Association between cellular HIV-1 DNA level and mortality in HIV-1 infected African adults starting ART with high CD4 counts

N’Takpé, Jean Baptiste; Gabillard, Delphine; Moh, Raoul; Gardiennet, Elise; Emieme, Arlette; Badjé, Anani; Kouamé, Gérard Menan; Toni, Thomas-d’Aquin; Karcher, Sophie; Carrou, Jérôme Le; Menan, Hervé; Danel, Christine; Eholié, Serge; Rouzioux, Christine; Anglaret, Xavier

doi:10.1016/j.ebiom.2020.102815

Cited by 7 publications

(13 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Peripheral blood mononuclear cells (PBMCs ) , plasma and serum were then stored at −80°C. After trial termination, PBMC HIV‐1 DNA [11] and plasma soluble vascular cell adhesion molecule‐1 (sVCAM‐1) levels were measured using samples frozen at baseline in all patients from immediate and deferred ART groups, and plasma sVCAM‐1 was measured at 12 months in patients from the immediate ART groups. Concentrations of sVCAM‐1 were assessed by sandwich enzyme‐linked immunosorbent assays (ELISAs) according to the manufacturer’s protocols (R&D Systems, Minneapolis, MN, USA).…”

Section: Methodsmentioning

confidence: 99%

Plasma sVCAM‐1, antiretroviral therapy and mortality in HIV‐1‐infected West African adults

et al. 2022

Self Cite

View full text Add to dashboard Cite

Objectives:We report the association between pre-antiretroviral therapy (pre-ART) soluble vascular cell adhesion molecule-1 (sVCAM-1) levels and long-term mortality in HIV-infected West African adults participating in a trial of early ART in West Africa (Temprano ANRS 12136 trial). Methods:The ART-naïve HIV-infected adults were randomly assigned to start ART immediately or defer ART until the WHO criteria were met. Participants who completed the trial follow-up were invited to participate in a post-trial phase (PTP). The PTP end-point was all-cause death. We used multivariable Cox proportional models to analyse the association between baseline sVCAM-1 and allcause death, adjusting for ART strategy, sex, CD4 count, plasma HIV-1 RNA and peripheral blood mononuclear cell HIV-1 DNA levels.Results: In all, 954 adults (77% women, median CD4 count of 387 cells/μL) were randomly assigned to start ART immediately (n = 477) or to defer initiation of ART (n = 477). They were followed for a median of 5.8 years [interquartile range (IQR): 5.2-6.3]. In multivariable analysis, the risk of death was significantly associated with baseline sVCAM-1 [≥1458 vs. < 1458 ng/mL; adjusted hazard ratio = 2.86, 95% confidence interval (CI): 1.60-5.11]. The 6-year probability of death rates were 14.4% (95%CI: 9.1-22.6) and 9.4% (5.4-16.1) in patients with baseline sVCAM-1 ≥ 1458 ng/mL randomized to deferred and immediate ART, respectively, and 3.8% (2.2-6.5) and 3.5% (1.9-6.3) in patients with baseline sVCAM-1 < 1458 ng/mL randomized to deferred and immediate ART. The median difference between pre-ART and 12-month sVCAM-1 levels in patients randomized to immediate ART was −252 (IQR: −587 to −61).Conclusions: Pre-ART sVCAM-1 levels were significantly associated with mortality, independently of whether ART was started immediately or deferred, but they significantly decreased after 12 months of ART.

show abstract

Section: Methodsmentioning

confidence: 99%

Plasma sVCAM‐1, antiretroviral therapy and mortality in HIV‐1‐infected West African adults

et al. 2022

Self Cite

View full text Add to dashboard Cite

show abstract

“…The HIV-1 DNA real-time PCR was carried out in the virology laboratory at the Necker University Hospital in Paris. The technique was based on amplification of the Long Terminal Repeat (LTR) gene, well adapted to HIV-1 non-B subtypes, and reference to the 8E5 cell line containing one HIV copy per cell (HIV DNA cell, Biocentric, Bandol, France) [ 13 ]. The threshold for the technique was five copies of HIV-1 DNA per PCR well.…”

Section: Methodsmentioning

confidence: 99%

Association of cellular HIV-1 DNA and virological success of antiretroviral treatment in HIV-infected sub-Saharan African adults

et al. 2022

Self Cite

View full text Add to dashboard Cite

Background HIV-1 DNA persists in infected cells, forming viral reservoirs. Pre-antiretroviral treatment (ART) HIV-1 DNA load was reported to predict ART success in European severely immunocompromised patients. The aim of this study was to determine whether HIV-1 DNA levels are associated with virological success in less severely immunocompromised patients who receive early ART in sub-Saharan Africa. Methods The association between pre-ART HIV-1 DNA and the virological response after 30 months on ART was studied in multivariate logistic regression in patients randomised to immediate ART groups in the Temprano trial, which assessed the benefits of early ART in HIV-infected adults in Côte d’Ivoire. HIV-1 DNA was quantified in peripheral blood mononuclear cell (PBMC) using real-time PCR. Results HIV-1 DNA levels were measured in 1013 patients. Their medians [IQR] of pre-ART CD4 count, HIV-1 RNA and HIV-1 DNA levels were 465 [379–578]/mm3, 4.7 [4.0–5.3] log10 copies/ml and 2.9 [2.5–3.2] log10 copies/million PBMC, respectively. Pre-ART HIV-1 DNA was significantly correlated with pre-ART HIV-1 RNA (R = 0.59, p < 0.0001). In multivariate analysis, HIV-1 DNA < 3 log10 copies/million PBMC was significantly associated with virological success at M30 after adjustment for other key variables (ART regimen, IPT, sex, age, WHO clinical stage, CD4 and HIV-1 RNA; aOR 1.57; 95% CI 1.08–2.30; p = 0.02). Conclusion Low HIV-1 DNA was statistically associated with virological success in this population of sub-Saharan African adults who started treatment with a median pre-ART CD4 count at 465/mm3. HIV-1 DNA could become a useful tool for guiding some therapeutic decisions in the test-and-treat era. Trial registration TEMPRANO ANRS 12136 ClinicalTrials.gov, number NCT00495651, date of registration 03/07/2007.

show abstract

“…The CD4 + percentage and absolute count (True Count technique on FACScan, Becton Dickinson) and plasma HIV-1 RNA (real-time polymerase-chain reaction assay, generic HIV viral load, Biocentric, threshold of detectability 50 copies/ml) were carried out in the CeDReS laboratory at the Treichville University Hospital in Côte d’Ivoire. PBMCs HIV-1 DNA (real-time PCR, Biocentric, Bandol, France) and inflammatory biomarkers (commercially available enzyme-linked immunosorbent assays) were carried out in France using techniques previously reported [ 17 , 18 ]. The technique was based on the amplification of the long terminal repeat (LTR) gene well adapted to HIV-1 non B sub-types and referring to the 8E5 cell line containing one HIV copy per cell (HIV DNA cell, Biocentric, Bandol, France).…”

Section: Methodsmentioning

confidence: 99%

Elite and viremic HIV-1 controllers in West Africa

N’Takpé

Gabillard

Moh

et al. 2021

Aids

Self Cite

View full text Add to dashboard Cite

Background: Data on HIV-1 controllers in Africa are scarce. We report the proportion of HIV-1 controllers in a group of adults prospectively monitored with frequent viral load measurements as part of a clinical trial in West Africa. Methods: For the Temprano trial, antiretroviral therapy (ART)-naive HIV-1 infected adults with no criteria for starting ART were randomized to start ART immediately or defer ART until the WHO starting criteria were met. Plasma viral load was measured every 6 months. The trial follow-up was 30 months. We considered all Temprano participants randomized to defer ART. Patients with all semestrial viral <2000 copies/ml and still off ART at month 30 were defined as HIV-1 controllers. Controllers with all viral loads <50 copies/ml were defined as elite controllers, the rest as viremic controllers. Results: Of the 1023 HIV-1-infected adults randomized in the Temprano deferred-ART group, 18 (1.8%) met the criteria for classification as HIV controllers, of whom seven (0.7%) were elite controllers and 11 (1.1%) viremic controllers. The HIV-1 controllers had low peripheral blood mononuclear cell HIV-1 DNA and low inflammatory marker levels. They maintained high CD4 + cell count and percentages and had a low morbidity rate. Discussion: HIV controllers exist in Africa at a proportion close to that reported elsewhere. They represent a small fraction of all HIV-1-infected patients but raise important questions. Further studies should assess whether starting ART might represent more risk than benefit for some controllers, and where it does, how to identify these patients before they start ART.

show abstract

Association between cellular HIV-1 DNA level and mortality in HIV-1 infected African adults starting ART with high CD4 counts

Cited by 7 publications

References 22 publications

Plasma sVCAM‐1, antiretroviral therapy and mortality in HIV‐1‐infected West African adults

Plasma sVCAM‐1, antiretroviral therapy and mortality in HIV‐1‐infected West African adults

Association of cellular HIV-1 DNA and virological success of antiretroviral treatment in HIV-infected sub-Saharan African adults

Elite and viremic HIV-1 controllers in West Africa

Contact Info

Product

Resources

About