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      Plasma HIV-2 RNA According to CD4 Count Strata among HIV-2-Infected Adults in the IeDEA West Africa Collaboration

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          Abstract

          Background

          Plasma HIV-1 RNA monitoring is one of the standard tests for the management of HIV-1 infection. While HIV-1 RNA can be quantified using several commercial tests, no test has been commercialized for HIV-2 RNA quantification. We studied the relationship between plasma HIV-2 viral load (VL) and CD4 count in West African patients who were either receiving antiretroviral therapy (ART) or treatment-naïve.

          Method

          A cross sectional survey was conducted among HIV-2-infected individuals followed in three countries in West Africa from March to December 2012. All HIV-2 infected-patients who attended one of the participating clinics were proposed a plasma HIV-2 viral load measurement. HIV-2 RNA was quantified using the new ultrasensitive in-house real-time PCR assay with a detection threshold of 10 copies/ mL (cps/mL).

          Results

          A total of 351 HIV-2-infected individuals participated in this study, of whom 131 (37.3%) were treatment naïve and 220 (62.7%) had initiated ART. Among treatment-naïve patients, 60 (46.5%) had undetectable plasma HIV-2 viral load (<10 cps/mL), it was detectable between 10-100 cps/mL in 35.8%, between 100-1000 cps/mL in 11.7% and >1000 cps/mL in 6.0% of the patients. Most of the treatment-naïve patients (70.2%) had CD4-T cell count ≥500 cells/mm 3 and 43 (46.7%) of these patients had a detectable VL (≥10 cps/mL). Among the 220 patients receiving ART, the median CD4-T cell count rose from 231 to 393 cells/mm 3 (IQR [259-561]) after a median follow-up duration of 38 months and 145 (66.0%) patients had CD4-T cell count ≤ 500 cells/mm 3 with a median viral load of 10 cps/mL (IQR [10-33]). Seventy five (34.0%) patients had CD4-T cell count ≥ 500 cells/mm 3, among them 14 (18.7%) had a VL between 10-100 cps/mL and 2 (2.6%) had VL >100 cps/mL.

          Conclusion

          This study suggests that the combination of CD4-T cell count and ultrasensitive HIV-2 viral load quantification with a threshold of 10 cps/mL, could improve ART initiation among treatment naïve HIV-2-infected patients and the monitoring of ART response among patients receiving treatment.

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          Most cited references18

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          Slower heterosexual spread of HIV-2 than HIV-1.

          Because of the similar virological properties of HIV types 1 and 2, HIV-2 was assumed to be as infectious and capable of inducing AIDS as HIV-1. Seroepidemiological studies have shown significant rates of HIV-2 infection in West Africa, and surveys from other regions of the world indicate that the spread of HIV-2 infection continues. However the pathogenic potential of HIV-2 is considered to be lower than that of HIV-1. It is therefore important to understand the transmission properties of HIV-2 and its contribution to the AIDS pandemic. Since 1985, we have prospectively studied 1452 registered female prostitutes in Dakar, Senegal, with sequential evaluation of their antibody status to HIV-1 and HIV-2. During the study the overall incidence of HIV-1 and HIV-2 was the same (1.11 per 100 person-years of observation [pyo]). However, the annual incidence of HIV-1 increased substantially: there was a 1.4-fold increased risk per year and thus a 12-fold increase in risk over the entire study period. The incidence of HIV-2 remained stable, despite higher HIV-2 prevalence. In our population the heterosexual spread of HIV-2 is significantly slower than that of HIV-1, which strongly suggests differences in the viruses' infectivity potential.
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            Evidence for continuing cross-species transmission of SIVsmm to humans: characterization of a new HIV-2 lineage in rural Côte d'Ivoire.

            HIV types 1 and 2 (HIV-1 and HIV-2) are the result of multiple cross-species transmissions of their simian counterparts (SIVs) to humans. We studied whether new SIVs lineages have been transmitted to humans in rural Côte d'Ivoire and identified a novel HIV-2 variant (HIV-2-07IC-TNP03) not related to any of the previously defined HIV-2 groups. This finding shows that sooty mangabey viruses continue to be transmitted to humans, causing new zoonotic outbreaks.
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              Inhibition of HIV-2 protease by HIV-1 protease inhibitors in clinical use.

              Over the past 10 years, protease inhibitors have been a key component in antiretroviral therapies for HIV/AIDS. While the vast majority of HIV/AIDS cases in the world are due to HIV-1, HIV-2 infection must also be addressed. HIV-2 is endemic to Western Africa, and has also appeared in European countries such as Portugal, Spain, and Estonia. Current protease inhibitors have not been optimized for treatment of HIV-2 infection; therefore, it is important to assess the effectiveness of currently FDA-approved protease inhibitors against the HIV-2 protease, which shares only 50% sequence identity with the HIV-1 protease. Kinetic inhibition assays were performed to measure the inhibition constants (K(i)) of the HIV-1 protease inhibitors indinavir, nelfinavir, saquinavir, ritonavir, amprenavir, lopinavir, atazanavir, tipranavir, and darunavir against the HIV-2 protease. Lopinavir, saquinavir, tipranavir, and darunavir exhibit the highest potency with K(i) values of 0.7, 0.6, 0.45, and 0.17 nm, respectively. These K(i) values are 84, 2, 24, and 17 times weaker than the corresponding values against the HIV-1 protease. In general, inhibitors show K(i) ratios ranging between 2 and 80 for the HIV-2 and HIV-1 proteases. The relative drop in potency is proportional to the affinity of the inhibitor against the HIV-1 protease and is related to specific structural characteristics of the inhibitors. In particular, the potency drop is high when the maximum cap size of the inhibitors consists of very few atoms. Caps are groups located at the periphery of the molecule that are added to core structures to increase the specificity of the inhibitor to its target. The caps positioned on the HIV-1 protease inhibitors affect selectivity through interactions with distinct regions of the binding pocket. The flexibility and adaptability imparted by the higher number of rotatable bonds in large caps enables an inhibitor to accommodate changes in binding pocket geometry between HIV-1 and HIV-2 protease.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                25 June 2015
                2015
                : 10
                : 6
                : e0129886
                Affiliations
                [1 ]Université de Bordeaux, ISPED, Centre INSERM U897- Epidémiologie-Biostatistique, Bordeaux, France
                [2 ]Inserm U897, ISPED, Université de Bordeaux, Bordeaux, France
                [3 ]Programme PACCI, site de recherche ANRS, Abidjan, Côte d’Ivoire
                [4 ]Département de Santé Publique, Université de Lomé, Lomé, Togo
                [5 ]AP-HP, Hôpital Necker Enfants Malades, Laboratoire de Virologie, Paris, France
                [6 ]Université Paris-Descartes, Sorbonne Paris Cité, Faculté de Médecine, EA7327, Paris, France
                [7 ]Service des Maladies Infectieuses et Tropicales, CHU de Treichville, Abidjan, Côte d’Ivoire
                [8 ]Hôpital de Jour, Service des Maladies Infectieuses et Tropicales, CHU SouroSanou, Bobo Dioulasso, Burkina-Faso
                [9 ]Centre de Prise en Charge des Personnes vivant avec le VIH, Hôpital du Point G, Bamako, Mali (service des Maladies Infectieuses)
                [10 ]Centre Médical de Suivi de Donneurs de Sang/CNTS/PRIMO-CI, Abidjan, Côte d’Ivoire
                [11 ]Laboratoire associé au Centre National de Référence du VIH, hôpital Charles Nicolle, CHU de Rouen, Rouen, France
                [12 ]GRAM, Equipe d’Accueil 2656, Faculté de Médecine-Pharmacie, Institut de Recherche et d'Innovation en Biomédecine, Université de Rouen, Rouen, France
                [13 ]INSERM, IAME, UMR 1137, Paris, France
                [14 ]Université Paris Diderot, Sorbonne Paris Cité, Paris, France
                [15 ]AP-HP, Hôpital Bichat-Claude Bernard, Laboratoire de Virologie, Paris, France
                CEA, FRANCE
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: DKE F. Dabis CR. Performed the experiments: VA. Analyzed the data: BT PAC. Contributed reagents/materials/analysis tools: DM AS AM JCP F. Damond SPE. Wrote the paper: BT DKE CR VA PAC F. Dabis F. Damond JCP. Enrolled the patients and supervised the study on clinical sites: DM AS AM SPE. Contributed to the critical review of the manuscript: DKE VA BT PAC AS DM AM SPE JCP F. Damond F. Dabis CR.

                Article
                PONE-D-15-08926
                10.1371/journal.pone.0129886
                4482391
                26111242
                c158bd9c-91e9-4c69-9597-05fcf132f9cc
                Copyright @ 2015

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

                History
                : 10 March 2015
                : 14 May 2015
                Page count
                Figures: 3, Tables: 1, Pages: 11
                Funding
                The HIV-2 Cohort of the WADA Collaboration is partly funded by the National Cancer Institute (NCI), the Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD), and the National Institute of Allergy and Infectious Diseases (NIAID) of the US National Institutes of Health (NIH), as part of the International Epidemiologic Databases to Evaluate AIDS (IeDEA) under Award # U01AI069919. The ANRS (France REcherche Nord &sudSida-hivHépatites: FRENSH) supported part of the laboratory work performed within this study. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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