MyMedR

Displaying publications 61 - 80 of 121 in total

Abstract:

Sort:

Fulltext Discovery of HIV entry inhibitors via a hybrid CXCR4 and CCR5 receptor pharmacophore-based virtual screening approach

Mirza MU, Saadabadi A, Vanmeert M, Salo-Ahen OMH, Abdullah I, Claes S, et al.

Eur J Pharm Sci, 2020 Dec 01;155:105537.
PMID: 32890663 DOI: 10.1016/j.ejps.2020.105537

Chemokine receptors are key regulators of cell migration in terms of immunity and inflammation. Among these, CCR5 and CXCR4 play pivotal roles in cancer metastasis and HIV-1 transmission and infection. They act as essential co-receptors for HIV and furnish a route to the cell entry. In particular, inhibition of either CCR5 or CXCR4 leads very often the virus to shift to a more virulent dual-tropic strain. Therefore, dual receptor inhibition might improve the therapeutic strategies against HIV. In this study, we aimed to discover selective CCR5, CXCR4, and dual CCR5/CXCR4 antagonists using both receptor- and ligand-based computational methods. We employed this approach to fully incorporate the interaction attributes of the binding pocket together with molecular dynamics (MD) simulations and binding free energy calculations. The best hits were evaluated for their anti-HIV-1 activity against CXCR4- and CCR5-specific NL4.3 and BaL strains. Moreover, the Ca2+ mobilization assay was used to evaluate their antagonistic activity. From the 27 tested compounds, three were identified as inhibitors: compounds 27 (CCR5), 6 (CXCR4) and 3 (dual) with IC50 values ranging from 10.64 to 64.56 μM. The binding mode analysis suggests that the active compounds form a salt bridge with the glutamates and π-stacking interactions with the aromatic side chains binding site residues of the respective co-receptor. The presented hierarchical virtual screening approach provides essential aspects in identifying potential antagonists in terms of selectivity against a specific co-receptor. The compounds having multiple heterocyclic nitrogen atoms proved to be relatively more specific towards CXCR4 inhibition as compared to CCR5. The identified compounds serve as a starting point for further development of HIV entry inhibitors through synthesis and quantitative structure-activity relationship studies.

Matched MeSH terms: HIV-1*
Fulltext Assessing subtypes and drug resistance mutations among HIV-1 infected children who failed antiretroviral therapy in Kelantan, Malaysia

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*
Fulltext Engineering and Validation of a Vector for Concomitant Expression of Rare Transfer RNA (tRNA) and HIV-1 nef Genes in Escherichia coli

Mualif SA, Teow SY, Omar TC, Chew YW, Yusoff NM, Ali SA

PLoS One, 2015;10(7):e0130446.
PMID: 26147991 DOI: 10.1371/journal.pone.0130446

Relative ease in handling and manipulation of Escherichia coli strains make them primary candidate to express proteins heterologously. Overexpression of heterologous genes that contain codons infrequently used by E. coli is related with difficulties such as mRNA instability, early termination of transcription and/or translation, deletions and/or misincorporation, and cell growth inhibition. These codon bias -associated problems are addressed by co-expressing ColE1-compatible, rare tRNA expressing helper plasmids. However, this approach has inadequacies, which we have addressed by engineering an expression vector that concomitantly expresses the heterologous protein of interest, and rare tRNA genes in E. coli. The expression vector contains three (argU, ileY, leuW) rare tRNA genes and a useful multiple cloning site for easy in-frame cloning. To maintain the overall size of the parental plasmid vector, the rare tRNA genes replaced the non-essential DNA segments in the vector. The cloned gene is expressed under the control of T7 promoter and resulting recombinant protein has a C-terminal 6His tag for IMAC-mediated purification. We have evaluated the usefulness of this expression vector by expressing three HIV-1 genes namely HIV-1 p27 (nef), HIV-1 p24 (ca), and HIV-1 vif in NiCo21(DE3) E.coli and demonstrated the advantages of using expression vector that concomitantly expresses rare tRNA and heterologous genes.

Matched MeSH terms: HIV-1/genetics
Three different patterns of CD4 recovery in a cohort of Chinese HIV patients following antiretroviral therapy - a five-year observational study

Naftalin CM, Wong NS, Chan DP, Wong KH, Reidpath DD, Lee SS

Int J STD AIDS, 2015 Oct;26(11):803-9.
PMID: 25281539 DOI: 10.1177/0956462414553826

To explore the heterogeneity of CD4 responses following highly active antiretroviral therapy, the patterns of CD4 recovery of HIV-1-infected Chinese patients who have been on their first antiretroviral regimen for ≥5 years were analysed. The CD4 trajectories were traced, smoothed and differentiated into three defined profiles. Half (56.3%) were 'satisfactory responders', with CD4 gain of >100 cells/μL and a peak of >350 cells/μL, plateauing before the end of Year 5. Thirty-three (24.4%) were 'continuing responders' whose CD4 rise persisted at Year 4-5. The remaining 26 (19.3%) were 'poor responders'. Presentation with AIDS before therapy was common not just among 'poor' but also paradoxically the 'continuing' responders. While a majority had responded well to antiretroviral therapy, older patients and those with AIDS diagnosis before initiation of therapy may never achieve a satisfactory level even with effective treatment. Categorization of HIV patients by their CD4 trajectory may support the prediction of immunological outcome over time, and ultimately inform treatment choices.

Matched MeSH terms: HIV-1/drug effects*; HIV-1/immunology
Broad neutralization response in a subset of HIV-1 subtype C-infected viraemic non-progressors from southern India

Nandagopal P, Bhattacharya J, Srikrishnan AK, Goyal R, Ravichandran Swathirajan C, Patil S, et al.

J Gen Virol, 2018 Mar;99(3):379-392.
PMID: 29458681 DOI: 10.1099/jgv.0.001016

Broadly neutralizing antibodies (bnAbs) have been considered to be potent therapeutic tools and potential vaccine candidates to enable protection against various clades of human immunodeficiency virus (HIV). The generation of bnAbs has been associated with enhanced exposure to antigen, high viral load and low CD4+ T cell counts, among other factors. However, only limited data are available on the generation of bnAbs in viraemic non-progressors that demonstrate moderate to high viraemia. Further, since HIV-1 subtype C viruses account for more than 50 % of global HIV infections, the identification of bnAbs with novel specificities is crucial to enable the development of potent tools to aid in HIV therapy and prevention. In the present study, we analysed and compared the neutralization potential of responses in 70 plasma samples isolated from ART-naïve HIV-1 subtype C-infected individuals with various disease progression profiles against a panel of 30 pseudoviruses. Among the seven samples that exhibited a neutralization breadth of ≥70 %, four were identified as 'elite neutralizers', and three of these were from viraemic non-progressors while the fourth was from a typical progressor. Analysis of the neutralization specificities revealed that none of the four elite neutralizers were reactive to epitopes in the membrane proximal external region (MPER), CD4-binding site and V1V2 or V3 glycan. However, two of the four elite neutralizers exhibited enhanced sensitivity towards viruses lacking N332 glycan, indicating high neutralization potency. Overall, our findings indicate that the identification of potent neutralization responses with distinct epitope specificities is possible from the as yet unexplored Indian population, which has a high prevalence of HIV-1 subtype C infection.

Matched MeSH terms: HIV-1
Chronic non-healing ulcers as presenting sign of acquired immunodeficiency syndrome

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
Fulltext A seroprevalence study of viral hepatitis E infection in human immunodeficiency virus type 1 infected subjects in Malaysia

Ng KP, He J, Saw TL, Lyles CM

Med J Malaysia, 2000 Mar;55(1):58-64.
PMID: 11072492 MyJurnal

Hepatitis E virus (HEV) is a RNA virus transmitted enterically. A study of anti-HEV antibodies in 145 human immunodeficiency virus type 1 (HIV-1) infected subjects found that 14.4% of them were reactive to anti-HEV antibodies. Anti-HEV IgG and anti-HEV IgM was detected in 10.3% and 4.1% of the subjects respectively. Prevalence of anti-HEV (either IgG or IgM) was similar across all adult ages (p = 0.154), between the three ethnic groups (p = 0.378), and across risk groups (p = 0.120). The results showed that HEV infection in subjects recruited in this study was most likely transmitted via faecal-route.

Matched MeSH terms: HIV-1*
Evaluation of a rapid test for the detection of antibodies to human immunodeficiency virus type 1 and 2

Ng KP, Saw TL, Baki A, He J, Singh N, Lyles CM

Int J STD AIDS, 1999 Jun;10(6):401-4.
PMID: 10414883

Hema-Strip HIV-1/2 is a one-step rapid test for the detection of anti-HIV-1/2 antibodies in whole blood. The test requires no expensive equipment and the results are available within 10-15 min. Using 72 known HIV-1 positive samples and 780 high-risk prisoners, the sensitivity and specificity of Hema-Strip HIV-1/2 was found to be comparable to microparticle enzyme immunoassay (MEIA). The data also indicated that Hema-Strip HIV-1/2 is an effective alternate testing system to conventional ELISA where the use of ELISA is not suitable and the result of the HIV testing is needed urgently.

Matched MeSH terms: HIV-1/immunology*
Fulltext HIV-1 transmission networks among men who have sex with men in Asia

Ng KT, Ng KY, Chen JH, Ng OT, Kamarulzaman A, Tee KK

Clin Infect Dis, 2014 Sep 15;59(6):910-1.
PMID: 24944233 DOI: 10.1093/cid/ciu480
Matched MeSH terms: HIV-1*
Fulltext Phylodynamic profile of HIV-1 subtype B, CRF01_AE and the recently emerging CRF51_01B among men who have sex with men (MSM) in Singapore

Ng KT, Ng KY, Khong WX, Chew KK, Singh PK, Yap JK, et al.

PLoS One, 2013;8(12):e80884.
PMID: 24312505 DOI: 10.1371/journal.pone.0080884

HIV-1 subtype B and CRF01_AE are the predominant infecting subtypes among men who have sex with men (MSM) in Singapore. The genetic history, population dynamics and pattern of transmission networks of these genotypes remain largely unknown. We delineated the phylodynamic profiles of HIV-1 subtype B, CRF01_AE and the recently characterized CRF51_01B strains circulating among the MSM population in Singapore. A total of 105 (49.5%) newly-diagnosed treatment-naïve MSM were recruited between February 2008 and August 2009. Phylogenetic reconstructions of the protease gene (HXB2: 2239 - 2629), gp120 (HXB2: 6942 - 7577) and gp41 (HXB2: 7803 - 8276) of the env gene uncovered five monophyletic transmission networks (two each within subtype B and CRF01_AE and one within CRF51_01B lineages) of different sizes (involving 3 - 23 MSM subjects, supported by posterior probability measure of 1.0). Bayesian coalescent analysis estimated that the emergence and dissemination of multiple sub-epidemic networks occurred between 1995 and 2005, driven largely by subtype B and later followed by CRF01_AE. Exponential increase in effective population size for both subtype B and CRF01_AE occurred between 2002 to 2007 and 2005 to 2007, respectively. Genealogical estimates suggested that the novel CRF51_01B lineages were probably generated through series of recombination events involving CRF01_AE and multiple subtype B ancestors. Our study provides the first insight on the phylodynamic profiles of HIV-1 subtype B, CRF01_AE and CRF51_01B viral strains circulating among MSM in Singapore.

Matched MeSH terms: HIV-1/genetics*
Fulltext Evolutionary history of HIV-1 subtype B and CRF01_AE transmission clusters among men who have sex with men (MSM) in Kuala Lumpur, Malaysia

Ng KT, Ong LY, Lim SH, Takebe Y, Kamarulzaman A, Tee KK

PLoS One, 2013;8(6):e67286.
PMID: 23840653 DOI: 10.1371/journal.pone.0067286

HIV-1 epidemics among men who have sex with men (MSM) continue to expand in developed and developing countries. Although HIV infection in MSM is amongst the highest of the key affected populations in many countries in Southeast Asia, comprehensive molecular epidemiological study of HIV-1 among MSM remains inadequate in the region including in Malaysia. Here, we reported the phylodynamic profiles of HIV-1 genotypes circulating among MSM population in Kuala Lumpur, Malaysia. A total of n = 459 newly-diagnosed treatment-naïve consenting subjects were recruited between March 2006 and August 2012, of whom 87 (18.9%) were self-reported MSM. Transmitted drug resistance mutations were absent in these isolates. Cumulatively, phylogenetic reconstructions of the pro-rt gene (HXB2∶2253-3275) showed that HIV-1 subtype B and CRF01_AE were predominant and contributed to approximately 80% of the total HIV-1 infection among MSM. In addition to numerous unique transmission lineages within these genotypes, twelve monophyletic transmission clusters of different sizes (2-7 MSM sequences, supported by posterior probability value of 1) were identified in Malaysia. Bayesian coalescent analysis estimated that the divergence times for these clusters were mainly dated between 1995 and 2005 with four major transmission clusters radiating at least 12 years ago suggesting that active spread of multiple sub-epidemic clusters occurred during this period. The changes in effective population size of subtype B showed an exponential growth within 5 years between 1988 and 1993, while CRF01_AE lineage exhibited similar expansion between 1993 and 2003. Our study provides the first insight of the phylodynamic profile of HIV-1 subtype B and CRF01_AE circulating among MSM population in Kuala Lumpur, Malaysia, unravelling the importance of understanding transmission behaviours as well as evolutionary history of HIV-1 in assessing the risk of outbreak or epidemic expansion.

Matched MeSH terms: HIV-1/genetics*
Genome sequence of a novel HIV-1 circulating recombinant form 54_01B from Malaysia

Ng KT, Ong LY, Takebe Y, Kamarulzaman A, Tee KK

J Virol, 2012 Oct;86(20):11405-6.
PMID: 22997423

We report here the first novel HIV-1 circulating recombinant form (CRF) 54_01B (CRF54_01B) isolated from three epidemiologically unlinked subjects of different risk groups in Malaysia. These recently sampled recombinants showed a complex genome organization composed of parental subtype B' and CRF01_AE, with identical recombination breakpoints observed in the gag, pol, and vif genes. Such a discovery highlights the ongoing active generation and spread of intersubtype recombinants involving the subtype B' and CRF01_AE lineages and indicates the potential of the new CRF in bridging HIV-1 transmission among different risk groups in Southeast Asia.

Matched MeSH terms: HIV-1/classification; HIV-1/genetics*; HIV-1/isolation & purification
Disparity in the percentage of CD4+ T lymphocytes and prognosis of HIV-infected intravenous drug users in Malaysia

Norazmi MN, Suarn S

Immunol Lett, 1994 Dec;43(3):177-82.
PMID: 7721330

The CD4+ T-lymphocyte absolute count (CD4ac), CD4+ T-lymphocyte percentage (CD4%) and total lymphocyte count (Løac) were assessed in HIV-seropositive intravenous drug users (IVDU) with reference to their correlation with the clinical categories A, B, and C as stipulated by the Centre of Disease Control and Prevention, USA (CDC) and with each other. It was found that while the CD4ac and Løac correlated with the clinical categories, CD4% did not. This may suggest that in our local setting, the CD4% may not necessarily be a suitable alternative marker to CD4ac as proposed by CDC. Furthermore, the CD4% of the normal subjects in this study was found to be relatively lower than the reported Caucasian levels. This may indicate that the use of the cut-off level of less than 14% as an AIDS-defining criteria may not be applicable for our HIV-seropositive IVDU. In addition, unlike the CD4ac which correlated directly with CD4% and Løac, the CD4% did not correlate with Løac. Therefore, due to the observed disparity with clinical status of patients and its possibly lower levels in our normal population, CD4% as a marker for staging HIV disease should be used with caution in our setting. Such findings may also have an impact on the use of established markers for the monitoring and classification of HIV-infected individuals in this region.

Matched MeSH terms: HIV-1/immunology*
Molecular diversity of HIV-1 and surveillance of transmitted drug resistance variants among treatment Naïve patients, 5 years after active introduction of HAART in Kuala Lumpur, Malaysia

Ong LY, Razak SN, Lee YM, Sri La Sri Ponnampalavanar S, Syed Omar SF, Azwa RI, et al.

J Med Virol, 2014 Jan;86(1):38-44.
PMID: 24127302 DOI: 10.1002/jmv.23772

Expansion of antiretroviral treatment programs have led to the growing concern for the development of antiretroviral drug resistance. The aims were to assess the prevalence of drug resistant HIV-1 variants and to identify circulating subtypes among HAART-naïve patients. Plasma specimens from N = 100 HIV+ HAART-naïve adult were collected between March 2008 and August 2010 and viral RNA were extracted for nested PCR and sequenced. PR-RT sequences were protein aligned and checked for transmitted drug resistance mutations. Phylogenetic reconstruction and recombination analysis were performed to determine the genotypes. Based on the WHO consensus guidelines, none of the recruited patients had any transmitted drug resistance mutations. When analyzed against the Stanford guidelines, 35% of patients had at least one reported mutation that may reduce drug susceptibility to PI (24%), NRTI (5%), and NNRTI (14%). The commonly detected mutation that may affect current first line therapy was V179D (3%), which may lead to reduced susceptibility to NNRTI. The predominant circulating HIV-1 genotypes were CRF01_AE (51%) and CRF33_01B (17%). The prevalence of unique recombinant forms (URF) was 7%; five distinct recombinant structures involving CRF01_AE and subtype B' were observed, among them a cluster of three isolates that could form a novel circulating recombinant form (CRF) candidate. Transmitted drug resistance prevalence among HAART-naïve patients was low in this cohort of patients in Kuala Lumpur despite introduction of HAART 5 years ago. Owing to the high genetic diversity, continued molecular surveillance can identify the persistent emergence of HIV-1 URF and novel CRF with significant epidemiological impact.

Matched MeSH terms: HIV-1/classification*; HIV-1/genetics*; HIV-1/isolation & purification
Fulltext Tuberculosis – HIV coinfection: the relationship between manifestation of tuberculosis and the degree of immunosuppression (CD4 counts)

Ong, C.K., Tan, W.C., Leong, K.N., Muttalif, A.R.

International e-Journal of Science, Medicine & Education, 2008;2(2):17-22.
MyJurnal

The incidence of tuberculosis (TB) is currently increasing. HIV induced immuno-suppression modifies the clinical presentation of TB. Our aim is to determine the differences in clinical presentation of HIV-TB co-infection based on their CD4 counts. This retrospective study looked at cases of adult active TB and HIV-1 co-infection treated in Penang Hospital from January 2004 to December 2005. Of the 820 patients treated for active TB, HIV-1 seropositivity rate was 12.6% (103 patients). Majority of HIV-1 co-infected patients presented with prolonged insidious and non-specific symptoms like weight loss, fever and night sweats. The clinical presentation of TB depended on the stage of HIV-1 infection and associated degree of immunodeficiency. Compared to the less immuno-compromised HIV-1 and TB co-infected population (CD4 > 200/mm3 ), patients with CD4 counts ≤ 200 are more likely to have atypical chest radiographs (P = 0.009). During active TB, the Mantoux test was positive in 12 (14.5%) HIV-1 infected patients with a CD4 counts ≤ 200/mm3 and in 16 (80%) of those with CD4 counts > 200/mm3 (P = 0.0001). In our series, the AFB smear / AFB culture and type of TB did not show obvious correlation with CD4 counts. Therefore to diagnose TB in severely immuno-compromised HIV patients, we need to have a high index of suspicion.

Matched MeSH terms: HIV-1
Characterization of a New HIV-1 CRF01_AE/B Recombinant Virus Form Among Men Who Have Sex with Men in Shanghai, China

Ou W, Li K, Feng Y, Huang Q, Ge Z, Sun J, et al.

AIDS Res Hum Retroviruses, 2019 04;35(4):414-418.
PMID: 30229664 DOI: 10.1089/AID.2018.0197

To date, there are 16 types of CRF01_AE/B circulating recombinant forms identified, and most of them are distributed in Asian countries such as China, Malaysia, and Singapore. Previous HIV molecular epidemiological surveys showed that CRF01_AE (27.6%) and B (9.6%) subtypes are predominant strains in mainland of China. At the same time, the HIV-1 virus spreads faster in the men who have sex with men (MSM) population than in other risk groups. In Shanghai district, ∼66.0% of newly reported cases were infected through homosexual transmission. In this study, we report a novel recombinant strain of CRF01_AE/B. The near full-length genome phylogenetic tree showed that the strain clustered with the CRF01_AE reference sequence and placed in the peripheral position within the branch of the CRF01_AE strain. Subregional evolutionary results indicated that the CRF01_AE subtype was derived from cluster 4 of CRF01_AE, which is mainly distributed in northern China. The subtype B was correlated with the U.S./Europe B, which are widely prevalent in the Chinese MSM population. In recent years, a large number of recombinant forms between CRF01_AE and B strains are continuously emerging in China. Therefore, understanding the current epidemic recombinant forms will have significant implications for prevention and treatment of HIV/AIDS.

Matched MeSH terms: HIV-1/genetics*; HIV-1/isolation & purification
Fulltext Evaluating immunologic response and clinical deterioration in treatment-naive patients initiating first-line therapies infected with HIV-1 CRF01_AE and subtype B

Oyomopito RA, Li PC, Sungkanuparph S, Phanuphak P, Tee KK, Sirisanthana T, et al.

J Acquir Immune Defic Syndr, 2013 Mar 01;62(3):293-300.
PMID: 23138836 DOI: 10.1097/QAI.0b013e31827a2e8f

BACKGROUND: HIV-1 group M viruses diverge 25%-35% in envelope, important for viral attachment during infection, and 10%-15% in the pol region, under selection pressure from common antiretrovirals. In Asia, subtypes B and CRF01_AE are common genotypes. Our objectives were to determine whether clinical, immunological, or virological treatment responses differed by genotype in treatment-naive patients initiating first-line therapy.
METHODS: Prospectively collected longitudinal data from patients in Thailand, Hong Kong, Malaysia, Japan, Taiwan, and South Korea were provided for analysis. Covariates included demographics, hepatitis B and C coinfections, baseline CD4 T lymphocyte count, and plasma HIV-1 RNA levels. Clinical deterioration (a new diagnosis of Centers for Disease Control and Prevention category B/AIDS-defining illness or death) was assessed by proportional hazards models. Surrogate endpoints were 12-month change in CD4 cell count and virologic suppression post therapy, evaluated by linear and logistic regression, respectively.
RESULTS: Of 1105 patients, 1036 (93.8%) infected with CRF01_AE or subtype B were eligible for inclusion in clinical deterioration analyses and contributed 1546.7 person-years of follow-up (median: 413 days, interquartile range: 169-672 days). Patients >40 years demonstrated smaller immunological increases (P = 0.002) and higher risk of clinical deterioration (hazard ratio = 2.17; P = 0.008). Patients with baseline CD4 cell counts >200 cells per microliter had lower risk of clinical deterioration (hazard ratio = 0.373; P = 0.003). A total of 532 patients (48.1% of eligible) had CD4 counts available at baseline and 12 months post therapy for inclusion in immunolgic analyses. Patients infected with subtype B had larger increases in CD4 counts at 12 months (P = 0.024). A total of 530 patients (48.0% of eligible) were included in virological analyses with no differences in response found between genotypes.
CONCLUSIONS: Results suggest that patients infected with CRF01_AE have reduced immunologic response to therapy at 12 months, compared with subtype B-infected counterparts. Clinical deterioration was associated with low baseline CD4 counts and older age. The lack of differences in virologic outcomes suggests that all patients have opportunities for virological suppression.

Matched MeSH terms: HIV-1/classification; HIV-1/genetics*
Risk group characteristics and viral transmission clusters in South-East Asian patients infected with human immunodeficiency virus-1 (HIV-1) circulating recombinant form (CRF) 01_AE and subtype B

Oyomopito RA, Chen YJ, Sungkanuparph S, Kantor R, Merati T, Yam WC, et al.

Kaohsiung J. Med. Sci., 2015 Sep;31(9):445-53.
PMID: 26362956 DOI: 10.1016/j.kjms.2015.07.002

Human immunodeficiency virus (HIV)-1 epidemics in Asian countries are driven by varying exposures. The epidemiology of the regional pandemic has been changing with the spread of HIV-1 to lower-risk populations through sexual transmission. Common HIV-1 genotypes include subtype B and circulating recombinant form (CRF) 01_AE. Our objective was to use HIV-1 genotypic data to better quantify local epidemics. TASER-M is a multicenter prospective cohort of HIV-infected patients. Associations between HIV exposure, patient sex, country of sample origin and HIV-1 genotype were evaluated by multivariate logistic regression. Phylogenetic methods were used on genotypic data to investigate transmission relationships. A total of 1086 patients from Thailand, Hong Kong, Malaysia and the Philippines were included in analyses. Proportions of male patients within countries varied (Thailand: 55.6%, Hong Kong: 86.1%, Malaysia: 81.4%, Philippines: 93.8%; p HIV-1 genotype. Homosexual exposure patients had higher odds of being infected with subtype B. Where HIV-1 genotypes circulate within countries or patient risk-groups, local monitoring of genotype-specific transmissions may play a role in focusing public health prevention strategies. Phylogenetic evaluations provide complementary information for surveillance and monitoring of viruses with high mutation rates such as HIV-1 and Ebola.

Matched MeSH terms: HIV-1/physiology*
Fulltext Performance of a Novel Low-Cost, Instrument-Free Plasma Separation Device for HIV Viral Load Quantification and Determination of Treatment Failure in People Living with HIV in Malaysia: a Diagnostic Accuracy Study

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*
Fulltext Transmitted drug resistance and antiretroviral treatment outcomes in non-subtype B HIV-1-infected patients in South East Asia

Phanuphak P, Sirivichayakul S, Jiamsakul A, Sungkanuparph S, Kumarasamy N, Lee MP, et al.

J Acquir Immune Defic Syndr, 2014 May 01;66(1):74-9.
PMID: 24413039 DOI: 10.1097/QAI.0000000000000108

BACKGROUND: We compared treatment outcomes of transmitted drug resistance (TDR) in patients on fully or partially sensitive drug regimens.
METHODS: Factors associated with survival and failure were analyzed using Cox proportional hazards and discrete time conditional logistic models.
RESULTS: TDR, found in 60 (4.1%) of 1471 Asian treatment-naive patients, was one of the significant predictors of failure. Patients with TDR to >1 drug in their regimen were >3 times as likely to fail compared to no TDR.
CONCLUSIONS: TDR was associated with failure in the context of non-fully sensitive regimens. Efforts are needed to incorporate resistance testing into national treatment programs.

Matched MeSH terms: HIV-1/drug effects*; HIV-1/genetics; HIV-1/isolation & purification

Filters

Please provide feedback to Administrator (afdal@afpm.org.my)

External Links