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Fulltext Extended-release Naltrexone Improves Viral Suppression Among Incarcerated Persons Living with HIV and Alcohol use Disorders Transitioning to the Community: Results From a Double-Blind, Placebo-Controlled Trial

Springer SA, Di Paola A, Barbour R, Azar MM, Altice FL

J Acquir Immune Defic Syndr, 2018 09 01;79(1):92-100.
PMID: 29781884 DOI: 10.1097/QAI.0000000000001759

OBJECTIVE: To determine whether extended-release naltrexone (XR-NTX) would improve or maintain viral suppression (VS) among incarcerated individuals with HIV and alcohol use disorders (AUDs) transitioning to the community.
DESIGN: A randomized, double-blind, placebo-controlled trial was conducted among incarcerated individuals with HIV and AUDs transitioning to the community from 2010 through 2016.
METHODS: Eligible participants (N = 100) were randomized 2:1 to receive 6 monthly injections of XR-NTX (n = 67) or placebo (n = 33) starting at release and continued for 6 months. The primary and secondary outcomes were the proportion that maintained or improved VS at <200 and <50 copies per milliliter from baseline to 6 months, respectively, using an intention-to-treat analysis.
RESULTS: Participants allocated to XR-NTX improved VS from baseline to 6 months for <200 copies per milliliter (48.0%-64.2%, P = 0.024) and for <50 copies per milliliter (31.0%-56.7%, P = 0.001), whereas the placebo group did not (<200 copies/mL: 64%-42.4%, P = 0.070; <50 copies/mL: 42.0%-30.3%, P = 0.292). XR-NTX participants were more likely to achieve VS than the placebo group at 6 months (<200 copies/mL: 64.2% vs. 42.4%; P = 0.041; <50 copies/mL: 56.7% vs. 30.3%; P = 0.015). XR-NTX independently predicted VS [<200 copies/mL: adjusted odds ratio (aOR) = 2.68, 95% confidence interval (CI) = 1.01 to 7.09, P = 0.047; <50 copies/mL: aOR = 4.54; 95% CI = 1.43 to 14.43, P = 0.009] as did receipt of ≥3 injections (<200 copies/mL: aOR = 3.26; 95% CI = 1.26 to 8.47, P = 0.010; <50 copies/mL: aOR = 6.34; 95% CI = 2.08 to 19.29, P = 0.001). Reductions in alcohol consumption (aOR = 1.43, 95% CI = 1.03 to 1.98, P = 0.033) and white race (aOR = 5.37, 95% CI = 1.08 to 27.72, P = 0.040) also predicted VS at <50 copies per milliliter.
CONCLUSIONS: XR-NTX improves or maintains VS after release to the community for incarcerated people living with HIV and AUDs.

Matched MeSH terms: HIV-1/genetics
Fulltext HIV-1 drug resistance mutations among antiretroviral-naive HIV-1-infected patients in Asia: results from the TREAT Asia Studies to Evaluate Resistance-Monitoring Study

Sungkanuparph S, Oyomopito R, Sirivichayakul S, Sirisanthana T, Li PC, Kantipong P, et al.

Clin Infect Dis, 2011 Apr 15;52(8):1053-7.
PMID: 21460324 DOI: 10.1093/cid/cir107

Of 682 antiretroviral-naïve patients initiating antiretroviral therapy in a prospective, multicenter human immunodeficiency virus type 1 (HIV-1) drug resistance monitoring study involving 8 sites in Hong Kong, Malaysia, and Thailand, the prevalence of patients with ≥1 drug resistance mutation was 13.8%. Primary HIV drug resistance is emerging after rapid scaling-up of antiretroviral therapy use in Asia.

Matched MeSH terms: HIV-1/genetics*
Fulltext Isolation and characterization of a replication-competent molecular clone of an HIV-1 circulating recombinant form (CRF33_01B)

Tee KK, Kusagawa S, Li XJ, Onogi N, Isogai M, Hase S, et al.

PLoS One, 2009;4(8):e6666.
PMID: 19688091 DOI: 10.1371/journal.pone.0006666

A growing number of emerging HIV-1 recombinants classified as circulating recombinant forms (CRFs) have been identified in Southeast Asia in recent years, establishing a molecular diversity of increasing complexity in the region. Here, we constructed a replication-competent HIV-1 clone for CRF33_01B (designated p05MYKL045.1), a newly identified recombinant comprised of CRF01_AE and subtype B. p05MYKL045.1 was reconstituted by cloning of the near full-length HIV-1 sequence from a newly-diagnosed individual presumably infected heterosexually in Kuala Lumpur, Malaysia. The chimeric clone, which contains the 5' LTR (long terminal repeat) region of p93JP-NH1 (a previously isolated CRF01_AE infectious clone), showed robust viral replication in the human peripheral blood mononuclear cells. This clone demonstrated robust viral propagation and profound syncytium formation in CD4+, CXCR4-expressing human glioma NP-2 cells, indicating that p05MYKL045.1 is a CXCR4-using virus. Viral propagation, however, was not detected in various human T cell lines including MT-2, M8166, Sup-T1, H9, Jurkat, Molt-4 and PM1. p05MYKL045.1 appears to proliferate only in restricted host range, suggesting that unknown viral and/or cellular host factors may play a role in viral infectivity and replication in human T cell lines. Availability of a CRF33_01B molecular clone will be useful in facilitating the development of vaccine candidates that match the HIV-1 strains circulating in Southeast Asia.

Matched MeSH terms: HIV-1/genetics
Identification of a novel circulating recombinant form (CRF33_01B) disseminating widely among various risk populations in Kuala Lumpur, Malaysia

Tee KK, Li XJ, Nohtomi K, Ng KP, Kamarulzaman A, Takebe Y

J Acquir Immune Defic Syndr, 2006 Dec 15;43(5):523-9.
PMID: 17031320

A molecular epidemiological investigation was conducted among various risk populations (n = 184) in Kuala Lumpur, Malaysia, in 2003 to 2005, on the basis of nucleotide sequences of protease and reverse transcriptase regions. In addition to circulating HIV-1 strains, including CRF01_AE (57.1%), subtype B (20.1%), and subtype C (0.5%), we detected a candidate with a new circulating recombinant form (CRF). We determined four near-full-length nucleotide sequences with identical subtype structure from epidemiologically unlinked individuals of different risk and ethnic groups. In this chimera, two short subtype B segments were inserted into the gag-RT region in a backbone of CRF01_AE. The recombinant structure was distinct from previously identified CRF15_01B in Thailand. In agreement with the current HIV nomenclature system, this constitutes a novel CRF (CRF33_01B). The overall prevalence of CRF33_01B is 19.0% (35/184). Although the prevalence of CRF33_01B is particularly high among injecting drug users (42.0%, 21/50), it is also detected in a substantial proportion of homo-/bisexual males (18.8%, 3/16) and heterosexuals (9.8%, 9/92). Moreover, unique recombinant forms composed of CRF01_AE and subtype B that have a significant structural relationship with CRF33_01B were detected in 1.6% (3/184) of study subjects, suggesting an ongoing recombination process in Malaysia. This new CRF seems to be bridging viral transmission between different risk populations in this country.

Matched MeSH terms: HIV-1/genetics
Emergence of HIV-1 CRF01_AE/B unique recombinant forms in Kuala Lumpur, Malaysia

Tee KK, Pon CK, Kamarulzaman A, Ng KP

AIDS, 2005 Jan 28;19(2):119-26.
PMID: 15668536

OBJECTIVES: To investigate the molecular epidemiology of HIV-1 and to screen for the emergence of intersubtype recombinants in Kuala Lumpur, Malaysia.
DESIGN: A molecular epidemiology study was conducted among HIV-1 seropositive patients attending the University Malaya Medical Center (UMMC) from July 2003 to June 2004.
METHODS: Protease (PR) and reverse transcriptase (RT) gene sequences were derived from drug resistance genotyping assay of 100 newly diagnosed or antiretroviral-naive patients. These were phylogenetically analysed to determine the subtypes and recombination breakpoint analyses were performed on intersubtype recombinants to estimate the recombination breakpoint(s).
RESULTS: CRF01_AE predominated in Kuala Lumpur with 65% in both PR and RT genes. B subtype was detected at 14% and 12% in PR and RT genes, respectively. C subtype was present at 1% in both genes. Overall, the concordance of PR and RT genes in discriminating subtypes/circulating recombinant forms (CRF) was high at 96%. In this study, novel CRF01_AE/B intersubtype recombinants were detected at high prevalence (22%), including those isolates with subtype discordance. Thai variants of CRF01_AE and B subtype were involved in the genesis of these unique recombinant forms (URF). Interestingly, 19 CRF01_AE/B intersubtype recombinant isolates shared similar recombination breakpoints in both PR and RT genes. Several distinct URF were also identified.
CONCLUSION: PR and RT genes can be utilized for subtype/CRF assessment with high degree of agreement, allowing concurrent surveillance of circulating HIV-1 subtypes with antiretroviral drug resistance genotyping tests. The emergence of highly identical CRF01_AE/B intersubtype recombinants suggests the possibility of the appearance of a new circulating recombinant form in Kuala Lumpur.

Matched MeSH terms: HIV-1/genetics*
Fulltext Transmission Networks of HIV-1 Among Men Who Have Sex With Men in East and Southeast Asia

Tee KK, Kantor R, Sungkanuparph S, Takebe Y, Li P, Ditangco R, et al.

J Acquir Immune Defic Syndr, 2015 Sep 01;70(1):e28-30.
PMID: 25835606 DOI: 10.1097/QAI.0000000000000614
Matched MeSH terms: HIV-1/genetics
Prevalence and pattern of drug resistance mutations among antiretroviral-treated HIV-1 patients with suboptimal virological response in Malaysia

Tee KK, Kamarulzaman A, Ng KP

Med Microbiol Immunol, 2006 Jun;195(2):107-12.
PMID: 16404607

To assess the prevalence of major drug resistance mutations in antiretroviral (ARV)-treated patients with detectable viral load (VL) in Kuala Lumpur, Malaysia, genotypic resistance testing was performed among treated human immunodeficiency virus type 1 (HIV-1) patients attending the University Malaya Medical Center between July 2003 and November 2004. The reverse transcriptase (RT) and protease genes from 36 plasma samples with detectable VL were examined for major mutations associated with ARV resistance as reported by the International AIDS Society-USA Drug Resistance Mutations Group. The prevalence of patients with at least one major mutation conferring drug resistance to nucleoside RT inhibitors (NRTIs), non-NRTIs (NNRTIs) or protease inhibitors (PIs) was 77.8%. In the RT gene, the frequency of mutations associated with NRTIs and NNRTIs resistance was 52.8 and 63.9%, respectively, with M184V and K103N mutations being selected most frequently by these drugs. A patient with Q151M mutation complex was also detected. Twenty-two percent of the patients had mutations associated with PIs. The following pattern of prevalence of ARV-resistant HIV-1 variants was observed: NNRTI-resistant > NRTI-resistant > PI-resistant. The prevalence of major drug resistance mutations among ARV-treated patients with detectable VL is high in Kuala Lumpur. Genotypic drug resistance testing is therefore important for monitoring patients experiencing ARV regimen failure.

Matched MeSH terms: HIV-1/genetics
Short communication: low prevalence of genotypic drug resistance mutations among antiretroviral-naive HIV type 1 patients in Malaysia

Tee KK, Kamarulzaman A, Ng KP

AIDS Res Hum Retroviruses, 2006 Feb;22(2):121-4.
PMID: 16478392

To assess the prevalence of mutations associated with drug resistance in antiretroviral-naive patients in Kuala Lumpur, Malaysia, genotypic resistance testing was conducted among drug-naive HIV-1 patients attending the University Malaya Medical Center (UMMC) between July 2003 and June 2004. Reverse transcriptase (RT) and protease genes of plasma virions were sequenced from 100 individuals. The majority of the patients were recently diagnosed. Codons 20-255 of the RT and 1-96 of the protease gene were examined for major and minor mutations associated with antiretroviral resistance reported by the International AIDS Society- USA (IAS-USA) Drug Resistance Mutations Group. The prevalence of patients with at least one major mutation conferring drug resistance was 1%, with only one patient having a Y181C amino acid substitution in the RT gene that confers high-level resistance to nevirapine and delavirdine. Minor mutations were detected in high prevalence in the protease gene. Amino acid substitutions I13V, E35D, and M36I were associated with CRF01_AE while L63P, V77I, and I93L were associated with subtype B. Baseline prevalence of major mutations associated with resistance to antiretroviral drugs was low among antiretroviral-naive HIV-1 patients, suggesting that routine drug resistance testing may be unnecessary for all individuals newly diagnosed with HIV or all patients beginning antiretroviral therapy.

Matched MeSH terms: HIV-1/genetics*
The evolving molecular epidemiology of HIV type 1 among injecting drug users (IDUs) in Malaysia

Tee KK, Saw TL, Pon CK, Kamarulzaman A, Ng KP

AIDS Res Hum Retroviruses, 2005 Dec;21(12):1046-50.
PMID: 16379608

Earlier studies in the 1990s indicate that human immunodeficiency virus type 1 (HIV-1) subtype B has been the predominant subtype among injecting drug users (IDUs) in Malaysia. More recent studies performed between 2003 and 2004, however, show a high prevalence of unique CRF01_AE/B intersubtype recombinants among IDUs. To determine the subtype distribution among IDUs in Kuala Lumpur prior to the emergence of CRF01_AE/B intersubtype recombinants, the gag-pol or the reverse transcriptase gene was sequenced from IDUs who were diagnosed as HIV positive between 1993 and 2002. Subtype B was present at 50.0% followed by CRF01_AE/B recombinant at 41.7%, with more CRF01_AE/B recombinants detected between 2000 and 2002. All CRF01_AE/B recombinants shared similar recombination patterns. Interestingly, we found that this potential new candidate of circulating recombinant form (CRF) could have emerged as early as the mid-1990s. The results showed evidence of changing HIV-1 molecular epidemiology toward the predominance of CRF01_AE/B intersubtype recombinants among IDUs in Kuala Lumpur.

Matched MeSH terms: 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 variants in South and South-East Asia

Tsuchie H, Saraswathy TS, Sinniah M, Vijayamalar B, Maniar JK, Monzon OT, et al.

Int J STD AIDS, 1995 Mar-Apr;6(2):117-20.
PMID: 7779924 DOI: 10.1177/095646249500600211

HIV spread in South and South-East Asia is most alarming, and genetic variability of HIV-1 is an important consideration in vaccine development. In this study, we examined the third variable (V3) region of env gene of HIV-1 variants prevalent in Thailand, Malaysia, India, and the Philippines. By phylogenetic tree analyses, an HIV-1 variant from an injecting drug user (IDU) in Thailand belonged to subtype B, and HIV-1 variants from 2 IDUs in Malaysia were classified into 2 subtypes, B and E. One HIV-1 variant from a male homosexual in the Philippines belonged to subtype B. Out of 8 HIV-1 variants from sexually transmitted disease patients in India, 7 belonged to subtype C, and one to subtype A. Although the total number of individuals examined in this study was limited, 4 HIV-1 subtypes were found in South and South-East Asia and large international movements of HIV-1-infected individuals in this region could induce global dissemination of these HIV-1 variants.

Matched MeSH terms: HIV-1/genetics*
Complex patterns of the HIV-1 epidemic in Kuala Lumpur, Malaysia: evidence for expansion of circulating recombinant form CRF33_01B and detection of multiple other recombinants

Wang B, Lau KA, Ong LY, Shah M, Steain MC, Foley B, et al.

Virology, 2007 Oct 25;367(2):288-97.
PMID: 17604072

The HIV protease-reverse transcriptase (PR-RT) (1047 bp), gp120-env (891 bp) and gp41-env (547 bp) regions from the plasma of 115 HIV-1-infected patients in Kuala Lumpur (KL), Malaysia were sequenced. Detailed phylogenetic and bootscanning analyses were performed to determine the mosaic structure of the HIV-1 strains and their recombination breakpoint(s). Among the 50 patient samples in which all three regions could be amplified, the HIV-1 CRF01_AE subtype (46%) was predominant followed by subtypes B (10%) and B' (6%). A total of 9/50 (18%) patients were infected with a CRF01_AE/B inter-subtype recombinant, displaying a recombinant form (RF)(PR-RT), CRF01_AE(gp120-env) and CRF01_AE(gp41-env). This RF was derived from the Thai variants of CRF01_AE and B' subtype, with two distinct B' subtype segments in the backbone of CRF01_AE, similar to the newly identified CRF33_01B. In addition, one sample demonstrated a close structural relationship with the new CRF33_01B in the PR-RT region but displayed B' segment in part of the env region (RF(PR-RT), CRF01_AE/B'(gp120-env) and B'(gp41-env)) indicating continuing evolution of CRF33_01B. The remaining 18% of samples were identified as unique recombinant forms (URFs).

Matched MeSH terms: HIV-1/genetics*

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