CD4 cell eligibility thresholds: an analysis of the time to antiretroviral treatment in HIV-1 seroconverters

Minga, Albert; Lewden, Charlotte; Gabillard, Delphine; Bomisso, Germain I; Toni, Thomas-dʼAquin; Emieme, Arlette; Yapo, Vincent; Inwoley, André; Salamon, Roger; Anglaret, Xavier

doi:10.1097/qad.0b013e32834625d3

Cited by 11 publications

(15 citation statements)

References 14 publications

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“…CD4 counts are determined as part of routine clinical care, a CD4 count below 350 cells/ μ L (or an AIDS-defining illness) at diagnosis is defined as late presentation [11, 12]. However, CD4 count is an imprecise measure of TI because its rate of decline is quite variable [13–16]. …”

Section: Introductionmentioning

confidence: 99%

Estimating time of HIV-1 infection from next-generation sequence diversity

2017

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Estimating the time since infection (TI) in newly diagnosed HIV-1 patients is challenging, but important to understand the epidemiology of the infection. Here we explore the utility of virus diversity estimated by next-generation sequencing (NGS) as novel biomarker by using a recent genome-wide longitudinal dataset obtained from 11 untreated HIV-1-infected patients with known dates of infection. The results were validated on a second dataset from 31 patients. Virus diversity increased linearly with time, particularly at 3rd codon positions, with little inter-patient variation. The precision of the TI estimate improved with increasing sequencing depth, showing that diversity in NGS data yields superior estimates to the number of ambiguous sites in Sanger sequences, which is one of the alternative biomarkers. The full advantage of deep NGS was utilized with continuous diversity measures such as average pairwise distance or site entropy, rather than the fraction of polymorphic sites. The precision depended on the genomic region and codon position and was highest when 3rd codon positions in the entire pol gene were used. For these data, TI estimates had a mean absolute error of around 1 year. The error increased only slightly from around 0.6 years at a TI of 6 months to around 1.1 years at 6 years. Our results show that virus diversity determined by NGS can be used to estimate time since HIV-1 infection many years after the infection, in contrast to most alternative biomarkers. We provide the regression coefficients as well as web tool for TI estimation.

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Section: Introductionmentioning

confidence: 99%

Estimating time of HIV-1 infection from next-generation sequence diversity

2017

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“…However, CD4 count is an 16 imprecise measure of TI because its rate of decline is quite variable. [12][13][14][15] …”

mentioning

confidence: 99%

Estimating time of HIV-1 infection from next-generation sequence diversity

Puller

Neher

Albert

2017

Preprint

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Estimating the time since infection (TI) in newly diagnosed HIV-1 patients is challenging, but important to understand the epidemiology of the infection. Existing biomarkers for the recent infection are relatively imprecise. Here we explore the utility of virus diversity estimated by next-generation sequencing (NGS) as novel biomarker by using a recent genome-wide longitudinal dataset obtained from 11 untreated HIV-1-infected patients with known dates of infection.Virus diversity increased linearly with time, particularly at 3rd codon positions, with little inter-patient variation. The precision of the TI estimate improved with increasing sequencing depth, showing the superiority of NGS over counting polymorphic sites in Sanger sequences, which is one of the alternative biomarkers. The full advantage of the high sequencing resolution of NGS was utilized with continuous diversity measures, average Hamming distance or site entropy, rather than the fraction of polymorphic sites. The precision depended on the genomic region and codon position and was highest when 3rd codon positions in the entire pol gene was used. For these data TI estimates had a mean absolute error of around 1 year. The error increased only slightly from around 0.6 years at a TI of 6 months to around 1.1 year at 6 years. In addition, NGS diversity compared favorably with other biomarkers for binary classification of patients as being recently or long-term infected.Our results show that virus diversity determined by NGS can be used to estimate time since HIV-1 infection with a precision that is better than most alternative biomarkers. Importantly, TI can be estimated many years after infection. We provide regression coefficients that can be used for TI estimation.

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“…As there was no such cohort study in Cameroon, we used data from a cohort of blood donors who had documented seroconversion between donations in Côte d’Ivoire (ANRS 1220 Primo-CI study) 11 , 12 . Blood donors had been invited to participate if they met the following criteria: diagnosed with HIV during a blood donation; HIV-seronegative at the preceding donation; less than 36 months had elapsed since seroconversion.…”

Section: Methodsmentioning

confidence: 99%

“…HIV: human immunodeficiency virus; IQR: interquartile range.Data sources: ANRS 1220 Primo-CI 11 , 12 …”

Section: Methodsmentioning

confidence: 99%

“…Thus, the CD4+ cell count at seroconversion and the rate of CD4+ cell count decline are both unknown. We generated the values of these two parameters for each HIV-infected individual starting ART by using data from seroconverters 11 , 12 . Specifically, for each individual included in the survey conducted in Cameroon, we simulated 200 sets of CD4+ cell count values at seroconversion and rates of CD4+ cell count decline, as follows.…”

Section: Methodsmentioning

confidence: 99%

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New indicators for delay in initiation of antiretroviral treatment: estimates for Cameroon

Ndawinz

Anglaret

Delaporte

et al. 2015

Bull. World Health Organ.

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ObjectiveTo propose two new indicators for monitoring access to antiretroviral treatment (ART) for human immunodeficiency virus (HIV); (i) the time from HIV seroconversion to ART initiation, and (ii) the time from ART eligibility to initiation, referred to as delay in ART initiation. To estimate values of these indicators in Cameroon.MethodsWe used linear regression to model the natural decline in CD4+ T-lymphocyte (CD4+ cell) numbers in HIV-infected individuals over time. The model was fitted using data from a cohort of 351 people in Côte d’Ivoire. We used the model to estimate the time from seroconversion to ART initiation and the delay in ART initiation in a representative sample of 4154 HIV-infected people who started ART in Cameroon between 2007 and 2010.FindingsIn Cameroon, the median CD4+ cell counts at ART initiation increased from 140 cells/μl (interquartile range, IQR: 66 to 210) in 2007–2009 to 163 cells/μl (IQR: 73 to 260) in 2010. The estimated average time from seroconversion to ART initiation decreased from 10.4 years (95% confidence interval, CI: 10.3 to 10.5) to 9.8 years (95% CI: 9.6 to 10.0). Delay in ART initiation increased from 3.4 years (95% CI: 3.1 to 3.7) to 5.8 years (95% CI: 5.6 to 6.2).ConclusionThe estimated time to initiate ART and the delay in ART initiation indicate that progress in Cameroon is insufficient. These indicators should help monitor whether public health interventions to accelerate ART initiation are successful.

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CD4 cell eligibility thresholds: an analysis of the time to antiretroviral treatment in HIV-1 seroconverters

Cited by 11 publications

References 14 publications

Estimating time of HIV-1 infection from next-generation sequence diversity

Estimating time of HIV-1 infection from next-generation sequence diversity

Estimating time of HIV-1 infection from next-generation sequence diversity

New indicators for delay in initiation of antiretroviral treatment: estimates for Cameroon

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