Agnès Sobry

Nevirapine versus efavirenz for patients co-infected with HIV and tuberculosis: a randomised non-inferiority trial

BACKGROUND In countries with a high incidence of HIV and tuberculosis co-infection, nevirapine and efavirenz are widely used as antiretroviral therapy but both interact with antituberculosis drugs. We aimed to compare efficacy and safety of a nevirapine-based antiretroviral therapy (started at full dose) with an efavirenz-based regimen in co-infected patients. METHODS We did a multicentre, open-label, randomised, non-inferiority trial at three health centres in Maputo, Mozambique. We enrolled adults (≥18 years) with tuberculosis and previously untreated HIV infection (CD4 cell counts <250 cells per μL) and alanine aminotransferase and total bilirubin concentrations of less than five times the upper limit of normal. 4-6 weeks after the start of tuberculosis treatment, we randomly allocated patients (1:1) with central randomisation, block sizes of two to six, and stratified by site and CD4 cell count to nevirapine (200 mg twice daily) or efavirenz (600 mg once daily), plus lamivudine and stavudine. The primary endpoint was virological suppression at 48 weeks (HIV-1 RNA <50 copies per mL) in all patients who received at least one dose of study drug (intention-to-treat population); death and loss to follow-up were recorded as treatment failure. The non-inferiority margin for the difference of efficacy was 10%. We assessed efficacy in intention-to-treat and per-protocol populations and safety in all patients who received study drug. This study is registered with ClinicalTrials.gov, number NCT00495326. FINDINGS Between October, 2007, and March, 2010, we enrolled 285 patients into each group. 242 (85%) patients in the nevirapine group and 233 (82%) patients in the efavirenz group completed follow-up. In the intention-to-treat population, 184 patients (64·6%, 95% CI 58·7-70·1) allocated nevirapine achieved virological suppression at week 48, as did 199 patients (69·8%, 64·1-75·1) allocated efavirenz (one-sided 95% CI of the difference of efficacy 11·7%). In the per-protocol population, 170 (70·0%, 63·8-75·7) of 243 patients allocated nevirapine achieved virological suppression at week 48, as did 194 (78·9%, 73·2-83·8) of 246 patients allocated efavirenz (one-sided 95% CI 15·4%). The median CD4 cell count at randomisation was 89 cells per μL. 15 patients substituted nevirapine with efavirenz and six patients substituted efavirenz with nevirapine. 20 patients allocated nevirapine (7%) had grade 3-4 increase of alanine aminotransferase compared with 17 patients allocated efavirenz (6%). Three patients had severe rash after receipt of nevirapine (1%) but no patients did after receipt of efavirenz. 18 patients in the nevirapine group died, as did 17 patients in the efavirenz group. INTERPRETATION Although non-inferiority of the nevirapine-regimen was not shown, nevirapine at full dose could be a safe, acceptable alternative for patients unable to tolerate efavirenz. FUNDING French Research Agency for HIV/AIDS and hepatitis (ANRS).

Prevalence of Buruli Ulcer in Akonolinga Health District, Cameroon: Results of a Cross Sectional Survey

Background Buruli ulcer (BU) is a chronic, indolent necrotizing disease of the skin and underlying tissues caused by Mycobacterium ulcerans, which may result in functional incapacity. In 2002, Médecins Sans Frontières (MSF) opened a BU programme in Akonolinga Hospital, Cameroon, offering antibiotic treatment, surgery and general medical care. Six hundred patients have been treated in the project to date. However, due to the nature of the disease and its stigmatization, determining the exact prevalence and burden of disease is difficult and current estimates may not reflect the magnitude of the problem. The objectives of this survey were to estimate the prevalence of BU in the health district of Akonolinga, describe the geographic extension of the highly endemic area within the health district, and determine the programme coverage and its geographical distribution. Methodology/Principal Findings We conducted a cross-sectional population survey using centric systematic area sampling (CSAS). A 15×15 km grid (quadrats of 225 km2) was overlaid on a map of Akonolinga district with its position chosen to maximize the area covered by the survey. Quadrats were selected if more than 50% of the quadrat was inside of the health district. The chiefdom located closest to the centre of each quadrat was selected and Buruli cases were identified using an active case finding strategy (the sensitivity of the strategy was estimated by capture-recapture). WHO-case definitions were used for nodules, plaque, ulcer, oedema and sequelae. Out of a total population of 103,000 inhabitants, 26,679 were surveyed within the twenty quadrats. Sensitivity of the case finding strategy was estimated to be 84% (95%CI 54–97%). The overall prevalence was 0.47% (n = 105) for all cases including sequelae and 0.25% (n = 56) for active stages of the disease. Five quadrats had a high prevalence of >0.6% to 0.9%, 5 a prevalence >0.3% to 0.6% and 10 quadrats <0.3%. The quadrats with the high prevalence were situated along the rivers Nyong and Mfoumou. Overall coverage of the project was 18% (12–27%) for all cases and 16% (9–18%) for active cases, but was limited to the quadrats neighbouring Akonolinga Hospital. Conclusions/Significance Prevalence was highest in the area neighbouring the Nyong River. Coverage was limited to the area close to the hospital and efforts have to be made to increase access to care in the high prevalence areas. Use of the CSAS method was particularly useful for project planning and to identify priority areas of intervention. An added benefit of the method is that the survey procedure incorporated an awareness campaign, providing information about the disease and treatment to the population.

HIV with non-communicable diseases in primary care in Kibera, Nairobi, Kenya: characteristics and outcomes 2010–2013

BACKGROUND Antiretroviral therapy (ART) has increased the life expectancy of people living with HIV (PLHIV); HIV is now considered a chronic disease. Non-communicable diseases (NCDs) and HIV care were integrated into primary care clinics operated within the informal settlement of Kibera, Nairobi, Kenya. We describe early cohort outcomes among PLHIV and HIV-negative patients, both of whom had NCDs. METHODS A retrospective analysis was performed of routinely collected clinic data from January 2010 to June 2013. All patients >14 years with hypertension and/or diabetes were included. RESULTS Of 2206 patients included in the analysis, 210 (9.5%) were PLHIV. Median age at enrollment in the NCD program was 43 years for PLHIV and 49 years for HIV-negative patients (p<0.0001). The median duration of follow up was 1.4 (IQR 0.7-2.1) and 1.0 (IQR 0.4-1.8) years for PLHIV and HIV-negative patients, respectively (p=0.003). Among patients with hypertension, blood pressure outcomes were similar, and for those with diabetes, outcomes for HbA1c, fasting glucose and cholesterol were not significantly different between the two groups. The frequency of chronic kidney disease (CKD) was 12% overall. Median age for PLHIV and CKD was 50 vs 55 years for those without HIV (p=0.005). CONCLUSIONS In this early comparison of PLHIV and HIV-negative patients with NCDs, there were significant differences in age at diagnosis but both groups responded similarly to treatment. This study suggests that integrating NCD care for PLHIV along with HIV-negative patients is feasible and achieves similar results.

Caseload, management and treatment outcomes of patients with hypertension and/or diabetes mellitus in a primary health care programme in an informal setting

In three primary health care clinics run by Médecins Sans Frontières in the informal settlement of Kibera, Nairobi, Kenya, we describe the caseload, management and treatment outcomes of patients with hypertension (HT) and/or diabetes mellitus (DM) receiving care from January 2010 to June 2012.

Applying the ICMJE authorship criteria to operational research in low-income countries: the need to engage programme managers and policy makers

1 Medical Department (Operational Research Unit), Medecins sans Frontieres, Operational Centre Brussels, MSF-Luxembourg, Luxembourg, Luxembourg 2 Department of Molecular and Cellular Interactions, Flemish Institute of Biotechnology, Brussels, Belgium 3 Department of Microbiology, Institute of Tropical Medicine, Antwerp, Belgium 4 Department of Obstetrics and Gynecology, University of Nairobi, Nairobi, Kenya 5 Centre for International Health, University of Bergen, Bergen, Norway 6 Center for Operational Research, International Union Against Tuberculosis and Lung Disease, Paris, France 7 International Union Against TB and Lung Disease, Kampala, Uganda 8 Medecins Sans Frontieres, Addis Ababa, Ethiopia 9 International Union Against Tuberculosis and Lung Disease, South East Asia office, New Delhi, India 10 Medecins Sans Frontieres, Somali Mission, Somalia 11 Medecins Sans Frontieres, Bujumbura, Burundi 12 National Institute for Medical Research, Dar Es Salaam, Tanzania 13 National Tuberculosis Control Programme, Harare, Zimbabwe 14 Medecins Sans Frontieres, Capetown, South Africa 15 Medecins Sans Frontieres, Nairobi, Kenya 16 Joint Center for Bioethics, University of Toronto, Toronto, Canada 17 London School of Hygiene and Tropical Medicine, London, UK

Nevirapine or efavirenz for tuberculosis and HIV coinfected patients: exposure and virological failure relationship

Objectives We describe nevirapine and efavirenz exposure on and off tuberculosis treatment and consequences for virological efficacy and tolerance in patients included in the ANRS 12146/12214-CARINEMO trial. Methods Participants were randomly selected to receive either nevirapine at 200 mg twice daily (n = 256) or efavirenz at 600 mg daily (n = 270), both combined with two nucleoside analogues. Blood samples were drawn 12 h after nevirapine or efavirenz administration, while on tuberculosis treatment and after tuberculosis treatment discontinuation. In 62 participants, samples taken 12 h after drug administration were drawn weekly for the first month of ART. Sixteen participants participated in an extensive pharmacokinetic study of nevirapine. Concentrations were compared with the therapeutic ranges of 3000–8000 ng/mL for nevirapine and 1000–4000 ng/mL for efavirenz. Results Nevirapine concentrations at the end of the first week of treatment (on antituberculosis drugs) did not differ from concentrations off tuberculosis treatment, but declined thereafter. Concentrations at steady-state were 4111 ng/mL at week 12 versus 6095 ng/mL at week 48 (P < 0.0001). Nevirapine concentrations <3000 ng/mL were found to be a risk factor for virological failure. Efavirenz concentrations were higher on than off tuberculosis treatment (2700 versus 2450 ng/mL, P < 0.0001). Conclusions The omission of the 2 week lead-in dose of nevirapine prevented low concentrations at treatment initiation but did not prevent the risk of virological failure. Results support the WHO recommendation to use efavirenz at 600 mg daily in patients on rifampicin-based antituberculosis therapy.

Preventable but neglected: rickets in an informal settlement Nairobi, Kenya

SETTING The primary care clinics of Médecins Sans Frontières within the informal settlement of Kibera, Nairobi, Kenya. OBJECTIVE To describe the demographic and clinical characteristics of children clinically diagnosed with rickets from September 2012 to October 2013. DESIGN Descriptive retrospective case review of diagnosis and treatment course with vitamin D and calcium using routine programme data. RESULTS Of the 82 children who met the clinical diagnosis of rickets, 57% were male, with a median age of 12 months and 14 months for females. Children with rickets were found to have ⩽3 hours/week sunlight exposure for 71% of the children and malnutrition in 39%. Clinical findings on presentation revealed gross motor developmental delays in 44%. The loss to follow-up rate during treatment was 40%. CONCLUSIONS This study found that rickets is a common clinical presentation among children living in the informal settlement of Kibera and that there are likely multiple factors within that environment contributing to this condition. As rickets is a simply and inexpensively preventable non-communicable disease, we suggest that routine vitamin D supplementation be formally recommended by the World Health Organization for well-child care in Africa, especially in the contexts of informal settlements.

Characteristics, medical management and outcomes of survivors of sexual gender-based violence, Nairobi, Kenya.

SETTING Médecins Sans Frontières Clinic for sexual gender-based violence (SGBV), Nairobi, Kenya. OBJECTIVES Among survivors of SGBV in 2011, to describe demographic characteristics and episodes of sexual violence, medical management, pregnancy and human immunodeficiency virus (HIV) related outcomes. DESIGN Retrospective review of clinical records and SGBV register. RESULTS Survivors attending the clinic increased from seven in 2007 to 866 in 2011. Of the 866 survivors included, 92% were female, 34% were children and 54% knew the aggressor; 73% of the assaults occurred inside a home and most commonly in the evening or at night. Post-exposure prophylaxis for HIV was given to 536 (94%), prophylaxis for sexually transmitted infections to 731 (96%) and emergency contraception to 358 (83%) eligible patients. Hepatitis B and tetanus toxoid vaccinations were given to 774 survivors, but respectively only 46% and 14% received a second injection. Eight (4.5%) of 174 women who underwent urine pregnancy testing were positive at 1 month. Of 851 survivors HIV-tested at baseline, 96 (11%) were HIV-positive. None of the 220 (29%) HIV-negative individuals who returned for repeat HIV testing after 3 months was positive. CONCLUSION Acceptable, good quality SGBV medical care can be provided in large cities of sub-Saharan Africa, although further work is needed to improve follow-up interventions.