Primary drug resistance and transmission analysis of HIV‐1 in acute and recent drug‐naïve seroconverters in Singapore

Abstract

ObjectivesThe aim of the study was to elucidate primary drug resistance and transmission of HIV-1 in acute and recent drug-naïve seroconverters in Singapore. MethodsAcute and recent HIV-1 seroconverters were enrolled in the study. The HIV-1 polymerase (pol) gene was sequenced and used for genotypic drug resistance analysis and phylogenetic analysis. HIV-1 transmission clusters were inferred from phylogenetic clustering analysis. ResultsOf the 60 subjects analysed, 95% were men, and 73.3% were men who have sex with men (MSM). Six HIV-1 subtypes were identified, including CRF01_AE (46.7%), subtypes B (30%), B 0 (15%) and G (1.7%), CRF33_01B (1.7%) and CRF34_01B (5%). Primary genotypic resistance was detected in only one (1.7%) subtype B variant. Thirty-one patients (51.7%) were phylogenetically clustered, of whom 90% reported having local risk exposure, compared with 59% of the patients who were not phylogenetically clustered [odds ratio (OR) 6.35, 95% confidence interval (CI) 1. 65-23.95]. MSM (OR 5.63,, high viral load (OR 4.28, 95% CI 1.37-13.36) and young age (OR 0.92, 95% CI 0.85-0.99) were independently associated with clustered individuals. ConclusionsIn Singapore, HIV-1 primary resistance is insignificant; individuals with seroconversion account for about half of onward transmission among recently infected seroconverters. MSM, high viral load and young age are factors that facilitate transmission. Early detection of these individuals is of paramount importance for the prevention of HIV-1 transmission.Keywords: HIV-1, molecular epidemiology, phylogenetics, primary resistance, seroconverter Accepted 20 January 2009 Introduction Primary or transmitted drug resistance in HIV-1 has been a significant clinical and public health concern with the widespread use of antiretroviral therapy (ART) world-wide, particularly in the developed world [1]. A number of recent studies conducted in the USA and Western European countries have shown that the prevalence rates of HIV-1 primary resistance range from approximately 8 to 16% in recently infected, drug-naïve individuals [2][3][4][5][6]. Although HIV-1 primary resistance is less prevalent in Asian countries, a recent report from Thailand has demonstrated a comparable prevalence rate (12.4%) to those reported in developed countries, presumably reflecting increased access to ART in Thailand [7].In Singapore, antiretrovirals have been available since the early 1990s and ART has been readily accessible from the year 2000 [8]. However, a previous study conducted in our centre showed that none of the 35 variants of CRF01_AE (which is the predominant subtype in both Thailand and Singapore) obtained from newly diagnosed, drug-naïve patients was drug-resistant [9]. As certain drug resistance mutations of HIV-1 can persist in transmitted viruses for only about 2 years [10,11] and the durations of HIV-1 infection for the subjects in the previous Singapore study [9] are unknown, it was necessary to further validate this finding and to obtain a more recent picture of primary resis...

New Trends of Primary Drug Resistance Among HIV Type 1-Infected Men Who Have Sex with Men in Liaoning Province, China

“…Infection with CRF01_AE as identified in this study has been confirmed through heterosexual transmission in China, and according to the recent reports MSM contact has become a major route of local CRF01_AE transmission in some cities of China and Singapore. [20][21][22] Our results suggest that MSM contact is becoming a major route of CRF01_AE transmission in China and that various forms of HIV transmission, including both homosexual and heterosexual behavior, likely exist among MSM of Liaoning province.…”

Molecular Epidemiology of HIV Type 1 in Singapore and Identification of Novel CRF01_AE/B Recombinant Forms

“…This result was similar to the findings of the study involving 60 recent seroconverters. 9 The transmission risk factor distribution comparing CRF01_AE, subtype B, and RF1 infection differed significantly ( p ¼ 0.001), with a higher proportion of RF1-infected patients compared to CRF01_AE or subtype B patients reporting MSM and bisexual risk (85% vs. 41% vs. 62%). The intermixing of subtypes within transmission risk groups and the higher prevalence of novel recombinants in high-risk groups mirror the developments observed in neighboring countries.…”

“…However, no novel recombinant forms were detected. 9 This study aimed to update the HIV-1 molecular epidemiology and to determine the presence of intersubtype recombinants in Singapore. The three genomic regions chosen for sequencing would allow detection of all subtypes and CRFs in Southeast Asia identified to date.…”

“…Similar to previous studies, the main circulating subtypes continued to be CRF01_AE (n ¼ 61, 56.0%) and subtype B (n ¼ 26, 23.9%). 4,9 The other strains detected were CRF02_AG (n ¼ 1), CRF07_BC (n ¼ 1), CRF15_01B (n ¼ 2), CRF33_01B (n ¼ 3), and CRF34_01B (n ¼ 1). Fourteen (12.8%) of the 109 samples did not follow the pattern of any reported subtypes or CRFs, suggesting possible novel recombinant forms.…”

Zero prevalence of primary drug resistance-associated mutations to protease inhibitors in HIV-1 drug-naive patients in and around Aligarh, India

“…PIs were introduced after 2008 by the Indian government in the ART program of India as second-line treatment regimens [2]. Resistance development may differ according to primary, secondary, or polymorphic mutations [7]. Primary mutation leads to reduced drug susceptibility directly, whereas secondary mutation leads to resistance in conjunction with primary mutation [8].…”