Displaying publications 101 - 120 of 122 in total

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  1. 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-1/drug effects*; HIV-1/physiology*
  2. Pham MD, Haile BA, Azwa I, Kamarulzaman A, Raman N, Saeidi A, et al.
    J Clin Microbiol, 2019 04;57(4).
    PMID: 30700508 DOI: 10.1128/JCM.01683-18
    HIV viral load (VL) testing is the recommended method for monitoring the response of people living with HIV and receiving antiretroviral therapy (ART). The availability of standard plasma VL testing in low- and middle-income countries (LMICs), and access to this testing, are limited by the need to use fresh plasma. Good specimen collection methods for HIV VL testing that are applicable to resource-constrained settings are needed. We assessed the diagnostic performance of the filtered dried plasma spot (FDPS), created using the newly developed, instrument-free VLPlasma device, in identifying treatment failure at a VL threshold of 1,000 copies/ml in fresh plasma. Performance was compared with that of the conventional dried blood spot (DBS). Venous blood samples from 201 people living with HIV and attending an infectious disease clinic in Malaysia were collected, and HIV VL was quantified using fresh plasma (the reference standard), FDPS, and DBS specimens. VL testing was done using the Roche Cobas AmpliPrep/Cobas TaqMan v2.0 assay. At a threshold of 1,000 copies/ml, the diagnostic performance of the FDPS was superior (sensitivity, 100% [95% confidence interval {CI}, 89.1 to 100%]; specificity, 100% [95% CI, 97.8 to 100%]) to that of the DBS (sensitivity, 100% [95% CI, 89.4 to 100%]; specificity, 36.8% [95% CI, 29.4 to 44.7%]) (P HIV VL measurement using the FDPS outperformed that with the DBS in identifying treatment failure at a threshold of 1,000 copies/ml and compared well with the quantification of VL in plasma. The FDPS can be an attractive alternative to fresh plasma for improving access to HIV VL monitoring among people living with HIV on ART in LMICs.
    Matched MeSH terms: HIV-1/genetics; HIV-1/isolation & purification*
  3. Kariminia A, Durier N, Jourdain G, Saghayam S, Do CV, Nguyen LV, et al.
    J Acquir Immune Defic Syndr, 2014 Sep 01;67(1):71-6.
    PMID: 24872132 DOI: 10.1097/QAI.0000000000000227
    OBJECTIVE: To evaluate the value of time-updated weight and height in predicting clinical progression, and immunological and virological failure in children receiving combination antiretroviral therapy (cART).

    METHODS: We used Cox regression to analyze data of a cohort of Asian children.

    RESULTS: A total of 2608 children were included; median age at cART was 5.7 years. Time-updated weight for age z score < -3 was associated with mortality (P < 0.001) independent of CD4% and < -2 was associated with immunological failure (P ≤ 0.03) independent of age at cART.

    CONCLUSIONS: Weight monitoring provides useful data to inform clinical management of children on cART in resource-limited settings.

    Matched MeSH terms: HIV-1/isolation & purification*
  4. Meyer JP, Cepeda J, Wu J, Trestman RL, Altice FL, Springer SA
    JAMA Intern Med, 2014 May;174(5):721-9.
    PMID: 24687044 DOI: 10.1001/jamainternmed.2014.601
    Human immunodeficiency virus (HIV) management in correctional settings is logistically feasible, but HIV-related outcomes before release have not been recently systematically examined.
    Matched MeSH terms: HIV-1/isolation & purification*
  5. Mohamad S, Deris ZZ, Yusoff NK, Ariffin TA, Shueb RH
    Braz J Infect Dis, 2012 May-Jun;16(3):284-8.
    PMID: 22729198
    Antiretroviral (ARV) therapy has dramatically reduced morbidity and mortality in human immunodeficiency virus 1 (HIV-1) infected children. However, development of ARV resistance in these children is a major public health problem due to lack of availability of and access to new drugs. This study was conducted in order to identify circulating HIV subtypes and recombinant forms and evaluate the drug resistance mutation patterns in 18 HIV-1 infected children failing ARV treatment in Kelantan, Malaysia. Genotyping for codon 1-99 of protease (PR) and 1-250 of reverse transcriptase (RT) were performed by polymerase chain reaction (PCR) amplification and DNA sequencing. Subsequently, these were phylogenetically analyzed to determine the subtypes. CRF33_01B (44.4%) was found to be the predominant HIV subtype, followed by B (27.8%), CRF15_01B (16.7%) and CRF01_AE (11.1%) subtypes. The most prevalent RT mutations were T215F/V/Y (66.7%), D67G/N (55.6%), K219Q/E/R (44.4%), M184V/I (38.9%), K70R/E (27.8%) and M41L (27.8%), associated with nucleoside reverse transcriptase inhibitors (NRTI) resistance; and K103N (55.6%), G190A (33.3%), and K101P/E/H (27.8%) associated with non-nucleoside reverse transcriptase inhibitors (NNRTI) resistance. The results showed a possible emergence of CRF33_01B as current predominant subtypes/circulating recombinant forms (CRFs), and a high frequency of primary mutations among HIV-1 infected children after failure of ARV therapy in Kelantan, Malaysia.
    Matched MeSH terms: HIV-1/genetics*
  6. Cain LE, Phillips A, Lodi S, Sabin C, Bansi L, Justice A, et al.
    AIDS, 2012 Aug 24;26(13):1691-705.
    PMID: 22546987
    OBJECTIVE: To compare regimens consisting of either efavirenz or nevirapine and two or more nucleoside reverse transcriptase inhibitors (NRTIs) among HIV-infected, antiretroviral-naive, and AIDS-free individuals with respect to clinical, immunologic, and virologic outcomes.

    DESIGN: Prospective studies of HIV-infected individuals in Europe and the US included in the HIV-CAUSAL Collaboration.

    METHODS: Antiretroviral therapy-naive and AIDS-free individuals were followed from the time they started an NRTI, efavirenz or nevirapine, classified as following one or both types of regimens at baseline, and censored when they started an ineligible drug or at 6 months if their regimen was not yet complete. We estimated the 'intention-to-treat' effect for nevirapine versus efavirenz regimens on clinical, immunologic, and virologic outcomes. Our models included baseline covariates and adjusted for potential bias introduced by censoring via inverse probability weighting.

    RESULTS: A total of 15 336 individuals initiated an efavirenz regimen (274 deaths, 774 AIDS-defining illnesses) and 8129 individuals initiated a nevirapine regimen (203 deaths, 441 AIDS-defining illnesses). The intention-to-treat hazard ratios [95% confidence interval (CI)] for nevirapine versus efavirenz regimens were 1.59 (1.27, 1.98) for death and 1.28 (1.09, 1.50) for AIDS-defining illness. Individuals on nevirapine regimens experienced a smaller 12-month increase in CD4 cell count by 11.49 cells/μl and were 52% more likely to have virologic failure at 12 months as those on efavirenz regimens.

    CONCLUSIONS: Our intention-to-treat estimates are consistent with a lower mortality, a lower incidence of AIDS-defining illness, a larger 12-month increase in CD4 cell count, and a smaller risk of virologic failure at 12 months for efavirenz compared with nevirapine.

    Matched MeSH terms: HIV-1/drug effects*
  7. Lodi S, Phillips A, Logan R, Olson A, Costagliola D, Abgrall S, et al.
    Lancet HIV, 2015 Aug;2(8):e335-43.
    PMID: 26423376 DOI: 10.1016/S2352-3018(15)00108-3
    BACKGROUND: Recommendations have differed nationally and internationally with respect to the best time to start antiretroviral therapy (ART). We compared effectiveness of three strategies for initiation of ART in high-income countries for HIV-positive individuals who do not have AIDS: immediate initiation, initiation at a CD4 count less than 500 cells per μL, and initiation at a CD4 count less than 350 cells per μL.

    METHODS: We used data from the HIV-CAUSAL Collaboration of cohort studies in Europe and the USA. We included 55,826 individuals aged 18 years or older who were diagnosed with HIV-1 infection between January, 2000, and September, 2013, had not started ART, did not have AIDS, and had CD4 count and HIV-RNA viral load measurements within 6 months of HIV diagnosis. We estimated relative risks of death and of death or AIDS-defining illness, mean survival time, the proportion of individuals in need of ART, and the proportion of individuals with HIV-RNA viral load less than 50 copies per mL, as would have been recorded under each ART initiation strategy after 7 years of HIV diagnosis. We used the parametric g-formula to adjust for baseline and time-varying confounders.

    FINDINGS: Median CD4 count at diagnosis of HIV infection was 376 cells per μL (IQR 222-551). Compared with immediate initiation, the estimated relative risk of death was 1·02 (95% CI 1·01-1·02) when ART was started at a CD4 count less than 500 cells per μL, and 1·06 (1·04-1·08) with initiation at a CD4 count less than 350 cells per μL. Corresponding estimates for death or AIDS-defining illness were 1·06 (1·06-1·07) and 1·20 (1·17-1·23), respectively. Compared with immediate initiation, the mean survival time at 7 years with a strategy of initiation at a CD4 count less than 500 cells per μL was 2 days shorter (95% CI 1-2) and at a CD4 count less than 350 cells per μL was 5 days shorter (4-6). 7 years after diagnosis of HIV, 100%, 98·7% (95% CI 98·6-98·7), and 92·6% (92·2-92·9) of individuals would have been in need of ART with immediate initiation, initiation at a CD4 count less than 500 cells per μL, and initiation at a CD4 count less than 350 cells per μL, respectively. Corresponding proportions of individuals with HIV-RNA viral load less than 50 copies per mL at 7 years were 87·3% (87·3-88·6), 87·4% (87·4-88·6), and 83·8% (83·6-84·9).

    INTERPRETATION: The benefits of immediate initiation of ART, such as prolonged survival and AIDS-free survival and increased virological suppression, were small in this high-income setting with relatively low CD4 count at HIV diagnosis. The estimated beneficial effect on AIDS is less than in recently reported randomised trials. Increasing rates of HIV testing might be as important as a policy of early initiation of ART.

    FUNDING: National Institutes of Health.

    Matched MeSH terms: HIV-1/genetics
  8. Ellegård R, Khalid M, Svanberg C, Holgersson H, Thorén Y, Wittgren MK, et al.
    Front Immunol, 2018;9:899.
    PMID: 29760706 DOI: 10.3389/fimmu.2018.00899
    Dendritic cells (DCs), natural killer (NK) cells, and T cells play critical roles during primary HIV-1 exposure at the mucosa, where the viral particles become coated with complement fragments and mucosa-associated antibodies. The microenvironment together with subsequent interactions between these cells and HIV at the mucosal site of infection will determine the quality of immune response that ensues adaptive activation. Here, we investigated how complement and immunoglobulin opsonization influences the responses triggered in DCs and NK cells, how this affects their cross talk, and what T cell phenotypes are induced to expand following the interaction. Our results showed that DCs exposed to complement-opsonized HIV (C-HIV) were less mature and had a poor ability to trigger IFN-driven NK cell activation. In addition, when the DCs were exposed to C-HIV, the cytotolytic potentials of both NK cells and CD8 T cells were markedly suppressed. The expression of PD-1 as well as co-expression of negative immune checkpoints TIM-3 and LAG-3 on PD-1 positive cells were increased on both CD4 as well as CD8 T cells upon interaction with and priming by NK-DC cross talk cultures exposed to C-HIV. In addition, stimulation by NK-DC cross talk cultures exposed to C-HIV led to the upregulation of CD38, CXCR3, and CCR4 on T cells. Together, the immune modulation induced during the presence of complement on viral surfaces is likely to favor HIV establishment, dissemination, and viral pathogenesis.
    Matched MeSH terms: HIV-1/immunology*
  9. 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: HIV-1/enzymology*
  10. William T, Parameswaran U, Lee WK, Yeo TW, Anstey NM, Ralph AP
    BMC Infect Dis, 2015;15:32.
    PMID: 25636334 DOI: 10.1186/s12879-015-0758-6
    BACKGROUND: Tuberculosis (TB) is generally well controlled in Malaysia, but remains an important problem in the nation's eastern states. In order to better understand factors contributing to high TB rates in the eastern state of Sabah, our aims were to describe characteristics of patients with TB at a large outpatient clinic, and determine the prevalence of HIV co-infection. Additionally, we sought to test sensitivity and specificity of the locally-available point-of-care HIV test kits.
    METHODS: We enrolled consenting adults with smear-positive pulmonary TB for a 2-year period at Luyang Clinic, Kota Kinabalu, Malaysia. Participants were questioned about ethnicity, smoking, prior TB, disease duration, symptoms and comorbidities. Chest radiographs were scored using a previously devised tool. HIV was tested after counselling using 2 point-of-care tests for each patient: the test routinely in use at the TB clinic (either Advanced Quality™ Rapid Anti-HIV 1&2, FACTS anti-HIV 1/2 RAPID or HIV (1 + 2) Antibody Colloidal Gold), and a comparator test (Abbott Determine™ HIV-1/2, Inverness Medical). Positive tests were confirmed by enzyme immunoassay (EIA), particle agglutination and line immunoassay.
    RESULTS: 176 participants were enrolled; 59 (33.5%) were non-Malaysians and 104 (59.1%) were male. Smoking rates were high (81/104 males, 77.9%), most had cavitary disease (51/145, 64.8%), and 81/176 (46.0%) had haemoptysis. The median period of symptoms prior to treatment onset was 8 weeks. Diabetes was present in 12. People with diabetes or other comorbidities had less severe TB, suggesting different healthcare seeking behaviours in this group. All participants consented to HIV testing: three (1.7%) were positive according to Determine™ and EIA, but one of these tested negative on the point-of-care test available at the clinic (Advanced Quality™ Rapid Anti-HIV 1&2). The low number of positive tests and changes in locally-available test type meant that accurate estimates of sensitivity and specificity were not possible.
    CONCLUSION: Patients had advanced disease at diagnosis, long diagnostic delays, low HIV co-infection rates, high smoking rates among males, and migrants may be over-represented. These findings provide important insights to guide local TB control efforts. Caution is required in using some point-of-care HIV tests, and ongoing quality control measures are of major importance.
    Study site: Klinik Kesihatan Luyang (Tuberculosis Clinic), Kota Kinabalu, Sabah, Malaysia,
    Matched MeSH terms: HIV-1/isolation & purification*
  11. Teow SY, Ali SA
    Pak J Pharm Sci, 2016 Nov;29(6):2119-2124.
    PMID: 28375134
    Peptides derived from HIV-1 transmembrane proteins have been extensively studied for antimicrobial activities, and they are known as antimicrobial peptides (AMPs). These AMPs have also been reported to potently combat the drug-resistant microbes. In this study, we demonstrated that peptide #6383 originated from HIV-1 MN strain membrane-spanning domain of gp41 was active (2-log reductions) at 100βg/mL (56.5βM) against methicillin-resistant Staphylococcus aureus (MRSA) in 10% and 50% human plasma-supplemented phosphate buffered saline (PBS). The activity was further enhanced (3-log reductions) in the presence of 5% human serum albumin (HSA) alone. All bactericidal activities were achieved within 6 hours. At 100μg/mL, the peptide showed only 13% toxicity against human erythrocytes. This peptide can serve as an attractive template for a design of a novel peptide antibiotic against drug-resistant bacteria. By sequence-specific engineering or modifications, we anticipated that the bactericidal activity and the reduced toxicity against human erythrocytes will be improved.
    Matched MeSH terms: HIV-1/chemistry*
  12. Covés-Datson EM, King SR, Legendre M, Swanson MD, Gupta A, Claes S, et al.
    Sci Rep, 2021 01 12;11(1):656.
    PMID: 33436903 DOI: 10.1038/s41598-020-80577-7
    Lectins, carbohydrate-binding proteins, have been regarded as potential antiviral agents, as some can bind glycans on viral surface glycoproteins and inactivate their functions. However, clinical development of lectins has been stalled by the mitogenicity of many of these proteins, which is the ability to stimulate deleterious proliferation, especially of immune cells. We previously demonstrated that the mitogenic and antiviral activities of a lectin (banana lectin, BanLec) can be separated via a single amino acid mutation, histidine to threonine at position 84 (H84T), within the third Greek key. The resulting lectin, H84T BanLec, is virtually non-mitogenic but retains antiviral activity. Decreased mitogenicity was associated with disruption of pi-pi stacking between two aromatic amino acids. To examine whether we could provide further proof-of-principle of the ability to separate these two distinct lectin functions, we identified another lectin, Malaysian banana lectin (Malay BanLec), with similar structural features as BanLec, including pi-pi stacking, but with only 63% amino acid identity, and showed that it is both mitogenic and potently antiviral. We then engineered an F84T mutation expected to disrupt pi-pi stacking, analogous to H84T. As predicted, F84T Malay BanLec (F84T) was less mitogenic than wild type. However, F84T maintained strong antiviral activity and inhibited replication of HIV, Ebola, and other viruses. The F84T mutation disrupted pi-pi stacking without disrupting the overall lectin structure. These findings show that pi-pi stacking in the third Greek key is a conserved mitogenic motif in these two jacalin-related lectins BanLec and Malay BanLec, and further highlight the potential to rationally engineer antiviral lectins for therapeutic purposes.
    Matched MeSH terms: HIV-1/drug effects
  13. Bhattacharya P, Ellegård R, Khalid M, Svanberg C, Govender M, Keita ÅV, et al.
    Elife, 2020 Sep 02;9.
    PMID: 32876566 DOI: 10.7554/eLife.57869
    HIV transmission via genital and colorectal mucosa are the most common routes of dissemination. Here, we explored the effects of free and complement-opsonized HIV on colorectal tissue. Initially, there was higher antiviral responses in the free HIV compared to complement-opsonized virus. The mucosal transcriptional response at 24 hr revealed the involvement of activated T cells, which was mirrored in cellular responses observed at 96 hr in isolated mucosal T cells. Further, HIV exposure led to skewing of T cell phenotypes predominantly to inflammatory CD4+ T cells, that is Th17 and Th1Th17 subsets. Of note, HIV exposure created an environment that altered the CD8+ T cell phenotype, for example expression of regulatory factors, especially when the virions were opsonized with complement factors. Our findings suggest that HIV-opsonization alters the activation and signaling pathways in the colorectal mucosa, which promotes viral establishment by creating an environment that stimulates mucosal T cell activation and inflammatory Th cells.
    Matched MeSH terms: HIV-1/immunology*
  14. Nasiri S, Barat T, Bidari-Zerehpoosh F, Mozafari N
    Malays Fam Physician, 2020;15(2):30-33.
    PMID: 32843942
    Atypical forms of herpes simplex virus (HSV) infections, which indicate severe impairment of cellular immunity can be challenging to diagnose. In this paper, we report the case of an atypical HSV infection presenting as chronic nonhealing wounds, which are the first sign of HIV, in a 50-year-old female patient. The lesions had emerged as two large, chronic, and painful ulcerations on the left buttock and labia major 8 months prior. The skin biopsy revealed multinucleated keratinocytes with ground glass nuclei and intranuclear Cowdry type A viral inclusions. A serologic test for HIV-1 was positive. Her CD4+ T-cell count was 42/mm3. Clinicians should be familiar with the dermatologic manifestations of HIV, as they are occasionally key to correctly suspecting an underlying HIV infection, allowing for early diagnosis and treatment.
    Matched MeSH terms: HIV-1
  15. Zain RM, Ibrahim N, Ismail S, Suppiah J, Mat Rahim NA, Thayan R
    Asian Pac J Trop Med, 2017 Jan;10(1):75-78.
    PMID: 28107870 DOI: 10.1016/j.apjtm.2016.12.005
    OBJECTIVE: To determine drug resistance mutations and the HIV-1 subtypes among antiretroviral treatment naive HIV-1 patients in Peninsular Malaysia.

    METHODS: A total of 45 samples from four hospitals that provide HIV viral load services were subjected to the amplification of the protease and two third of reverse transcriptase regions of the pol gene by RT-PCR and Sanger sequencing. Drug resistance mutation (DRM) interpretation reports the presence of mutations related to protease inhibitors (PIs), Nucleoside reverse-transcriptase inhibitors (NRTI) and Non-nucleoside reverse-transcriptase inhibitors (NNRTI) based on analysis using Stanford HIV database program.

    RESULTS: DRMs were identified in 35% of patients, among which 46.7% of them showed minor resistance to protease inhibitor with A71V and L10l were the commonest DRMs detected. About 21.4% and 50.0% of patients had mutations to NRTIs and NNRTIs, respectively. CRF01_AE was found to be the predominant HIV-1 subtype.

    CONCLUSIONS: These findings have served as an initial crucial data in determining the prevalence of transmitted HIV-1 drug resistance for the country. However, more samples from various parts of the country need to be accumulated and analyzed to provide overall HIV-1 drug resistance in the country.

    Matched MeSH terms: HIV-1
  16. 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-1/immunology
  17. 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-1/isolation & purification
  18. Sudjaritruk T, Teeraananchai S, Kariminia A, Lapphra K, Kumarasamy N, Fong MS, et al.
    J Int AIDS Soc, 2020 Jul;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: HIV-1
  19. Lim SH, Mburu G, Bourne A, Pang J, Wickersham JA, Wei CKT, et al.
    PLoS One, 2017;12(9):e0182838.
    PMID: 28902857 DOI: 10.1371/journal.pone.0182838
    OBJECTIVE: We examined willingness to use pre-exposure prophylaxis (PrEP) for HIV prevention among men who have sex with men (MSM) in Malaysia.

    METHODS: An online survey of 990 MSM was conducted between March and April 2016. Eligibility criteria included being biological male, Malaysian citizen, 18 years of age or above, identifying as MSM, and being HIV negative or unknown status. Participants' demographics, sexual and drug use behaviors, attitudes towards PrEP, and preferences regarding future access to PrEP were collected. Bivariate analysis and logistic regression were performed to determine factors associated with willingness to use PrEP.

    RESULTS: Fewer than half of participants (44%) knew about PrEP before completing the survey. Overall, 39% of the sample were willing to take PrEP. Multivariate logistic regression indicated that Malay men (AOR: 1.73, 95% CI:1.12, 2.70), having 2 or more male anal sex partners in the past 6 months (AOR: 1.98, 95% CI: 1.29, 3.05), previous knowledge of PrEP (AOR: 1.40, 95%CI: 1.06, 1.86), lack of confidence in practising safer sex (AOR: 1.36, 95% CI: 1.02, 1.81), and having ever paid for sex with a male partner (AOR: 1.39, 95% CI: 1.01, 1.91) were independently associated with greater willingness to use PrEP, while men who identified as heterosexual were less willing to use PrEP (AOR, 0.36, 95% CI: 0.13, 0.97). Majority of participants preferred to access PrEP at affordable cost below 100 Malaysian Ringgit (USD25) per month from community based organisations followed by private or government hospitals.

    CONCLUSIONS: Overall, MSM in Malaysia reported a relatively low level of willingness to use PrEP, although willingness was higher among those previously aware of PrEP. There is a need to provide PrEP at affordable cost, increase demand and awareness of PrEP, and to provide access to this preventative medication via diverse, integrated and tailored sexual health services.

    Matched MeSH terms: HIV-1
  20. Cale EM, Gorman J, Radakovich NA, Crooks ET, Osawa K, Tong T, et al.
    Immunity, 2017 05 16;46(5):777-791.e10.
    PMID: 28514685 DOI: 10.1016/j.immuni.2017.04.011
    Most HIV-1-specific neutralizing antibodies isolated to date exhibit unusual characteristics that complicate their elicitation. Neutralizing antibodies that target the V1V2 apex of the HIV-1 envelope (Env) trimer feature unusually long protruding loops, which enable them to penetrate the HIV-1 glycan shield. As antibodies with loops of requisite length are created through uncommon recombination events, an alternative mode of apex binding has been sought. Here, we isolated a lineage of Env apex-directed neutralizing antibodies, N90-VRC38.01-11, by using virus-like particles and conformationally stabilized Env trimers as B cell probes. A crystal structure of N90-VRC38.01 with a scaffolded V1V2 revealed a binding mode involving side-chain-to-side-chain interactions that reduced the distance the antibody loop must traverse the glycan shield, thereby facilitating V1V2 binding via a non-protruding loop. The N90-VRC38 lineage thus identifies a solution for V1V2-apex binding that provides a more conventional B cell pathway for vaccine design.
    Matched MeSH terms: HIV-1/immunology*
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