Influence of HLA Class I Haplotypes on HIV-1 Seroconversion and Disease Progression in Pumwani Sex Worker Cohort

Raghavan, Subharekha; Peters, Harold O.; Mendoza, Luís Hurtado de; Bielawny, Thomas; Ngugi, Elizabeth; Kimani, Joshua; Wachihi, Charles; Plummer, Francis A.; Luo, Ma

doi:10.1371/journal.pone.0101475

Cited by 7 publications

(8 citation statements)

References 32 publications

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“…This is in agreement with the literature on disease progression and viral control [26–29], although the relationships between B*57 and disease control often appear to be more robust, suggesting that this allele may play a stronger role in clinical outcomes than viral suppression. Previous studies have reported B*45 to be associated with poor clinical outcomes of HIV infection [30] or higher HIV loads [31], but here we found that volunteers with B*45:01 were not associated with control; however, the allele remained in our final model, suggesting that it may play some role in characterizing viral control. Some studies have suggested the presence of the B*58:02 allele to be unfavorable [32]; similarly, our data suggested that persons with the allele may be less likely to control HIV (aOR, 0.5 [95% CI, .2–1.0]).…”

Section: Discussioncontrasting

confidence: 65%

Control of the HIV-1 Load Varies by Viral Subtype in a Large Cohort of African Adults With Incident HIV-1 Infection

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Rida²,

Kilembe

et al. 2019

The Journal of Infectious Diseases

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Few human immunodeficiency virus (HIV)–infected persons can maintain low viral levels without therapeutic intervention. We evaluate predictors of spontaneous control of the viral load (hereafter, “viral control”) in a prospective cohort of African adults shortly after HIV infection. Viral control was defined as ≥2 consecutively measured viral loads (VLs) of ≤10 000 copies/mL after the estimated date of infection, followed by at least 4 subsequent measurements for which the VL in at least 75% was ≤10 000 copies/mL in the absence of ART. Multivariable logistic regression characterized predictors of viral control. Of 590 eligible volunteers, 107 (18.1%) experienced viral control, of whom 25 (4.2%) maintained a VL of 51–2000 copies/mL, and 5 (0.8%) sustained a VL of ≤50 copies/mL. The median ART-free follow-up time was 3.3 years (range, 0.3–9.7 years). Factors independently associated with control were HIV-1 subtype A (reference, subtype C; adjusted odds ratio [aOR], 2.1 [95% confidence interval {CI}, 1.3–3.5]), female sex (reference, male sex; aOR, 1.8 [95% CI, 1.1–2.8]), and having HLA class I variant allele B*57 (reference, not having this allele; aOR, 1.9 [95% CI, 1.0–3.6]) in a multivariable model that also controlled for age at the time of infection and baseline CD4+ T-cell count. We observed strong associations between infecting HIV-1 subtype, HLA type, and sex on viral control in this cohort. HIV-1 subtype is important to consider when testing and designing new therapeutic and prevention technologies, including vaccines.

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Section: Discussioncontrasting

confidence: 65%

Control of the HIV-1 Load Varies by Viral Subtype in a Large Cohort of African Adults With Incident HIV-1 Infection

Price

Rida²,

Kilembe

et al. 2019

The Journal of Infectious Diseases

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“…Due to lack of regulatory approval, characterization of host genetic background was not undertaken in this study. Past studies have shown that certain HLA class I alleles B*35, Cw*04, A*30, B*45 are linked with accelerated disease progression,[ 42 , 43 ] while alleles A*7401 and B*57 appears to be protective. [ 44 , 45 ]…”

Section: Discussionmentioning

confidence: 99%

Association between HIV genotype, viral load and disease progression in a cohort of Thai men who have sex with men with estimated dates of HIV infection

et al. 2018

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BackgroundDifferences between HIV genotypes may affect HIV disease progression. We examined infecting HIV genotypes and their association with disease progression in a cohort of men who have sex with men with incident HIV infection in Bangkok, Thailand.MethodsWe characterized the viral genotype of 189 new HIV infections among MSM identified between 2006–2014 using hybridization and sequencing. Plasma viral load (PVL) was determined by PCR, and CD4+ T-cell counts were measured by flow cytometry. We used Generalized Estimating Equations to examine factors associated with changes in CD4+ T-cell counts. Factors associated with immunologic failure were analyzed using Cox proportional hazard models.ResultsAmong 189 MSM, 84% were infected with CRF01_AE, 11% with recombinant B/CRF01_AE and 5% with subtype B. CD4+ T-cell decline rates were 68, 65, and 46 cells/μL/year for CRF01_AE, recombinants, and subtype B, respectively, and were not significantly different between HIV subtypes. CD4+ T-cell decline rate was significantly associated with baseline PVL and CD4+ T-cell counts (p <0.001). Progression to immunologic failure was associated with baseline CD4+ T-cell ≤ 500 cells/μL (AHR 1.97; 95% CI 1.14–3.40, p = 0.015) and PVL > 50,000 copies/ml (AHR 2.03; 1.14–3.63, p = 0.017). There was no difference in time to immunologic failure between HIV subtypes.ConclusionAmong HIV-infected Thai MSM, low baseline CD4+ T-cell and high PVL are associated with rapid progression. In this cohort, no significant difference in CD4+ T-cell decline rate or time to immunologic failure was seen between CRF01_AE and other infecting HIV subtypes.

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“…The interactive effect of CD4+ T cell responses restricted by the 16 HLA class II alleles and the genetic diversity of these different HLA class II alleles could influence perinatal HIV transmission. In a previous study we have observed interactive effect of HLA class I alleles in HIV seroconversion and disease progression in the Pumwani sex worker cohort [ 37 ]. Our current study has shown the interactive effect of HLA class II genes on perinatal HIV transmission.…”

Section: Discussionmentioning

confidence: 99%

HLA Class II Antigens and Their Interactive Effect on Perinatal Mother-To-Child HIV-1 Transmission

et al. 2015

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HLA class II antigens are central in initiating antigen-specific CD4+ T cell responses to HIV-1. Specific alleles have been associated with differential responses to HIV-1 infection and disease among adults. This study aims to determine the influence of HLA class II genes and their interactive effect on mother-child perinatal transmission in a drug naïve, Mother-Child HIV transmission cohort established in Kenya, Africa in 1986. Our study showed that DRB concordance between mother and child increased risk of perinatal HIV transmission by three fold (P = 0.00035/Pc = 0.0014, OR: 3.09, 95%CI, 1.64-5.83). Whereas, DPA1, DPB1 and DQB1 concordance between mother and child had no significant influence on perinatal HIV transmission. In addition, stratified analysis showed that DRB1*15:03+ phenotype (mother or child) significantly increases the risk of perinatal HIV-1 transmission. Without DRB1*15:03, DRB1 discordance between mother and child provided 5 fold protection (P = 0.00008, OR: 0.186, 95%CI: 0.081-0.427). However, the protective effect of DRB discordance was diminished if either the mother or the child was DRB1*15:03+ phenotype (P = 0.49-0.98, OR: 0.7-0.99, 95%CI: 0.246-2.956). DRB3+ children were less likely to be infected perinatally (P = 0.0006, Pc = 0.014; OR:0.343, 95%CI:0.183-0.642). However, there is a 4 fold increase in risk of being infected at birth if DRB3+ children were born to DRB1*15:03+ mother compared to those with DRB1*15:03- mother. Our study showed that DRB concordance/discordance, DRB1*15:03, children’s DRB3 phenotype and their interactions play an important role in perinatal HIV transmission. Identification of genetic factors associated with protection or increased risk in perinatal transmission will help develop alternative prevention and treatment methods in the event of increases in drug resistance of ARV.

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Influence of HLA Class I Haplotypes on HIV-1 Seroconversion and Disease Progression in Pumwani Sex Worker Cohort

Cited by 7 publications

References 32 publications

Control of the HIV-1 Load Varies by Viral Subtype in a Large Cohort of African Adults With Incident HIV-1 Infection

Control of the HIV-1 Load Varies by Viral Subtype in a Large Cohort of African Adults With Incident HIV-1 Infection

Association between HIV genotype, viral load and disease progression in a cohort of Thai men who have sex with men with estimated dates of HIV infection

HLA Class II Antigens and Their Interactive Effect on Perinatal Mother-To-Child HIV-1 Transmission

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