Displaying publications 81 - 89 of 89 in total

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  1. Bere A, Tayib S, Kriek JM, Masson L, Jaumdally SZ, Barnabas SL, et al.
    Clin Immunol, 2014 Feb;150(2):210-9.
    PMID: 24440646 DOI: 10.1016/j.clim.2013.12.005
    HIV-infected individuals experience more persistent HPV infections and are less likely to resolve genital warts. This study compared phenotype and functions of NK and T cells from genital warts and blood from 67 women. We compared in vitro functional responses of NK and T cells by multiparametric flow cytometry. HIV+ women had significantly lower frequencies of CD4 T cells in warts (p = 0.001) and blood (p = 0.001). While the distribution of NK cell subsets was similar, HIV+ women tended to have lower frequencies of CD56(Dim) NK cells in both blood (p = 0.0001) and warts (p = 0.006) than HIV- women. Wart NK cells from HIV+ women expressed significantly lower CD107a and produced IFN-γ. HAART status was not associated with differences in NK cell functionality. We conclude that wart NK cells from HIV+ women have defects in their ability to degranulate and/or secrete IFN-γ, which may provide insights into why HIV+ women fail to spontaneously resolve genital warts.
    Matched MeSH terms: Antiretroviral Therapy, Highly Active
  2. Yeak J, Iqbal T, Zahari M, Ismail F
    Int J STD AIDS, 2019 07;30(8):802-809.
    PMID: 31046617 DOI: 10.1177/0956462418825353
    Matched MeSH terms: Antiretroviral Therapy, Highly Active
  3. 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: Antiretroviral Therapy, Highly Active
  4. Lee SC, Chua LL, Yap SH, Khang TF, Leng CY, Raja Azwa RI, et al.
    Sci Rep, 2018 09 24;8(1):14277.
    PMID: 30250162 DOI: 10.1038/s41598-018-32585-x
    We explored the gut microbiota profile among HIV-infected individuals with diverse immune recovery profiles following long-term suppressive ART and investigated the relationship between the altered bacteria with markers of immune dysfunction. The microbiota profile of rectal swabs from 26 HIV-infected individuals and 20 HIV-uninfected controls were examined. Patients were classified as suboptimal responders, sIR (n = 10, CD4 T-cell <350 cells/ul) and optimal responders, oIR (n = 16, CD4 T-cell >500 cells/ul) after a minimum of 2 years on suppressive ART. Canonical correlation analysis(CCA) and multiple regression modelling were used to explore the association between fecal bacterial taxa abundance and immunological profiles in optimal and suboptimal responders. We found Fusobacterium was significantly enriched among the HIV-infected and the sIR group. CCA results showed that Fusobacterium abundance was negatively correlated with CD4 T-cell counts, but positively correlated with CD4 T-cell activation and CD4 Tregs. Multiple linear regression analysis adjusted for age, baseline CD4 T-cell count, antibiotic exposure and MSM status indicated that higher Fusobacterium relative abundance was independently associated with poorer CD4 T-cell recovery following ART. Enrichment of Fusobacterium was associated with reduced immune recovery and persistent immune dysfunction following ART. Modulating the abundance of this bacterial taxa in the gut may be a viable intervention to improve immune reconstitution in our setting.
    Matched MeSH terms: Antiretroviral Therapy, Highly Active
  5. Han WH, Yong JY, Yong SS, Faheem NAA, Toh YF, Chew MF, et al.
    Australas J Dermatol, 2021 Aug;62(3):286-291.
    PMID: 33729571 DOI: 10.1111/ajd.13580
    INTRODUCTION: The majority of patients with Human Immunodeficiency Virus (HIV) will have cutaneous manifestation during their disease course. We report the spectrum of cutaneous manifestations and clinicopathological concordance in the diagnosis of skin diseases in patients with HIV.

    METHODS: A retrospective review of all cutaneous manifestations of HIV-infected patients with skin biopsy-proven histopathological confirmation, treated in the University of Malaya Medical Centre, from 2016 till 2018, was performed. Clinical characteristics and histopathological correlation of these patients were reviewed.

    RESULTS: A total of 38 cases were included where the median age was 40.5 (interquartile range (IQR) 13.3). The median duration of HIV diagnosis to the development of skin disease was 3 years (IQR 7.8). Majority of our patients were male (89.5%, n = 34), and the commonest mode of transmission is men who have sex with men (36.8%, n = 14). Most patients (92.1%, n = 35) had Acquired Immunodeficiency Syndrome when they presented with skin diseases, predominantly non-infectious types (51.4%, n = 19). Commonest skin diseases include eczema (n = 7) and pruritic papular eruption of HIV (n = 6). Papules and plaques were the commonest morphology for both infectious and non-infectious skin diseases. Duration of HIV diagnosis (P = 0.018) and non-compliance to Highly Active Antiretroviral Therapy (HAART) (P = 0.014) were significantly associated with the development of non-infectious skin diseases. Overall, clinicopathological concordance was 84.2% in our centre.

    CONCLUSION: A wide spectrum of cutaneous diseases can occur in HIV patients depending on the degree of immunosuppression. skin biopsy along with appropriate stains, and microbiological cultures are important in helping clinicians clinch the right diagnosis.

    Matched MeSH terms: Antiretroviral Therapy, Highly Active
  6. Che Nordin MA, Teow SY
    Molecules, 2018 Feb 06;23(2).
    PMID: 29415435 DOI: 10.3390/molecules23020335
    The discovery of highly active antiretroviral therapy (HAART) in 1996 has significantly reduced the global mortality and morbidity caused by the acquired immunodeficiency syndrome (AIDS). However, the therapeutic strategy of HAART that targets multiple viral proteins may render off-target toxicity and more importantly results in drug-resistant escape mutants. These have been the main challenges for HAART and refinement of this therapeutic strategy is urgently needed. Antibody-mediated treatments are emerging therapeutic modalities for various diseases. Most therapeutic antibodies have been approved by Food and Drug Administration (FDA) mainly for targeting cancers. Previous studies have also demonstrated the promising effect of therapeutic antibodies against HIV-1, but there are several limitations in this therapy, particularly when the viral targets are intracellular proteins. The conventional antibodies do not cross the cell membrane, hence, the pathogenic intracellular proteins cannot be targeted with this classical therapeutic approach. Over the years, the advancement of antibody engineering has permitted the therapeutic antibodies to comprehensively target both extra- and intra-cellular proteins in various infections and diseases. This review aims to update on the current progress in the development of antibody-based treatment against intracellular targets in HIV-1 infection. We also attempt to highlight the challenges and limitations in the development of antibody-based therapeutic modalities against HIV-1.
    Matched MeSH terms: Antiretroviral Therapy, Highly Active
  7. 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: Antiretroviral Therapy, Highly Active
  8. Yap SH, Abdullah NK, McStea M, Takayama K, Chong ML, Crisci E, et al.
    PLoS One, 2017;12(10):e0186000.
    PMID: 29016635 DOI: 10.1371/journal.pone.0186000
    BACKGROUND: Co-infections with human herpesvirus (HHV) have been associated with residual chronic inflammation in antiretroviral (ART)-treated human immunodeficiency virus (HIV)-infected individuals. However, the role of HHV in modulating the tryptophan-kynurenine pathway and clinical outcomes in HIV-infected individuals is poorly understood. Thus, we investigated the seroprevalence of four common HHVs among treated HIV-infected participants and their impact on kynurenine/tryptophan (K/T) ratio and long-term CD4 T-cell recovery in HIV/HHV co-infected participants.

    METHOD: In this cross-sectional study, HIV-infected participants receiving suppressive ART for a minimum of 12 months were recruited from the University Malaya Medical Centre (UMMC), Malaysia. Stored plasma was analyzed for CMV, VZV, HSV-1 and HSV-2 IgG antibody levels, immune activation markers (interleukin-6, interferon-γ, neopterin and sCD14), kynurenine and tryptophan concentrations. The influence of the number of HHV co-infection and K/T ratio on CD4 T-cell recovery was assessed using multivariate Poisson regression.

    RESULTS: A total of 232 HIV-infected participants were recruited and all participants were seropositive for at least one HHV; 96.1% with CMV, 86.6% with VZV, 70.7% with HSV-1 and 53.9% with HSV-2. K/T ratio had a significant positive correlation with CMV (rho = 0.205, p = 0.002), VZV (rho = 0.173, p = 0.009) and a tendency with HSV-2 (rho = 0.120, p = 0.070), with CMV antibody titer demonstrating the strongest modulating effect on K/T ratio among the four HHVs assessed in SOM analysis. In multivariate analysis, higher K/T ratio (p = 0.03) and increasing number of HHV co-infections (p<0.001) were independently associated with poorer CD4 T-cell recovery following 12 months of ART initiation.

    CONCLUSION: Multiple HHV co-infections are common among ART-treated HIV-infected participants in the developing country setting and associated with persistent immune activation and poorer CD4 T-cell recovery.

    Matched MeSH terms: Antiretroviral Therapy, Highly Active
  9. Boyd MA, Amin J, Mallon PW, Kumarasamy N, Lombaard J, Wood R, et al.
    Lancet HIV, 2017 01;4(1):e13-e20.
    PMID: 27815068 DOI: 10.1016/S2352-3018(16)30189-8
    BACKGROUND: Lipoatrophy is one of the most feared complications associated with the use of nucleoside or nucleotide reverse transcriptase inhibitors (N[t]RTIs). We aimed to assess soft-tissue changes in participants with HIV who had virological failure of a first-line antiretroviral (ART) regimen containing a non-nucleoside reverse transcriptase inhibitor plus two N(t)RTIs and were randomly assigned to receive a second-line regimen containing a boosted protease inhibitor given with either N(t)RTIs or raltegravir.

    METHODS: Of the 37 sites that participated in the randomised, open-label, non-inferiority SECOND-LINE study, eight sites from five countries (Argentina, India, Malaysia, South Africa, and Thailand) participated in the body composition substudy. All sites had a dual energy x-ray absorptiometry (DXA) scanner and all participants enrolled in SECOND-LINE were eligible for inclusion in the substudy. Participants were randomly assigned (1:1), via a computer-generated allocation schedule, to receive either ritonavir-boosted lopinavir plus raltegravir (raltegravir group) or ritonavir-boosted lopinavir plus two or three N(t)RTIs (N[t]RTI group). Randomisation was stratified by site and screening HIV-1 RNA. Participants and investigators were not masked to group assignment, but allocation was concealed until after interventions were assigned. DXA scans were done at weeks 0, 48, and 96. The primary endpoint was mean percentage and absolute change in peripheral limb fat from baseline to week 96. We did intention-to-treat analyses of available data. This substudy is registered with ClinicalTrials.gov, number NCT01513122.

    FINDINGS: Between Aug 1, 2010, and July 10, 2011, we recruited 211 participants into the substudy. The intention-to-treat population comprised 102 participants in the N(t)RTI group and 108 participants in the raltegravir group, of whom 91 and 105 participants, respectively, reached 96 weeks. Mean percentage change in limb fat from baseline to week 96 was 16·8% (SD 32·6) in the N(t)RTI group and 28·0% (37·6) in the raltegravir group (mean difference 10·2%, 95% CI 0·1-20·4; p=0·048). Mean absolute change was 1·04 kg (SD 2·29) in the N(t)RTI group and 1·81 kg (2·50) in the raltegravir group (mean difference 0·6, 95% CI -0·1 to 1·3; p=0·10).

    INTERPRETATION: Our findings suggest that for people with virological failure of a first-line regimen containing efavirenz plus tenofovir and lamivudine or emtricitabine, the WHO-recommended switch to a ritonavir-boosted protease inhibitor plus zidovudine (a thymidine analogue nucleoside reverse transcriptase inhibitor) and lamivudine might come at the cost of peripheral lipoatrophy. Further study could help to define specific groups of people who might benefit from a switch to an N(t)RTI-sparing second-line ART regimen.

    FUNDING: The Kirby Institute and the Australian National Health and Medical Research Council.

    Matched MeSH terms: Antiretroviral Therapy, Highly Active
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