Nik Yusoff NK, Razali KA, Nallusamy R, TREAT Asia Pediatric HIV Observational Database (TApHOD)
    J Paediatr Child Health, 2015 Feb;51(2):204-8.
    PMID: 25142757 DOI: 10.1111/jpc.12712
    To describe outcome and examine factors associated with mortality among human immunodeficiency virus (HIV)-infected children in Malaysia after anti-retroviral therapy (ART).
    Matched MeSH terms: HIV Infections/drug therapy*
  4. Martin A, Moore C, Mallon PW, Hoy J, Emery S, Belloso W, et al.
    AIDS, 2013 Sep 24;27(15):2403-11.
    PMID: 23921615 DOI: 10.1097/01.aids.0000432534.47217.b4
    To compare changes over 48 weeks in bone mineral density (BMD) between participants randomized to lopinavir/ritonavir (LPV/r) + raltegravir (RAL) or LPV/r + 2-3 nucleoside/nucleotide reverse transcriptase inhibitors (N(t)RTIs) as second line therapy.
    Matched MeSH terms: HIV Infections/drug therapy*
  5. del Amo J, Moreno S, Bucher HC, Furrer H, Logan R, Sterne J, et al.
    Clin Infect Dis, 2012 May;54(9):1364-72.
    PMID: 22460971 DOI: 10.1093/cid/cis203
    BACKGROUND: The lower tuberculosis incidence reported in human immunodeficiency virus (HIV)-positive individuals receiving combined antiretroviral therapy (cART) is difficult to interpret causally. Furthermore, the role of unmasking immune reconstitution inflammatory syndrome (IRIS) is unclear. We aim to estimate the effect of cART on tuberculosis incidence in HIV-positive individuals in high-income countries.

    METHODS: The HIV-CAUSAL Collaboration consisted of 12 cohorts from the United States and Europe of HIV-positive, ART-naive, AIDS-free individuals aged ≥18 years with baseline CD4 cell count and HIV RNA levels followed up from 1996 through 2007. We estimated hazard ratios (HRs) for cART versus no cART, adjusted for time-varying CD4 cell count and HIV RNA level via inverse probability weighting.

    RESULTS: Of 65 121 individuals, 712 developed tuberculosis over 28 months of median follow-up (incidence, 3.0 cases per 1000 person-years). The HR for tuberculosis for cART versus no cART was 0.56 (95% confidence interval [CI], 0.44-0.72) overall, 1.04 (95% CI, 0.64-1.68) for individuals aged >50 years, and 1.46 (95% CI, 0.70-3.04) for people with a CD4 cell count of <50 cells/μL. Compared with people who had not started cART, HRs differed by time since cART initiation: 1.36 (95% CI, 0.98-1.89) for initiation <3 months ago and 0.44 (95% CI, 0.34-0.58) for initiation ≥3 months ago. Compared with people who had not initiated cART, HRs <3 months after cART initiation were 0.67 (95% CI, 0.38-1.18), 1.51 (95% CI, 0.98-2.31), and 3.20 (95% CI, 1.34-7.60) for people <35, 35-50, and >50 years old, respectively, and 2.30 (95% CI, 1.03-5.14) for people with a CD4 cell count of <50 cells/μL.

    CONCLUSIONS: Tuberculosis incidence decreased after cART initiation but not among people >50 years old or with CD4 cell counts of <50 cells/μL. Despite an overall decrease in tuberculosis incidence, the increased rate during 3 months of ART suggests unmasking IRIS.

    Matched MeSH terms: HIV Infections/drug therapy*
  6. Sumatoh HR, Oliver BG, Kumar M, Elliott JH, Vonthanak S, Vun MC, et al.
    Biomark Med, 2011 Dec;5(6):847-53.
    PMID: 22103621 DOI: 10.2217/bmm.11.79
    Immune restoration disease (IRD) associated with Mycobacterium tuberculosis parallels the reconstitution of a pathogen-specific Th1 response. However, it is not clear whether humoral responses to M. tuberculosis antigens also rise, or whether antibody levels predict IRD. Here, humoral immunity to M. tuberculosis antigens was investigated in four Asian cohorts.
    Matched MeSH terms: HIV Infections/drug therapy
  7. Wolfe D, Carrieri MP, Shepard D
    Lancet, 2010 Jul 31;376(9738):355-66.
    PMID: 20650513 DOI: 10.1016/S0140-6736(10)60832-X
    We review evidence for effectiveness, cost-effectiveness, and coverage of antiretroviral therapy (ART) for injecting drug users (IDUs) infected with HIV, with particular attention to low-income and middle-income countries. In these countries, nearly half (47%) of all IDUs infected with HIV are in five nations--China, Vietnam, Russia, Ukraine, and Malaysia. In all five countries, IDU access to ART is disproportionately low, and systemic and structural obstacles restrict treatment access. IDUs are 67% of cumulative HIV cases in these countries, but only 25% of those receiving ART. Integration of ART with opioid substitution and tuberculosis treatment, increased peer engagement in treatment delivery, and reform of harmful policies--including police use of drug-user registries, detention of drug users in centres offering no evidence-based treatment, and imprisonment for possession of drugs for personal use--are needed to improve ART coverage of IDUs.
    Matched MeSH terms: HIV Infections/drug therapy*
  8. Tan DB, Yong YK, Tan HY, Kamarulzaman A, Tan LH, Lim A, et al.
    HIV Med, 2008 May;9(5):307-16.
    PMID: 18400078 DOI: 10.1111/j.1468-1293.2008.00565.x
    A proportion of HIV patients beginning antiretroviral therapy (ART) develop immune restoration disease (IRD). Immunological characteristics of IRD were investigated in a cohort of HIV patients beginning therapy in Kuala Lumpur, Malaysia.
    Matched MeSH terms: HIV Infections/drug therapy
  9. George C, Yesoda A, Jayakumar B, Lal L
    J Clin Pharm Ther, 2009 Feb;34(1):33-40.
    PMID: 19125901 DOI: 10.1111/j.1365-2710.2008.00988.x
    This prospective, observational, study evaluates the clinical outcomes, drug utilization patterns, and adherence to treatment of patients on highly active anti retroviral therapy (HAART) at a government institution in Kerala, India.
    Matched MeSH terms: HIV Infections/drug therapy*
  10. Lim A, Tan D, Price P, Kamarulzaman A, Tan HY, James I, et al.
    AIDS, 2007 Jul 31;21(12):1525-34.
    PMID: 17630546
    To examine the relationships between blood CD4 natural regulatory T (Treg) cells, plasma HIV RNA level, CD4 T-cell count and immune activation in untreated HIV-infected patients and immunodeficient patients beginning antiretroviral therapy (ART), using a novel phenotype to define Treg cells (CD25CD127CD4). Data were compared with established Treg cell markers (FoxP3, CTLA-4 and GITR).
    Matched MeSH terms: HIV Infections/drug therapy
  11. Saeidi A, Tien Tien VL, Al-Batran R, Al-Darraji HA, Tan HY, Yong YK, et al.
    PLoS One, 2015;10(4):e0124659.
    PMID: 25894562 DOI: 10.1371/journal.pone.0124659
    Mucosal-associated invariant T (MAIT) cells are evolutionarily conserved antimicrobial MR1-restricted CD8(+) T cells co-expressing the semi-invariant TCR Vα7.2, and are numerous in the blood and mucosal tissues of humans. MAIT cells appear to undergo exhaustion in chronic viral infections. However, their role in human immunodeficiency virus type 1 (HIV-1) mono-infection and HIV/tuberculosis (TB) co-infection have seldom been elaborately investigated. We conducted a cross-sectional study to investigate the frequencies and phenotypes of CD161(++)CD8(+) T cells among anti-retroviral therapy (ART)/anti-TB therapy (ATT) treatment-naïve HIV/TB co-infected, ART/TB treated HIV/TB co-infected, ART naïve HIV-infected, ART-treated HIV-infected patients, and HIV negative healthy controls (HCs) by flow cytometry. Our data revealed that the frequency of MAIT cells was severely depleted in HIV mono- and HIV/TB co-infections. Further, PD-1 expression on MAIT cells was significantly increased in HIV mono- and HIV-TB co-infected patients. The frequency of MAIT cells did not show any significant increase despite the initiation of ART and/or ATT. Majority of the MAIT cells in HCs showed a significant increase in CCR6 expression as compared to HIV/TB co-infections. No marked difference was seen with expressions of chemokine co-receptor CCR5 and CD103 among the study groups. Decrease of CCR6 expression appears to explain why HIV-infected patients display weakened mucosal immune responses.
    Matched MeSH terms: HIV Infections/drug therapy
  12. Reid G, Kamarulzaman A, Sran SK
    Int J Drug Policy, 2007 Mar;18(2):136-40.
    PMID: 17689356
    In Malaysia the response to illicit drug use has been largely punitive with the current goal of the Malaysian government being to achieve a drug-free society by 2015. This paper outlines the results of a desk-based situation assessment conducted over a 3-week period in 2004. Additional events, examined in 2005, were also included to describe more recent policy developments and examine how these came about. Despite punitive drug policy there has been a substantial rise in the number of drug users in the country. Over two-thirds of HIV/AIDS cases are among injecting drug users (IDUs) and there has been an exponential rise in the number of cases reported. Further, data suggest high risk drug use practices are widespread. Harm reduction initiatives have only recently been introduced in Malaysia. The successful piloting of substitution therapies, in particular methadone and buprenorphine, is cause for genuine hope for the rapid development of such interventions. In 2005 the government announced it will allow methadone maintenance programmes to operate beyond the pilot phase and needle and syringe exchange programmes will be established to serve the needs of IDUs.
    Matched MeSH terms: HIV Infections/drug therapy
  13. Tee KK, Kamarulzaman A, Ng KP
    AIDS Res Hum Retroviruses, 2006 Feb;22(2):121-4.
    PMID: 16478392
    To assess the prevalence of mutations associated with drug resistance in antiretroviral-naive patients in Kuala Lumpur, Malaysia, genotypic resistance testing was conducted among drug-naive HIV-1 patients attending the University Malaya Medical Center (UMMC) between July 2003 and June 2004. Reverse transcriptase (RT) and protease genes of plasma virions were sequenced from 100 individuals. The majority of the patients were recently diagnosed. Codons 20-255 of the RT and 1-96 of the protease gene were examined for major and minor mutations associated with antiretroviral resistance reported by the International AIDS Society- USA (IAS-USA) Drug Resistance Mutations Group. The prevalence of patients with at least one major mutation conferring drug resistance was 1%, with only one patient having a Y181C amino acid substitution in the RT gene that confers high-level resistance to nevirapine and delavirdine. Minor mutations were detected in high prevalence in the protease gene. Amino acid substitutions I13V, E35D, and M36I were associated with CRF01_AE while L63P, V77I, and I93L were associated with subtype B. Baseline prevalence of major mutations associated with resistance to antiretroviral drugs was low among antiretroviral-naive HIV-1 patients, suggesting that routine drug resistance testing may be unnecessary for all individuals newly diagnosed with HIV or all patients beginning antiretroviral therapy.
    Matched MeSH terms: HIV Infections/drug therapy
  14. 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: HIV Infections/drug therapy*
  15. Chew CS, Cherry CL, Kamarulzaman A, Yien TH, Aghafar Z, Price P
    Dis Markers, 2011;31(5):303-9.
    PMID: 22048272 DOI: 10.3233/DMA-2011-0844
    Chemokines influence the migration of leukocytes to secondary lymphoid tissue and sites of inflammation. In HIV patients, they are implicated in inflammatory complications of antiretroviral therapy (ART), notably Immune Reconstitution Disease (IRD) and Sensory Neuropathy (SN). However most chemokines have not been monitored as patients begin ART or correlated with IRD and SN.
    Matched MeSH terms: HIV Infections/drug therapy*
  16. Tan HY, Yong YK, Shankar EM, Paukovics G, Ellegård R, Larsson M, et al.
    J Immunol, 2016 05 15;196(10):4052-63.
    PMID: 27076678 DOI: 10.4049/jimmunol.1502203
    Tuberculosis-associated immune reconstitution inflammatory syndrome (TB-IRIS) complicates combination antiretroviral therapy (cART) in up to 25% of patients with HIV/TB coinfection. Monocytes and IL-18, a signature cytokine of inflammasome activation, are implicated in TB-IRIS pathogenesis. In this study, we investigated inflammasome activation both pre- and post-cART in TB-IRIS patients. HIV/TB patients exhibited higher proportions of monocytes expressing activated caspase-1 (casp1) pre-cART, compared with HIV patients without TB, and patients who developed TB-IRIS exhibited the greatest increase in casp1 expression. CD64(+) monocytes were a marker of increased casp1 expression. Furthermore, IL-1β, another marker of inflammasome activation, was also elevated during TB-IRIS. TB-IRIS patients also exhibited greater upregulation of NLRP3 and AIM2 inflammasome mRNA, compared with controls. Analysis of plasma mitochondrial DNA levels showed that TB-IRIS patients experienced greater cell death, especially pre-cART. Plasma NO levels were lower both pre- and post-cART in TB-IRIS patients, providing evidence of inadequate inflammasome regulation. Plasma IL-18 levels pre-cART correlated inversely with NO levels but positively with monocyte casp1 expression and mitochondrial DNA levels, and expression of IL-18Rα on CD4(+) T cells and NK cells was higher in TB-IRIS patients, providing evidence that IL-18 is a marker of inflammasome activation. We propose that inflammasome activation in monocytes/macrophages of HIV/TB patients increases with ineffective T cell-dependent activation of monocytes/macrophages, priming them for an excessive inflammatory response after cART is commenced, which is greatest in patients with TB-IRIS.
    Matched MeSH terms: HIV Infections/drug therapy
  17. Yong YK, Shankar EM, Westhorpe CL, Maisa A, Spelman T, Kamarulzaman A, et al.
    Medicine (Baltimore), 2016 Aug;95(31):e4477.
    PMID: 27495090 DOI: 10.1097/MD.0000000000004477
    HIV-infected individuals on antiretroviral therapy (ART) are at increased risk of cardiovascular disease (CVD). Given the relationship between innate immune activation and CVD, we investigated the association of single-nucleotide polymorphisms (SNPs) in TLR4 and CD14 and carotid intima-media thickness (cIMT), a surrogate measurement for CVD, in HIV-infected individuals on ART and HIV-uninfected controls as a cross-sectional, case-control study. We quantified the frequency of monocyte subsets (CD14, CD16), markers of monocyte activation (CD38, HLA-DR), and endothelial adhesion (CCR2, CX3CR1, CD11b) by flow cytometry. Plasma levels of lipopolysaccharide, sCD163, sCD14, sCX3CL1, and sCCL2, were measured by ELISA. Genotyping of TLR4 and CD14 SNPs was also performed. The TT genotype for CD14/-260SNP but not the CC/CT genotype was associated with elevated plasma sCD14, and increased frequency of CD11b+CD14+ monocytes in HIV-infected individuals. The TT genotype was associated with lower cIMT in HIV-infected patients (n = 47) but not in HIV-uninfected controls (n = 37). The AG genotype for TLR4/+896 was associated with increased CX3CR1 expression on total monocytes among HIV-infected individuals and increased sCCL2 and fibrinogen levels in HIV-uninfected controls. SNPs in CD14/-260 and TLR4/+896 were significantly associated with different markers of systemic and monocyte activation and cIMT that differed between HIV-infected participants on ART and HIV-uninfected controls. Further investigation on the relationship of these SNPs with a clinical endpoint of CVD is warranted in HIV-infected patients on ART.
    Matched MeSH terms: HIV Infections/drug therapy*
  18. Sakkhachornphop S, Hadpech S, Wisitponchai T, Panto C, Kantamala D, Utaipat U, et al.
    Viruses, 2018 11 13;10(11).
    PMID: 30428529 DOI: 10.3390/v10110625
    Certain proteins have demonstrated proficient human immunodeficiency virus (HIV-1) life cycle disturbance. Recently, the ankyrin repeat protein targeting the HIV-1 capsid, AnkGAG1D4, showed a negative effect on the viral assembly of the HIV-1NL4-3 laboratory strain. To extend its potential for future clinical application, the activity of AnkGAG1D4 in the inhibition of other HIV-1 circulating strains was evaluated. Chimeric NL4-3 viruses carrying patient-derived Gag/PR-coding regions were generated from 131 antiretroviral drug-naïve HIV-1 infected individuals in northern Thailand during 2001⁻2012. SupT1, a stable T-cell line expressing AnkGAG1D4 and ankyrin non-binding control (AnkA32D3), were challenged with these chimeric viruses. The p24CA sequences were analysed and classified using the K-means clustering method. Among all the classes of virus classified using the p24CA sequences, SupT1/AnkGAG1D4 demonstrated significantly lower levels of p24CA than SupT1/AnkA32D3, which was found to correlate with the syncytia formation. This result suggests that AnkGAG1D4 can significantly interfere with the chimeric viruses derived from patients with different sequences of the p24CA domain. It supports the possibility of ankyrin-based therapy as a broad alternative therapeutic molecule for HIV-1 gene therapy in the future.
    Matched MeSH terms: HIV Infections/drug therapy
  19. Springer SA, Di Paola A, Azar MM, Barbour R, Biondi BE, Desabrais M, et al.
    J Acquir Immune Defic Syndr, 2018 05 01;78(1):43-53.
    PMID: 29373393 DOI: 10.1097/QAI.0000000000001634
    OBJECTIVE: To determine whether extended-release naltrexone (XR-NTX) would improve or maintain viral suppression (VS) among prisoners or jail detainees with HIV and opioid use disorder (OUD) transitioning to the community.

    DESIGN: A 4-site, prospective randomized double-blind, placebo-controlled trial was conducted among prison and jail inmates with HIV and OUD transitioning to the community from September 2010 through March 2016.

    METHODS: Eligible participants (N = 93) were randomized 2:1 to receive 6 monthly injections of XR-NTX (n = 66) or placebo (n = 27) starting at release and observed for 6 months. The primary outcome was the proportion that maintained or improved VS (<50 copies/mL) from baseline to 6 months.

    RESULTS: Participants allocated to XR-NTX significantly improved to VS (<50 copies/mL) from baseline (37.9%) to 6 months (60.6%) (P = 0.002), whereas the placebo group did not (55.6% at baseline to 40.7% at 6 months P = 0.294). There was, however, no statistical significant difference in VS levels at 6 months between XR-NTX (60.6%) vs. placebo (40.7%) (P = 0.087). After controlling for other factors, only allocation to XR-NTX (adjusted odds ratio = 2.90; 95% confidence interval = 1.04 to 8.14, P = 0.043) was associated with the primary outcome. Trajectories in VS from baseline to 6 months differed significantly (P = 0.017) between treatment groups, and the differences in the discordant values were significantly different as well (P = 0.041): the XR-NTX group was more likely than the placebo group to improve VS (30.3% vs. 18.5%), maintain VS (30.3% vs. 27.3), and less likely to lose VS (7.6% vs. 33.3%) by 6 months.

    CONCLUSIONS: XR-NTX improves or maintains VS after release to the community for incarcerated people living with HIV with OUD.

    Matched MeSH terms: HIV Infections/drug therapy*
  20. 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.

    Matched MeSH terms: HIV Infections/drug therapy*
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