Dataset Information

Association Between Single-Nucleotide Polymorphisms in HLA Alleles and Human Immunodeficiency Virus Type 1 Viral Load in Demographically Diverse, Antiretroviral Therapy-Naive Participants From the Strategic Timing of AntiRetroviral Treatment Trial.

ABSTRACT: The impact of variation in host genetics on replication of human immunodeficiency virus type 1 (HIV-1) in demographically diverse populations remains uncertain. In the current study, we performed a genome-wide screen for associations of single-nucleotide polymorphisms (SNPs) to viral load (VL) in antiretroviral therapy-naive participants (n = 2440) with varying demographics from the Strategic Timing of AntiRetroviral Treatment (START) trial. Associations were assessed using genotypic data generated by a customized SNP array, imputed HLA alleles, and multiple linear regression. Genome-wide significant associations between SNPs and VL were observed in the major histocompatibility complex class I region (MHC I), with effect sizes ranging between 0.14 and 0.39 log10 VL (copies/mL). Supporting the SNP findings, we identified several HLA alleles significantly associated with VL, extending prior observations that the (MHC I) is a major host determinant of HIV-1 control with shared genetic variants across diverse populations and underscoring the limitations of genome-wide association studies as being merely a screening tool.

SUBMITTER: Ekenberg C

PROVIDER: S-EPMC6743845 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

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Association Between Single-Nucleotide Polymorphisms in HLA Alleles and Human Immunodeficiency Virus Type 1 Viral Load in Demographically Diverse, Antiretroviral Therapy-Naive Participants From the Strategic Timing of AntiRetroviral Treatment Trial.

Ekenberg Christina C Tang Man-Hung MH Zucco Adrian G AG Murray Daniel D DD MacPherson Cameron Ross CR Hu Xiaojun X Sherman Brad T BT Losso Marcelo H MH Wood Robin R Paredes Roger R Molina Jean-Michel JM Helleberg Marie M Jina Nureen N Kityo Cissy M CM Florence Eric E Polizzotto Mark N MN Neaton James D JD Lane H Clifford HC Lundgren Jens D JD

The Journal of infectious diseases 20190901 8

The impact of variation in host genetics on replication of human immunodeficiency virus type 1 (HIV-1) in demographically diverse populations remains uncertain. In the current study, we performed a genome-wide screen for associations of single-nucleotide polymorphisms (SNPs) to viral load (VL) in antiretroviral therapy-naive participants (n = 2440) with varying demographics from the Strategic Timing of AntiRetroviral Treatment (START) trial. Associations were assessed using genotypic data genera ...[more]

PMID: 31219150

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Project description:ObjectivesA proportion of HIV-positive people have condomless sex. Antiretroviral treatment (ART) reduces infectiousness, but a substantial proportion of HIV-diagnosed people are not yet on ART. We describe baseline self-reported risk behaviours in ART-naïve Strategic Timing of AntiRetroviral Treatment (START) trial participants.MethodsAll START participants completed a risk behaviour questionnaire. Data were collected on sociodemographics, lifestyle factors, health and wellbeing status and clinical status. Recent sexual behaviour and HIV transmission beliefs in the context of ART were also assessed. The primary interest was in condomless sex with serodifferent partners (CLS-D) in the past two months.ResultsA total of 4601 of 4685 HIV-positive participants (98%) completed the questionnaire [2559 men who have sex with men (MSM), 803 heterosexual men and 1239 women]. Region of recruitment was Europe/Israel, 33%; South America/Mexico, 25%; Africa, 22%; other, 21%. Median age was 36 years [interquartile range (IQR) 29, 44 years]. Forty-five per cent reported white ethnicity and 31% black ethnicity. Two per cent had HIV viral load < 50 HIV-1 RNA copies/mL. Seventeen per cent (767 of 4601) reported CLS-D; 20% of MSM compared with 10% of heterosexual men and 14% of women. MSM were also more likely to report multiple CLS-D partners. Possible risk limitation measures (reported by more than half of those who had CLS-D) were seropositioning (receptive anal CLS-D only) or withdrawal (insertive anal CLS-D always without ejaculation). CLS-D was more commonly reported by participants from South America/Mexico and North America compared with Europe; among heterosexual men and women CLS-D was also more commonly reported among participants from Africa compared with Europe. Knowledge of ART impact on transmission risk was low.ConclusionsA substantial minority recruited to the START study reported CLS-D at baseline. CLS-D reporting was higher in MSM than heterosexuals and varied significantly according to region of recruitment. A substantial proportion of MSM reporting CLS-D appear to take transmission risk limitation measures.

Project description:HIV infection and certain antiretroviral therapy (ART) medications increase atherosclerotic cardiovascular disease risk, mediated, in part, through traditional cardiovascular disease risk factors. We studied cardiovascular disease risk factor changes in the START (Strategic Timing of Antiretroviral Treatment) trial, a randomized study of immediate versus deferred ART initiation among HIV-positive persons with CD4+ cell counts >500 cells/mm3. Mean change from baseline in risk factors and the incidence of comorbid conditions were compared between groups. The characteristics among 4685 HIV-positive START trial participants include a median age of 36 years, a CD4 cell count of 651 cells/mm3, an HIV viral load of 12 759 copies/mL, a current smoking status of 32%, a median systolic/diastolic blood pressure of 120/76 mm Hg, and median levels of total cholesterol of 168 mg/dL, low-density lipoprotein cholesterol of 102 mg/dL, and high-density lipoprotein cholesterol of 41 mg/dL. Mean follow-up was 3.0 years. The immediate and deferred ART groups spent 94% and 28% of follow-up time taking ART, respectively. Compared with patients in the deferral group, patients in the immediate ART group had increased total cholesterol and low-density lipoprotein cholesterol and higher use of lipid-lowering therapy (1.2%; 95% CI, 0.1-2.2). Concurrent increases in high-density lipoprotein cholesterol with immediate ART resulted in a 0.1 lower total cholesterol to high-density lipoprotein cholesterol ratio (95% CI, 0.1-0.2). Immediate ART resulted in 2.3% less BP-lowering therapy use (95% CI, 0.9-3.6), but there were no differences in new-onset hypertension or diabetes mellitus. Among HIV-positive persons with preserved immunity, immediate ART led to increases in total cholesterol and low-density lipoprotein cholesterol but also concurrent increases in high-density lipoprotein cholesterol and decreased use of blood pressure medications. These opposing effects suggest that, in the short term, the net effect of early ART on traditional cardiovascular disease risk factors may be clinically insignificant." URL: http://www.clinicaltrials.gov. Unique identifier: NCT00867048.

Dataset Information

Association Between Single-Nucleotide Polymorphisms in HLA Alleles and Human Immunodeficiency Virus Type 1 Viral Load in Demographically Diverse, Antiretroviral Therapy-Naive Participants From the Strategic Timing of AntiRetroviral Treatment Trial.

Publications

Association Between Single-Nucleotide Polymorphisms in HLA Alleles and Human Immunodeficiency Virus Type 1 Viral Load in Demographically Diverse, Antiretroviral Therapy-Naive Participants From the Strategic Timing of AntiRetroviral Treatment Trial.

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