• The 2014–2015 Ebola Outbreak in West Africa: Hands On

      Vetter, P; Dayer, JA; Schibler, M; Allegranzi, B; Brown, D; Calmy, A; Christie, D; Eremin, S; Hagon, O; Henderson, D; et al. (BioMed Central, 2016-05-05)
      The International Consortium for Prevention and Infection Control (ICPIC) organises a biannual conference (ICPIC) on various subjects related to infection prevention, treatment and control. During ICPIC 2015, held in Geneva in June 2015, a full one-day session focused on the 2014–2015 Ebola virus disease (EVD) outbreak in West Africa. This article is a non-exhaustive compilation of these discussions. It concentrates on lessons learned and imagining a way forward for the communities most affected by the epidemic. The reader can access video recordings of all lectures delivered during this one-day session, as referenced. Topics include the timeline of the international response, linkages between the dynamics of the epidemic and infection prevention and control, the importance of community engagement, and updates on virology, diagnosis, treatment and vaccination issues. The paper also includes discussions from public health, infectious diseases, critical care and infection control experts who cared for patients with EVD in Africa, in Europe, and in the United Sates and were involved in Ebola preparedness in both high- and low-resource settings and countries. This review concludes that too little is known about the pathogenesis and treatment of EVD, therefore basic and applied research in this area are urgently required. Furthermore, it is clear that epidemic preparedness needs to improve globally, in particular through the strengthening of health systems at local and national levels. There is a strong need for culturally sensitive approaches to public health which could be designed and delivered by social scientists and medical professionals working together. As of December 2015, this epidemic killed more than 11,000 people and infected more than 28,000; it has also generated more than 17,000 survivors and orphans, many of whom face somatic and psychological complications. The continued treatment and rehabilitation of these people is a public health priority, which also requires an integration of specific medical and social science approaches, not always available in West Africa.
    • Adverse events associated with nevirapine use in pregnancy: a systematic review and meta-analysis

      Ford, N; Calmy, A; Andrieux-Meyer, I; Hargreaves, S; Mills, E J; Shubber, Z; Médecins Sans Frontières, Geneva, Switzerland. nathan.ford@msf.org (Lippincott Williams & Wilkins, 2013-04-24)
      The risk of adverse drug events associated with nevirapine (NVP) is suggested to be greater in pregnant women. We conducted a systematic review and meta-analysis of severe adverse events in HIV-positive women who initiated NVP while pregnant.
    • Female Genital Schistosomiasis and HIV: Research urgently needed to improve understanding of the health impacts of this important co-infection

      O’Brien, DP; Ford, N; Djirmay, AG; Calmy, A; Vitoria, M; Jensen, TO; Christinet, V (Lippincott Williams & Wilkins, 2019-01)
      Evidence suggests that there are important interactions between HIV and Female Genital Schistosomiasis (FGS) that may have significant effects on individual and population health. However, the exact way they interact and the health impacts of the interactions are not well understood. In this paper we discuss what is known about the interactions between FGS and HIV, and the potential impact of the interactions. This includes the likelihood that FGS is an important health problem for HIV positive women in schistosoma-endemic areas potentially associated with an increased risk of mortality, cancer and infertility. Additionally, it may be significantly impacting the HIV epidemic in sub-Saharan Africa by making young women more susceptible to HIV. We call for immediate action and argue that research is urgently required to address these knowledge gaps and propose a research agenda to achieve this.
    • Female Genital Schistosomiasis and HIV: Research Urgently Needed to Improve Understanding of the Health Impacts of This Important Coinfection

      O'Brien, D; Ford, N; Djirmay, AG; Calmy, A; Vitoria, M; Jensen, TO; Christinet, V (Lippincott Williams and Wilkins, 2019-04-15)
      Evidence suggests that there are important interactions between HIV and female genital schistosomiasis (FGS) that may have significant effects on individual and population health. However, the exact way they interact and the health impacts of the interactions are not well understood. In this article, we discuss what is known about the interactions between FGS and HIV, and the potential impact of the interactions. This includes the likelihood that FGS is an important health problem for HIV-positive women in Schistosoma-endemic areas potentially associated with an increased risk of mortality, cancer, and infertility. In addition, it may be significantly impacting the HIV epidemic in sub-Saharan Africa by making young women more susceptible to HIV. We call for immediate action and argue that research is urgently required to address these knowledge gaps and propose a research agenda to achieve this.
    • Female Genital Schistosomiasis and HIV: Research Urgently Needed to Improve Understanding of the Health Impacts of This Important Coinfection.

      O'Brien, DP; Ford, Nathan; Djirmay, AG; Calmy, A; Vitoria, M; Jensen, TO; Christinet, V (Lippincott Williams and Wilkins, 2019-04-15)
      Evidence suggests that there are important interactions between HIV and female genital schistosomiasis (FGS) that may have significant effects on individual and population health. However, the exact way they interact and the health impacts of the interactions are not well understood. In this article, we discuss what is known about the interactions between FGS and HIV, and the potential impact of the interactions. This includes the likelihood that FGS is an important health problem for HIV-positive women in Schistosoma-endemic areas potentially associated with an increased risk of mortality, cancer, and infertility. In addition, it may be significantly impacting the HIV epidemic in sub-Saharan Africa by making young women more susceptible to HIV. We call for immediate action and argue that research is urgently required to address these knowledge gaps and propose a research agenda to achieve this.
    • First-line and second-line antiretroviral therapy.

      Calmy, A; Pascual, F; Ford, N (Elsevier, 2004)
    • Generic Fixed-Dose Combination Antiretroviral Treatment in Resource-Poor Settings: Multicentric Observational Cohort

      Calmy, A; Pinoges, L; Szumilin, E; Zachariah, R; Ford, N; Ferradini, L; MSF, Campaign for Access to Essential Medicines, 78 rue de Lausanne, 1205 Geneva, Switzerland. acalmy@stvincents.com.au (2006-05-12)
      BACKGROUND: The use fixed-dose combination (FDC) is a critical tool in improving HAART. Studies on the effectiveness of combined lamivudine, stavudine and nevirapine (3TC/d4T/NVP) are scarce. OBJECTIVE: To analyse 6861 patients in a large observational cohort from 21 Médecins Sans Frontieres (MSF) HIV/AIDS programmes taking 3TC/d4T/NVP, with subcohort analyses of patients at 12 and 18 months of treatment. METHODS: Survival was analysed using Kaplan-Meier method and factors associated with progression to death with Cox proportional hazard ratio. RESULTS: Median baseline CD4 cell count at initiating of FDC was 89 cells/microl [interquartile range (IQR), 33-158]. The median follow-up time was 4.1 months (IQR, 1.9-7.3). The incidence rate of death during follow-up was 14.2/100 person-years [95% confidence interval (CI), 13.8-14.5]. Estimates of survival (excluding those lost to follow-up) were 0.93 (95% CI, 92-94) at 6 months (n = 2,231) and 0.90 (95% CI, 89-91) at 12 months (n = 472). Using a Cox model, the following factors were associated with death: male gender, symptomatic infection, body mass index < 18 kg/m and CD4 cell count 15-50 cells/microl or < 15 cells/microl. Subcohort analysis of 655 patients after 1 year of follow-up (M12 FDC cohort) revealed that 77% remained on HAART, 91% of these still on the FDC regimen; 5% discontinued the FDC because of drug intolerance. At 18 months, 77% of the patients remained on HAART. CONCLUSIONS: Positive outcomes for d4T/3TC/NVP are reported for up to 18 months in terms of efficacy and safety.
    • High rates of active hepatitis B and C co-infections in HIV-1 infected Cameroonian adults initiating antiretroviral therapy

      Laurent, C; Bourgeois, A; Mpoudi-Ngolé, E; Kouanfack, C; Ciaffi, L; Nkoué, N; Mougnutou, R; Calmy, A; Koulla-Shiro, S; Ducos, J; et al. (2009-07-29)
      OBJECTIVES: To investigate the presence of hepatitis B virus (HBV) DNA and hepatitis C virus (HCV) RNA in HIV-infected patients initiating antiretroviral therapy in Cameroon. METHODS: Baseline blood samples from 169 patients were tested retrospectively for hepatitis B surface antigens (HBsAg), anti-hepatitis B core (anti-HBc), anti-HCV and - if HBsAg or anti-HCV result was positive or indeterminate - for HBV DNA or HCV RNA, respectively, using the Cobas Ampliprep/Cobas TaqMan quantitative assay (Roche Diagnostics GmbH, Mannheim, Germany). RESULTS: HBV DNA was detected in 14 of the 18 patients with positive or indeterminate HBsAg results [8.3% of the total study population, 95% confidence interval (CI) 4.6-13.5]. The median HBV viral load was 2.47 x 10(7) IU/mL [interquartile range (IQR) 3680-1.59 x 10(8); range 270 to >2.2 x 10(8)]. Twenty-one patients (12.4%, 95% CI 7.9-18.4) were found with HCV RNA (all with positive HCV serology). The median HCV viral load was 928 000 IU/mL (IQR 178 400-2.06 x 10(6); range 640-5.5 x 10(6)). No patient was co-infected with HBV and HCV. In multivariate analysis, HCV co-infection was associated with greater age [>or=45 years vs. <45 years, odds ratio (OR) 11.89, 95% CI 3.49-40.55, P<0.001] and abnormal serum alanine aminotransferase level [>or=1.25 x upper limit of normal (ULN) vs. <1.25 x ULN, OR 7.81, 95% CI 1.54-39.66, P=0.01]; HBV co-infection was associated with abnormal serum aspartate aminotransferase level (OR 4.33, 95% CI 1.32-14.17, P=0.02). CONCLUSIONS: These high rates of active HBV and HCV co-infections in HIV-positive Cameroonian patients requiring antiretroviral therapy underline the need to promote: (i) screening for HBV and HCV before treatment initiation; (ii) accessibility to tenofovir (especially in HBV-endemic African countries); and (iii) accessibility to treatment for HBV and HCV infections.
    • Highly active antiretroviral therapy in resource-poor settings: the experience of Medecins Sans Frontieres

      Tassie, J M; Szumilin, E; Calmy, A; Goemaere, E; Medecins Sans Fronteres (2003-09)
      We describe the short-term results of highly active antiretroviral therapy (HAART) in seven projects in low and middle income countries. A total of 743 adults were included, and clinical, immunological and virological responses were analysed. At 6 months, outcomes were similar to those observed in western countries, and the probability of remaining on treatment was 94%. The challenge now is to extend access to HAART to the millions in urgent need.
    • Highly Active Antiretroviral Therapy in Resource-Poor Settings: The Experience of Médecins Sans Frontières.

      Tassie, J M; Szumilin, E; Calmy, A; Goemaere, E; Epicentre, Paris, France. (2003-09-05)
      We describe the short-term results of highly active antiretroviral therapy (HAART) in seven projects in low and middle income countries. A total of 743 adults were included, and clinical, immunological and virological responses were analysed. At 6 months, outcomes were similar to those observed in western countries, and the probability of remaining on treatment was 94%. The challenge now is to extend access to HAART to the millions in urgent need.
    • HIV drug resistance.

      Calmy, A; Pascual, F; Ford, N (Massachusetts Medical Society, 2004-06-24)
    • HIV Viral Load Monitoring in Resource-Limited Regions: Optional or Necessary?

      Calmy, A; Ford, N; Hirschel, B; Reynolds, S; Lynen, L; Goemaere, E; Garcia de la Vega, F; Perrin, L; Rodriguez, W; Medecins sans Frontieres, Access to Medicines Campaign, Geneva, 1211, Switzerland. acalmy@gmail.com (Published by: Infectious Diseases Society of America, 2007-01-01)
      Although it is a standard practice in high-income countries, determination of the human immunodeficiency virus (HIV) load is not recommended in developing countries because of the costs and technical constraints. As more and more countries establish capacity to provide second-line therapy, and as costs and technological constraints associated with viral load testing decrease, the question of whether determination of the viral load is necessary deserves attention. Viral load testing could increase in importance as a guide for clinical decisions on when to switch to second-line treatment and on how to optimize the duration of the first-line treatment regimen. In addition, the viral load is a particularly useful tool for monitoring adherence to treatment, performing sentinel surveillance, and diagnosing HIV infection in children aged <18 months. Rather than considering viral load data to be an unaffordable luxury, efforts should be made to ensure that viral load testing becomes affordable, simple, and easy to use in resource-limited settings.
    • How developing world concerns need to be part of drug development plans: A case study of four emerging antiretrovirals

      van Roey, J; von Schoen-Angerer, T; Ford, N; Calmy, A; Médecins Sans Frontières, Campaign for Access to Essential Medecins, Geneva, Switzerland; Médecins Sans Frontières, Khayelitsha, South Africa; Geneva Teaching Hospital, Geneva, Switzerland (2008-07)
      Clinical trials are usually designed to meet registration requirements in developed countries, and do not always address key concerns for use in developing countries. Four late-stage investigational new drugs - rilpivirine, etravirine, raltegravir and maraviroc - show potential to improve antiretroviral therapy. However, a number of issues could limit their use in developing countries, including dose selection, treatment strategy, combination with other drugs, use in specific populations and reliance on expensive tests. Key research questions relevant for developing countries need to be answered early in the drug development process to ensure maximum benefit for the majority.
    • (The Lancet)red: a missed opportunity.

      Calmy, A; Pascual, F; Shettle, S; de la Vega, F G; Ford, N (Elsevier, 2006-09-23)
    • Management of BU-HIV co-infection

      O'Brien, D P; Ford, N; Vitoria, M; Christinet, V; Comte, E; Calmy, A; Stienstra, Y; Eholie, S; Asiedu, K (2014-06-20)
      Buruli Ulcer (BU)-HIV co-infection is an important emerging management challenge for BU disease. Limited by paucity of scientific studies, guidance for management of this co-infection has been lacking.
    • Managing Advanced HIV Disease in a Public Health Approach.

      Ford, N; Meintjes, G; Calmy, A; Bygrave, H; Migone, C; Vitoria, M; Penazzato, M; Vojnov, L; Doherty, M (Oxford University Press, 2018-03-04)
      In 2017, the World Health Organization (WHO) published guidelines for the management of advanced human immunodeficiency virus (HIV) disease within a public health approach. Recent data suggest that more than a third of people starting antiretroviral therapy (ART) do so with advanced HIV disease, and an increasing number of patients re-present to care at an advanced stage of HIV disease following a period of disengagement from care. These guidelines recommend a standardized package of care for adults, adolescents, and children, based on the leading causes of morbidity and mortality: tuberculosis, severe bacterial infections, cryptococcal meningitis, toxoplasmosis, and Pneumocystis jirovecii pneumonia. A package of targeted interventions to reduce mortality and morbidity was recommended, based on results of 2 recent randomized trials that both showed a mortality reduction associated with delivery of a simplified intervention package. Taking these results and existing recommendations into consideration, WHO recommends that a package of care be offered to those presenting with advanced HIV disease; depending on age and CD4 cell count, the package may include opportunistic infection screening and prophylaxis, including fluconazole preemptive therapy for those who are cryptococcal antigen positive and without evidence of meningitis. Rapid ART initiation and intensified adherence interventions should also be proposed to everyone presenting with advanced HIV disease.
    • The marriage of science and optimized HIV care in resource-limited settings

      Calmy, A; Pizzocolo, C; Pizarro, L; Brücker, G; Murphy, R; Katlama, C; Strategies in Resource-Limited Settings Working Group; Campaign for Access to Essential Medicines, Médecins Sans Frontières, Geneva; Geneva University, Geneva, Switzerland; Solidarité Théapeutique et Initiatives contre le Sida, Paris; Université Paris 11, Faculté de Médicine Paris-Sud, Le Kremlin-Bicêtre, Paris; Université Pierre et Marie Curie, Paris, France (2008-11-12)
    • Rationing antiretroviral therapy in Africa--treating too few, too late.

      Ford, N; Mills, E; Calmy, A; Medical unit, Médecins sans Frontières, and School of Public Health and Family Medicine, University of Cape Town, South Africa. (2009-04-30)
    • Resistance profiles after different periods of exposure to a first-line antiretroviral regimen in a Cameroonian cohort of HIV type-1-infected patients.

      Soria, A; Porten, K; Fampou-Toundji, J; Galli, L; Mougnutou, R; Buard, V; Kfutwah, A; Vessière, A; Rousset, D; Teck, R; et al. (2009-08)
      BACKGROUND: The lack of HIV type-1 (HIV-1) viral load (VL) monitoring in resource-limited settings might favour the accumulation of resistance mutations and thus hamper second-line treatment efficacy. We investigated the factors associated with resistance after the initiation of antiretroviral therapy (ART) in the absence of virological monitoring. METHODS: Cross-sectional VL sampling of HIV-1-infected patients receiving first-line ART (nevirapine or efavirenz plus stavudine or zidovudine plus lamivudine) was carried out; those with a detectable VL were genotyped. RESULTS: Of the 573 patients undergoing VL sampling, 84 were genotyped. The mean number of nucleoside/nucleotide reverse transcriptase inhibitor (NRTI) mutations increased with the duration of ART exposure (P=0.02). Multivariable analysis showed that patients with a CD4+ T-cell count < or =50 cells/mm(3) at ART initiation (baseline) had a higher mean number of both NRTI and non-NRTI (NNRTI) mutations than those with a baseline CD4+ T-cell count >50 cells/mm(3) (2.10 versus 0.56; P<0.0001; and 1.65 versus 0.76; P=0.005, respectively). A baseline CD4+ T-cell count < or =50 cells/mm(3) predicted > or =1 NRTI mutation (adjusted odds ratio [AOR] 7.49, 95% confidence interval [CI] 2.20-32.14), > or =1 NNRTI mutation (AOR 4.25, 95% CI 1.36-15.48), > or =1 thymidine analogue mutation (AOR 8.45, 95% CI 2.16-40.16) and resistance to didanosine (AOR 6.36, 95% CI 1.49-32.29) and etravirine (AOR 4.72, 95% CI 1.53-15.70). CONCLUSIONS: Without VL monitoring, the risk of drug resistance increases with the duration of ART and is associated with lower CD4+ T-cell counts at ART initiation. These data might help define strategies to preserve second-line treatment options in resource-limited settings.
    • Second-line antiretroviral therapy in resource-limited settings: the experience of Médecins Sans Frontières

      Pujades-Rodriguez, M; O'Brien, D; Humblet, P; Calmy, A; Epicentre, Paris, France; Médecins Sans Frontières, Paris, France; Campaign for Access to Essential Medicines, Geneva, Switzerland (2008-07-11)
      OBJECTIVES: To describe the use of second-line protease-inhibitor regimens in Médecins Sans Frontières HIV programmes, and determine switch rates, clinical outcomes, and factors associated with survival. DESIGN/METHODS: We used patient data from 62 Médecins Sans Frontières programmes and included all antiretroviral therapy-naive adults (> 15 years) at the start of antiretroviral therapy and switched to a protease inhibitor-containing regimen with at least one nucleoside reverse transcriptase inhibitor change after more than 6 months of nonnucleoside reverse transcriptase inhibitor first-line use. Cumulative switch rates and survival curves were estimated using Kaplan-Meier methods, and mortality predictors were investigated using Poisson regression. RESULTS: Of 48,338 adults followed on antiretroviral therapy, 370 switched to a second-line regimen after a median of 20 months (switch rate 4.8/1000 person-years). Median CD4 cell count at switch was 99 cells/microl (interquartile ratio 39-200; n = 244). A lopinavir/ritonavir-based regimen was given to 51% of patients and nelfinavir-based regimen to 43%; 29% changed one nucleoside reverse transcriptase inhibitor and 71% changed two nucleoside reverse transcriptase inhibitors. Median follow-up on second-line antiretroviral therapy was 8 months, and probability of remaining in care at 12 months was 0.86. Median CD4 gains were 90 at 6 months and 135 at 12 months. Death rates were higher in patients in World Health Organization stage 4 at antiretroviral therapy initiation and in those with CD4 nadir count less than 50 cells/microl. CONCLUSION: The rate of switch to second-line treatment in antiretroviral therapy-naive adults on non-nucleoside reverse transcriptase inhibitor-based first-line antiretroviral therapy was relatively low, with good early outcomes observed in protease inhibitor-based second-line regimens. Severe immunosuppression was associated with increased mortality on second-line treatment.