Assessment of Simple Risk Markers for Early Mortality Among HIV-Infected Patients in Guinea-Bissau: a Cohort Study
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BMJ Open: first published as 10.1136/bmjopen-2012-001587 on 14 November 2012. Downloaded from Open Access Research Assessment of simple risk markers for early mortality among HIV-infected patients in Guinea-Bissau: a cohort study Inés Oliveira,1,2 Andreas Andersen,1 Alcino Furtado,1 Candida Medina,3 David da Silva,3 Zacarias J da Silva,1,4 Peter Aaby,1,5 Alex Lund Laursen,6 Christian Wejse,6,7 Jesper Eugen-Olsen,2 for the Bissau HIV cohort study group To cite: Oliveira I, ABSTRACT et al ARTICLE SUMMARY Andersen A, Furtado A, . Background: Decisions about when to start an Assessment of simple risk antiretroviral therapy (ART) are normally based on CD4 markers for early mortality Article focus cell counts and viral load (VL). However, these among HIV-infected patients ▪ The measurement of CD4 cell counts and viral in Guinea-Bissau: measurements require equipment beyond the capacity load require equipment beyond the capacity of a cohort study. BMJ Open of most laboratories in low-income and middle-income most laboratories in low-income and middle- 2012;2:e001587. settings. Thus, there is an urgent need to identify and income countries. doi:10.1136/bmjopen-2012- test simple markers to guide the optimal time for ▪ There is an urgent need to test simple markers 001587 starting and for monitoring the effect of ART in to guide the optimal time for starting antiretro- developing countries. viral therapy (ART) in these settings. ▸ Prepublication history and Objectives: (1) To evaluate anthropometric ▪ The objectives of the study were: (1) to evaluate additional material for this measurements and measurement of plasma-soluble anthropometric measurements and a soluble paper are available online. To form of the urokinase plasminogen activator receptor form of the urokinase plasminogen activator view these files please visit (suPAR) levels as potential risk factors for early receptor (suPAR) levels as potential risk factors the journal online mortality among HIV-infected patients; (2) to assess for early mortality in an urban cohort of (http://dx.doi.org/10.1136/ whether these markers could help identify patients to HIV-infected patients in Bissau and (2) to assess bmjopen-2012-001587). whom ART should be prioritised and (3) to determine whether these markers may add information to http://bmjopen.bmj.com/ Received 31 May 2012 if these markers may add information to CD4 cell count CD4 cell count and aid in selection of patients Accepted 26 August 2012 when VL is not available. most in need of ART. Design: An observational study. This final article is available Setting: The largest ART centre in Bissau, Guinea- Key messages ▪ A low body mass index, low middle-upper-arm- for use under the terms of Bissau. circumference (MUAC), low CD4 cell count and the Creative Commons Participants: 1083 ART-naïve HIV-infected patients. Attribution Non-Commercial high suPAR plasma levels were independent pre- 2.0 Licence; see Outcome measures: Associations between baseline dictors of early mortality in patients enrolled in anthropometric measurements, CD4 cell counts, http://bmjopen.bmj.com this cohort. on September 27, 2021 by guest. Protected copyright. plasma suPAR levels and survival were examined using ▪ Mortality among patients with a low CD4 cell Cox proportional hazards models. count, low MUAC or low BMI was concentrated ≤ 2 Results: Low body mass index (BMI 18.5 kg/m ), in the highest suPAR quartile. ≤ low mid-upper-arm-circumference (MUAC 250 mm), ▪ MUAC and suPAR could be useful in identifying ≤ μ low CD4 cell count ( 350 cells/ l) and high suPAR patients at the highest risk of short-term mortal- plasma levels (>5.3 ng/ml) were independent ity and may aid triage for ART when CD4 cell predictors of death. Furthermore, mortality among count is not available or when there is shortness patients with low CD4 cell count, low MUAC or of antiretroviral drugs. low BMI was concentrated in the highest suPAR quartile. Conclusions: Irrespective of ART initiation and baseline CD4 count, MUAC and suPAR plasma levels INTRODUCTION were independent predictors of early mortality in Since its introduction in the mid-1990s, anti- For numbered affiliations see this urban cohort. These markers could be useful in retroviral therapy (ART) has reduced the end of article. identifying patients at the highest risk of short-term morbidity and mortality of HIV-infected mortality and may aid triage for ART when CD4 cell – patients worldwide.1 3 Nevertheless, despite Correspondence to count is not available or when there is shortness of Dr Jesper Eugen-Olsen; antiretroviral drugs. progress, access to these lifesaving drugs [email protected] remains limited where the need is the Oliveira I, Andersen A, Furtado A, et al. BMJ Open 2012;2:e001587. doi:10.1136/bmjopen-2012-001587 1 BMJ Open: first published as 10.1136/bmjopen-2012-001587 on 14 November 2012. Downloaded from Risk markers for early mortality among HIV-infected patients in Guinea-Bissau easily measured on all patients, including bedridden ARTICLE SUMMARY ones, and does not require further calculations. Strengths and limitations of this study Nevertheless, studies assessing this marker in HIV adults ▪ Data presented could help health providers to identify patients in LMICs are scarce. fl with the highest risk of short-term mortality and to prioritise SuPAR is a risk biomarker protein that re ects the 21 treatment among eligible patients in a context of poor health- level of immune activation and inflammation. It is care infrastructure. known that immune activation plays an important role – ▪ There are several limitations to this study. First, information on in the pathogenesis of HIV infection.22 25 High blood all four investigated risk factors (CD4, suPAR, BMI and MUAC) levels of suPAR have been associated with poor clinical was only available in 58% (628/1083) of our population. outcome and independently predict mortality in Second, WHO-stage, pregnancy status and comorbidities pre- non-ART-treated HIV infected patients.15 24 26 27 sented at the time of inclusion were not recorded in the data- Furthermore, plasma concentrations of suPAR can be base. Third, contact information for some patients was not measured using a simple ELISA or lateral flow quick sufficient to allow active tracing in case of missed appoint- ments. Thus, it is likely that patients lost to follow-up may tests and thus require less-sophisticated laboratory infra- include unascertained deaths and that the effects of the risk structure than that needed for routine measurements of factors are underestimated in our work. CD4 count or plasma VL. The rollout of ART in Guinea-Bissau started in 2005. All treatments are free of charge in the country, however greatest, especially in subSaharan Africa.4 Treating HIV during the later years frequent shortages of ARV drugs patients in low-income and middle-income countries and reagents for CD4 count equipment, have hampered (LMICs) means working in a context of poor healthcare the management of HIV patients in the country and has infrastructure and limited human resources.5 To provide enforced clinicians to prioritise treatment among eli- sustainable access to ART to these regions, models of gible patients.28 care must be adapted to the realities of the developing The objectives of the present study were: (1) to evalu- world.6 Simplification and decentralisation of treatment ate anthropometric measurements, other than weight are essential components of a successful strategy for loss and measurement of suPAR levels as potential risk scaling-up ART.6 In this concept of simplification the factors for early mortality in an urban cohort of HIV-1, whole process of providing antiretroviral (ARV) drugs HIV-2 and HIV-double-infected patients; (2) to examine should be covered, starting with setting simple inclusion whether these markers could help in identifying patients criteria for an ART. In industrialised countries, decisions to whom ART should be prioritised when CD4 cell about when to start combined ART are based on CD4 count is not available or in situations of shortness of T-cell (CD4) cell count and plasma viral load (VL), two ARV drugs and (3) to assess whether these markers may of the strongest predictors of survival in HIV patients.78 add information to CD4 cell count and aid in selection http://bmjopen.bmj.com/ However, these measurements require equipment of patients most in need of ART among eligible patients beyond the capacity of most laboratories in LMICs.910 when VL is not available. Until accessible and affordable means of measuring CD4 cell count and VL become widely available, there is an urgent need to develop and test simple markers or METHODS clinical criteria to guide the optimal time for starting ART Setting in the developing world.11 Previous studies have shown The Republic of Guinea-Bissau has an estimated popula- that HIV patients with low haemoglobin level, low body tion of 1 600 000 inhabitants and an economy based pri- on September 27, 2021 by guest. Protected copyright. 12–14 fi mass index (BMI), advanced WHO-clinical stage, marily on farming and shing activities. More than 2/3 29 high-plasma levels of a soluble form of the urokinase plas- of the population lives below the poverty line. Ranking minogen activator receptor (suPAR)15 or with detectable 176 out of 187 countries on the United Nations Human cryptococcal antigenaemia16 17 are at a higher risk of dying Development Index 2011, it is one of the poorest coun- 30 during the first months of follow-up.18 tries in the world. The HIV National Programme was Weight loss is the only nutritional criterion used in the implemented by the Ministry of Health (MINSAP) in WHO classification system19 but has the disadvantage 2005. The combined ART is free of charge in the that it is not available at the first consultations because country, the cost being fully subsidised by the Global most patients do not know their normal weight.13 BMI Fund to Fight AIDS, Tuberculosis (TB) and Malaria, the (weight in kilograms divided by height in metres Brazilian Government and other international part- 31 squared) has been confirmed to be an easy-to-measure ners.