BackgroundEbola virus disease (EVD) is a highly lethal condition for which no specific treatment has proven efficacy. In September 2014, while the Ebola outbreak was at its peak, the World Health Organization released a short list of drugs suitable for EVD research. Favipiravir, an antiviral developed for the treatment of severe influenza, was one of these. In late 2014, the conditions for starting a randomized Ebola trial were not fulfilled for two reasons. One was the perception that, given the high number of patients presenting simultaneously and the very high mortality rate of the disease, it was ethically unacceptable to allocate patients from within the same family or village to receive or not receive an experimental drug, using a randomization process impossible to understand by very sick patients. The other was that, in the context of rumors and distrust of Ebola treatment centers, using a randomized design at the outset might lead even more patients to refuse to seek care.Therefore, we chose to conduct a multicenter non-randomized trial, in which all patients would receive favipiravir along with standardized care. The objectives of the trial were to test the feasibility and acceptability of an emergency trial in the context of a large Ebola outbreak, and to collect data on the safety and effectiveness of favipiravir in reducing mortality and viral load in patients with EVD. The trial was not aimed at directly informing future guidelines on Ebola treatment but at quickly gathering standardized preliminary data to optimize the design of future studies.Methods and FindingsInclusion criteria were positive Ebola virus reverse transcription PCR (RT-PCR) test, age ≥ 1 y, weight ≥ 10 kg, ability to take oral drugs, and informed consent. All participants received oral favipiravir (day 0: 6,000 mg; day 1 to day 9: 2,400 mg/d). Semi-quantitative Ebola virus RT-PCR (results expressed in “cycle threshold” [Ct]) and biochemistry tests were performed at day 0, day 2, day 4, end of symptoms, day 14, and day 30. Frozen samples were shipped to a reference biosafety level 4 laboratory for RNA viral load measurement using a quantitative reference technique (genome copies/milliliter). Outcomes were mortality, viral load evolution, and adverse events. The analysis was stratified by age and Ct value. A “target value” of mortality was defined a priori for each stratum, to guide the interpretation of interim and final analysis.Between 17 December 2014 and 8 April 2015, 126 patients were included, of whom 111 were analyzed (adults and adolescents, ≥13 y, n = 99; young children, ≤6 y, n = 12). Here we present the results obtained in the 99 adults and adolescents. Of these, 55 had a baseline Ct value ≥ 20 (Group A Ct ≥ 20), and 44 had a baseline Ct value < 20 (Group A Ct < 20). Ct values and RNA viral loads were well correlated, with Ct = 20 corresponding to RNA viral load = 7.7 log10 genome copies/ml. Mortality was 20% (95% CI 11.6%–32.4%) in Group A Ct ≥ 20 and 91% (95% CI 78.8%–91.1%) in Group A Ct < 20. Both mortality 95% CIs i...

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These data give new arguments to reinforce the hypothesis that, in this region, ART should be started before the CD4 cell count drops below 350 cells/mul. Further studies should assess whether patients with low BMI, low haemoglobin, high viral load or past history of tuberculosis should start ART earlier.

National Research Agency on AIDS and Viral Hepatitis (ANRS).

BackgroundCervical cancer screening is not yet standard of care of women attending HIV care clinics in Africa and presents operational challenges that need to be addressed.MethodsA cervical cancer screening program based on visual inspection methods was conducted in clinics providing antiretroviral treatment (ART) in Abidjan, Côte d'Ivoire. An itinerant team of midwives was in charge of proposing cervical cancer screening to all HIV-positive women enrolled in ART clinics as well as to HIV-negative women who were attending the Abidjan national blood donor clinic. Positively screened women were systematically referred to a colposcopic examination. A phone-based tracking procedure was implemented to reach positively screened women who did not attend the medical consultation. The association between HIV status and cervical cancer screening outcomes was estimated using a multivariate logistic model.ResultsThe frequency of positive visual inspection was 9.0% (95% CI 8.0-10.0) in the 2,998 HIV-positive women and 3.9% (95% CI 2.7-5.1) in the 1,047 HIV-negative ones (p < 10-4). In multivariate analysis, HIV infection was associated with a higher risk of positive visual inspection [OR = 2.28 (95% CI 1.61-3.23)] as well as more extensive lesions involving the endocervical canal [OR = 2.42 (95% CI 1.15-5.08)]. The use of a phone-based tracking procedure enabled a significant reduction of women not attending medical consultation after initial positive screening from 36.5% to 19.8% (p < 10-4).ConclusionThe higher frequency of positive visual inspection among HIV-positive women supports the need to extend cervical cancer screening program to all HIV clinics in West Africa. Women loss to follow-up after being positively screened is a major concern in cervical screening programs but yet, partly amenable to a phone tracking procedure.