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Impact of viral load and the duration of primary infection on HIV transmission: systematic review and meta-analysis.

ABSTRACT: HIV 'treatment as prevention' (TasP) describes early treatment of HIV-infected patients intended to reduce viral load and transmission. Crucial assumptions for estimating TasP's effectiveness are the underlying estimates of transmission risk. We aimed to determine transmission risk during primary infection, and describe the relation of HIV transmission risk to viral load.A systematic review and meta-analysis.We searched PubMed and Embase databases for studies that established a relationship between viral load and transmission risk, or primary infection and transmission risk, in serodiscordant couples. We analysed assumptions about the relationship between viral load and transmission risk, and between duration of primary infection and transmission risk.We found 36 eligible articles, based on six different study populations. Studies consistently found that higher viral loads lead to higher HIV transmission rates, but assumptions about the shape of this increase varied from exponential increase to saturation. The assumed duration of primary infection ranged from 1.5 to 12 months; for each additional month, the log10 transmission rate ratio between primary and asymptomatic infection decreased by 0.40.Assumptions and estimates of the relationship between viral load and transmission risk, and the relationship between primary infection and transmission risk, vary substantially and predictions of TasP's effectiveness should take this uncertainty into account.

SUBMITTER: Blaser N

PROVIDER: S-EPMC4058443 | biostudies-literature | 2014 Apr

REPOSITORIES: biostudies-literature

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Impact of viral load and the duration of primary infection on HIV transmission: systematic review and meta-analysis.

Blaser Nello N Wettstein Celina C Estill Janne J Vizcaya Luisa Salazar LS Wandeler Gilles G Egger Matthias M Keiser Olivia O

AIDS (London, England) 20140401 7

<h4>Objectives</h4>HIV 'treatment as prevention' (TasP) describes early treatment of HIV-infected patients intended to reduce viral load and transmission. Crucial assumptions for estimating TasP's effectiveness are the underlying estimates of transmission risk. We aimed to determine transmission risk during primary infection, and describe the relation of HIV transmission risk to viral load.<h4>Design</h4>A systematic review and meta-analysis.<h4>Methods</h4>We searched PubMed and Embase database ...[more]

PMID: 24691205

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Project description:IntroductionGuidelines for antiretroviral therapy recommend enhanced adherence counselling be provided to individuals with an initial elevated viral load before making a decision whether to switch antiretroviral regimen. We undertook this systematic review to estimate the proportion of patients with an initial elevated viral load who resuppress following enhanced adherence counselling.MethodsTwo databases and two conference abstract sites were searched from January 2012 to October 2019 for studies reporting the number of patients with an elevated viral load whose viral load was undetectable when subsequently assessed. Data were pooled using random effects meta-analysis.ResultsFifty-eight studies reported outcomes of 45,720 viraemic patients, mostly from Africa (48 studies), and among patients on first-line antiretroviral therapy (43 studies). Almost half (46.1%, 95% CI 42.6% to 49.5%) of patients with an initial elevated viral load resuppressed following an enhanced adherence intervention. Of those on first-line ART with confirmed virological failure (6280 patients, 21 studies), only 53.4% (40.1% to 66.8%) were appropriately switched to a different regimen. Resuppression was higher among studies that provided details of adherence support. The proportion resuppressing was lower among children (31.2%, 21.1% to 41.3%) and adolescents (40.4%, 15.7% to 65.2%) compared to adults (50.4%, 42.6% to 58.3%). No important differences were observed by date of study publication, gender, viral failure threshold, publication status, time between viral loads or treatment regimen. Information on resistance testing among people with an elevated viral load was inconsistently reported.ConclusionsThe findings of this review suggest that in settings with limited resources, current guideline recommendations to provide enhanced adherence counselling can result in resuppression of a substantial number of these patients, avoiding unnecessary drug regimen changes. Appropriate action on viral load results is limited across a range of settings, highlighting the importance of viral load cascade analyses to identify gaps and focus quality improvement to ensure that action is taken on the results of viral load testing.

Project description:BackgroundViral load kinetics and duration of viral shedding are important determinants for disease transmission. We aimed to characterise viral load dynamics, duration of viral RNA shedding, and viable virus shedding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in various body fluids, and to compare SARS-CoV-2, SARS-CoV, and Middle East respiratory syndrome coronavirus (MERS-CoV) viral dynamics.MethodsIn this systematic review and meta-analysis, we searched databases, including MEDLINE, Embase, Europe PubMed Central, medRxiv, and bioRxiv, and the grey literature, for research articles published between Jan 1, 2003, and June 6, 2020. We included case series (with five or more participants), cohort studies, and randomised controlled trials that reported SARS-CoV-2, SARS-CoV, or MERS-CoV infection, and reported viral load kinetics, duration of viral shedding, or viable virus. Two authors independently extracted data from published studies, or contacted authors to request data, and assessed study quality and risk of bias using the Joanna Briggs Institute Critical Appraisal Checklist tools. We calculated the mean duration of viral shedding and 95% CIs for every study included and applied the random-effects model to estimate a pooled effect size. We used a weighted meta-regression with an unrestricted maximum likelihood model to assess the effect of potential moderators on the pooled effect size. This study is registered with PROSPERO, CRD42020181914.Findings79 studies (5340 individuals) on SARS-CoV-2, eight studies (1858 individuals) on SARS-CoV, and 11 studies (799 individuals) on MERS-CoV were included. Mean duration of SARS-CoV-2 RNA shedding was 17·0 days (95% CI 15·5-18·6; 43 studies, 3229 individuals) in upper respiratory tract, 14·6 days (9·3-20·0; seven studies, 260 individuals) in lower respiratory tract, 17·2 days (14·4-20·1; 13 studies, 586 individuals) in stool, and 16·6 days (3·6-29·7; two studies, 108 individuals) in serum samples. Maximum shedding duration was 83 days in the upper respiratory tract, 59 days in the lower respiratory tract, 126 days in stools, and 60 days in serum. Pooled mean SARS-CoV-2 shedding duration was positively associated with age (slope 0·304 [95% CI 0·115-0·493]; p=0·0016). No study detected live virus beyond day 9 of illness, despite persistently high viral loads, which were inferred from cycle threshold values. SARS-CoV-2 viral load in the upper respiratory tract appeared to peak in the first week of illness, whereas that of SARS-CoV peaked at days 10-14 and that of MERS-CoV peaked at days 7-10.InterpretationAlthough SARS-CoV-2 RNA shedding in respiratory and stool samples can be prolonged, duration of viable virus is relatively short-lived. SARS-CoV-2 titres in the upper respiratory tract peak in the first week of illness. Early case finding and isolation, and public education on the spectrum of illness and period of infectiousness are key to the effective containment of SARS-CoV-2.FundingNone.

Project description:Viral load (VL) monitoring is the standard of care in developing country settings for detecting HIV treatment failure. Since 2010 the World Health Organization has recommended a phase-in approach to VL monitoring in resource-limited settings. We conducted a systematic review of the accuracy and precision of HIV VL technologies for treatment monitoring.A search of Medline and Embase was conducted for studies evaluating the accuracy or reproducibility of commercially available HIV VL assays. 37 studies were included for review including evaluations of the Amplicor Monitor HIV-1 v1.5 (n?=?25), Cobas TaqMan v2.0 (n?=?11), Abbott RealTime HIV-1 (n?=?23), Versant HIV-1 RNA bDNA 3.0 (n?=?15), Versant HIV-1 RNA kPCR 1.0 (n?=?2), ExaVir Load v3 (n?=?2), and NucliSens EasyQ v2.0 (n?=?1). All currently available HIV VL assays are of sufficient sensitivity to detect plasma virus levels at a lower detection limit of 1,000 copies/mL. Bias data comparing the Abbott RealTime HIV-1, TaqMan v2.0 to the Amplicor Monitor v1.5 showed a tendency of the Abbott RealTime HIV-1 to under-estimate results while the TaqMan v2.0 overestimated VL counts. Compared to the Amplicor Monitor v1.5, 2-26% and 9-70% of results from the Versant bDNA 3.0 and Abbott RealTime HIV-1 differed by greater than 0.5log10. The average intra and inter-assay variation of the Abbott RealTime HIV-1 were 2.95% (range 2.0-5.1%) and 5.44% (range 1.17-30.00%) across the range of VL counts (2log10-7log10).This review found that all currently available HIV VL assays are of sufficient sensitivity to detect plasma VL of 1,000 copies/mL as a threshold to initiate investigations of treatment adherence or possible treatment failure. Sources of variability between VL assays include differences in technology platform, plasma input volume, and ability to detect HIV-1 subtypes. Monitoring of individual patients should be performed on the same technology platform to ensure appropriate interpretation of changes in VL. Prospero registration # CD42013003603.

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Impact of viral load and the duration of primary infection on HIV transmission: systematic review and meta-analysis.

Publications

Impact of viral load and the duration of primary infection on HIV transmission: systematic review and meta-analysis.

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