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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
Genome sequences of a novel HIV-1 CRF53_01B identified in Malaysia

Chow WZ, Al-Darraji H, Lee YM, Takebe Y, Kamarulzaman A, Tee KK

J Virol, 2012 Oct;86(20):11398-9.
PMID: 22997419

A novel HIV-1 genotype designated CRF53_01B was recently characterized from three epidemiologically unrelated persons in Malaysia. Here we announced three recently isolated full-length genomes of CRF53_01B, which is likely to be phylogenetically linked to CRF33_01B, circulating widely in Southeast Asia. The genome sequences may contribute to HIV-1 molecular surveillance and future vaccine development in the region.

Matched MeSH terms: HIV-1/genetics*; HIV-1/isolation & purification
Fulltext HIV transmission through breast milk: the science behind the understanding of current trends and future research

Prameela KK

Med J Malaysia, 2012 Dec;67(6):644-51.
PMID: 23770969 MyJurnal

Breastmilk protects the infant from many diseases and many short- term and long- term benefits accrue. At the same time it is also known that breastfeeding acts as a vehicle for some infective agents. It is now accepted that breastmilk transmission of Human Immunodeficiency Virus- 1 (HIV-1) is an important mode of paediatric infection . Despite this fact, many researchers have observed that corresponding to the volume of milk consumed by the infant, maternal transmission via breastmilk is still comparatively low. Some have noted the long latency period of breastmilk HIV transmission with evidence of numerous anti-HIV factors in breastmilk. Although there are accepted standard guidelines on infant feeding in mothers who are HIV positive in many countries, it maybe equally important to realize gaps in our knowledge of mother- to -child HIV transmission. From an evolutionary perspective, the role of the mammary epithelial cell (MEC) and of breastmilk , in contributing to and possibly in influencing HIV-1 transmission is intriguing. The presence of HIV-1 or of other viruses in maternal milk seem to be a requisite to spur immunological defenses to optimize necessary protection to the infant. This article reviews some aspects of the science of HIV transmission through breastmilk and reflects the concept -based understanding of current policies on HIV and breastfeeding. At the same time, it highlights uncertainties in this field and the urgency for future research in this direction. Accepting current notions of breastmilk HIV transmission, greater deliberation by research may throw more light on why breastfeeding with its abundant advantages is fraught with the hazards of transmission of a deadly disease.

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 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*
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 Acquisition of HIV by African-born residents of Victoria, Australia: insights from molecular epidemiology

Lemoh C, Ryan CE, Sekawi Z, Hearps AC, Aleksic E, Chibo D, et al.

PLoS One, 2013;8(12):e84008.
PMID: 24391866 DOI: 10.1371/journal.pone.0084008

African-born Australians are a recognised "priority population" in Australia's Sixth National HIV/AIDS Strategy. We compared exposure location and route for African-born people living with HIV (PLHIV) in Victoria, Australia, with HIV-1 pol subtype from drug resistance assays and geographical origin suggested by phylogenetic analysis of env gene. Twenty adult HIV positive African-born Victorian residents were recruited via treating doctors. HIV exposure details were obtained from interviews and case notes. Viral RNA was extracted from participant stored plasma or whole blood. The env V3 region was sequenced and compared to globally representative reference HIV-1 sequences in the Los Alamos National Library HIV Database. Twelve participants reported exposure via heterosexual sex and two via iatrogenic blood exposures; four were men having sex with men (MSM); two were exposed via unknown routes. Eight participants reported exposure in their countries of birth, seven in Australia, three in other countries and two in unknown locations. Genotype results (pol) were available for ten participants. HIV env amplification was successful in eighteen cases. HIV-1 subtype was identified in all participants: eight both pol and env; ten env alone and two pol alone. Twelve were subtype C, four subtype B, three subtype A and one subtype CRF02_AG. Reported exposure location was consistent with the phylogenetic clustering of env sequences. African Australians are members of multiple transnational social and sexual networks influencing their exposure to HIV. Phylogenetic analysis may complement traditional surveillance to discern patterns of HIV exposure, providing focus for HIV prevention programs in mobile populations.

Matched MeSH terms: HIV-1/genetics; HIV-1/pathogenicity*
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*
Fulltext Multifaceted Impact of Host C-C Chemokine CCL2 in the Immuno-Pathogenesis of HIV-1/M. tuberculosis Co-Infection

Ansari AW, Kamarulzaman A, Schmidt RE

Front Immunol, 2013;4:312.
PMID: 24109479 DOI: 10.3389/fimmu.2013.00312

Active tuberculosis remains the leading cause of death among the HIV-1 seropositive individuals. Although significant success has been achieved in bringing down the number of HIV/AIDS-related mortality and morbidity following implementation of highly active anti-retroviral therapy (HAART). Yet, co-infection of Mycobacterium tuberculosis (Mtb) has posed severe clinical and preventive challenges in our efforts to eradicate the virus from the body. Both HIV-1 and Mtb commonly infect macrophages and trigger production of host inflammatory mediators that subsequently regulate the immune response and disease pathogenesis. These inflammatory mediators can impose beneficial or detrimental effects on each pathogen and eventually on host. Among these, inflammatory C-C chemokines play a central role in HIV-1 and Mtb pathogenesis. However, their role in lung-specific mechanisms of HIV-1 and Mtb interaction are poorly understood. In this review we highlight current view on the role of C-C chemokines, more precisely CCL2, on HIV-1: Mtb interaction, potential mechanisms of action and adverse clinical consequences in a setting HIV-1/Mtb co-infection. Targeting common chemokine regulators of HIV-1/Mtb pathogenesis can be an attractive and potential anti-inflammatory intervention in HIV/AIDS-related comorbidities.

Matched MeSH terms: HIV-1
Fulltext Dissecting the dynamics of HIV-1 protein sequence diversity

Hu Y, Tan PT, Tan TW, August JT, Khan AM

PLoS One, 2013;8(4):e59994.
PMID: 23593157 DOI: 10.1371/journal.pone.0059994

The rapid mutation of human immunodeficiency virus-type 1 (HIV-1) and the limited characterization of the composition and incidence of the variant population are major obstacles to the development of an effective HIV-1 vaccine. This issue was addressed by a comprehensive analysis of over 58,000 clade B HIV-1 protein sequences reported over at least 26 years. The sequences were aligned and the 2,874 overlapping nonamer amino acid positions of the viral proteome, each a possible core binding domain for human leukocyte antigen molecules and T-cell receptors, were quantitatively analyzed for four patterns of sequence motifs: (1) "index", the most prevalent sequence; (2) "major" variant, the most common variant sequence; (3) "minor" variants, multiple different sequences, each with an incidence less than that of the major variant; and (4) "unique" variants, each observed only once in the alignment. The collective incidence of the major, minor, and unique variants at each nonamer position represented the total variant population for the position. Positions with more than 50% total variants contained correspondingly reduced incidences of index and major variant sequences and increased minor and unique variants. Highly diverse positions, with 80 to 98% variant nonamer sequences, were present in each protein, including 5% of Gag, and 27% of Env and Nef, each. The multitude of different variant nonamer sequences (i.e. nonatypes; up to 68%) at the highly diverse positions, represented by the major, multiple minor, and multiple unique variants likely supported variants function both in immune escape and as altered peptide ligands with deleterious T-cell responses. The patterns of mutational change were consistent with the sequences of individual HXB2 and C1P viruses and can be considered applicable to all HIV-1 viruses. This characterization of HIV-1 protein mutation provides a foundation for the design of peptide-based vaccines and therapeutics.

Matched MeSH terms: HIV-1/classification; HIV-1/genetics*
Fulltext Production and purification of polymerization-competent HIV-1 capsid protein p24 (CA) in NiCo21(DE3) Escherichia coli

Teow SY, Mualif SA, Omar TC, Wei CY, Yusoff NM, Ali SA

BMC Biotechnol, 2013;13:107.
PMID: 24304876 DOI: 10.1186/1472-6750-13-107

HIV genome is packaged and organized in a conical capsid, which is made up of ~1,500 copies of the viral capsid protein p24 (CA). Being a primary structural component and due to its critical roles in both late and early stages of the HIV replication cycle, CA has attracted increased interest as a drug discovery target in recent years. Drug discovery studies require large amounts of highly pure and biologically active protein. It is therefore desirable to establish a simple and reproducible process for efficient production of HIV-1 CA.

Matched MeSH terms: HIV-1/genetics*; HIV-1/physiology
Fulltext Molecular diversity of HIV-1 among people who inject drugs in Kuala Lumpur, Malaysia: massive expansion of circulating recombinant form (CRF) 33_01B and emergence of multiple unique recombinant clusters

Chow WZ, Ong LY, Razak SH, Lee YM, Ng KT, Yong YK, et al.

PLoS One, 2013;8(5):e62560.
PMID: 23667490 DOI: 10.1371/journal.pone.0062560

Since the discovery of HIV-1 circulating recombinant form (CRF) 33_01B in Malaysia in the early 2000 s, continuous genetic diversification and active recombination involving CRF33_01B and other circulating genotypes in the region including CRF01_AE and subtype B' of Thai origin, have led to the emergence of novel CRFs and unique recombinant forms. The history and magnitude of CRF33_01B transmission among various risk groups including people who inject drugs (PWID) however have not been investigated despite the high epidemiological impact of CRF33_01B in the region. We update the most recent molecular epidemiology of HIV-1 among PWIDs recruited in Malaysia between 2010 and 2011 by population sequencing and phylogenetic analysis of 128 gag-pol sequences. HIV-1 CRF33_01B was circulating among 71% of PWIDs whilst a lower prevalence of other previously dominant HIV-1 genotypes [subtype B' (11%) and CRF01_AE (5%)] and CRF01_AE/B' unique recombinants (13%) were detected, indicating a significant shift in genotype replacement in this population. Three clusters of CRF01_AE/B' recombinants displaying divergent yet phylogenetically-related mosaic genomes to CRF33_01B were identified and characterized, suggestive of an abrupt emergence of multiple novel CRF clades. Using rigorous maximum likelihood approach and the Bayesian Markov chain Monte Carlo (MCMC) sampling of CRF33_01Bpol sequences to elucidate the past population dynamics, we found that the founder lineages of CRF33_01B were likely to have first emerged among PWIDs in the early 1990 s before spreading exponentially to various high and low-risk populations (including children who acquired infections from their mothers) and later on became endemic around the early 2000 s. Taken together, our findings provide notable genetic evidence indicating the widespread expansion of CRF33_01B among PWIDs and into the general population. The emergence of numerous previously unknown recombinant clades highlights the escalating genetic complexity of HIV-1 in the Southeast Asian region.

Matched MeSH terms: HIV-1/genetics*; HIV-1/physiology*
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 Optimization of human immunodeficiency virus treatment during incarceration: viral suppression at the prison gate

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*
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
Fulltext Antiretroviral drug resistance and HIV-1 subtypes among treatment-naive prisoners in Kelantan, Malaysia

Ariffin TA, Mohamad S, Yusuf WN, Shueb RH

J Infect Dev Ctries, 2014 Aug;8(8):1063-7.
PMID: 25116676 DOI: 10.3855/jidc.4095

INTRODUCTION: The widespread use of highly active antiretroviral therapy (HAART) and continuous reports of HIV-1 strains developing resistance to these drugs is rather alarming, as transmission of resistant viruses to newly infected persons is possible. This study aimed to determine HIV-1 subtypes and the prevalence of primary mutations associated with antiretroviral (ARV) resistance among treatment-naive prisoners on the east coast of Malaysia.
METHODOLOGY: Viral RNA was extracted from plasma samples of 21 treatment-naive prisoners. Protease (PR) and reverse transcriptase (RT) regions were amplified and sequenced. Stanford HIV database algorithms were used for interpretation of resistance, and phylogenetic analysis was performed for subtype assignment.
RESULTS: In the PR gene, no antiviral resistance-associated mutation was detected. For RT-associated mutations, K103N was the most prevalent in sequenced samples (14.3%). Genetic subtyping on the pol gene revealed that the majority of the prisoners were infected with subtype CRF33_01B (52.4%).
CONCLUSION: Continuous surveillance of newly infected individuals is required to help strategize the best antiviral treatment for these patients.

Matched MeSH terms: HIV-1/classification; HIV-1/drug effects*; HIV-1/genetics*; HIV-1/isolation & purification
Fulltext Weight as predictors of clinical progression and treatment failure: results from the TREAT Asia Pediatric HIV Observational Database

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*
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 Cross-border sexual transmission of the newly emerging HIV-1 clade CRF51_01B

Cheong HT, Ng KT, Ong LY, Chook JB, Chan KG, Takebe Y, et al.

PLoS One, 2014;9(10):e111236.
PMID: 25340817 DOI: 10.1371/journal.pone.0111236

A novel HIV-1 recombinant clade (CRF51_01B) was recently identified among men who have sex with men (MSM) in Singapore. As cases of sexually transmitted HIV-1 infection increase concurrently in two socioeconomically intimate countries such as Malaysia and Singapore, cross transmission of HIV-1 between said countries is highly probable. In order to investigate the timeline for the emergence of HIV-1 CRF51_01B in Singapore and its possible introduction into Malaysia, 595 HIV-positive subjects recruited in Kuala Lumpur from 2008 to 2012 were screened. Phylogenetic relationship of 485 amplified polymerase gene sequences was determined through neighbour-joining method. Next, near-full length sequences were amplified for genomic sequences inferred to be CRF51_01B and subjected to further analysis implemented through Bayesian Markov chain Monte Carlo (MCMC) sampling and maximum likelihood methods. Based on the near full length genomes, two isolates formed a phylogenetic cluster with CRF51_01B sequences of Singapore origin, sharing identical recombination structure. Spatial and temporal information from Bayesian MCMC coalescent and maximum likelihood analysis of the protease, gp120 and gp41 genes suggest that Singapore is probably the country of origin of CRF51_01B (as early as in the mid-1990s) and featured a Malaysian who acquired the infection through heterosexual contact as host for its ancestral lineages. CRF51_01B then spread rapidly among the MSM in Singapore and Malaysia. Although the importation of CRF51_01B from Singapore to Malaysia is supported by coalescence analysis, the narrow timeframe of the transmission event indicates a closely linked epidemic. Discrepancies in the estimated divergence times suggest that CRF51_01B may have arisen through multiple recombination events from more than one parental lineage. We report the cross transmission of a novel CRF51_01B lineage between countries that involved different sexual risk groups. Understanding the cross-border transmission of HIV-1 involving sexual networks is crucial for effective intervention strategies in the region.

Matched MeSH terms: HIV-1/genetics*
Fulltext Genome Sequence of a Complex HIV-1 Unique Recombinant Form Involving CRF01_AE, Subtype B, and Subtype B' Identified in Malaysia

Chow WZ, Nizam S, Ong LY, Ng KT, Chan KG, Takebe Y, et al.

Genome Announc, 2014;2(2).
PMID: 24675847 DOI: 10.1128/genomeA.00139-14

A complex HIV-1 unique recombinant form involving subtypes CRF01_AE, B, and B' was recently identified from an injecting drug user in Malaysia. A total of 13 recombination breakpoints were mapped across the near-full-length genome of isolate 10MYPR226, indicating the increasingly diverse molecular epidemiology and frequent linkage among various high-risk groups.

Matched MeSH terms: HIV-1

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