• Cotrimoxazole prophylaxis for HIV-positive TB patients in developing countries.

      Zachariah, R; Massaquoi, M; Medecins sans Frontieres, Operational Research HIV-TB, Medical department, Brussels Operational Center, 68 Rue de Gaspench, L-1617 Luxemburg. zachariah@internet.lu (2006-04)
      Despite provisional recommendations from the World Health Organization and UNAIDS that cotrimoxazole (CTX) prophylaxis be offered to all individuals living with AIDS, including HIV-positive patients with TB, its routine use in developing countries particularly Africa has been minimal. Concerns were expressed regarding its effectiveness in areas of high bacterial resistance, that its widespread use might substantially increase bacterial cross-resistance in the community and that this intervention might promote resistance of malaria parasites to sulphadoxine-pyrimethamine. We review the current evidence on the above concerns and highlight the main operational considerations related to implementing CTX prophylaxis as a basic component of care for HIV-positive TB patients in developing countries.
    • Development of dual-class antiretroviral drug resistance in a child coinfected with HIV and tuberculosis: a case report from KwaZulu-Natal, South Africa.

      Murphy, R A; France, H; Sunpath, H; Gordon, M L; Marconi, V; Kuritzkes, D R; McIntosh, K; Massachusetts General Hospital, and Brigham and Women's Hospital, Boston, MA, USA. richard.murphy@newyork.msf.org (Published by Oxford University Press, 2009-02)
      The treatment of concurrent HIV and tuberculosis (TB) in children <3 years of age has not been well-studied and is complicated by potential drug-drug interactions. The recommended antiretroviral therapy (ART) in coinfected children in South Africa consists of full-strength ritonavir, lamivudine and stavudine. We report on a child initiated on this regimen, during concurrent TB treatment, who promptly developed an adverse reaction, virologic failure and dual-class antiretroviral drug resistance, compromising subsequent salvage ART.
    • Earlier versus later start of antiretroviral therapy in HIV-infected adults with tuberculosis.

      Blanc, F-X; Sok, T; Laureillard, D; Borand, L; Rekacewicz, C; Nerrienet, E; Madec, Y; Marcy, O; Chan, S; Prak, N; Kim, C; Lak, K K; Hak, C; Dim, B; Sin, C I; Sun, S; Guillard, B; Sar, B; Vong, S; Fernandez, M; Fox, L; Delfraissy, J-F; Goldfeld, A E; Pneumology Unit, Internal Medicine Department, Bicêtre Hospital, Assistance Publique–Hôpitaux de Paris, Le Kremlin-Bicêtre, France. xavier.blanc@bct.aphp.fr (2011-10-20)
      Tuberculosis remains an important cause of death among patients infected with the human immunodeficiency virus (HIV). Robust data are lacking with regard to the timing for the initiation of antiretroviral therapy (ART) in relation to the start of antituberculosis therapy.
    • The Effect of Complete Integration of HIV and TB Services on Time to Initiation of Antiretroviral Therapy: A Before-After Study.

      Kerschberger, Bernhard; Hilderbrand, Katherine; Boulle, Andrew M; Coetzee, David; Goemaere, Eric; De Azevedo, Virginia; Van Cutsem, Gilles; Médecins sans Frontières, Khayelitsha, Cape Town, South Africa; Centre for Infectious Disease Epidemiology and Research, School of Public Health and Family Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa; South African Medical Unit, Médecins sans Frontières, Johannesburg, South Africa; City of Cape Town, Health Directorate, Khayelitsha, South Africa. (2012-10)
      Studies have shown that early ART initiation in TB/HIV co-infected patients lowers mortality. One way to implement earlier ART commencement could be through integration of TB and HIV services, a more efficient model of care than separate, vertical programs. We present a model of full TB/HIV integration and estimate its effect on time to initiation of ART.
    • Eye exam with indirect ophthalmoscopy for diagnosis of disseminated tuberculosis in patients with HIV/AIDS

      Heiden, David; Margolis, Todd P; Lowinger, Alan; Saranchuk, Peter (BMJ Publishing Group, 2013-05-01)
    • HIV and tuberculosis--science and implementation to turn the tide and reduce deaths.

      Harries, Anthony D; Lawn, Stephen D; Getahun, Haileyesus; Zachariah, Rony; Havlir, Diane V; International Union Against Tuberculosis and Lung Disease, Paris, France. adharries@theunion.org (2012-10)
      Every year, HIV-associated tuberculosis (TB) deprives 350,000 mainly young people of productive and healthy lives.People die because TB is not diagnosed and treated in those with known HIV infection and HIV infection is not diagnosed in those with TB. Even in those in whom both HIV and TB are diagnosed and treated, this often happens far too late. These deficiencies can be addressed through the application of new scientific evidence and diagnostic tools.
    • How can the community contribute in the fight against HIV/AIDS and tuberculosis? An example from a rural district in Malawi.

      Zachariah, R; Teck, R; Buhendwa, L; Labana, S; Chinji, C; Humblet, P; Harries, A D; Médecins sans Frontières, Medical Department (Operational Research), Brussels Operational Center, Belgium. zachariah@internet.lu (Elsevier, 2006-02)
      This paper describes (a) the experience of initiating community involvement in HIV/AIDS and tuberculosis (TB) activities in a rural district in Malawi and (b) some of the different ways in which the community is contributing in the fight against these two diseases and the outcomes of their involvement. During a 2-year period, a total of 21,358 (41%) of 52,510 HIV tests performed at voluntary counselling and HIV testing (VCT) sites in the district were conducted by lay community counsellors. A team of 465 community volunteers, 1,362 trained family caregivers and 9 community nurses provided care and support to 5,106 HIV-positive individuals, of whom 2,006 (39%) were in WHO stage III or IV. All those in WHO stage III or IV were on co-trimoxazole prophylaxis and 895 (45%) of these were also on antiretroviral treatment. A total of 2,714 TB patients, of whom 1627 (60%) were HIV-positive, also received care and support. A total of 1,694 orphans were trained in vocational skills. Twelve vegetable gardens and three maize farms were set up, and pre-school activities were organised for 900 orphans. Communities can play an important contributory role in reducing the burden of HIV/AIDS and TB and in mitigating its impact. Despite this, community resources in most settings are often under-exploited and their role remains undefined.
    • Human resources for control of tuberculosis and HIV-associated tuberculosis.

      Harries, A D; Zachariah, R; Bergström, K; Blanc, L; Salaniponi, F; Elzinga, G; National Tuberculosis Control Programme, Lilongwe, Malawi. adharries@malawi.net (2005-02)
      The global targets for tuberculosis (TB) control were postponed from 2000 to 2005, but on current evidence a further postponement may be necessary. Of the constraints preventing these targets being met, the primary one appears to be the lack of adequately trained and qualified staff. This paper outlines: 1) the human resources and skills for global TB and human immunodeficiency virus (HIV) TB control, including the human resources for implementing the DOTS strategy, the additional human resources for implementing joint HIV-TB control strategies and what is known about human resource gaps at global level; 2) the attempts to quantify human resource gaps by focusing on a small country in sub-Saharan Africa, Malawi; and 3) the main constraints to human resources and their possible solutions, under six main headings: human resource planning; production of human resources; distribution of the work-force; motivation and staff retention; quality of existing staff; and the effect of HIV/AIDS. We recommend an urgent shift in thinking about the human resource paradigm, and exhort international policy makers and the donor community to make a concerted effort to bridge the current gaps by investing for real change.
    • Impact of HIV-Associated Conditions on Mortality in People Commencing Anti-Retroviral Therapy in Resource Limited Settings

      Marshall, Catherine S; Curtis, Andrea J; Spelman, Tim; O'Brien, Daniel P; Greig, Jane; Shanks, Leslie; du Cros, Philipp; Casas, Esther C; da Fonseca, Marcio Silveira; Athan, Eugene; Elliott, Julian H; Infectious Diseases Unit, Alfred Hospital, Melbourne, Australia. catherine.marshall@nt.gov.au (PLoS, 2013-07)
      To identify associations between specific WHO stage 3 and 4 conditions diagnosed after ART initiation and all cause mortality for patients in resource-limited settings (RLS). DESIGN, SETTING: Analysis of routine program data collected prospectively from 25 programs in eight countries between 2002 and 2010.
    • Integrating tuberculosis and HIV care in the primary care setting in South Africa.

      Coetzee, D; Hilderbrand, K; Goemaere, E; Matthys, F; Boelaert, M; Infectious Disease Research Unit, School of Public Health and Family Medicine, University of Cape Town, Observatory, South Africa. dcoetzee@cormack.uct.ac.za (2004-06)
      BACKGROUND: In many countries including South Africa, the increasing human immunodeficiency virus (HIV) and tuberculosis (TB) epidemics have impacted significantly on already weakened public health services. This paper reviews the scope, process and performance of the HIV and TB services in a primary care setting where antiretroviral therapy is provided, in Khayelitsha, South Africa, in order to assess whether there is a need for some form of integration. METHODS: The scope and process of both services were assessed through observations of the service and individual and group interviews with key persons. The performance was assessed by examining the 2001-2002 reports from the health information system and clinical data. RESULTS: The TB service is programme oriented to the attainment of an 85% cure rate amongst smear-positive patients while the HIV service has a more holistic approach to the patient with HIV. The TB service is part of a well-established programme that is highly standardized. The HIV service is in the pilot phase. There is a heavy load at both services and there is large degree of cross-referral between the two services. There are lessons that can be learnt from each service. There is an overlap of activities, duplication of services and under-utilization of staff. There are missed opportunities for TB and HIV prevention, diagnosis and management. CONCLUSIONS: The study suggests that there may be benefits to integrating HIV and TB services. Constraints to this process are discussed.
    • Low uptake of antiretroviral therapy after admission with human immunodeficiency virus and tuberculosis in KwaZulu-Natal, South Africa.

      Murphy, R A; Sunpath, H; Taha, B; Kappagoda, S; Maphasa, K T M; Kuritzkes, D R; Smeaton, L; Doctors Without Borders USA, New York, USA; McCord Hospital, South Africa; Harvard Medical School, Massachusetts, USA; Division of Infectious Disease and Geographic Medicine, California, USA; Zoe-Life, South Africa; Section of Retroviral Therapeutics, Massachusetts, USA; Centre for Biostatistics in AIDS Research, Massachusetts, USA (2010-07-01)
      A prospective cohort study was conducted among human immunodeficiency virus (HIV) infected in-patients with tuberculosis (TB) or other opportunistic infections (OIs) in South Africa to estimate subsequent antiretroviral therapy (ART) uptake and survival.
    • Outcomes and safety of concomitant nevirapine and rifampicin treatment under programme conditions in Malawi.

      Moses, M; Zachariah, R; Tayler-Smith, K; Misinde, D; Foncha, C; Manzi, M; Bauerfeind, A; Mwagomba, B; Kwanjana, J; Harries, A D; Médecins sans Frontières, Thyolo District, Thyolo, Malawi. (2010-02)
      SETTING: Thyolo District Hospital, rural Malawi. OBJECTIVES: To report on 1) clinical, immunological and virological outcomes and 2) safety among human immunodeficiency virus (HIV) infected patients with tuberculosis (TB) who received concurrent nevirapine (NVP) and rifampicin (RMP) based treatment. DESIGN: Retrospective cohort study. METHODS: Analysis of programme data, June-December 2007. RESULTS: Of a total of 156 HIV-infected TB patients who started NVP-based antiretroviral treatment, 136 (87%) completed TB treatment successfully, 16 (10%) died and 5 (4%) were transferred out. Mean body weight and CD4 gain (adults) were respectively 4.4 kg (95%CI 3.3-5.4) and 140 cells/mm(3) (95%CI 117-162). Seventy-four per cent of patients who completed TB treatment and had a viral load performed (n = 74) had undetectable levels (<50 copies/ml), while 17 (22%) had a viral load of 50-1000 copies/ml. Hepatotoxicity was present in 2 (1.3%) patients at baseline. Two patients developed Grade 2 and one developed Grade 3 alanine transaminase enzyme elevations during TB treatment (incidence rate per 10 years of follow-up 4.2, 95%CI 1.4-13.1). There were no reported deaths linked to hepatotoxicity. CONCLUSIONS: In a rural district in Malawi, concomitant NVP and RMP treatment is associated with good TB treatment outcomes and appears safe. Further follow-up of patients would be useful to ascertain the longer-term effects of this concurrent treatment.
    • Outcomes of nevirapine- and efavirenz-based antiretroviral therapy when coadministered with rifampicin-based antitubercular therapy

      Boulle, A; Van Cutsem, G; Cohen, K; Hilderbrand, K; Mathee, S; Abrahams, M; Goemaere, E; Coetzee, D; Maartens, G; School of Public Health and Family Medicine, University of Cape Town, Cape Town, South Africa; Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Cape Town, South Africa; Médecins Sans Frontières, Cape Town, South Africa; Site B Community Health Centre, Department of Health, Provincial Government of the Western Cape, Cape Town, South Africa (2008-08-06)
      CONTEXT: Rifampicin-based antitubercular therapy reduces the plasma concentrations of nevirapine and efavirenz. The virological consequences of these interactions are not well described. OBJECTIVE: To assess the effectiveness and tolerability of concomitant efavirenz- or nevirapine-based combination antiretroviral therapy and rifampicin-based antitubercular therapy. DESIGN, SETTING, AND PARTICIPANTS: Cohort analysis of prospectively collected routine clinical data in a community-based South African antiretroviral treatment program. Antiretroviral treatment-naive adults enrolled between May 2001 and June 2006 were included in the analysis, and were followed up until the end of 2006. INTERVENTIONS: Patients starting antiretroviral therapy with or without concurrent antitubercular therapy received either efavirenz or nevirapine at standard doses. Patients developing tuberculosis while taking antiretroviral therapy that included nevirapine were either changed to efavirenz or continued taking nevirapine. MAIN OUTCOME MEASURES: Viral load of 400 copies/mL or more after 6, 12, and 18 months of antiretroviral therapy; time to the first viral load of 400 copies/mL or more; time to confirmed virological failure (2 consecutive values > or = 5000 copies/mL); time to death; and time to treatment-limiting toxicity were assessed. RESULTS: The analysis included 2035 individuals who started antiretroviral therapy with efavirenz (1074 with concurrent tuberculosis) and 1935 with nevirapine (209 with concurrent tuberculosis). There were no differences in time to death or substitution of either antiretroviral drug for toxicity with and without concurrent tuberculosis. Patients starting nevirapine with concurrent tuberculosis were at a higher risk of elevated viral load most notably at 6 months (16.3%; 95% confidence interval [CI], 10.6%-23.5%) than those without tuberculosis (8.3%; 95% CI, 6.7%-10.0%; adjusted odds ratio [OR], 2.1; 95% CI, 1.2-3.4; and in the combined estimate, adjusted OR, 1.7; 95% CI, 1.2-2.6). In the time-to-event analysis of confirmed virological failure (2 consecutive values of > or = 5000 copies/mL), patients starting nevirapine with concurrent tuberculosis developed virological failure sooner (adjusted hazard ratio [HR] 2.2; 95% CI, 1.3-3.7). There were no differences between patients starting efavirenz with and without concurrent tuberculosis (adjusted OR, 1.1; 95% CI, 0.8-1.5 [combined estimate] and adjusted HR, 1.1; 95% CI, 0.6-2.0, respectively). There was no difference in time to virological rebound in patients free of tuberculosis and those developing tuberculosis during follow-up while taking nevirapine (adjusted HR, 1.0; 95% CI, 0.5-2.0) or efavirenz (adjusted HR, 0.8; 95% CI, 0.4-1.7). CONCLUSION: In this cohort study, virological outcomes were inferior when nevirapine-based antiretroviral therapy was commenced while taking antitubercular treatment (vs without concurrent tuberculosis) but comparable when starting efavirenz-based antiretroviral therapy (vs without concurrent tuberculosis) or when tuberculosis developed while taking established nevirapine- or efavirenz-based therapies.
    • 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.
    • Plasma Concentrations, Efficacy and Safety of Efavirenz in HIV-Infected Adults Treated for Tuberculosis in Cambodia (ANRS 1295-CIPRA KH001 CAMELIA Trial).

      Borand, Laurence; Madec, Yoann; Laureillard, Didier; Chou, Monidarin; Marcy, Olivier; Pheng, Phearavin; Prak, Narom; Kim, Chindamony; Lak, Khemarin Kim; Hak, Chanroeun; Dim, Bunnet; Nerrienet, Eric; Fontanet, Arnaud; Sok, Thim; Goldfeld, Anne E; Blanc, François-Xavier; Taburet, Anne-Marie (Public Library of Science, 2014)
      To assess efavirenz plasma concentrations and their association with treatment efficacy and tolerance of efavirenz 600 mg daily in HIV-tuberculosis co-infected patients.
    • They call it "patient selection" in Khayelitsha: the experience of Médecins Sans Frontières-South Africa in enrolling patients to receive antiretroviral treatment for HIV/AIDS

      Fox, Renée C; Goemaere, Eric; University of Pennsylvania, Philadelphia, USA; Médecins Sans Frontières (MSF) - South Africa (2006-05-02)
    • Time to initiation of antiretroviral therapy among patients with HIV-associated tuberculosis in Cape Town, South Africa

      Lawn, Stephen D; Campbell, Lucy; Kaplan, Richard; Boulle, Andrew; Cornell, Morna; Kerschberger, Bernhard; Morrow, Carl; Little, Francesca; Egger, Matthias; Wood, Robin; The Desmond Tutu HIV Centre, Institute for Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa; Department of Clinical Research, Faculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, London, UK; Department of Statistical Sciences, Faculty of Science, University of Cape Town, South Africa; School of Public Health and Family Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa; Medecins Sans Frontieres, Cape Town, South Africa; Division of International and Environmental Health, Institute of Social and Preventive Medicine (ISPM), University of Bern, Switzerland (Lippincott Williams & Wilkins, 2011-06-01)
      We studied the time interval between starting tuberculosis treatment and commencing antiretroviral treatment (ART) in HIV-infected patients (n = 1433; median CD4 count 71 cells per microliter, interquartile range: 32-132) attending 3 South African township ART services between 2002 and 2008. The overall median delay was 2.66 months (interquartile range: 1.58-4.17). In adjusted analyses, delays varied between treatment sites but were shorter for patients with lower CD4 counts and those treated in more recent calendar years. During the most recent period (2007-2008), 4.7%, 19.7%, and 51.1% of patients started ART within 2, 4, and 8 weeks of tuberculosis treatment, respectively. Operational barriers must be tackled to permit further acceleration of ART initiation as recommended by 2010 WHO ART guidelines.
    • 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; Boulle, Andrew; Wood, Robin; Henostroza, German; Egger, Matthias; Institute of Social and Preventive Medicine (ISPM), University of Bern, Bern, Switzerland. lfenner@ispm.unibe.ch (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.
    • Voluntary Counselling, HIV Testing and Adjunctive Cotrimoxazole Reduces Mortality in Tuberculosis Patients in Thyolo, Malawi.

      Zachariah, R; Spielmann M P; Chinji, C; Gomani, P; Arendt, V; Hargreaves, N J; Salaniponi, F M L; Harries, A D; Medecins Sans Frontieres-Luxembourg, Blantyre, Malawi. zachariah@internet.Lu (2003-05-02)
      OBJECTIVES: To assess the feasibility and effectiveness of voluntary counselling, HIV testing and adjunctive cotrimoxazole in reducing mortality in a cohort of tuberculosis (TB) patients registered under routine programme conditions in a rural district of Malawi. DESIGN: 'Before' and 'after' cohort study using historical controls. METHODS: Between 1 July 1999 and 30 June 2000 all TB patients were started on standardized anti-TB treatment, and offered voluntary counselling and HIV testing (VCT). Those found to be HIV-positive were offered cotrimoxazole at a dose of 480 mg twice daily, provided there were no contraindications. Side-effects were monitored clinically. End-of-treatment outcomes in this cohort (intervention group) were compared with a cohort registered between 1 July 1998 and 30 June 1999 in whom VCT and cotrimoxazole was not offered (control group). FINDINGS: A total of 1986 patients was registered in the study: 1061 in the intervention group and 925 in the control cohort. In the intervention group, 1019 (96%) patients were counselled pre-test, 964 (91%) underwent HIV testing and 938 (88%) were counselled post-test. The overall HIV-seroprevalence rate was 77%. A total of 693 patients were given cotrimoxazole of whom 14 (2%) manifested minor dermatological reactions. The adjusted relative risk of death in the intervention group compared with the control group was 0.81 (P < 0.001). The number needed to treat with VCT and adjunctive cotrimoxazole to prevent one death during anti-TB treatment was 12.5. INTERPRETATION: This study shows that VCT and adjunctive cotrimoxazole is feasible, safe and reduces mortality rates in TB patients under routine programme conditions.