A Trial of Early Antiretrovirals and Isoniazid Preventive Therapy in Africa

BACKGROUND: In sub-Saharan Africa, the burden of human immunodeficiency virus (HIV)-associated tuberculosis is high. We conducted a trial with a 2-by-2 factorial design to assess the benefits of early antiretroviral therapy (ART), 6-month isoniazid preventive therapy (IPT), or both among HIV-infected adults with high CD4+ cell counts in Ivory Coast. METHODS: We included participants who had HIV type 1 infection and a CD4+ count of less than 800 cells per cubic millimeter and who met no criteria for starting ART according to World Health Organization (WHO) guidelines. Participants were randomly assigned to one of four treatment groups: deferred ART (ART initiation according to WHO criteria), deferred ART plus IPT, early ART (immediate ART initiation), or early ART plus IPT. The primary end point was a composite of diseases included in the case definition of the acquired immunodeficiency syndrome (AIDS), non-AIDS-defining cancer, non-AIDS-defining invasive bacterial disease, or death from any cause at 30 months. We used Cox proportional models to compare outcomes between the deferred-ART and early-ART strategies and between the IPT and no-IPT strategies. RESULTS: A total of 2056 patients (41% with a baseline CD4+ count of ≥500 cells per cubic millimeter) were followed for 4757 patient-years. A total of 204 primary end-point events were observed (3.8 events per 100 person-years; 95% confidence interval [CI], 3.3 to 4.4), including 68 in patients with a baseline CD4+ count of at least 500 cells per cubic millimeter (3.2 events per 100 person-years; 95% CI, 2.4 to 4.0). Tuberculosis and invasive bacterial diseases accounted for 42% and 27% of primary end-point events, respectively. The risk of death or severe HIV-related illness was lower with early ART than with deferred ART (adjusted hazard ratio, 0.56; 95% CI, 0.41 to 0.76; adjusted hazard ratio among patients with a baseline CD4+ count of ≥500 cells per cubic millimeter, 0.56; 95% CI, 0.33 to 0.94) and lower with IPT than with no IPT (adjusted hazard ratio, 0.65; 95% CI, 0.48 to 0.88; adjusted hazard ratio among patients with a baseline CD4+ count of ≥500 cells per cubic millimeter, 0.61; 95% CI, 0.36 to 1.01). The 30-month probability of grade 3 or 4 adverse events did not differ significantly among the strategies. CONCLUSIONS: In this African country, immediate ART and 6 months of IPT independently led to lower rates of severe illness than did deferred ART and no IPT, both overall and among patients with CD4+ counts of at least 500 cells per cubic millimeter. (Funded by the French National Agency for Research on AIDS and Viral Hepatitis; TEMPRANO ANRS 12136 ClinicalTrials.gov number, NCT00495651.)

Action to protect the independence and integrity of global health research

Storeng KT, Abimbola S, Balabanova D, et al. Action to protect the independence and integrity of global health research. BMJ GLOBAL HEALTH. 2019;4(3): e001746

Mecanismes et etiologies des insuffisances mitrales primaires severes a l’institut de cardiologie d’Abidjan

Introduction : Les insuffisances mitrales primaires sont fréquentes dans notre contexte. La prise en charge dépend de sa sévérité mais aussi du mécanisme et de l’étiologie. L’objectif de cette étude était d’évaluer les mécanismes et les étiologies des insuffisances mitrales primaires sévères à l’Institut de Cardiologie d’Abidjan en Côte d’Ivoire.Méthodologie : Nous avons mené une étude prospective, transversale et analytique dans le service des explorations externes de l’Institut de Cardiologie d’Abidjan (ICA) du 01 janvier 2018 au 30 Octobre 2019.Résultats : 214 patients ont bénéficié d’un screening échocardiographique transthoracique soit 1.9% des échocardiographies  transthoraciques réalisées dans la période d’étude. La prévalence de l’insuffisance mitrale primaire sévère était de 36 % des  valvulopathies devant les insuffisances aortiques à 32% et les rétrécissements aortique et mitrale respectivement à 16,4% et 15,6%. L’âge était de 26 +/- 9 ans. On notait une prédominance masculine à 57%. Le niveau socio-économique était bas dans 90,4% des cas avec 67% de patients sans couverture sanitaire et 50% sans ou avec un niveau d’instruction primaire. Le temps moyen de contact avec l’institut de cardiologie était de 5 ans. La moitié des patients avait un antécédent d’orthopnée. Les difficultés financières étaient le principal obstacle à la prise en charge chirurgicale dans 62% des cas. L’évaluation des mécanismes en fonction de la classification de CARPENTIER faisait état de 21% de type 1, 6% de type 2 et 79% de type 3. Quant à l’étiologie elle était dominée par le rhumatisme à 69%, la dystrophie à 5%, l’endocardite infectieuse dans 10% et 16% de cause dégénérative.Conclusion : Les insuffisances mitrales primaires touchent des sujets jeunes, économiquement faibles avec un mécanisme restrictif prédominant. L’étiologie rhumatismale reste encore prépondérante dans notre contexte. Mots-clés : Insuffisance mitrale primaire sévère, échocardiographie transthoracique, mécanisme, étiologie.   English title: Mecanisms and etiology of severe primary mitral regurgitation at the Abidjan Heart Institute Introduction: Primary mitral regurgitations are common in our context. Management depends on severity, mechanism and etiology. The objective of this study was to evaluate the mechanisms and etiology of severe primary mitral regurgitation at the Abidjan heartinstitute in Côte d’Ivoire. Methodology: We conducted a prospective, cross-cutting and analytical study in the external explorations department of the Abidjan Heart Institute (ICA) from 01 January 2018 to 30 October 2019. Results: 214 patients benefited from a transthoracic echocardiographic screening, i.e. 1.9% of the transthoracic echocardiograms performed during the study period. The prevalence of severe primary mitral regurgitation was 36%, followed by aorticregurgitation at 32% and aortic and mitral stenosis at 16.4% and 15.6% respectively. The age was 26 +/- 9 years. Male predominance was noted at 57%. The socio-economic level was low in 90.4% of cases with 67% of patients without health coverage and 50% withoutor with primary education. The average time of contact with the Heart Institute was 5 years. Half of the patients had a history of orthopnea. Financial difficulties were the main barrier to surgical management in 62% of cases. The evaluation of mechanisms according to CARPENTIER's classification was 21% Type 1, 6% Type 2 and 79% Type 3. The etiology was dominated by rheumatism in 69%, dystrophy in 5%, infectious endocarditis in 10% and 16% of degenerative causes. Conclusion: Primary mitral regurgitation affects young, economically weak subjects with a predominant restrictive mechanism. Rheumatic etiology still remains predominant in our context

Contribution of tuberculosis to slim disease in Africa.

OBJECTIVES--To assess the contribution of tuberculosis to the aetiology of the HIV wasting syndrome (slim) in Africa, a condition usually considered an enteropathy. METHODS--Clinical examination and representative necropsy study of adult patients positive for HIV. SETTING--Hospital medical wards in Abidjan, Ivory Coast. SUBJECTS--Adults positive for HIV. MAIN OUTCOME MEASURES--CD4 T lymphocyte counts before death, clinical and anthropometric data, and gross and microscopic pathology. RESULTS--Necropsy was done on 212 HIV positive adults. Tuberculosis was found in 41 of 93 with the clinical HIV wasting syndrome and in 32 of 119 without (odds ratio 2.1, 95% confidence interval 1.2 to 4.0). A significant association existed between the prevalence of tuberculosis at necropsy and the degree of cadaveric wasting (no wasting 25% (15/59); moderate wasting 40% (23/58); skeletal wasting 44% (42/95); P = 0.02). Wasting was also associated with a history of chronic diarrhoea, but no association existed between diarrhoea and tuberculosis. Median CD4 T lymphocyte counts were lowest in wasted patients irrespective of findings at necropsy and in those with chronic diarrhoea (< 60 x 10(6)/l). CONCLUSION--Wasting and chronic diarrhoea are late stage manifestations of HIV disease in Africa. The importance of tuberculosis as a contributing factor in the pathogenesis of the slim syndrome has been underestimated. In nearly half of patients dying with severe wasting, tuberculosis was the dominant pathological finding