Effect of HIV Infection on Sickle Cell Disease Outcomes (EFHISA)

About This Grant

Sickle cell disease (SCD) affects approximately 100,000 Americans, making it the most common inherited blood disorder in the United States. Over 1.2 million people are living with HIV in the U.S. Both chronic illnesses are endemic in overlapping geographic areas and reported in thousands of U.S. patients. A systematic review found conflicting conclusions on the effect of HIV on SCD and revealed numerous knowledge gaps, including the clinical profile of SCD patients living with HIV (PLWHIV), and the impact of HIV infection and HIV treatment on SCD outcomes. The clinical management of the comorbidity is currently uncertain in the U.S. because of lack of evidence. The previous studies were unable to include SCD severity due to the phenotype variability within SCD genotypes that may have different associations with severity of SCD and HIV status. Although the study results will be applicable to the medical care of Americans with HIV and SCD, the study will be conducted in Cameroon because the higher HIV prevalence allows the enrollment of more HIV+ patients with SCD. In addition, four of the five SCD genotypes are found in Central Africa allowing the study of this important covariate. Findings from Cameroon are generalizable in the U.S. because the diagnosis, the pathophysiology, and the ART regimens are similar. Based upon the genotypic, clinical, and biological particularities of SCD the project will address the gap in knowledge on the effects of HIV infection on SCD in two Specific Aims: Aim 1: We shall establish a clinical registry that includes all SCD patients to measure HIV prevalence, demographic and clinical characteristics in Cameroon. This will be a cross-sectional and descriptive study involving all SCD patients registered and followed-up in in the country. The investigators will screen all the 866 patients for HIV to confirm their status and to potentially identify new HIV positive patients. This research phase will describe the baseline clinical profile of SCD, determine the frequency of HIV infection in SCD patients and compare socio-demographic and clinical factors between HIV+ and HIV- SCD patients. Aim 2: Using a sample from the same patient population, we shall conduct a cross-sectional study on a matched random sampling of 48 HIV-positive SCD patients, and 96 HIV-negative SCD patients. Additionally, we shall randomly select 48 consenting HIV positive non-SCD patients among the HIV patients currently followed-up at the YUTH HIV care center as a second control group for the study. We shall measure prospectively the levels of biological markers of thrombosis, hemolysis, inflammation and organ failure and compare them according to HIV status. We shall assess if the SCD genotype will be an effect modifier of the relation between HIV status and SCD biological markers. The medical registry and data collected during this exploratory study will serve as the preliminary data for a future R01 application. The study will provide important data to improve specific ways US care through future interventional studies on immune system modulation, targeted infection prophylaxis, iron management, tailored ART regimens and gene therapy optimization in American SCD patients living with HIV.