Supplementary Material for: Does Sickle Cell Disease Protect against HIV Infection: A Systematic Review

Objective: The aim of this systematic review was to investigate if SCD protects against HIV infection by determining the association between SCD and the incidence and virulence of HIV infection.
Methods: This is a systematic review that used MEDLINE, PubMed, CINAHL, and Academic Search Complete as data sources. Articles describing the relationship of SCD with HIV infection were included in this review. Hence, the effect measures were converted to correlation coefficients and synthesized accordingly to examine the putative protective role of SCD over HIV infection. Independent full-text screening and data extraction were conducted on all eligible studies. The risk of bias was assessed using the mixed methods appraisal tool. We employed a random-effects model of meta-analysis to estimate the pooled prevalence. We computed Cochrane's Q statistics, I2, and prediction interval to quantify effect size heterogeneity.
Results: SCD reduces the risk of HIV infection by 75% (OR = 0.25; r = -0.36, p < 0.001; I2 = 71.65). There was no publication bias (Egger’s t-value = 0.411; p = 0.721) (Figure 2). Similarly, risk of HIV virulence was reduced by 77% (OR = 0.23; r= -0.38; p < 0.001; I2 = 63.07).The mechanisms implicated in the protective influence of SCD include autosplenectomy, reduced CCR5 expression, and increased expression of heme and iron-regulated genes.
Conclusions: Sickle cell disease appears protective of HIV infection and slows HIV progression.
PROSPERO registration Number: CRD42022304490