TY - JOUR
T1 - Late presentation with HIV in Africa
T2 - phenotypes, risk, and risk stratification in the REALITY trial
AU - Siika, Abraham
AU - McCabe, Leanne
AU - Bwakura-Dangarembizi, Mutsa
AU - Kityo, Cissy
AU - Mallewa, Jane
AU - Berkley, Jay
AU - Maitland, Kath
AU - Griffiths, Anna
AU - Baleeta, Keith
AU - Mudzingwa, Shepherd
AU - Abach, James
AU - Nathoo, Kusum
AU - Thomason, Margaret J.
AU - Prendergast, Andrew J.
AU - Walker, Ann Sarah
AU - Gibb, Diana M.
AU - Mugyenyi, P.
AU - Kityo, C.
AU - Musiime, V.
AU - Wavamunno, P.
AU - Nambi, E.
AU - Ocitti, P.
AU - Ndigendawani, M.
AU - Kemigisa, M.
AU - Acen, J.
AU - Olebo, D.
AU - Mpamize, G.
AU - Amone, A.
AU - Okweny, D.
AU - Mbonye, A.
AU - Nambaziira, F.
AU - Rweyora, A.
AU - Kangah, M.
AU - Kabaswahili, V.
AU - Abach, J.
AU - Abongomera, G.
AU - Omongin, J.
AU - Aciro, I.
AU - Philliam, A.
AU - Arach, B.
AU - Ocung, E.
AU - Amone, G.
AU - Miles, P.
AU - Adong, C.
AU - Tumsuiime, C.
AU - Kidega, P.
AU - Otto, B.
AU - Apio, F.
AU - Baleeta, K.
AU - O'Hare, B.
AU - REALITY Trial Team
N1 - REALITY was funded by the Joint Global Health Trials Scheme (JGHTS) of the UK Department for International Development, the Wellcome Trust, and Medical Research Council (MRC) (grant number G1100693). Additional funding support was provided by the PENTA Foundation and core support to the MRC Clinical Trials Unit at University College London (grant numbers MC_UU_12023/23 and MC_UU_12023/26). Cipla Ltd, Gilead Sciences, ViiV Healthcare/GlaxoSmithKline, and Merck Sharp & Dohme donated drugs for REALITY, and ready-to-use supplementary food was purchased from Valid International. A. J. P. is funded by the Wellcome Trust (grant number 108065/Z/15/Z). J. A. B. is funded by the JGHTS (grant number MR/M007367/1). The Malawi-Liverpool–Wellcome Trust Clinical Research Programme, University of Malawi College of Medicine (grant number 101113/Z/13/Z) and the Kenya Medical Research Institute (KEMRI)/Wellcome Trust Research Programme, Kilifi (grant number 203077/Z/16/Z) are supported by strategic awards from the Wellcome Trust, United Kingdom. Permission to publish was granted by the Director of KEMRI. This supplement was supported by funds from the Bill & Melinda Gates Foundation.
PY - 2018/4/1
Y1 - 2018/4/1
N2 - Background. Severely immunocompromised human immunodefciency virus (HIV)-infected individuals have high mortality shortly afer starting antiretroviral therapy (ART). We investigated predictors of early mortality and "late presenter" phenotypes. Methods. Te Reduction of EArly MortaLITY (REALITY) trial enrolled ART-naive adults and children =5 years of age with CD4 counts <100 cells/μL initiating ART in Uganda, Zimbabwe, Malawi, and Kenya. Baseline predictors of mortality through 48 weeks were identifed using Cox regression with backwards elimination (exit P >.1). Results. Among 1711 included participants, 203 (12%) died. Mortality was independently higher with older age; lower CD4 count, albumin, hemoglobin, and grip strength; presence of World Health Organization stage 3/4 weight loss, fever, or vomiting; and problems with mobility or self-care at baseline (all P <.04). Receiving enhanced antimicrobial prophylaxis independently reduced mortality (P =.02). Of fve late-presenter phenotypes, Group 1 (n = 355) had highest mortality (25%; median CD4 count, 28 cells/μL), with high symptom burden, weight loss, poor mobility, and low albumin and hemoglobin. Group 2 (n = 394; 11% mortality; 43 cells/μL) also had weight loss, with high white cell, platelet, and neutrophil counts suggesting underlying inflammation/infection. Group 3 (n = 218; 10% mortality) had low CD4 counts (27 cells/μL), but low symptom burden and maintained fat mass. Te remaining groups had 4%-6% mortality. Conclusions. Clinical and laboratory features identifed groups with highest mortality following ART initiation. A screening tool could identify patients with low CD4 counts for prioritizing same-day ART initiation, enhanced prophylaxis, and intensive follow-up.
AB - Background. Severely immunocompromised human immunodefciency virus (HIV)-infected individuals have high mortality shortly afer starting antiretroviral therapy (ART). We investigated predictors of early mortality and "late presenter" phenotypes. Methods. Te Reduction of EArly MortaLITY (REALITY) trial enrolled ART-naive adults and children =5 years of age with CD4 counts <100 cells/μL initiating ART in Uganda, Zimbabwe, Malawi, and Kenya. Baseline predictors of mortality through 48 weeks were identifed using Cox regression with backwards elimination (exit P >.1). Results. Among 1711 included participants, 203 (12%) died. Mortality was independently higher with older age; lower CD4 count, albumin, hemoglobin, and grip strength; presence of World Health Organization stage 3/4 weight loss, fever, or vomiting; and problems with mobility or self-care at baseline (all P <.04). Receiving enhanced antimicrobial prophylaxis independently reduced mortality (P =.02). Of fve late-presenter phenotypes, Group 1 (n = 355) had highest mortality (25%; median CD4 count, 28 cells/μL), with high symptom burden, weight loss, poor mobility, and low albumin and hemoglobin. Group 2 (n = 394; 11% mortality; 43 cells/μL) also had weight loss, with high white cell, platelet, and neutrophil counts suggesting underlying inflammation/infection. Group 3 (n = 218; 10% mortality) had low CD4 counts (27 cells/μL), but low symptom burden and maintained fat mass. Te remaining groups had 4%-6% mortality. Conclusions. Clinical and laboratory features identifed groups with highest mortality following ART initiation. A screening tool could identify patients with low CD4 counts for prioritizing same-day ART initiation, enhanced prophylaxis, and intensive follow-up.
KW - Africa
KW - HIV
KW - Immunosuppression
KW - Mortality
U2 - 10.1093/cid/cix1142
DO - 10.1093/cid/cix1142
M3 - Article
AN - SCOPUS:85043387525
SN - 1058-4838
VL - 66
SP - S140-S146
JO - Clinical Infectious Diseases
JF - Clinical Infectious Diseases
IS - Issue suppl_2
ER -
