• A national survey of the impact of rapid scale-up of antiretroviral therapy on health-care workers in Malawi: effects on human resources and survival.

      Makombe, S D; Jahn, A; Tweya, H; Chuka, S; Yu, J K L; Hochgesang, M; Aberle-Grasse, J; Pasulani, O; Schouten, E J; Kamoto, K; Harries, A D; HIV Unit, Ministry of Health, Lilongwe, Malawi. (WHO, 2007-11)
      OBJECTIVE: To assess the human resources impact of Malawis rapidly growing antiretroviral therapy (ART) programme and balance this against the survival benefit of health-care workers who have accessed ART themselves. METHODS: We conducted a national cross-sectional survey of the human resource allocation in all public-sector health facilities providing ART in mid-2006. We also undertook a survival analysis of health-care workers who had accessed ART in public and private facilities by 30 June 2006, using data from the national ART monitoring and evaluation system. FINDINGS: By 30 June 2006, 59 581 patients had accessed ART from 95 public and 28 private facilities. The public sites provided ART services on 2.4 days per week on average, requiring 7% of the clinician workforce, 3% of the nursing workforce and 24% of the ward clerk workforce available at the facilities. We identified 1024 health-care workers in the national ART-patient cohort (2% of all ART patients). The probabilities for survival on ART at 6 months, 12 months and 18 months were 85%, 81% and 78%, respectively. An estimated 250 health-care workers lives were saved 12 months after ART initiation. Their combined work-time of more than 1000 staff-days per week was equivalent to the human resources required to provide ART at the national level. CONCLUSION: A large number of ART patients in Malawi are managed by a small proportion of the health-care workforce. Many health-care workers have accessed ART with good treatment outcomes. Currently, staffing required for ART balances against health-care workers lives saved through treatment, although this may change in the future.
    • Navigating the risks of prevention of mother to child transmission (PMTCT) of HIV services in Kibera, Kenya: Barriers to engaging and remaining in care

      Thomson, KA; Telfer, B; Opondo Awiti, P; Munge, J; Ngunga, M; Reid, A (Public Library of Science, 2018-01-24)
      Within the first year of implementation, 43% of women who tested HIV positive at their first antenatal care visit were no longer retained and being followed in the free prevention of mother to child transmission (PMTCT) of HIV program offered by the Kenyan Ministry of Health and Médecins Sans Frontières in the informal settlement of Kibera, Nairobi. This study aimed to explore barriers to enrolling and remaining engaged in PMTCT services throughout the pregnancy and postpartum periods. Qualitative data from 31 focus group discussions and 35 in-depth interviews across six stakeholder groups that included women, men, and PMTCT service providers were analyzed. Using an inductive exploratory approach, four researchers coded the data and identified key themes. Five themes emerged from the data that may influence attrition from PMTCT service in this setting: 1) HIV in the context of Kibera, 2) knowledge of HIV status, 3) knowledge of PMTCT, 4) disclosure of HIV status, and 5) male partner support for PMTCT services. A new HIV diagnosis during pregnancy immediately triggered an ongoing risk assessment of perceived hazards in the home, community, and clinic environments that could occur as a result of female participation in PMTCT services. Male partners were a major influence in this risk assessment, but were generally unaware of PMTCT services. To preserve relationships with male partners, meet community expectations of womanhood, and maintain confidentiality while following recommendations of healthcare providers, women had to continuously weigh the risks and benefits of PMTCT services and interventions. Community-based HIV testing and PMTCT education, male involvement in antenatal care, and counseling customized to assist each woman in her own unique risk assessment, may improve uptake of and retention in care and optimize the HIV prevention benefit of PMTCT interventions.
    • Nevirapine versus Efavirenz for patients co-infected with HIV and Tuberculosis: A Randomised Non-Inferiority Trial

      Bonnet, Maryline; Bhatt, Nilesh; Baudin, Elisabeth; Silva, Carlota; Michon, Christophe; Taburet, Anne-Marie; Ciaffi, Laura; Sobry, Agnès; Bastos, Rui; Nunes, Elizabete; Rouzioux, Christine; Jani, Ilesh; Calmy, Alexandra; Epicentre, Paris, France. Electronic address: maryline.bonnet@geneva.msf.org. (2013-02-19)
      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).
    • Nevirapine- and efavirenz-associated hepatotoxicity under programmatic conditions in Kenya and Mozambique.

      Chu, K M; Manzi, M; Zuniga, I; Biot, M; Ford, N P; Rasschaert, F; Zachariah, R; South African Medical Unit, Médecins Sans Frontières Johannesburg, PO Box 32117, Braamfontein 2017, South Africa. kathryn.chu@joburg.msf.org (2012-06)
      To describe the frequency, risk factors, and clinical signs and symptoms associated with hepatotoxicity (HT) in patients on nevirapine- or efavirenz-based antiretroviral therapy (ART), we conducted a retrospective cohort analysis of patients attending the ART clinic in Kibera, Kenya, from April 2003 to December 2006 and in Mavalane, Mozambique, from December 2002 to March 2007. Data were collected on 5832 HIV-positive individuals who had initiated nevirapine- or efavirenz-based ART. Median baseline CD4+ count was 125 cells/μL (interquartile range [IQR] 55-196). Over a median follow-up time of 426 (IQR 147-693) days, 124 (2.4%) patients developed HT. Forty-one (54.7%) of 75 patients with grade 3 HT compared with 21 (80.8%) of 26 with grade 4 had associated clinical signs or symptoms (P = 0.018). Four (5.7%) of 124 patients with HT died in the first six months compared with 271 (5.3%) of 5159 patients who did not develop HT (P = 0.315). The proportion of patients developing HT was low and HT was not associated with increased mortality. Clinical signs and symptoms identified 50% of grade 3 HT and most cases of grade 4 HT. This suggests that in settings where alanine aminotransferase measurement is not feasible, nevirapine- and efavirenz-based ART may be given safely without laboratory monitoring.
    • Nevirapine-associated early hepatotoxicity: incidence, risk factors, and associated mortality in a primary care ART programme in South Africa.

      Chu, Kathryn M; Boulle, Andrew M; Ford, Nathan; Goemaere, Eric; Asselman, Valerie; Van Cutsem, Gilles; South African Medical Unit, Médecins Sans Frontières, Johannesburg, South Africa. kathryn.chu@joburg.msf.org (2010-02)
      BACKGROUND: The majority of antiretroviral treatment programmes in sub-Saharan Africa are scaling up antiretroviral treatment using a fixed dose first-line antiretroviral regimen containing stavudine, lamivudine, and nevirapine. One of the primary concerns with the use of this regimen is nevirapine-associated hepatotoxicity. METHODOLOGY/PRINCIPAL FINDINGS: Study participants were 1809 HIV-infected, antiretroviral naïve adults initiating nevirapine-based antiretroviral therapy between November 2002 and December 2006. The primary outcome was early hepatotoxicity. Secondary outcomes were associations with hepatotoxicity and mortality at six months. The cumulative proportion of early hepatotoxicity ranged from 1.0-2.0% giving an incidence-rate at 102 days of 3.6-7.6 per 100 person-years. Median time to hepatotoxicity was 32 (IQR 28-58) days. At 12 weeks, only 8% of patients had alanine aminotransferase monitoring at all the time-points recommended by national guidelines. No association was found between age, gender, baseline CD4 count, concurrent tuberculosis infection, prior participation in a prevention of mother-to-child-transmission program, or baseline weight and early hepatotoxicity. There was no association between early hepatotoxicity and mortality. CONCLUSIONS: The cumulative proportion of early hepatotoxicity in nevirapine based antiretroviral therapy was low in this resource-constrained setting. Hepatotoxicity was not associated with mortality. Frequent routine monitoring of alanine aminotransferase proved difficult to implement in this public sector primary care programme. Focused monitoring in the first month may be a more cost-effective and pragmatic option in settings with limited resources. Correlation with clinical signs and symptoms may allow future alanine aminotransferase testing to be dictated by clinical criteria.
    • No association between human herpesvirus 6 reactivation and cryptococcosis in human immunodeficiency virus-infected patients

      Micol, Romain; Buchy, Philippe; Galimand, Julie; Veasna, Duong; Ferradini, Laurent; Balkan, Suna; Guerin, Philippe Jean; Martin, Pierre-Régis; Fontanet, Arnaud; Lortholary, Olivier; Rouzioux, Christine; Leruez-Ville, Marianne; Unite de Virologie, Hopital Necker-Enfants Malades, Universite Rene Descartes, Paris, France; Unite de Virologie, Institut Pasteur du Cambodge, Phnom Penh, Cambodia; Medecins Sans Frontieres, Hopital Prea Bath Norodom Sihanouk, Phnom Penh, Cambodia; Medecins Sans Frontieres, Paris, France; Epicentre, Paris, France; Medecins Du Monde, Hopital Kosamak, Phnom Penh, Cambodia; Unite d’Epidemiologie des Maladies Emergentes, Institut Pasteur, Paris, France; Service des Maladies Infectieuses et Tropicales, Universite Rene Descartes, Hopital Necker-Enfants Malades, Centre d’Infectiologie Necker-Pasteur, Paris, France (2009-02-01)
    • Nutrition outcomes of HIV-infected malnourished adults treated with ready-to-use therapeutic food in sub-Saharan Africa: a longitudinal study.

      Ahoua, Laurence; Umutoni, Chantal; Huerga, Helena; Minetti, Andrea; Szumilin, Elisabeth; Balkan, Suna; Olson, David M; Nicholas, Sarala; Pujades-Rodríguez, Mar; Epicentre, Médecins Sans Frontières, Paris, France. laurence_ahoua@yahoo.fr (BioMed Central home, 2011-01)
      Among people living with HIV/AIDS, nutritional support is increasingly recognized as a critical part of the essential package of care, especially for patients in sub-Saharan Africa. The objectives of the study were to evaluate the outcomes of HIV-positive malnourished adults treated with ready-to-use therapeutic food and to identify factors associated with nutrition programme failure.
    • Offering Integrated Care for HIV/AIDS, Diabetes and Hypertension within Chronic Disease Clinics in Cambodia.

      Janssens, B; Van Damme, W; Raleigh, B; Gupta, J; Khem, S; Soy Ty, K; Vun, M; Ford, N; Zachariah, R; Médecins Sans Frontières, Phnom Penh, Cambodia. b.janssens@bigfoot.com (WHO, 2007-11)
      PROBLEM: In Cambodia, care for people with HIV/AIDS (prevalence 1.9%) is expanding, but care for people with type II diabetes (prevalence 5-10%), arterial hypertension and other treatable chronic diseases remains very limited. APPROACH: We describe the experience and outcomes of offering integrated care for HIV/AIDS, diabetes and hypertension within the setting of chronic disease clinics. LOCAL SETTING: Chronic disease clinics were set up in the provincial referral hospitals of Siem Reap and Takeo, 2 provincial capitals in Cambodia. RELEVANT CHANGES: At 24 months of care, 87.7% of all HIV/AIDS patients were alive and in active follow-up. For diabetes patients, this proportion was 71%. Of the HIV/AIDS patients, 9.3% had died and 3% were lost to follow-up, while for diabetes this included 3 (0.1%) deaths and 28.9% lost to follow-up. Of all diabetes patients who stayed more than 3 months in the cohort, 90% were still in follow-up at 24 months. LESSONS LEARNED: Over the first three years, the chronic disease clinics have demonstrated the feasibility of integrating care for HIV/AIDS with non-communicable chronic diseases in Cambodia. Adherence support strategies proved to be complementary, resulting in good outcomes. Services were well accepted by patients, and this has had a positive effect on HIV/AIDS-related stigma. This experience shows how care for HIV/AIDS patients can act as an impetus to tackle other common chronic diseases.
    • Opportunities to improve storage and transportation of blood specimens for CD4 testing in a rural district in Zimbabwe using BD vacutainer CD4 stabilization tubes: a stability and diagnostic accuracy study

      Fajardo, Emmanuel; Metcalf, Carol; Mbofana, Elton; van Vyve, Charlotte; Munyaradzi, Dhodho; Simons, Sandra; Kuhudzayi, Misheck; Bygrave, Helen (BioMed Central, 2014-10-22)
      BackgroundCD4+ T-cell testing of blood specimens collected in standard EDTA Vacutainer tubes and transported at ambient temperature, must be completed within 48 hours with the BD FACSCount¿ flow cytometer, restricting specimen collection in remote clinics with no on-site testing and limited specimen transport services. We conducted a study in Buhera District, Zimbabwe, to assess the stability and accuracy of CD4+ T-cell results of samples collected in Stabilization Tubes (ST) and stored at ambient temperature for varying time periods.MethodsPaired EDTA and ST samples were collected from 51 HIV-positive patients aged 18 years and older. CD4+ T-cell testing was done on arrival in the laboratory (Day 0). ST samples were retested on Days 3, 5, and 7. Nineteen ST samples were stored for an additional week and retested on Day 14.ResultsThere was a strong correlation between absolute CD4+ T-cell counts measured in the EDTA Day 0 reference sample and Day 7 ST sample (Spearman¿s rho: 0.9778; mean difference: ¿4.9 cells/¿L and limits of agreement (LOA): 98.5 and 88.7 cells/¿L); and the reference sample and Day 14 ST sample (Spearman¿s rho: 0.9632; mean difference 5.1 cells/¿L and LOA: ¿99.6 and 109.8 cells/¿L. Using a 350 cells/¿L threshold, the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were all 100% on Day 7, and 83.3%, 100%, 100% and 92.9% on Day 14. Using a 500 cells/¿L threshold, the sensitivity, specificity, PPV and NVP were 100%, 88.5%, 88.5% and 100% on Day 7 and 88.9%, 80.0%, 80.0% and 88.9% on Day 14.ConclusionsCD4 ST can be used and stored up to 7 days as a reliable alternative to standard EDTA tubes in settings where CD4+ T-cell testing within 48 hours is not feasible. Despite the small sample size, results suggest that ST may be stored up to 14 days at room temperature for CD4 testing, without compromising accuracy. However, further studies with larger sample sizes are needed to confirm this preliminary finding.
    • Optimal Timing of Antiretroviral Treatment Initiation in HIV-Positive Children and Adolescents: a Multiregional Analysis from Southern Africa, West Africa and Europe

      Schomaker, M; Leroy, V; Wolfs, T; Technau, KG; Renner, L; Judd, A; Sawry, S; Amorissani-Folquet, M; Noguera-Julian, A; Tanser, F; Eboua, F; Navarro, Maria L; Chimbetete, C; Amani-Bosse, C; Warszawski, J; Phiri, S; N’Gbeche, S; Cox, V; Koueta, F; Giddy, J; Sygnaté-Sy, H; Raben, D; Chêne, G; Davies, MA (Oxford University Press, 2016-06-24)
      Background: There is limited knowledge about the optimal timing of antiretroviral treatment initiation in older children and adolescents. Methods: A total of 20 576 antiretroviral treatment (ART)-naïve patients, aged 1-16 years at enrolment, from 19 cohorts in Europe, Southern Africa and West Africa, were included. We compared mortality and growth outcomes for different ART initiation criteria, aligned with previous and recent World Health Organization criteria, for 5 years of follow-up, adjusting for all measured baseline and time-dependent confounders using the g-formula. Results: Median (1st;3rd percentile) CD4 count at baseline was 676 cells/mm3 (394; 1037) (children aged ≥ 1 and < 5 years), 373 (172; 630) (≥ 5 and < 10 years) and 238 (88; 425) (≥ 10 and < 16 years). There was a general trend towards lower mortality and better growth with earlier treatment initiation. In children < 10 years old at enrolment, by 5 years of follow-up there was lower mortality and a higher mean height-for-age z-score with immediate ART initiation versus delaying until CD4 count < 350 cells/mm3 (or CD4% < 15% or weight-for-age z-score < -2) with absolute differences in mortality and height-for-age z-score of 0.3% (95% confidence interval: 0.1%; 0.6%) and -0.08 (-0.09; -0.06) (≥ 1 and < 5 years), and 0.3% (0.04%; 0.5%) and -0.07 (-0.08; -0.05) (≥ 5 and < 10 years). In those aged > 10 years at enrolment we did not find any difference in mortality or growth with immediate ART initiation, with estimated differences of -0.1% (-0.2%; 0.6%) and -0.03 (-0.05; 0.00), respectively. Growth differences in children aged < 10 years persisted for treatment thresholds using higher CD4 values. Regular follow-up led to better height and mortality outcomes. Conclusions: Immediate ART is associated with lower mortality and better growth for up to 5 years in children < 10 years old. Our results on adolescents were inconclusive.
    • Out-of-pocket costs of AIDS care in China: are free antiretroviral drugs enough?

      Moon, S; Van Leemput, L; Durier, N; Jambert, E; Dahmane, A; Jie, Y; Wu, G; Philips, M; Hu, Y; Saranchuk, P; Médecins Sans Frontières, Beijing, China and Brussels, Belgium. suerie_moon@yahoo.com (2008-09)
      Financial access to HIV care and treatment can be difficult for many people in China, where the government provides free antiretroviral drugs but does not cover the cost of other medically necessary components, such as lab tests and drugs for opportunistic infections. This article estimates out-of-pocket costs for treatment and care that a person living with HIV/AIDS in China might face over the course of one year. Data comes from two treatment projects run by Médecins Sans Frontières in Nanning, Guangxi Province and Xiangfan, Hubei Province. Based on the national treatment guidelines, we estimated costs for seven different patient profiles ranging from WHO Clinical Stages I through IV. We found that patients face significant financial barriers to even qualify for the free ARV program. For those who do, HIV care and treatment can be a catastrophic health expenditure, with cumulative patient contributions ranging from approximately US$200-3939/year in Nanning and US$13-1179/year in Xiangfan, depending on the patient's clinical stage of HIV infection. In Nanning, these expenses translate as up to 340% of an urban resident's annual income or 1200% for rural residents; in Xiangfan, expenses rise to 116% of annual income for city dwellers and 295% in rural areas. While providing ARV drugs free of charge is an important step, the costs of other components of care constitute important financial barriers that may exclude patients from accessing appropriate care. Such barriers can also lead to undesirable outcomes in the future, such as impoverishment of AIDS-affected households, higher ARV drug-resistance rates and greater need for complex, expensive second-line antiretroviral drugs.
    • Outcomes after two years of providing antiretroviral treatment in Khayelitsha, South Africa.

      Coetzee, D; Hildebrand, K; Boulle, A; Maartens, G; Louis, F; Labatala, V; Reuter, H; Ntwana, N; Goemaere, E; Infectious Disease Epidemiology Unit, School of Public Health and Family Medicine, University of Cape Town, Anzio Road, Observatory 7925, South Africa. (2004-04-09)
      BACKGROUND: A community-based antiretroviral therapy (ART) programme was established in 2001 in a South African township to explore the operational issues involved in providing ART in the public sector in resource-limited settings and demonstrate the feasibility of such a service. METHODS: Data was analysed on a cohort of patients with symptomatic HIV disease and a CD4 lymphocyte count < 200 x 10 cells/l. The programme used standardized protocols (using generic medicines whenever possible), a team-approach to clinical care and a patient-centred approach to promote adherence. RESULTS: Two-hundred and eighty-seven adults naive to prior ART were followed for a median duration of 13.9 months. The median CD4 lymphocyte count was 43 x 10 cells/l at initiation of treatment, and the mean log10 HIV RNA was 5.18 copies/ml. The HIV RNA level was undetectable (< 400 copies/ml) in 88.1, 89.2, 84.2, 75.0 and 69.7% of patients at 3, 6, 12, 18 and 24 months respectively. The cumulative probability of remaining alive was 86.3% at 24 months on treatment for all patients, 91.4% for those with a baseline CD4 lymphocyte count > or =50 x 10 cells/l, and 81.8% for those with a baseline CD4 lymphocyte count < 50 x 10 cells/l. The cumulative probability of changing a single antiretroviral drug by 24 months was 15.1% due to adverse events or contraindications, and 8.4% due to adverse events alone. CONCLUSIONS: ART can be provided in resource-limited settings with good patient retention and clinical outcomes. With responsible implementation, ART is a key component of a comprehensive response to the epidemic in those communities most affected by HIV.
    • Outcomes After Virologic Failure of First-Line ART in South Africa

      Murphy, Richard A; Sunpath, Henry; Lu, Zhigang; Chelin, Neville; Losina, Elena; Gordon, Michelle; Ross, Douglas; Ewusi, Aba D; Matthews, Lynn T; Kuritzkes, Daniel R; Marconi, Vincent C; Operational Support Unit, Doctors Without Borders, New York, New York; McCord Hospital, Durban, South Africa; Massachusetts General Hospital, Boston, Massachusetts, USA; Nelson Mandela School of Medicine, Durban; St. Mary’s Hospital, Mariannhill, South Africa; Harvard Medical School; Division of Infectious Diseases, Beth Israel Deaconess Medical Center; Section of Retroviral Therapeutics, Brigham and Women’s Hospital, Boston, Massachusetts; Infectious Disease Service, San Antonio Military Medical Center, Fort Sam Houston, Texas; Emory University School of Medicine, Atlanta, Georgia, USA (2010-04-24)
      To determine initial 24-week outcomes among prospectively enrolled patients with failure of initial antiretroviral therapy (ART).
    • 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 for Efavirenz versus Nevirapine-Containing Regimens for Treatment of HIV-1 Infection: A Systematic Review and Meta-Analysis

      Pillay, Prinitha; Ford, Nathan; Shubber, Zara; Ferrand, Rashida A; Wits Reproductive Health and HIV Institute, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa. prinithapillay@yahoo.co.uk (PLoS, 2013-07)
      There is conflicting evidence and practice regarding the use of the non-nucleoside reverse transcriptase inhibitors (NNRTI) efavirenz (EFV) and nevirapine (NVP) in first-line antiretroviral therapy (ART).
    • Outcomes of a remote, decentralized health center-based HIV/AIDS antiretroviral program in Zambia, 2003 to 2007

      Elema, R; Mills, C; Yun, O; Lokuge, K; Ssonko, C; Nyirongo, N; Mtonga, V; Zulu, H; Tu, D; Verputten, M; O'Brien, D P; Médecins Sans Frontières-Holland, Lusaka/Nchelenge, Zambia; Médecins Sans Frontières-Holland, Amsterdam, Netherlands; Médecins Sans Frontières-USA, New York; Ministry of Health, Lusaka/Nchelenge, Zambia; Médecins Sans Frontières-Holland, Vancouver, Canada (2009-02-11)
      A cross-sectional study of patients living with HIV/ AIDS treated during 2003 to 2007 in decentralized, rural health centers in Zambia was performed to measure virological outcomes after 12 months of antiretroviral therapy and identify factors associated with virological failure. Data from 228 patients who started antiretroviral therapy >12 months prior were analyzed. In all, 93% received stavudine + lamivudine + nevirapine regimens, and median antiretroviral therapy duration was 23.5 months (interquartile range 20-28). Of the 205 patients tested for viral load, 177 (86%) had viral load <1000 copies/mL. Probability of developing virological failure (viral load >1000 copies/mL) was 8.9% at 24 months and 19.6% at 32 months. Predictors for virological failure were <100% adherence, body mass index <18.5 kg/m(2), and women <40 years old. Of those with virological failure who underwent 3 to 6 months of intensive adherence counseling, 45% obtained virological success. In a remote, resource-limited setting in decentralized health centers, virological and immunological assessments of patients on antiretroviral therapy >12 months showed that positive health outcomes are achievable.
    • Outcomes of antiretroviral therapy over a 10-year period of expansion: a multicohort analysis of African and Asian HIV programs.

      Grimsrud, Anna; Balkan, Suna; Casas, Esther C; Lujan, Johnny; Van Cutsem, Gilles; Poulet, Elisabeth; Myer, Landon; Pujades-Rodriguez, Mar (2014-10-01)
      Little is known about the evolution of program outcomes associated with rapid expansion of antiretroviral therapy (ART) in resource-limited settings. We describe temporal trends and assess associations with mortality and loss to follow-up (LTFU) in HIV cohorts from 8 countries.
    • 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.
    • Outcomes of patients with Kaposi's sarcoma who start antiretroviral therapy under routine programme conditions in Malawi.

      Makombe, S D; Harries, A D; Yu, J K L; Hochgesang, M; Mhango, E; Weigel, R; Pasulani, O; Fitzgerald, M; Schouten, E J; Libamba, E; Clinical HIV Unit, Ministry of Health, PO Box 30377, Lilongwe, Malawi. (Royal Society of Medicine, 2008-01)
      AIDS-associated Kaposi's sarcoma (KS) is the most common AIDS-related malignancy in sub-Saharan Africa, with a generally unfavourable prognosis. We report on six-month and 12-month cohort treatment outcomes of human immunodeficiency virus (HIV)-positive KS patients and HIV-positive non-KS patients treated with antiretroviral therapy (ART) in public sector facilities in Malawi. Data were collected from standardized antiretroviral (ARV) patient master cards and ARV patient registers. Between July and September 2005, 7905 patients started ART-488 (6%) with a diagnosis of KS and 7417 with a non-KS diagnosis. Between January and March 2005, 4580 patients started ART-326 (7%) with a diagnosis of KS and 4254 with a non-KS diagnosis. At six-months and 12-months, significantly fewer KS patients were alive and significantly more had died or defaulted compared to non-KS patients. HIV-positive KS patients on ART in Malawi have worse outcomes than other patients on ART. Methods designed to improve these outcomes must be found.
    • Outcomes of the South African National Antiretroviral Treatment Programme for children: the IeDEA Southern Africa collaboration.

      Davies, Mary-Ann; Keiser, Olivia; Technau, Karl; Eley, Brian; Rabie, Helena; van Cutsem, Gilles; Giddy, Janet; Wood, Robin; Boulle, Andrew; Egger, Matthias; Moultrie, Harry; School of Public Health and Family Medicine, University of Cape Town. Mary-Ann.Davies@uct.ac.za (2009-10)
      OBJECTIVES: To assess paediatric antiretroviral treatment (ART) outcomes and their associations from a collaborative cohort representing 20% of the South African national treatment programme. DESIGN AND SETTING: Multi-cohort study of 7 public sector paediatric ART programmes in Gauteng, Western Cape and KwaZulu-Natal provinces. SUBJECTS: ART-naive children (< or = 16 years) who commenced treatment with > or = 3 antiretroviral drugs before March 2008. OUTCOME MEASURES: Time to death or loss to follow-up were assessed using the Kaplan-Meier method. Associations between baseline characteristics and mortality were assessed with Cox proportional hazards models stratified by site. Immune status, virological suppression and growth were described in relation to duration of ART. RESULTS: The median (interquartile range) age of 6 078 children with 9 368 child-years of follow-up was 43 (15 - 83) months, with 29% being < 18 months. Most were severely ill at ART initiation. More than 75% of children were appropriately monitored at 6-monthly intervals with viral load suppression (< 400 copies/ml) being 80% or above throughout 36 months of treatment. Mortality and retention in care at 3 years were 7.7% (95% confidence interval 7.0 - 8.6%) and 81.4% (80.1 - 82.6%), respectively. Together with young age, all markers of disease severity (low weight-for-age z-score, high viral load, severe immune suppression, stage 3/4 disease and anaemia) were independently associated with mortality. CONCLUSIONS: Dramatic clinical benefit for children accessing the national ART programme is demonstrated. Higher mortality in infants and those with advanced disease highlights the need for early diagnosis of HIV infection and commencement of ART.