• Accuracy of immunological criteria for identifying virological failure in children on antiretroviral therapy - The IeDEA Southern Africa Collaboration.

      Davies, Mary-Ann; Boulle, Andrew; Eley, Brian; Moultrie, Harry; Technau, Karl; Rabie, Helena; van Cutsem, Gilles; Giddy, Janet; Wood, Robin; Egger, Matthias; et al. (2011-08-11)
      Objectives  To determine the diagnostic accuracy of World Health Organization (WHO) 2010 and 2006 as well as United States Department of Health and Human Services (DHHS) 2008 definitions of immunological failure for identifying virological failure (VF) in children on antiretroviral therapy (ART). Methods  Analysis of data from children (<16 years at ART initiation) at South African ART sites at which CD4 count/per cent and HIV-RNA monitoring are performed 6-monthly. Incomplete virological suppression (IVS) was defined as failure to achieve ≥1 HIV-RNA ≤400 copies/ml between 6 and 15 months on ART and viral rebound (VR) as confirmed HIV-RNA ≥5000 copies/ml in a child on ART for ≥18 months who had achieved suppression during the first year on treatment. Results  Among 3115 children [median (interquartile range) age 48 (20-84) months at ART initiation] on treatment for ≥1 year, sensitivity of immunological criteria for IVS was 10%, 6% and 26% for WHO 2006, WHO 2010 and DHHS 2008 criteria, respectively. The corresponding positive predictive values (PPV) were 31%, 20% and 20%. Diagnostic accuracy for VR was determined in 2513 children with ≥18 months of follow-up and virological suppression during the first year on ART with sensitivity of 5% (WHO 2006/2010) and 27% (DHHS 2008). PPV results were 42% (WHO 2010), 43% (WHO 2006) and 20% (DHHS 2008). Conclusion  Current immunological criteria are unable to correctly identify children failing ART virologically. Improved access to viral load testing is needed to reliably identify VF in children.
    • Antiretroviral treatment uptake and attrition among HIV-positive patients with tuberculosis in Kibera, Kenya

      Tayler-Smith, K.; Zachariah, R.; Manzi, M.; Kizito, W.; Vandenbulcke, A.; Sitienei, J.; Chakaya, J.; Harries, A. D. (2011-11)
    • Benefit of viral load testing for confirmation of immunological failure in HIV patients treated in rural Malawi.

      Kanapathipillai, Rupa; McGuire, Megan; Mogha, Robert; Szumilin, Elisabeth; Heinzelmann, Annette; Pujades-Rodriguez, Mar; Médecins Sans Frontières, Chiradzulu, Malawi  Monash Medical Centre, Clayton, Vic., Australia  Epicentre, Paris, France  Médecins Sans Frontières, Paris, France. (2011-09-01)
      Objective  Viral load testing is used in the HIV programme of Chiradzulu, Malawi, to confirm the diagnosis of immunological failure to prevent unnecessary switching to second-line therapy. Our objective was to quantify the benefit of this strategy for management of treatment failure in a large decentralized HIV programme in Africa. Methods  Retrospective analysis of monitoring data from adults treated with first-line antiretroviral regimens for >1 year and meeting the WHO immunological failure criteria in an HIV programme in rural Malawi. The positive predictive value of using immunological failure criteria to diagnose virological failure (viral load >5000 copies/ml) was estimated. Results  Of the 227 patients with immunological failure (185 confirmed with a repeat CD4 measurement), 155 (68.2%) had confirmatory viral load testing. Forty-four (28.4%) had viral load >5000 copies/ml and 57 (36.8%) >1000 copies/ml. Positive predictive value was 28.4% (95% CI 21.4-36.2%). Repeat CD4 count testing showed that 41% of patients initially diagnosed with immunological failure did no longer meet failure criteria. Conclusions  Our results support the need for confirming all cases of immunological failure with viral load testing before switching to second-line ART to optimize the use of resources in developing countries.
    • Burden and outcome of HIV infection and other morbidities in health care workers attending an Occupational Health Program at the Provincial Hospital of Tete, Mozambique.

      Casas, Esther Carrillo; Decroo, Tom; Mahoudo, Jules Aimé Bonou; Baltazar, Jesus Maria; Dores, Carla Das; Cumba, Luisa; De Weggheleire, Anja; Huyst, Veerle; Bottieau, Emmanuel; Department of Clinical Sciences, Institute of Tropical Medicine, Antwerp, Belgium  Médecins Sans Frontières, Tete, Mozambique  Provincial Hospital of Tete, Tete, Mozambique  Provincial Health Directorate of Tete, Tete, Mozambique. (2011-08-18)
      Objectives  To investigate the burden and outcome of HIV infection and other morbidities amongst a Mozambican hospital staff. Methods  Within an occupational health service set up in April 2008 in the provincial hospital of Tete, Mozambique, we offered to all staff members an initial clinical, laboratory and radiological screening and followed them up prospectively until April 2010. Results  A total of 47.5% of 423 health workers attended the program. The cohort (female-to-male ratio: 2.2; mean age: 39 years) consisted mostly of auxiliary staff (43%) and nurses (29.8%). At initial screening, 71% were asymptomatic. HIV infection (28.4%) and tuberculosis (TB) (21%) were the main reported antecedent illnesses. Laboratory screening revealed anaemia (haemoglobin level <10 mg/dl) in 9% participants, abnormal liver enzymes in 23.9% and a reactive non-treponemal syphilis test in 5%. Of 145 performed chest X-rays, 13% showed abnormalities. All 113 health workers not recently tested for HIV were screened, and 31 were newly diagnosed with HIV infection (resulting in an overall HIV prevalence of 43.8%). Nine cases of TB were diagnosed at screening/during follow-up. In April 2010, all but one of the participants were alive. All HIV-infected health workers under antiretroviral therapy were actively followed-up. Conclusion  Serious conditions were frequently diagnosed in health workers, in particular HIV infection. Mid-term outcome was favourable within this program. Creation of screening and care services dedicated to caregivers should be of highest priority in similar African settings.
    • Community-supported models of care for people on HIV treatment in sub-Saharan Africa.

      Bemelmans, Marielle; Baert, Saar; Goemaere, Eric; Wilkinson, Lynne; Vandendyck, Martin; van Cutsem, Gilles; Silva, Carlota; Perry, Sharon; Szumilin, Elisabeth; Gerstenhaber, Rodd; et al. (2014-08)
      Further scale-up of antiretroviral therapy (ART) to those in need while supporting the growing patient cohort on ART requires continuous adaptation of healthcare delivery models. We describe several approaches to manage stable patients on ART developed by Médecins Sans Frontières together with Ministries of Health in four countries in sub-Saharan Africa.
    • Cryptococcal meningitis in HIV-infected patients: a longitudinal study in Cambodia.

      Espié, Emmanuelle; Pinoges, Loretxu; Balkan, Suna; Chanchhaya, Ngeth; Molfino, Lucas; Narom, Prak; Pujades-Rodríguez, Mar; Epicentre, Médecins Sans Frontières, 8 rue Saint Sabin, Paris, France. (2010-11)
      To describe the frequency of diagnosis of cryptococcosis among HIV-infected patients in Phnom Penh, Cambodia, at programme entry, to investigate associated risk factors, and to determine the incidence of cryptococcal meningitis.
    • Demographic characteristics and opportunistic diseases associated with attrition during preparation for antiretroviral therapy in primary health centres in Kibera, Kenya.

      Tayler-Smith, K; Zachariah, R; Manzi, M; Kizito, W; Vandenbulcke, A; Dunkley, S; von Rege, D; Reid, T; Arnould, L; Suleh, A; et al. (2011-05)
      Using routine data from HIV-positive adult patients eligible for antiretroviral therapy (ART), we report on routinely collected demographic characteristics and opportunistic diseases associated with pre-ART attrition (deaths and loss to follow-up). Among 2471 ART eligible patients, enrolled between January 2005 and November 2008, 446 (18%) were lost to attrition pre-ART. Adjusted risk factors significantly associated with pre-ART attrition included age <35 years (Odds Ratio, OR 1.4, 95% Confidence Interval, CI 1.1-1.8), severe malnutrition (OR 1.5, 95% CI 1.1-2.0), active pulmonary tuberculosis (OR 1.6, 95% CI 1.1-2.4), severe bacterial infections including severe bacterial pneumonia (OR 1.9, 95% CI 1.2-2.8) and prolonged unexplained fever (>1 month), (OR 2.6, 95% CI 1.3-5.2). This study highlights a number of clinical markers associated with pre-ART attrition that could serve as 'pointers' or screening tools to identify patients who merit fast-tracking onto ART and/or closer clinical attention and follow-up.
    • Does HIV status affect the Aetiology, Bacterial Resistance Patterns and Recommended Empiric Antibiotic Treatment in adult patients with bloodstream infection in Cambodia?

      Phe, Thong; Vlieghe, Erika; Reid, Tony; Harries, Anthony D; Lim, Kruy; Thai, Sopheak; De Smet, Birgit; Veng, Chhunheng; Kham, Chun; Ieng, Sovann; et al. (2013-01-07)
      OBJECTIVE: The microbiologic causes of bloodstream infections (BSI) may differ between HIV-positive and HIV-negative patients and direct initial empiric antibiotic treatment (i.e. treatment before culture results are available). We retrospectively assessed community-acquired BSI episodes in adults in Cambodia according to HIV status for spectrum of bacterial pathogens, antibiotic resistance patterns and appropriateness of empiric antibiotics. METHODS: Blood cultures were systematically performed in patients suspected of BSI in a referral hospital in Phnom Penh, Cambodia. Data were collected between 1 January 2009 and 31 December 2011. RESULTS: A total of 452 culture-confirmed episodes of BSI were recorded in 435 patients, of whom 17.9% and 82.1% were HIV-positive and HIV-negative, respectively. Escherichia coli accounted for one-third (n = 155, 32.9%) of 471 organisms, with similar rates in both patient groups. Staphylococcus aureus and Salmonella cholereasuis were more frequent in HIV-positive vs. HIV-negative patients (17/88 vs. 38/383 (P = 0.02) and 10/88 vs. 5/383 (P < 0.001)). Burkholderia pseudomallei was more common in HIV-negative than in HIV-positive patients (39/383 vs. 2/88, P < 0.001). High resistance rates among commonly used antibiotics were observed, including 46.6% ceftriaxone resistance among E. coli isolates. Empiric antibiotic treatments were similarly appropriate in both patient groups but did not cover antibiotic-resistant E. coli (both patient groups), S. aureus (both groups) and B. pseudomallei (HIV-negative patients). CONCLUSION: The present data do not warrant different empiric antibiotic regimens for HIV-positive vs. HIV-negative patients in Cambodia. The overall resistance rates compromise the appropriateness of the current treatment guidelines.
    • Immunovirological outcomes and resistance patterns at 4 years of antiretroviral therapy use in HIV-infected patients in Cambodia

      Pujades-Rodríguez, Mar; Schramm, Birgit; Som, Leakena; Nerrienet, Eric; Narom, Prak; Chanchhaya, Ngeth; Ferradini, Laurent; Balkan, Suna; Epicentre, Paris, France; Medecins Sans Frontieres, Phnom Penh, Cambodia; HIV⁄Hepatitis Laboratory, Pasteur Institute, Phnom Penh, Cambodia; Khmero-Sovietic Friendship Hospital, Phnom Penh, Cambodia; Medecins Sans Frontieres, Paris, France (2011-02-01)
      Objectives  To report immunovirological outcomes and resistance patterns in adults treated with triple combination antiretroviral therapy (cART) for 4 years in an HIV programme of Phnom Penh, Cambodia. Methods  It is a longitudinal study and cross-sectional evaluation of adults receiving cART for 4 years. CD4 cell counts and HIV-1 RNA were quantified, and resistance patterns were determined. Drug-related toxicity was assessed by clinicians and through laboratory testing. Results  After 4 years of cART start, the cumulative probability of retention in care was 0.80 and survival among patients not lost to follow-up was 0.85. A total of 349 patients (98% of eligible) participated in the cross-sectional evaluation. Ninety per cent were receiving first-line therapy, 29% stavudine- and 58% zidovudine-containing regimens (compared with 94% and 3% at cART initiation). Ninety-three per cent of patients were clinically asymptomatic, and severe lipodystrophy and dyslipidemia were diagnosed in 7.2% and 4.0%, respectively. Good treatment adherence was reported by 83% of patients. Median CD4 T-cell count was 410 cells/μl [IQR 290-511], and 90% of patients had >200 cells/μl. Only 15 (4%) patients had detectable HIV viral load (eight had <200 CD4 cells/μl), five had thymidine analogue mutations, and nine were resistant to two drug classes. In an intention-to-treat analysis, 26.1% (95% CI 22.0-30.5) of patients had failed first-line therapy. Conclusions  In this Cambodian cohort of adults who started cART at an advanced stage of HIV disease, we observed good clinical and immunovirological outcomes and self-reported treatment adherence at 4 years of therapy.
    • 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.
    • Mortality and Clinical Outcomes in Children Treated With Antiretroviral Therapy in Four African Vertical Programs During The First Decade of Paediatric HIV Care, 2001-2010

      Ben-Farhat, J; Schramm, B; Nicolay, N; Wanjala, S; Szumilin, E; Balkan, S; Pujades-Rodríguez, M (Wiley-Blackwell, 2016-12-19)
      To assess mortality and clinical outcomes in children treated with antiretroviral therapy in four African vertical programs between 2001 and 2010.
    • Paediatric HIV care in sub-Saharan Africa: clinical presentation and 2-year outcomes stratified by age group

      Ben-Farhat, Jihane; Gale, Marianne; Szumilin, Elisabeth; Balkan, Suna; Poulet, Elisabeth; Pujades-Rodríguez, Mar (John Wiley & Sons Ltd, 2013-09)
      To examine age differences in mortality and programme attrition amongst paediatric patients treated in four African HIV programmes.
    • Providing universal access to antiretroviral therapy in Thyolo, Malawi through task shifting and decentralization of HIV/AIDS care.

      Bemelmans, Marielle; Van Den Akker, Thomas; Ford, Nathan; Philips, Mit; Zachariah, Rony; Harries, Anthony; Schouten, Erik; Hermann, Katharina; Mwagomba, Beatrice; Massaquoi, Moses; et al. (2010-12)
      Objective  To describe how district-wide access to HIV/AIDS care was achieved and maintained in Thyolo District, Malawi. Method  In mid-2003, the Ministry of Health and Médecins Sans Frontières developed a model of care for Thyolo district (population 587 455) based on decentralization of care to health centres and community sites and task shifting. Results  After delegating HIV testing and counseling to lay counsellors, uptake of testing increased from 1300 tests per month in 2003 to 6500 in 2009. Shifting responsibility for antiretroviral therapy (ART) initiations to non-physician clinicians almost doubled ART enrolment, with a majority of initiations performed in peripheral health centres. By the end 2009, 23 261 people had initiated ART of whom 11 042 received ART care at health-centre level. By the end of 2007, the universal access targets were achieved, with nearly 9000 patients alive and on ART. The average annual cost for achieving these targets was €2.6 per inhabitant/year. Conclusion  The Thyolo programme has demonstrated the feasibility of district-wide access to ART in a setting with limited resources for health. Expansion and decentralization of HIV/AIDS service-capacity to the primary care level, combined with task shifting, resulted in increased access to HIV services with good programme outcomes despite staff shortages.
    • Self-transfer and mortality amongst adults lost to follow-up in ART programmes in low and middle-income countries: systematic review and meta-analysis

      Wilkinson, Lynne S; Skordis-Worrall, Jolene; Ajose, Olawale; Ford, Nathan (Wiley-Blackwell, 2014-11-22)
      To ascertain estimates of adult patients, recorded as lost to follow-up (LTFU) within antiretroviral treatment (ART) programmes, who have self-transferred care, died or truly stopped ART in low- and middle-income countries.
    • Strategies to improve patient retention on antiretroviral therapy in sub-Saharan Africa.

      Harries, Anthony D; Zachariah, Rony; Lawn, Stephen D; Rosen, Sydney; International Union against Tuberculosis and Lung Disease, Paris, France. adharries@theunion.org (2010-06)
      The scale-up of antiretroviral therapy (ART) has been one of the success stories of sub-Saharan Africa, where coverage has increased from about 2% in 2003 to more than 40% 5 years later. However, tempering this success is a growing concern about patient retention (the proportion of patients who are alive and remaining on ART in the health system). Based on the personal experience of the authors, 10 key interventions are presented and discussed that might help to improve patient retention. These are (1) the need for simple and standardized monitoring systems to track what is happening, (2) reliable ascertainment of true outcomes of patients lost to follow-up, (3) implementation of measures to reduce early mortality in patients both before and during ART, (4) ensuring uninterrupted drug supplies, (5) consideration of simple, non-toxic ART regimens, (6) decentralization of ART care to health centres and the community, (7) a reduction in indirect costs for patients particularly in relation to transport to and from clinics, (8) strengthening links within and between health services and the community, (9) the use of ART clinics to deliver other beneficial patient or family-orientated packages of care such as insecticide-treated bed nets, and (10) innovative (thinking 'out of the box') interventions. High levels of retention on ART are vital for individual patients, for credibility of programmes and for on-going resource and financial support.
    • Tuberculosis and the risk of opportunistic infections and cancers in HIV-infected patients starting ART in Southern Africa.

      Fenner, Lukas; Reid, Stewart E; Fox, Matthew P; Garone, Daniela; Wellington, Maureen; Prozesky, Hans; Zwahlen, Marcel; Schomaker, Michael; Wandeler, Gilles; Kancheya, Nzali; et al. (2013-02)
      To investigate the incidence of selected opportunistic infections (OIs) and cancers and the role of a history of tuberculosis (TB) as a risk factor for developing these conditions in HIV-infected patients starting antiretroviral treatment (ART) in Southern Africa.
    • Very early mortality in patients starting antiretroviral treatment at primary health centres in rural Malawi.

      Zachariah, Rony; Harries, Katie; Moses, Massaquoi; Manzi, Marcel; Line, Arnould; Mwagomba, Beatrice; Harries, Anthony D; Medecins Sans Frontieres, Medical Department, Brussels, Belgium. zachariah@internet.lu (2009-07-15)
      OBJECTIVES: To report on the cumulative proportion of deaths occurring within 3 months of starting antiretroviral treatment (ART) and to identify factors associated with such deaths, among adults at primary health centres in a rural district of Malawi. METHODS: Retrospective cohort study: from June 2006 to April 2008, deaths occurring over a 3-month period were determined and risk factors examined. RESULTS: A total of 2316 adults (706 men and 1610 women; median age 35 years) were included in the analysis and followed up for a total of 1588 person-years (PY); 277 (12%) people died, of whom 206 (74%) people died within 3 months of initiating ART (cumulative incidence: 13.0; 95% confidence interval: 11.3-14.8 per 100 PY of follow-up). Significant risk factors associated with early deaths included male sex, WHO stage 4 disease, oesophageal or persistent oral candidiasis and unexplained presumed or measured weight loss >10%. One in every 3 patients who either died or was lost to follow up had unexplained weight loss >10%, and survival in this group was significantly different from patients without this condition. CONCLUSIONS: Seven in 10 individuals initiating ART at primary health centres die early. Specific groups of patients are at higher risk of such mortality and should receive priority attention, care and support.
    • Viewpoint: Why do we need a point-of-care CD4 test for low-income countries?

      Zachariah, R; Reid, S D; Chaillet, P; Massaquoi, M; Schouten, E J; Harries, A D; Médecins sans Frontières, Operational Centre Brussels; CD4 Initiative, Institute for Global Health, UK; Clinton Health Access Initiative, Liberia; Department of HIV/AIDS, Ministry of Health, Malawi; Management Sciences for Health, Malawi; International Union against Tuberculosis and Lung Disease, France; London School of Hygiene and Tropical Medicine, UK (2010-11-02)
      In this paper, we discuss the reasons why we urgently need a point-of-care (POC) CD4 test, elaborate the problems we have experienced with the current technology which hampers CD4-count coverage and highlight the ideal characteristics of a universal CD4 POC test. It is high-time that CD4 technology is simplified and adapted for wider use in low-income countries to change the current paradigm of restricted access once and for all.