Association of HIV infection with clinical and laboratory characteristics of sickle cell disease
Authors: Belisário André Rolim , Blatyta Paula F. , Vivanco Diana , Oliveira Claudia Di Lorenzo , Carneiro-Proietti Anna Bárbara , Sabino Ester Cerdeira , de Almeida-Neto Cesar , Loureiro Paula , Máximo Cláudia , de Oliveira Garcia Mateos Sheila , Flor-Park Miriam V. , de Oliveira Werneck Rodrigues Daniela , Afonso Mota Rosimere , Gonçalez Thelma T. , Hoffmann Thomas J. , Kelly Shannon , Custer Brian ,   for the Recipient Epidemiology and Donor Evaluation Study-III (REDS-III) International Component Brazil, Sabino Ester C. , Alencar Cecilia , Mendrone Alfredo , de Almeida Neto Cesar , Capuani Ligia , Park Miriam , Blatyta Paula , de Freitas Carneiro-Proietti Anna Bárbara , Teixeira Carolina Miranda , Salomon Tassila , de Oliveira Franciane Mendes , Reis Valquíria , Mota Rosemere Afonso , Sales José Wilson , de Oliveira Werneck Daniela , Loureiro Paula , Araújo Aderson , do Carmo Valgueir Maria , Lobo Clarisse , Maximo Claudia , Ferreira João Eduardo , Oikawa Márcio Katsumi , Takecian Pedro Losco , Ozahata Mina Cintho , de Carvalho Rodrigo Muller , Custer Brian Scott , Busch Michael P. , Kelly Shannon , Gonçalez Thelma Therezinha , Brambilla Donald , Preiss Liliana R. , McClure Christopher 
Published: August 2020

Abstract
Background
Sickle cell disease (SCD) is a multisystem disorder characterized by a wide spectrum of clinical manifestations and severity. Studies investigating potential effects of co-morbid human immunodeficiency virus (HIV) and SCD have produced conflicting results, and additional investigations are needed to elucidate whether the interaction between the two disease states might impact both HIV and SCD clinical outcomes. The association of HIV infection with clinical and laboratory characteristics of patients with SCD was assessed.

Methods
This nested case-control study included individuals with SCD with HIV treated at six Brazilian SCD centers. Clinical and laboratory data were abstracted from medical records. HIV positive participants were compared to age, gender, center, and SCD genotype matched HIV negative participants (ratio 1:4). Individual clinical outcomes as well as a composite outcome of any SCD complication and a composite outcome of any HIV-related complication were compared between the two groups.

Results
Fifteen HIV positive participants were included, 12 (80%) alive and 3 (20%) deceased. Most of the HIV positive patients had HbSS (60%; n = 9), 53% (n = 8) were female, and mean age was 30 ± 13 years. The frequency of individual SCD complications of acute chest syndrome/pneumonia, sepsis/bacteremia, pyelonephritis, ischemic stroke, hemorrhagic stroke, abnormal transcranial Doppler (TCD), and pulmonary hypertension was higher in HIV positive participants when compared to HIV negative, although analyzed individually none were statistically significant. HIV positive participants had significantly higher risk of any SCD complication and of a composite HIV-related complication compared to the HIV negative group (HR = 4.6; 95%CI 1.1–19.6; P = 0.04 and HR = 7.7; 95%CI 1.5–40.2; P = 0.02, respectively). There was a non-significant trend towards higher risk of any infections in participants with HIV positive (HR = 3.5; 95%CI 0.92–13.4; P = 0.07). Laboratory parameters levels were not significantly different in individuals with and without HIV.

Conclusions
In summary, our study in SCD patients shows that those with HIV have an increased risk of any SCD complication and HIV-related complications, as well as a suggestive but not significantly increased risk of infections.