Doctor Educationis / Background: In an attempt to avert the HIV/AIDS epidemic, more research has been conducted to determine why the epidemic is more devastating in Southern African countries than anywhere else in the world. Heterosexual transmission is believed to be driving the epidemic in many sub-Saharan African countries. Recent research has indicated that having concurrent sexual partners is one of the factors contributing to the fast spread of HIV transmission in this region.Aim: This study aimed to describe the level of knowledge about the risk of HIV transmission posed by concurrent sexual partnering as well as beliefs and practices about concurrent partnering among education students at the Rundu College of Education(RCE) in the Kavango region of Namibia. Concurrent partnering was defined as a situation where a person has more than one sexual partner at the same time, during the twelve months preceding the study.Methodology: There were 374 students registered for the 2009 academic year at RCE.All registered students were targeted for the study and 278 completed the questionnaire,yielding a response rate of 73.4%. The survey described prevalence of concurrent partnering, knowledge about risk posed by concurrent partnering as well as beliefs about concurrent partnering.Data collected was analyzed using Statistical Programs for Social Sciences (SPSS).Descriptive statistics were used to describe the prevalence of sexual concurrency,knowledge about risk posed by concurrent partnering and beliefs about concurrent partnering among the study population. Frequency of concurrency was cross tabulated with demographic variables like age group, sex and year of study as well as by knowledge and beliefs about sexual concurrent partnering.Results: The prevalence of concurrency in this sample was 9.4% with significantly higher prevalence (13.0%) among male students compared to females (5.3%). Males reported knowledge levels of 85.7% to 88.4% while females reported knowledge levels of 89.3% and 93.1%. More men (28.8%) than women (10.7%) agreed with the statement that sexual concurrency is a sign of manhood (p=0.00). Further, more male students(27.9%) compared to female students (6.1%) agreed with the statement that sexual concurrency is part of African culture and should continue (p=0.00).Conclusion: The study results show a high knowledge of risk posed by concurrency. It further reveals that a high number of people believe that concurrency is acceptable especially among men.HIV prevention activities promoting partner reduction and mutual fidelity should be implemented. Such activities should focus more on behavior change rather than on information giving. There is a need to create platforms for community members to debate on cultural beliefs about sexual concurrency.

Quinze ans après la mise en place et l’accès élargi au traitement antirétroviral (TAR) dans les pays du Sud, la suppression virale, objectif clé de son efficacité, n’est pas atteinte chez de nombreux patients infectés par le VIH. Contrairement aux pays du Nord, où un TAR souvent plus puissant et plus robuste couplé à un suivi virologique de routine limite l’émergence de la résistance, la situation des patients vivant actuellement dans les pays du Sud est beaucoup plus préoccupante. La recherche opérationnelle menée ici vise à améliorer leur prise en charge basée sur l’approche globale de santé publique de l’OMS, et aussi leur suivi. Alors qu’elle est recommandée en routine depuis 2013, la charge virale (CV) du VIH est peu accessible et le suivi des patients reste principalement clinique voire immunologique.Dans plusieurs pays d’Afrique Centrale et de l’Ouest, nous avons documenté une multi-résistance chez presque la totalité des patients en échec virologique après une longue durée de TAR de 1ère ligne, composé de 2 inhibiteurs nucléosidiques de la transcriptase inverse (INTI, 3TC+AZT/d4T) associés à 1 inhibiteur non nucléosidique de la transcriptase inverse (INNTI, EFV/NVP). Cette résistance compromet aussi l’efficacité des INNTIs de 2ème génération, de façon importante, et aussi celle du TDF qui est actuellement recommandé en 2ème ligne. De façon plus inhabituelle, nous avons aussi rapporté que les CV élevées(>5 log10 copies/mL) étaient associées à une multi-résistance plutôt qu’à un défaut d’observance chez ces patients largement asymptomatiques. Sans véritable amélioration du suivi, au travers d’un accès élargi au test de CV permettant un diagnostic précoce de l’échec virologique, une nouvelle épidémie potentielle causée par des souches résistantes pourrait émerger en Afrique subsaharienne. Elle pourrait compromettre les efforts à réaliser pour atteindre l’objectif « 90-90-90 » (90% des infections diagnostiquées, 90% des patients diagnostiqués sous TAR, 90% des patients traités en succès virologique durable) de l’ONUSIDA et de l’OMS en 2020. En outre, notre deuxième étude menée au sein d’un hôpital de district camerounais illustre le fait que ces objectifs ambitieux seront probablement encore plus difficiles à atteindre en zones décentralisées, disposant souvent d’infrastructures de laboratoires inadaptées pour accueillir des plateformes de CV complexes.Nous avons ensuite transféré avec succès un test de CV ouvert et polyvalent universel au sein d’un laboratoire national de référence au Cameroun, capable de détecter les VIH-1 M, N, O et P, ainsi que leurs ancêtres simiens. Avec ce test RT-qPCR VIH-1/SIVcpz/SIVgor, nous avons mesuré une meilleure quantification des variants du VIH-1 M (+0.47 log10 copies/mL), comparé au test Abbott RealTime HIV-1 approuvé par la FDA. Au seuil d’échec virologique de l’OMS (1 000 copies/mL), la concordance des résultats entre les deux tests était de 95%, avec une meilleure sensibilité pour le nouveau test.Nous avons finalement cherché à savoir comment adapter ce test ouvert à une application optimale à grande échelle sur du sang séché sur papier buvard (DBS, dried blood spot en anglais), pour rendre la CV accessible en zones décentralisées, en l’absence actuelle de tests de CV simples (POC, point of care en anglais). Nous avons comparé différentes méthodes d’extraction des acides nucléiques pour réduire l’impact de l’ADN pro-viral afin d’améliorer en vain la spécificité du test sur DBS. Nous avons plutôt montré qu’avec la plupart des tests de CV par RT-qPCR, de nombreux patients pourraient être candidats pour refaire une CV de façon inappropriée (voire changer de TAR pour une 2ème ligne), ce qui induirait un surcoût programmatique.En conclusion, ces travaux de thèse ont contribué à améliorer les connaissances sur l’efficacité réelle des programmes et services de TAR, ainsi que sur l’utilisation d’outils de suivi virologique adaptés aux patients vivant avec le VIH dans les pays du Sud. / Fifteen years after the introduction and expanded access to antiretroviral therapy (ART) in resource limited countries (RLC), viral suppression, a key objective of its effectiveness is not achieved in many patients infected with HIV. Unlike developed countries, where often more powerful and robust ART coupled with a routine virological monitoring limit the emergence of resistance, the current situation of RLC is more worrying. Operational research conducted here aims to improve care and monitoring of patients living in these countries, and receiving ART according to the WHO public health approach. While recommended routinely since 2013, HIV viral load (VL) is rarely available and monitoring remains primarily clinical or immunological.In several countries in Central Africa and West, we documented high rates of HIV drug resistance (HIVDR) (99%) and multi-drug resistance (97%) in patients with virologic failure after long-term first-line ART, consisting of 2 nucleoside reverse transcriptase inhibitors (NRTI, 3TC+AZT/d4T) associated with 1 non-NRTI (NNRTI, EFV/NVP). This multi-drug resistance also reduces significantly the effectiveness of second-generation NNRTIs and of the NRTI, TDF, which is now currently recommended in 2nd line by the WHO. More unusually, we also reported that high VLs (> 5 log 10 copies / ml) are associated with multi-resistance rather than an insufficient adherence in these patients who were largely asymptomatic. Without improvement of patient monitoring, through expanded access to VL testing to enable early diagnosis of virological failure, a potential new epidemic caused by HIVDR strains could emerge in sub-Saharan Africa. This could jeopardize efforts to achieve the "90-90-90" objective (90% of diagnosed infections, 90% of diagnosed patients on ART, 90% of patients treated durable virologic success) of UNAIDS and WHO in 2020. Moreover, our second study in a district hospital in Cameroon illustrates that these ambitious targets will probably be even more difficult to achieve in decentralized areas, often having inadequate laboratory infrastructure to acquire complex VL platforms.We then successfully transferred an open and polyvalent universal VL assay in a national reference laboratory in Cameroon. This assay can detect HIV-1 group M, N, O and P and their simian ancestors. With this RT-qPCR HIV-1/SIVcpz/SIVgor assay, HIV-1 M variants were better quantified (+0.47 log10 copies / mL) compared to Abbott RealTime HIV-1 assay which is approved by the FDA. At the VL threshold of virological failure defined by the WHO (1000 copies/mL), the correlation of the results between the two tests was 95%, with a higher sensitivity for the new test.We finally explored how to adapt this open test at optimal large-scale application for dried blood spot (DBS), to make VL testing available in decentralized areas, given the current lack of point of care test for VL. We compared different extraction methods of nucleic acids that could potentially reduce the contribution of the pro-viral DNA present in DBS, with the aim to improve their specificity without success. Instead, we have shown that with most of the RT-qPCR VL assays, many patients would be inappropriately eligible to perform a repeated VL testing (or switched to a costly 2nd line ART), which increase significantly costs of national programs.In conclusion, the studies from this thesis have contributed to improve current knowledge about the effectiveness of ART programs and services and also on the use of virological monitoring tools adapted to patients living with HIV in RLCs.

Introdução: A AIDS (Síndrome da Imunodeficiência Adquirida) é caracterizada por uma disfunção grave no sistema imunológico causada por uma infecção por HIV (Human Immunodeficiency Virus). A quantificação da viremia (carga viral) é uma ferramenta muito útil no monitoramento dos pacientes infectados pelo HIV, sendo um marcador de progressão da doença e eficácia do tratamento. A estimativa incorreta da carga viral pode levar à decisão terapêutica equivocada, portanto métodos acurados de quantificação se fazem necessários. Diversas técnicas comerciais estão disponíveis para a quantificação da carga viral do HIV-1: a maioria destas se baseiam na detecção de ácidos nucléicos e outras na detecção de enzimas e antígenos. O grau de automação varia nas diferentes técnicas assim como os procedimentos de isolamento, amplificação e detecção. A correlação e a concordância entre estas técnicas têm sido estudadas e há relatos de discordância entre os valores de carga viral produzidos por diferentes métodos. O conhecimento sobre o efeito das variações entre as técnicas se faz necessário para assegurar a interpretação adequada dos resultados. A interpretação dos resultados correta é particularmente importante quando estes estão próximos a pontos de corte utilizados para definições de rebote viral e falha virológica. Objetivos: O objetivo deste estudo é comparar as técnicas de PCR (Cobas AmpliPrep TaqMan HIV-1 v2.0) e b-DNA (Siemens Versant HIV-1 RNA 3.0) para quantificação do HIV-1. Métodos: 1000 amostras recebidas no HIV/GUM Research Laboratory do Chelsea and Westminster Hospital para quantificação da carga viral do HIV-1 durante os meses de Dezembro de 2009 e Janeiro de 2010 foram testadas pelos métodos de PCR (Cobas AmpliPrep TaqMan HIV-1 v2.0) e b-DNA (Siemens Versant HIV-1 RNA 3.0). Resultados: Uma superquantificação sistemática foi observada nos resultados testados por PCR. Esta superquantificação ficou evidente nos resultados entre 50 e 250 cópias. Uma concordância elevada foi observada na análise dos pontos de corte de 500 e 1000 copias/mL. Uma correlação linear forte foi observada entre estas técnicas na análise das amostras que obtiveram resultados dentro do limite comum de detecção de ambas as técnicas, porém o nível de concordância foi insatisfatório. Conclusão: A superquantificação observada nos resultados obtidos pelo Cobas AmpliPrep TaqMan HIV- 1 v2.0 em relação ao bDNA Siemens Versant HIV-1 RNA 3.0 é provavelmente o resultado de uma sensibilidade aumentada desta técnica. Nós recomendamos cautela quando resultados de duas metodologias diferentes são comparados, especialmente quando se comparam metodologias convencionais com aquelas baseadas em PCR em tempo real. / Introduction: AIDS (Acquired Immunodeficiency Syndrome) is characterised by a severe immune dysfunction caused by the HIV (Human Immunodeficiency Virus). The HIV viral load quantification is an essential tool to monitor HIV-infected patients. The HIV quantification is a disease progression marker and it is a key indicator in treatment efficacy. Inaccurate viral RNA values may subsequently lead to inappropriate treatment decisions hence accurate quantification methods are necessary. Several different methodologies are available to quantify the HIV viral load: a number of them are based on nucleic acid detection and others in detection of enzymes and antigens. Automation is also variable among these methods in addition to differences in isolation, amplification and detection. Several studies have been carried out to evaluate their correlation and agreement and some have evidenced discordant viral load values assessed by different assays. The knowledge about these differences should be taken in to account when analysing viral load results, particularly when low-level viraemia is concerned or those close to endpoints employed for definition of virological failure. Objectives: In this study, two methods to quantify viral load are evaluated: one is based on real-time PCR (AmpliPrep TaqMan HIV-1 v2.0) and the other is based on branched-DNA technology (Siemens Versant HIV-1 RNA 3.0). Methods: 1000 plasma samples received at the HIV/GUM Research Laboratory within Chelsea and Westminster Hospital for HIV-1 viral load quantification between December 2009 and January 2010 were tested by both Cobas AmpliPrep TaqMan HIV-1 v2.0 and Siemens Versant HIV-1 RNA 3.0 methods. Results: Results obtained show that Cobas AmpliPrep TaqMan HIV-1 v2.0 PCR systematically overquantifies the viral loads results when compared to bDNA Siemens Versant HIV-1 RNA 3.0. Conclusion: The overquantification by Cobas AmpliPrep TaqMan HIV-1 v2.0 over bDNA Siemens Versant HIV-1 RNA 3.0 is likely to be a result of its increased sensitivity. We recommend caution when comparing results from different methodologies, especially when a conventional assay and a real-time PCR assay are concerned.

No description available.

In the United States, individuals of Hispanic ethnicity receive disproportionately lower-quality healthcare. These healthcare disparities exacerbate unequal access to quality healthcare services, including disparities in cardiovascular disease (CVD) and human immunodeficiency virus (HIV) care. Research on the role of ethnicity on the CVD outcomes of people living with HIV (PLWH) has been limited. We hypothesize that immunological (CD4+ cell count) and virological (HIV viral load) control may play a role in the development of acute myocardial infarction (AMI) among PLWH, and that Hispanic ethnicity may worsen these outcomes. To verify our hypotheses, we conducted a retrospective cross-sectional study to investigate the strength and direction of association between CD4+ cell count (immunological cohort, n=513) and HIV viral load (virological cohort, n=261) on AMI among respondents of the All of Us Research Program. Hispanic and non-Hispanic respondents for both cohorts were comparable in terms of demographic characteristics, except for a significantly different distribution by race. While we identified increased proportion of non-Hispanic individuals with AMI in the immunologic (6.0% vs. 1.0%; P=0.04) and virologic (5.8% vs. 0%; P=0.007) cohorts, we were not able to identify CD4+ cell count or viral load as significant predictors significantly increasing the likelihood of AMI. Potential explanations discussed include self-selection bias resulting in incomplete laboratory data and an underpowered sample size. While the sample in this study did not support an increased likelihood of AMI by ethnicity, the results should be interpreted carefully in light of the limitations and the established pathophysiological and epidemiological associations posited, underscoring the importance of future research efforts that better represent ethnic minorities and the associations between HIV infection and CVD.

Contexte : La surveillance de la charge virale (CV) et les dépistages des infections sexuellement transmissibles et par le sang (ITSS) sont indispensables à la prise en charge du VIH. L’utilisation de ces soins pendant la pandémie de la Covid-19 au Québec reste largement inconnue. Objectif : Mesurer et comparer les taux de surveillance de la CV et des dépistages des ITSS en période pré et per-pandémique chez les personnes vivant avec le VIH (PVVIH) à Montréal. Méthodes : Dans une étude de cohorte avec devis pré-post, 1702 PVVIH ont été retenues. Des modèles de régression de Poisson avec effet aléatoire sur l'individu ont estimé les taux, les ratios de taux d'incidence (IRR), leurs intervalles de confiance à 95 % (IC95%) ainsi que des termes d’interaction entre la variable de la période et les covariables. Résultats : La période pré-pandémique était associée à une diminution du taux de surveillance de la CV (IRR=0,58, IC95% 0,55-0,60) et du taux de dépistage des ITSS (IRR=0,65, IC95% 0,62-0,68). La diminution de la surveillance de la CV pendant la période per-pandémique était plus importante avec l’utilisation de drogues par injection, une augmentation de la distance et une CV détectable au début de l’étude. La diminution de dépistage des ITSS était plus importante avec une augmentation d’âge et de la distance. La suppression virologique et les pourcentages de positivité des ITSS sont demeurés constants au cours des périodes. Les taux d'incidence des ITSS ont diminué en période per-pandémique. Conclusion : Une diminution du suivi a été observée en période per-pandémique. Nos résultats suggèrent que ces réductions n'ont pas eu d'impact sur la suppression virologique ou l’incidence des ITSS. / Context: Routine viral load (VL) monitoring and sexually transmitted infections (STI) screenings are integral parts of HIV care. In Québec, the effects of the Covid-19 pandemic on accessibility to care and resulting inequalities remain widely unknown. Objective: We aimed to measure and compare rates of VL monitoring and STI screenings before and during the COVID-19 pandemic amongst people living with HIV (PLWHIV) in Montréal. Methods: A cohort study with pre-post design followed 1702 PLWHIV. Poisson regression models with individual clustering were used to estimate testing rates, incidence rate ratios (IRR), their 95 % confidence intervals (95%CI) and interaction terms between the period variable and other covariates. Results: The per-pandemic period was associated with a decrease in VL monitoring (IRR=0.58, 95%CI 0.55-0.60) and STI screening (IRR=0.65, 95%CI 0.62-0.68). The per-pandemic period intensified VL monitoring gaps with intravenous drug use, distance from the testing center and a detectable VL at the beginning of the study. STI screening gaps were amplified during the per-pandemic period by an increase in age and in distance. VL suppression and STI positivity percentages remained unchanged while STI incidence rates decreased. Conclusion: A significant decline in VL monitoring and STI screening was observed during the per-pandemic period. Our findings suggest that these reductions had no impact on the virological suppression or STI incidence in PLWHIV.

We report on a stem cell-transplanted patient with B cell chronic lymphatic leukemia who presented with a subacute onset of focal neurological deficits, gait abnormalities, emotional lability and dementia. Progressive multifocal leukoencephalopathy was diagnosed by magnetic resonance imaging (MRI) of the brain and detection of JC virus genome in the cerebrospinal fluid. Cidofovir and the 5HT2A receptor antagonist chlorpromazine were subsequently administered. A follow-up MRI of the brain 2 weeks after initiation of the antiviral therapy displayed progress of the demyelination, and the patient died 3 months after onset of the neurological symptoms. This report highlights the need for the development of novel and potent strategies for treatment of progressive multifocal leukoencephalopathy. / Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.

Le VPH-16 de même que certains VPH, dont le VPH-18, causent le cancer du col utérin. Son intégration dans le génome humain pourrait être un marqueur de progression de l’infection. Les charges virales totale et intégrée sont présentement mesurées en quantifiant par PCR en temps réel les gènes E6 (RT-E6) et E2 (RT-E2-1) du VPH-16. Nous avons évalué l’impact du polymorphisme du gène E2 sur la quantification de l’ADN du VPH-16 dans des spécimens cliniques. Dans un premier temps, le gène E2 de 135 isolats de VPH-16 (123 appartenaient au clade Européen et 12 à des clades non- Européens) fut séquencé. Ensuite, un test de PCR en temps réel ciblant les séquences conservées dans E2 (RT-E2-2) fut développé et optimisé. Cent trente-neuf spécimens (lavages cervicaux et vaginaux) provenant de 74 participantes (58 séropositives pour le VIH, 16 séronégatives pour le VIH) ont été étudiés avec les trois tests E2 (RT-E2-2), E6 (RT-E6) et E2 (RT-E2-1). Les ratios de la quantité d’ADN de VPH-16 mesuré avec RT-E2-2 et RT-E2-1 dans les isolats Européens (médiane, 1.02; intervalle, 0.64-1.80) et Africains 1 (médiane, 0.80; intervalle, 0.53-1.09) sont similaires (P=0.08). Par contre, les ratios mesurés avec les isolats Africains 2 (médiane, 3.23; intervalle, 1.92-3.49) ou Asiatique- Américains (médiane, 3.78; intervalle, 1.47-37) sont nettement supérieurs à ceux obtenus avec les isolats Européens (P<0.02 pour chaque comparaison). Les distributions des quantités de E2 contenues dans les 139 échantillons mesurées avec RT-E2-2 (médiane, 6150) et RT-E2-1 (médiane, 8960) étaient statistiquement différentes (P<0.0001). Nous avons observé que les charges virales totale (odds ratio (OR) OR, 2.16 95% intervalle de confiance (IC) 1.11-4.19), et épisomale du VPH-16 (OR, 2.14 95% IC 1.09-4.19), mais pas la présence de formes intégrées (OR, 3.72 95% IC 1.03-13.4), sont associées aux néoplasies intraepitheliales cervicales de haut grade (CIN-2,3), et ce, en contrôlant pour des facteurs confondants tels que l’âge, le taux de CD4 sanguin, l’infection au VIH, et le polymorphisme de VPH-16. La proportion des échantillons ayant un ratio E6/E2 > 2 pour les femmes sans lésion intraépithéliale (7 de 35) est similaire à celle des femmes avec CIN-2,3 (5 de 11, p=0.24) ou avec CIN- 1 (4 de14, P=0.65). Le polymorphisme du gène E2 est un facteur qui influence la quantification des charges intégrées de VPH-16. / Episomal and integrated HPV-16 loads are currently estimated by quantitation with real-time PCR of HPV-16 E6 (RT-E6) and E2 (RT-E2-1) DNA. We assessed the impact of HPV-16 E2 polymorphism on quantitation of integrated HPV-16 DNA in clinical specimens. First, HPV-16 E2 was sequenced from 135 isolates (123 from European and 12 from non-European lineages). A novel assay targeting conserved HPV-16 E2 sequences (RT-E2-2) was optimized and applied with RT-E6 and RTE2- 1 on 139 HPV-16-positive cervicovaginal lavages collected from 74 women (58 HIV-seropositive, 16 HIV-seronegative). Ratios of HPV-16 DNA copies measured with RT-E2-2 and RT-E2-1 with European (median, 1.02; range, 0.64-1.80) and African 1 (median, 0.80; range, 0.53-1.09) isolates were similar (P=0.08). Ratios obtained with African 2 (median, 3.23; range, 1.92-3.49) or Asian-American (median, 3.78; range, 1.47-37) isolates were greater than those with European isolates (P<0.02 for each comparison). Distributions of HPV-16 E2 copies measured in 139 samples with RT-E2-2 (median, 6150) and RT-E2-1 (median, 8960) were different (P<0.0001). HPV-16 total (odds ratio (OR) OR, 2.16 95% confidence interval (CI) 1.11-4.19), episomal (OR, 2.14 95% CI 1.09-4.19) but not integrated (OR, 3.72 95% CI 1.03-13.4) load, were associated with high-grade cervical intraepithelial neoplasia (CIN-2,3) after controlling for age, CD4 count and HIV, and HPV-16 polymorphism. The proportion of samples with an E6/E2 ratio >2 in women without SIL (7 of 35) was similar to that of women with CIN-2,3 (5 of 11, P=0.24) or CIN-1 (4 of 14, P=0.65). E2 polymorphism was a factor that influenced measures of HPV-16 integrated load.

L’histoire naturelle de l’infection anale par le virus du papillome de type 16 (VPH-16) est mal définie pour les hommes ayant des relations sexuelles avec d’autres hommes (HARSAHs) VIH-séropositifs. Le but de cette étude était d’évaluer l’association entre la charge épisomale et intégrée du VPH-16 et la progression de la néoplasie intraépithéliale anale (AIN). Les charges épisomales et intégrées du VPH-16 furent mesurées par PCR quantitatif en temps réel sur 665 spécimens anaux obtenus de 135 hommes VPH-16-positifs participant à l’étude prospective HIPVIRG (Human Immunodeficiency and Papilloma VIrus Research Group). Le grade de l’AIN fut déterminé sur des biopsies obtenues lors des anuscopies à haute résolution périodiques. L’intégration du VPH-16 fut confirmée par DIPS-PCR pour démontrer la présence de jonctions virales-cellulaires. La charge épisomale du VPH-16 [ratio de cote (OR) 1.5, intervalle de confiance (IC) à 95%=1.1–2.1], le nombre de types de VPH [OR 1.4 (IC 95%=1.1–1.8)] et le tabagisme actuel [OR 4.8 (IC 95%=1.3–18.6)], mais non la charge intégrée, furent associés aux lésions de haut-grade (AIN-2,3) après ajustement pour l’âge et le décompte des lymphocytes CD4. La charge épisomale du VPH-16 était le seul facteur prédictif de progression de l’AIN de bas-grade (AIN-1) vers l’AIN-2,3 [OR 8.0 (IC 95%=1.2–55.4)]. Les spécimens avec une charge épisomale du VPH-16 élevée étaient moins susceptibles de contenir de l’intégration [OR 0.5 (IC 95%=0.3–0.8)]. L’intégration du VPH-16 fut détectée en absence d’AIN, dans l’AIN-1 et dans l’AIN-2,3. L’analyse des jonctions virales-cellulaires ne permit pas d’identifier un site d’intégration spécifique. / The natural history of human papillomavirus type 16 (HPV-16) anal infection is undefined among HIV-seropositive men having sex with men (MSM). The aim of this study was to assess the association between HPV-16 episomal and integrated viral loads and the progression of anal intraepithelial neoplasia (AIN). HPV-16 episomal and integrated loads were measured on 665 specimens from 135 HPV-16-positive men participating in the prospective HIPVIRG (Human Immunodeficiency and Papilloma VIrus Research Group) study. AIN grade was evaluated on biopsies obtained during periodical high-resolution anoscopies. HPV-16 integration was confirmed by DIPS-PCR to demonstrate the presence of viral-cellular junctions. HPV-16 episomal loads [odds ratio (OR) 1.5, 95% confidence interval (CI)=1.1–2.1], burden of HPV infection [OR 1.4 (95% CI=1.1–1.8)] and current smoking [4.8 (95% CI=1.3–18.6)], but not integrated loads, were associated with high-grade lesions (AIN-2,3) after age and CD4 counts adjustment. A high HPV-16 episomal load was the only predictive factor of progression from low-grade AIN to high-grade AIN [OR 8.0 (95% CI=1.2–55.4)]. Specimens with higher HPV-16 episomal loads were less likely to contain integration [OR 0.5 (95% CI=0.3–0.8)]. HPV-16 integration was detected in the absence of AIN, in AIN-1 and in AIN-2,3. The analysis of the viral-cellular junctions did not allow identifying a specific site of integration.

Clinical laboratory test results are integral to patient management. Important aspects of laboratory tests’ contributions are the use of the test information and the role they have in facilitating efficient and effective use of healthcare resources. Methods of measuring those contributions were examined using quantitative HCV RNA test results (HCV VL) in therapeutic management decisions as a model. Test precision is important in those decisions; therefore, the clinical use was evaluated by studying the impact that knowledge of inherent assay imprecision had on clinicians’ decisions. A survey describing a simulated patient at a decision point for HCV triple-combination therapy management was sent to 1491 hepatology clinicians. Participants saw HCV RNA results at five different levels and were asked to choose to: continue therapy, discontinue therapy, or repeat the test. Test results were presented both with and without the 95% confidence intervals (CIs). Three of the VLs had CIs that overlapped the therapeutic decision level. Participants saw both sets of results in random order. Demographics and practice preferences were also surveyed. One-hundred-thirty-eight responses were received. Adherence to clinical guidelines was demonstrated in self-reported behaviors and in most decisions. However, participants chose to repeat the test up to 37% of the time. The impact of the knowledge of assay imprecision did not have a statistically significant effect on clinicians’ decisions. To determine economic value, an analytic decision-tree model was developed. Transition probabilities, costs, and Quality of Life values were derived from published literature. Survey respondents’ decisions were used as model inputs. Across all HCV VL levels, the calculated test value was approximately $2600, with up to $17,000 in treatment-related cost savings per patient at higher HCV VLs. The test value prevailed regardless of the presence or absence of CIs, and despite repeat testing. The calculated value in cost savings/patient was up to 100 times the investment for HCV VL testing. Laboratory tests are investments in efficient uses of healthcare resources. Proper interpretation and use of their information is integral to that value. This type of analysis can inform institutional decisions and higher level policy discussions.