Sickle cell disease (SCD) may confer some protection against human immunodeficiency virus (HIV) infection, reducing the risk of infection by 75% (odds ratio [OR], 0.25, r=-0.36, P <.001; I2=71.65), according to a recently published systematic review.

Moreover, HIV virulence was reduced by 77% (OR, 0.23, r=-0.38, P <.001; I2=63.07). These findings are in agreement with those of previous studies.

Previous studies have also reported lower rates of HIV-related death and progression due to acquired immunodeficiency syndrome (AIDS) among patients with SCD than in the general population. However, findings regarding the association between SCD and HIV infection have been somewhat inconsistent.

“SCD is hypothesized to have a protective effect against HIV infection by an enhanced immunological defense in which increased inflammation, iron metabolism, and immunologic alterations create an unfavorable environment for HIV replication,” the authors explained.

Sickle cell trait seems to alter 2 receptors on CD4+ T cells that mediate viral entrance as well as C-C motif chemokine receptor 5 (CCR5) and C-X-C motif chemokine receptor 4 (CXCR4), which act as coreceptors and are involved in the early and late stages of viral infection, respectively. For instance, the frequency of the CCR532 allele of the CCR5 gene, which has a 32-base pair deletion in the coding region, may be higher in SCD patients than in healthy individuals. This allele is responsible for the lack of cell surface expression of CCR5 in homozygotes.

Another aspect that might contribute to the protective effect of SCD against HIV infection and virulence is the occurrence of autosplenectomy.

“There seems to be a paradoxical relationship between autosplenectomy and susceptibility to infection,” Nwagha et al wrote. “Autosplenectomy may account for the long-term lack of progression of HIV-1 in infected SCD patients on the one hand and a susceptibility to sepsis from bacterial infections on the other hand.”

The review conducted by Nwagha et al included 6 studies. Half reported a lower risk of HIV infection in patients with sickle cell anemia, while the other half suggested lower HIV virulence. Five were conducted in the United States, and 1 was conducted in Uganda. Overall, the studies enrolled 7417 patients, 61.7% of whom were male, with a mean age of 26 years.


Nwagha TU, Ugwu AO, Nweke M. Does sickle cell disease protect against HIV infection: a systematic review. Med Princ Pract. Published online September 12, 2022. doi:10.1159/000526993