Human immunodeficiency virus type 1 drug resistance in a subset of mothers and their infants receiving antiretroviral treatment in Ouagadougou, Burkina Faso

The emergence of HIV-1 drug resistance (HIVDR) is a public health problem that affects women and children. Local data of HIVDR is critical to improving their care and treatment. So, we investigated HIVDR in mothers and infants receiving antiretroviral therapy (ART) at Saint Camille Hospital of Ouagadougou, Burkina Faso. This study included 50 mothers and 50 infants on ART. CD4 and HIV-1 viral load were determined using FACSCount and Abbott m2000rt respectively. HIVDR was determined in patients with virologic failure using ViroSeq HIV-1 Genotyping System kit on the 3130 Genetic Analyzer. The median age was 37.28 years in mothers and 1.58 year in infants. Sequencing of samples showed subtypes CRF02_AG (55.56%), CRF06_cpx (33.33%) and G (11.11%). M184V was the most frequent and was associated with highlevel resistance to 3TC, FTC, and ABC. Other mutations such as T215F/Y, D67N/E, K70R, and K219Q were associated with intermediate resistance to TDF, AZT, and 3TC. No mutation to LPV/r was detected among mothers and infants. The findings of HIVDR in some mothers and infants suggested the change of treatment for these persons

Inconclusive results with HIV serodiagnosis algorithms, and HIV-1 and HIV-2 co-infection in North-eastern Democratic Republic of Congo

Background:Inconclusive serodiagnosis of HIV infection is particularly frequent in Central Africa. The aims of this study were to: (i) determine the rate of inconclusive results with the two-test algorithm that the WHO proposed in 1997 (WHO II) versus the three-test algorithm (revised in 2012 and consolidated in 2015 by WHO) for HIV testing, and (ii) determine the prevalence of HIV-1 and HIV-2 co-infection in the north-eastern region of the Democratic Republic of the Congo (DRC).Methods:A multicentre cross-sectional study was performed between March and June 2016 in Kisangani and Bunia, the capital cities of Tshopo and Ituri provinces respectively. Alere Determine HIV-1/2 (Alere Medical Co. Ltd., Japan), Uni-GoldTM HIV (Trinity Biotech Manufacturing Ltd., Ireland) and recomLine HIV-1 and HIV-2 IgG (Biosynex, France) were the first, second and third tests in the serial algorithm.Results : The rate of inconclusive results was 1.1% (95% CI: 0.4 to 3.1) with the two-test algorithm and 0.4% (95% CI: 0.1 to 2.1) with the three-test algorithm (p less than 0.001). The prevalence of HIV-1 and HIV-2 co-infection among HIV positive sera was 16.7% (95% CI: 4.7 to 44.8).Conclusion:The three-test algorithm HIV testing strategy significantly reduces the rate of inconclusive results. In addition, the prevalence of HIV-1 and HIV-2 co-infection is higher in a context where HIV-2 infection is poorly documented. Large-scale research is essential to clarify these results

Dried blood spot specimen quality and validation of a new pre-analytical processing method for qualitative HIV-1 PCR, KwaZulu-Natal, South Africa

Background: Poor quality dried blood spot (DBS) specimens are usually rejected by virology laboratories; affecting early infant diagnosis of HIV. The practice of combining two incompletely-filled DBS in one specimen preparation tube during pre-analytical specimen processing (i.e.; the two-spot method) has been implemented to reduce the number of specimens being rejected for insufficient volume.Objectives: This study analysed laboratory data to describe the quality of DBS specimens and the use of the two-spot method over a one-year period; then validated the two-spot method against the standard (one-spot) method.Methods: Data on HIV-1 PCR test requests submitted in 2014 to the Department of Virology at Inkosi Albert Luthuli Central Hospital in KwaZulu-Natal province; South Africa were analysed to describe reasons for specimen rejection; as well as results of the two-spot method. The accuracy; lower limit of detection and precision of the two-spot method were assessed.Results: Of the 88 481 specimens received; 3.7% were rejected for pre-analytical problems. Of those; 48.9% were rejected as a result of insufficient specimen volume. Two health facilities had significantly more specimen rejections than other facilities. The two-spot method prevented 10 504 specimen rejections. The Pearson correlation coefficient comparing the standard to the two-spot method was 0.997.Conclusions: The two-spot method was comparable with the standard method of pre-analytical specimen processing. Two health facilities were identified for targeted retraining on specimen quality. The two-spot method of DBS specimen processing can be used as an adjunct to retraining; to reduce the number of specimens rejected and improve linkage to care

Profil épidémiologique des patientes suivies dans un protocole de prévention de la transmission mère-enfant du VIH-1 au CHU Sylvanus Olympio

But : Les objectifs de notre étude étaient de décrire les caractéristiques sociodémographiques et obstétricales des patientes d'un protocole de prévention de la transmission mère-enfant du VIH1 au Togo.Patients et méthodes : Nous avons réalisé une étude prospective transversale de type suivi de cohorte dans le site PTME du CHU Sylvanus Olympio. Elle s'était étendue du 27 juin 2011 au 27 juin 2015.Résultats : Au total 255 femmes ont été incluses. L'âge moyen de nos patientes était de 30 ans. Les revendeuses étaient de 38,8% et les femmes au foyer représentaient 17,6%. 48,2% de nos patients avaient un niveau scolaire secondaire. Les célibataires ont représenté 36,1% et 54,5% étaient mariées monogames. 64% des patientes ont été dépistées positives au VIH au cours de leur grossesse et 80,7% étaient au stade clinique I de l'OMS. Quarante-quatre virgule cinq pour cent (44,5%) des patientes ont consulté pour la première fois au 1er trimestre de grossesse.Conclusion : Les résultats de cette étude révèlent que la majorité de nos patientes était jeune, asymptomatique et a majoritairement été dépistée dans notre maternité

Quantification de la charge virale et tests de résistance du VIH-1 aux ARV à partir d'échantillons DBS (Dried Blood Spots) chez des patients Guinéens sous traitement antirétroviral

Problematique: Comme dans plusieurs pays du Sud; le suivi virologique des patients sous traitement antiretroviral (TARV) en Guinee est timide voire inexistant dans certaines localites. Le but de cette etude etait d'evaluer la faisabilite technique et logistique de l'utilisation des DBS dans les tests de charge virale (CV) et de genotypage. Methode: De septembre a octobre 2010; les DBS ont ete prepares a partir de prelevements sanguins de patients adultes sous TARV. Le delai d'envoi des echantillons au laboratoire de reference etait de 30 jours maximum apres le prelevement et se faisait a temperature ambiante. La CV a ete quantifiee et les echantillons de patients en echec virologique (CV = 3 log10 copies/mL) ont ete genotypes selon le protocole de l'ANRS. L'algorithme de Stanford version 6.0.8 a ete utilise pour l'analyse et l'interpretation des mutations de resistance.Resultats: Parmi les 136 patients inclus; 129 et 7 etaient respectivement sous premiere et deuxieme ligne de traitement avec une mediane de suivi de 35 mois [IQR: 6-108]. L'echec virologique a ete note chez 33 patients. Parmi eux; 84.8% (n = 28/33) ont beneficie d'un genotypage. Le taux de resistance global etait de 14% (n = 19/136). Le CRF02_AG etait le sous type viral le plus prevalent (82%; n = 23). Conclusion: En plus de montrer la faisabilite technique et logistique des tests de CV et de genotypage a partir des DBS; ces resultats montrent l'interet de leurs utilisations dans le suivi virologique des patients sous TARV. Cette etude a permis egalement de documenter l'echec virologique; la resistance aux ARV et la diversite genetique du VIH-1 en Guinee

Diverse genetic subtypes of HIV-1 among female sex workers in Ibadan, Nigeria

Genetic diversity is the hallmark of HIV-1 infection. It differs among geographical regions throughout the world. This study was undertaken to identify the predominant HIV-1 subtypes among infected female sex workers (FSWs) in Nigeria. Methods: Two hundred and fifty FSWs from brothels in Ibadan Nigeria were screened for HIV antibody using ELISA. All reactive samples were further tested by the Western Blot Techniques. Peripheral Blood Mononuclear Cells (PBMCs) were separated from the blood samples of each subject. Fragments of HIV Proviral DNA was amplified and genetic subtypes of HIV-1 was determined by direct sequencing of the env and gag genes of the viral genome followed by phylogenetic analysis . Results: The age of the FSWs ranged from 15 to 55 years old (Mean = 25.8years; SD =3.74). Majority were Nigerians while others (1.6 ) were from neighboring West Africa countries. Four ( 1.6 ) of the FSWs were active for less than one year as sex workers; and the mean length of sex work was 2.80 years ( Range = 1.0 - 15.0 years ). Sixty-four (25.6) of the 250 CSWs were positive for HIV-1 while 7 (2-8) had dual infections to HIV-1 / HIV-2. Among the 34 HIV-1 strains characterized by sequencing; 19 (55-9) were subtype G; 9 (26.5) CRF02_A/G; 3 (8.8) CRF06_cpx while 1 (2.9) each were identified as subtype C; CRF01_A/E and CRF09_cpx respectively. Nineteen (55.9) of the FSWs with subtype G had been active in the sex work for between one to five years. The youngest of the HIV -1 infected FSWs with sexual activity of less than a year had subtype G strain. There is a significant probability that infection with this subtype occurred with a short incubation period (p 0.05). Conclusion: This study showed a wide range of HIV- 1 subtypes among FSWs in Nigeria. The situation poses serious challenge for the design of HIV vaccine candidate for use in Nigeria

Genital ulcer diseases among HIV_infected female commercial sex workers in Ibadan, Nigeria

We evaluated the prevalence and association of Genital Ulcer Diseases (GUDs) among HIV-1 infected female commercial sex workers (FCSWs) in Ibadan; Nigeria. A total of 25O FCSWs from brothels in Ibadan were tested for presence of antibodies to HIV and Syphilis. Pelvic examinations for signs of sexually transmitted infections (STIs) were carried out on the subjects. Endocervical and high vaginal swabs were collected from each of the subjects to establish laboratory diagnosis of STIs. Their age ranged from 15 to 55 years (Mean = 25.8yrs; SD =3.74). Majority (246/250) were Nigerians; while 1.6were from neighboring West African countries. Sixty four (25.6) of the subjects were positive for HIV-1 while seven (2.8) had dual HIV-1/2 infection. Analysis of the STIs showed that 49 (19.6) of the CSWs had GUDs. Herpes genitalis was the commonest GUDs as it occurred in 25 (10) of the subjects. Other STIs identified were chancroid (5.6); syphilis (4.0) and lymphogranuloma venerum (LGV) (4). Sixteen (64.0) of the CSWs with herpes genitalis had HIV-1 infection. The risk ratio of herpes genitalis for HIV acquisition was 3.0 (95CI: 2.0 - 4.4). Syphilis and chancroid were also foundto be significantly associated with increased risk of HIV infection (p0.0001). The adjusted odd ratios for Herpes genitalis; chancroid; and syphilis were 3.7(1-13.0; p0.05); 19.8 (2.7-13 .0; p0.05) and 19.1(1-231.0; p 0.05) respectively. There is need to educate FCSWs continually to adopt safer sexual behaviours; seek early diagnosis and treatment of GUDs to reduce their risk of transmitting HIV infection

Diagnosis and Monitoring of HIV Infection

The latest statistics indicate that the number of people infected with human immunodeficiency virus type 1 (HIV-1) worldwide is 40.3 million; 25.8 million of whom live in sub-Saharan Africa. In 2004; 29.5 of South African women attending antenatal clinics were infected. The virus infects people of all ages and social classes. A diagnosis of HIV has serious physical; emotional and social implications for the patient. HIV-infected patients are susceptible to numerous opportunistic and other infections; as well as to non-infectious backdiseases such as tumours. They eventually require lifelong treatment with potentially toxic medication. It is therefore essential that a timeous and correct diagnosis be made. An understanding of the tests available for the diagnosis and monitoring of HIV is essential for all clinicians working in South Africa. Tests available for the diagnosis of HIV in patients older than 18 months include HIV-specific antibody assays; fourth-generation combination antibody-antigen assays and Western Blot. The diagnosis of HIV infection in infants younger than 18 months requires detection of the virus itself by means of p24 antigen detection or HIV DNA PCR. The CD4+ T lymphocyte count and HIV viral load are used for monitoring disease progression and response to therapy

Independent divergences in the CD4 binding site and V3 loop encoded in two seroprevalent Ugandan HIV-1 clinical isolates

"Two major epitopes expressed in HIV-1 have been recently shown to play a central role in virus neutralization. One of these important specificities is a type-specific or group-specific; principal neutralizing determinant (PND) located in the V3 loop of gp120. The other is a more broadly neutralizing determinant associated with the CD4 binding site. Structural and serological studies of the variation in these epitopes have become important in vaccine research. This report describes the analysis of the DNA clones encoding a region of gp120 that overlaps the V3 loop and the putative CD4 recognition site in two new African isolates; UG06c and UG23c. Phylogenetic analyses of the DNA sequences showed that the new African isolates clustered with two very distinct subtypes of HIV-1. UG06c was grouped with U455; D687; and Z321; previously classified as ""HIV-1 subtype A"" in the AIDS and human retroviruses database; and UG23c was grouped with MAL; JY1; NDK; ELI; and Z2Z6 classified as ""HIV-1 subtype D."" Considerable variation was apparent in the V3 loop. The divergence included the presence of the hexapeptides GP-GRSF and GLGQAL at the cap of the loop in UG06c and UG23c; respectively. The GPGR tetrapeptide in UG06c formed a beta-turn configuration similar to that of MN or IIIB. The beta-turn was not found to be a likely conformation for GLGQ. The amino acids previously implicated in CD4 binding and the associated neutralizing activity were relatively conserved. To assess a possible impact of the sequence and conformational variations on serological reactivity; UG06c and UG23c were subjected to neutralization assay.(ABSTRACT TRUNCATED AT 250 WORDS)"

Non-isotopic polymerase chain reaction methods for the detection of HIV-1 in Ugandan mothers and infants

Two non-isotopic polymerase chain reaction (PCR) methods were evaluated by testing blood from 41 HIV-1-seropositive and 16 HIV-1-seronegative Ugandan mothers and 56 of their children (aged 0.5-15.0 months). Amplification of HIV-1 sequences was performed in duplicate using a biotinylated primer pair to the gag region (SK 462-431) and nested primer pairs (JA 17-20) to the pol region of HIV-1. gag sequences were hybridized using a microtiter plate coated with the SK 102 probe followed by colorimetric detection using an avidin-horseradish peroxidase conjugate and tetramethylbenzidine/peroxide substrate. pol sequences were detected on agarose gel stained with ethidium bromide. Results of HIV-1 PCR analysis showed that 40 out of 41 (98pc) seropositive mothers and 10 out of 29 (34pc) seropositive children had detectable HIV-1 gag and pol sequences. None of the 16 seronegative mothers nor 27 seronegative or Western blot-indeterminate children had detectable HIV-1 sequences. Our results suggest that non-isotopic PCR methods are sensitive; specific; and potentially useful in the early diagnosis of HIV-1 infection in developed and developing countries

An overview of the epidemiology of HIV-1 infection in Kagera region; Tanzania

This series of studies in the Kagera Region have shown that the prevalence of HIV-1 infection in the regions differs considerably from one area to another with a high urban prevalence

The Rural Marketing System and HIV-1 Transmission in Uganda: Implications for Interventions

Objective: The paper examines the role of the rural marketing system in the spread of HIV infection in Rakai District. Implications for public health interventions are discussed. Methods: Medical-anthropological data (qualitative and quantitative) from a 13 month field study (1992-93) are presented. Results: A complex system of mobile rural markets which rotate around the district on a regular basis and bring large urban traders into contact with rural populations is identified. Three types of markets serve as centers of commerce and social activity. (1) Large markets of cattle; marchandise; and produce draw pastorilists and others into contact with highly infected traders from urban areas. These markets move to 4 different locations bi-weekly. Considerable socialising occurs in the evenings when people spend the night at the market sites. (2) Intermediate markets move to 6 different locations biweekly and are attended by smaller traders who sell goods purchased in (1). (3) Smaller rural markets are open daily and attended by villagers and traders from (1) and (2). The markets also serve as meeting places for adolescents and young adults. Sexual activity is common. Conclusion: the marketing system appears to play a significant role as a vehicle for HIV transmission from urban to rural trading centers and remote villages. Public health interventions need to be designed for the rural

HIV-1 Infection in Women and Children : The Future of AFrican Children

Objectives: To highlight the future crisis of African children due to HIV/AIDS in women and children. Methods: A review of available data and projections of HIV/AIDS in women and children in Africa. Results and Discussion: It is estimated that 3 out of 10 million infected people worldwide are women of children bearing age; 50of them in Africa. East and Central Africa ; 10-36of prenatal women in some urban areas are HIV positive. HIV positive women have 25-40chnaces of infecting their new borns vertically. Such infected children have a 25chance of dying before age one; and 80by age 5. Thus maternal and paediatric HIV/AIDS poses a socio-economic crisis for Africa. In East and Central Africa; 1:10 AIDS cases are children and estimated that during the 1990s; 2.9 million women and 2.7 million chidlren will die of AIDS. The children of HIV+ mothers who survive may have no-one to care for them. hence there is emerging an orphan crisis in this region. The traditional African extended family can no longer cope. There is also a rise in street children with attendant dangers of juvenile deliquency; drug and sex abuse; STDs including HIV and crime. Conclusions and Recommendations: African children face major crises requiring urgent attention:- 1. Increased morbidity/mortality rates. 2. Increasing numbers of orphans and street children

HIV-1 seroprevalence and risk perception in a rural areas of SW Uganda. (p.96)

The objectives was to determine HIV-1 seroprevalence and individual subjects' assessment of their risk of HIV infection in a rual area of SW Uganda. In preparation for a trial to assess ways of reducing HIV-1 infection in a rural Ugandan population; a serum sample was collected from; and a KABP questionnaire administered to all consenting adults in selected villages.Results: Data were available for 2108 adults from three administrative parishes. Age and sex standardised HIV-1 seroprevalence results ranged from 7to 11. In females highest rates were in those aged 25-34 years (20) and in males in those aged 25 - 44 years(1). The percentage of those who considered themselves at risk of HIV-1 infection was similar between males and females and higher in seropositive (65) than seronegatives (51); 12said they did not know. Of the 1108 considering themeslves at risk 51cited their partners behavior; 14(21males;9females) referred only to their own behavior; and 3gave both reasons; 21mentioned other transmission routes and these included insects (2) and sharing sharp items (4). For the 680 considering themselves not at risk the commonest reasons given were sexual abstinance (51( and avoidance of risky sexual behaviour (21); only 2said they used condoms. In this rural population; with an adult HIV-1 seroprevalence of about 10; half of the people consider themselves at risk of infection. Few of them more males than females) consider their own behaviour of partners. These findings have important implications for HIV/AIDS control programmes

HIV-1 seroprevalence rates in women attending prenatal clinics in Kampala; Uganda. (p.96)

The objective was to determine the HIV-1 seroprevalence in expectant women in Kampala. HIV-1 antibody status (by ELISA -Cambridge Biotech; with comformatory ELISA-Wellcozyme on positives); obstetric and socio-demographic characteristics were determined on a random proportionate to-size sample of 1002 expectant consenting women seeking care at 11 prenatal units in Kampala between august and December of 1993. HIV-1 age-specific rates were determined. Chi-square analysis; tests for linear trend in rates and 95CI were used to determine significance of seroprevalence rates. Results showed overall seroprevalence of HIV-1 for the study population (mean age

An evaluation of the probe hydridization method for large scale population studies of HIV-1 strain variation in Uganda

A strategy was developed for a long-term; large scale study of HIV-1 genetic variation in Uganda. Our approach was based on the premisethat DNA sequencing is costly and time consiming with respect to screening largenumbers of specimens. We adopted a dot-blod hybridization method using oligonucleotide probes specific for HIV-1 subtypes A and D in the envC2V3 region to screen for HIV-1 subtypes in Uganda. Specicimens which could not be subtyped in this way were sequenced directly. Genomic DNA from 72 HIV-1 seropositive subjects were amplified by PCR in the envC2V3 region. The results of dot-blot hybridization indicated that 40 were subtype A and 29 were subtype D. The remaining three specimens could not be typed due to either non-binding to probes of both subtypes or non specific binding. Hybdridization results were compared with results obtained by sequence phylogenetic analysis. Sequences were generated from 50 DNA specimens and analysis in the C2V3 region showed that 29 were subtype A and 21 were subtype D. Sequences were also generated from the immuno-dominant env gp41 region (384bp fragment) from specimens for which C2V3 sequences were not available. Phylogenetic analysis of these sequences indicated that 8 were subtype A and 8 were subtype D. Regardless of the region of the HIV genome under study sequence data fully supports the subtype assignment derived from hybridization data. Our findings suggest that probe hybridization using A and D subtype specific probes will be effective for large scale screening og the HIV-infected populationin Uganda. Application of this method should lead to significant savings in cost and time for large; population-based investigations

HIV-1 sereoprevalence and risk perception in a rural area of SW Uganda

The objective was determine the HIV-1 Seroprevalence and individual subjects assessment of their risk of HIV infection in a rural areas of SW Uganda. In preparation for a trial to assess ways of reducing HIV-1 infection in a rural Ugandan population; a serum sample was collected from; and a KABP questionnaire administered to; all consenting adults in selected villages. Data were available for 2108 adults from three administrative parishes. Age and sex standardised HIV-1 seroprevalence results ranged from 7to 11. In females highest rates were in those aged 25-34 years (20) and in males in those aged 24-44 years (1). The percentage of those who considered themselves at risk of HIV-1 infection was similar between males and females and higher in seropositives (65) thean seronegatives (51); 12said they did not know. Of the 1108 considering themselves at risk 51cited only their partner's behaviour; 14(21males; 9females) referred only to their own behaviour; and as 3gave both reasons; 21mentioned other transmission routes and these included insects (2) and sharing sharp items (4). For the 680 considering themselves not at risdk the commonset reasons given were sexual abstinence (51) and avoidance of risky sexual behaviour (21); only 2said they used condoms. Conclusions: In this rural population; with an adult HIV-1 seroprevalence of about 10; half of the people consider themselves ar risk of infection. Few of them (more males than females) consider their own behaviour a possible reason for this. Risk is more often attributed to the behaviour of partners. These findings have important implications for HIV/AIDS control programmes

Frequency with which psychiatric disorder associated with a positive HIV- serostatus as seen in persons attending a TASO Clinic in Mulago

The prevalence of HIV-1 infection among adults in Uganda is estimated to be about 12. However the rate and nature of psychological disorder among persons living with HIV/AIDS in Uganda is unknown.This study was therefore carried out to determine the nature and pattern of psychological disorder in HIV/AIDS. A total of 252 HIV-1 positive patients attending the specialised AIDS clinic at TASO Mulago had a physical examination and were interviewed using the General Health Questionnaire (GDQ-28). Forty eight percent of the patients fulfilled the criteria for AIDS related complex; 49.2for AIDS and 2.8 were asymptomatic according to WHO diagnostic criteria. At least 74 of the patients suffered from psychological disorder using a thershold cut off point of 5/6 on the GHQ-28The HIV clinical stage was significantly related to the overall psychological disorder (p=0.007); depression (p=0.01) and social dysfunction (p=0.02) but not anxiaety and somatic symptoms. At multivariant analysis the HIV clinical stage and the number of counselling sessions attended before the study were the two factors that had a significant effect on psychological disorder. Two other factors which had a significant association with psychological disorder namely age of the patient (p=0.04) and duration since HIV test was done (p=0.02) did not feature as significant factors at multivariant analysis. In conclusion HIV-1 infection appears to be associated with significant psychological morbidity. It appears that current counselling services do not adequately address personal psychological needs of people living with HIV/AIDS. There is therefore a need for further studies where the actual prevalence of psychological disorder; the specific psychiatric diagnoses; and hence the appropriate remedial measures can be determined

Syndrome des Anticorps Anti-Phospholipides (SAPL) secondaire à une infection par le VIH-1

Il s'agissait d'une femme âgée de 32 ans, aux antécédents de deux mort-nés en 2005 et 2006 et de zona brachial la même année. Elle était hospitalisée pour des nécroses des quatre derniers doigts de la main gauche dans un contexte de syndrome infectieux. Les anticorps anti VIH1 et anti-cardiolipine étaient positifs. Le bilan thrombophilique, les anticorps anti DNA natifs et anti ECT étaient négatifs. Quatre ans après le début du traitement par Combivir-névirapine avec ascension du taux de CD4, elle a développé une gangrène ischémique du membre inférieur droit par thrombose artérielle de la fémorale primitive homolatérale. Le dosage du lupus anticoagulant était successivement positif à un intervalle de 12 semaines. Le diagnostic de syndrome des anticorps anti-phospholipides secondaire à une infection par le VIH1 était retenu. Il n'existe pas ce jour de récidive sous anti-vitamine K