Unveiling an Atypical Response to HIV-1 Infection by the Patient Carrier of the Beta-S Globin Gene and Duffy Antigen Gene Double Mutation

It is generally accepted that red blood cell mutations have an effect on the carrier’s response when exposed to certain pathogen agents. The present study was designed, in the Democratic Republic of Congo (DRC), to investigate the potential impact of the Duffy gene mutation associated with the carrier high susceptibility for HIV infection and, the low AIDS progress of the patient carrier of sickle-cell trait gene. A descriptive cross-sectional study was conducted over a period of four years from 2013 to 2017 in Lubumbashi (Capital of the HautKatanga, the Southernmost province of the Democratic Republic of Congo). Three cohorts were identified including: 194 patients with homozygous (βS/βS) mutation of sickle-cell anemia (i.e. Sickle Cell Disease, SCD) and their susceptibility to HIV-1 infection; 21 HIV-1 infected heterozygous (βA/βS) patients; 59 none βS carrier (βA/βA) of the general population. Furthermore, HIV-1 infected were also divided in two categories with or without antiretroviral therapy (ART). All patients were subjected to HIV-1 antibody and viral load detection, CD4+T-cell count, sickle-cell trait diagnosis (i.e. βS gene) and, Duffy antigen detection. All participants were Duffy group negative (Duffy-46C/C). Among 194 homozygous (βS/βS) SCD patients, only two were found HIV1 positive with a rate of 1.03% as compared to 4% observed in DRC from the general population. One of the two homozygous (βS/βS) SCD patients HIV-1 positive, without ARV, showed an HIV-1 viral load of 14,185 copies/ml, when the non-carriers (βA/βA) HIV-1 positive patients, with ARV therapy, have a four-time higher viral load average of 56,088 copies/ml. Moreover, two heterozygous (βA/βS) patients HIV-1 positive patients, without ARV therapy, presented a significant (p<0.01) lower viral load average of 7,401 copies/ml as compared to the non-carriers (βA/βA) HIV-1 positive patients either with or without ARV therapy. The homozygous (βS/βS) SCD patients presented a CD4+Tcell count of of 450 CD4/mm3 respectively higher as compared to 244 and 431 CD4/mm3 of the two HIV-1 positive heterozygous (βA/ βS) patients and the 8 non-carriers (βA/βA) HIV-1 positive patients, all without ARV therapy. However, when one compared the CD4+Tcell count of heterozygous (βA/βS) HIV-1 patients and βA/βA HIV-1 patients under ARV therapy, the former presented a significant (p<0.01) higher CD4 count than the latter. In conclusion, the one homozygous (βS/βS) SCD Duffy-46C/C HIV-1 positive patients without ARV therapy, showed, a higher CD4+Tcell count, without significant reduction of viral load, without any AIDS clinical signs. Furthermore, the heterozygous (βA/ βS) HIV-1 patients disclosed a significant higher CD4+Tcell count as well as a viral load reduction, therefore appeared to be better responder to ARV therapy than the (βA/βA) HIV-1 positive patients. As it has been generally observed, African homozygous and heterozygous (βA/βS) patients, systematically bared the double βS and Duffy -46C/C mutations and appear less susceptible to HIV-1 infection, whereas the two simultaneous mutations demonstrated a potential to work in synergy acting to slow progression of HIV disease.