ART initiation in an outpatient treatment center in Dakar, Senegal: A retrospective cohort analysis (1998-2015).

OBJECTIVE: To examine how patient characteristics combined with ART eligibility expansions affect the initiation of antiretroviral therapy (ART) among eligible patients attending a referral center in Senegal from 1998 to 2015. METHODS: This is a retrospective observational study carried out at the outpatient treatment Centre (Centre de Traitement Ambulatoire) in Dakar, Senegal, based on computerized medical records, gathered from 1998 to 2015, of ART-naïve patients over 15 years of age. ART eligibility was defined as (CD4 count below 200) or as (WHO stage 4) or as (WHO stage 3 with (CD4 count below 350 or with unavailable CD4 count)) in 1998-2010; as (CD4 count below 350) or as (WHO stage 3 or 4) in 2011-2013; as (CD4 count below 500) or as (WHO stage 3 or 4) in 2014-2015. Four periods were defined according to ART eligibility expansions and Senegal's HIV care history: 1998-2003 (P 1), 2004-2010 (P 2), 2011-2013 (P3), and 2014-2015 (P4). Patients were expected to participate financially in their treatment during the first period (P1). RESULTS: A total of 3651 patient records were included. The median patient age was 40 years (IQR: 32-48). Women represented 56% of the population. The median CD4 count was 183 cells/mm3. Overall, 53% of patients had CD4 < 200 cells/mm3 at entry. This proportion reached 45% in 2014-2015. 2535 patients (69%) were eligible for therapy, including 1503 (41%) who started ART. The proportion of treated patients among those who were eligible at entry or later increased steadily from 25%, 47%, 75% to 82% in the four periods, respectively. The median time to treatment decreased from 5.6 months (IQR: 3-11) in P1 to 0.8 months (IQR: 0-2) in P4. Eligible patients with more advanced disease (CD4<200 cells/mm3 and/or clinical stage 3 or 4) were more likely to be ART initiated than those with CD4≥200 cells/mm3 and/or clinical stage 1 or 2 at each stage of ART eligibility expansion. CONCLUSION: ART eligibility expansions were marked by a sharp increase in the proportion of eligible patients initiating treatment. These results show that in terms of management, the target of "Test and Treat" can be easily reached but that HIV testing will remain a key element to improve treatment success, as illustrated by the high proportion of people with advanced stage of infection at the time of ART initiation.

Years of life lost due to metastatic melanoma in 12 countries.

BACKGROUND: Regionally or distantly metastatic melanoma (stages IIIB/C and IV) place a high burden on society. To quantify this burden, this study estimated years of life lost (YLL) per patient for adults with metastatic melanoma in 12 countries in 2014. METHODS: General population growth and life expectancy were estimated from the Organization for Economic Co-operation and Development data and life tables for each country. Incidence of melanoma and mortality rates for the disease were based on GLOBOCAN and US registry data. The prevalence of metastatic melanoma was calculated using mortality rates and survival data from patients with melanoma. YLL per patient was estimated by the difference between the disease-free life expectancy and the life expectancy with metastatic melanoma. RESULTS: YLL per patient were as follows: Australia, men = 19.9 years, women = 22.7 years; Brazil, 16.3, 19.8; Canada, 19.4, 22.3; France, 18.8, 23.1; Germany, 18.3, 20.8; Italy, 19.3, 22.7; Mexico, 17.2, 19.0; the Netherlands, 18.5, 21.5; Spain, 19.2, 23.1; Sweden 19.4, 22.0; the UK, 18.7, 21.2; and the US, 17.9, 20.6. CONCLUSIONS: The burden of metastatic melanoma as measured by YLL is substantial in all 12 countries; although there is variation across countries and between men and women.

Safety, immunogenicity, and efficacy of the candidate tuberculosis vaccine MVA85A in healthy adults infected with HIV-1: a randomised, placebo-controlled, phase 2 trial.

BACKGROUND: HIV-1 infection is associated with increased risk of tuberculosis and a safe and effective vaccine would assist control measures. We assessed the safety, immunogenicity, and efficacy of a candidate tuberculosis vaccine, modified vaccinia virus Ankara expressing antigen 85A (MVA85A), in adults infected with HIV-1. METHODS: We did a randomised, double-blind, placebo-controlled, phase 2 trial of MVA85A in adults infected with HIV-1, at two clinical sites, in Cape Town, South Africa and Dakar, Senegal. Eligible participants were aged 18-50 years, had no evidence of active tuberculosis, and had baseline CD4 counts greater than 350 cells per µL if they had never received antiretroviral therapy or greater than 300 cells per µL (and with undetectable viral load before randomisation) if they were receiving antiretroviral therapy; participants with latent tuberculosis infection were eligible if they had completed at least 5 months of isoniazid preventive therapy, unless they had completed treatment for tuberculosis disease within 3 years before randomisation. Participants were randomly assigned (1:1) in blocks of four by randomly generated sequence to receive two intradermal injections of either MVA85A or placebo. Randomisation was stratified by antiretroviral therapy status and study site. Participants, nurses, investigators, and laboratory staff were masked to group allocation. The second (booster) injection of MVA85A or placebo was given 6-12 months after the first vaccination. The primary study outcome was safety in all vaccinated participants (the safety analysis population). Safety was assessed throughout the trial as defined in the protocol. Secondary outcomes were immunogenicity and vaccine efficacy against Mycobacterium tuberculosis infection and disease, assessed in the per-protocol population. Immunogenicity was assessed in a subset of participants at day 7 and day 28 after the first and second vaccination, and M tuberculosis infection and disease were assessed at the end of the study. The trial is registered with ClinicalTrials.gov, number NCT01151189. FINDINGS: Between Aug 4, 2011, and April 24, 2013, 650 participants were enrolled and randomly assigned; 649 were included in the safety analysis (324 in the MVA85A group and 325 in the placebo group) and 645 in the per-protocol analysis (320 and 325). 513 (71%) participants had CD4 counts greater than 300 cells per µL and were receiving antiretroviral therapy; 136 (21%) had CD4 counts above 350 cells per µL and had never received antiretroviral therapy. 277 (43%) had received isoniazid prophylaxis before enrolment. Solicited adverse events were more frequent in participants who received MVA85A (288 [89%]) than in those given placebo (235 [72%]). 34 serious adverse events were reported, 17 (5%) in each group. MVA85A induced a significant increase in antigen 85A-specific T-cell response, which peaked 7 days after both vaccinations and was primarily monofunctional. The number of participants with negative QuantiFERON-TB Gold In-Tube findings at baseline who converted to positive by the end of the study was 38 (20%) of 186 in the MVA85A group and 40 (23%) of 173 in the placebo group, for a vaccine efficacy of 11·7% (95% CI -41·3 to 44·9). In the per-protocol population, six (2%) cases of tuberculosis disease occurred in the MVA85A group and nine (3%) occurred in the placebo group, for a vaccine efficacy of 32·8% (95% CI -111·5 to 80·3). INTERPRETATION: MVA85A was well tolerated and immunogenic in adults infected with HIV-1. However, we detected no efficacy against M tuberculosis infection or disease, although the study was underpowered to detect an effect against disease. Potential reasons for the absence of detectable efficacy in this trial include insufficient induction of a vaccine-induced immune response or the wrong type of vaccine-induced immune response, or both. FUNDING: European & Developing Countries Clinical Trials Partnership (IP.2007.32080.002), Aeras, Bill & Melinda Gates Foundation, Wellcome Trust, and Oxford-Emergent Tuberculosis Consortium.