aDepartment of Internal Medicine and Infectious Diseases, France
bDepartment of Molecular Biology, France
cDepartment of Clinical Haematology, Lariboisière Hospital, France
dImmeuble SCOR, Paris la Défense, Paris, France.
Received 29 May, 2009
Revised 24 August, 2009
Accepted 3 September, 2009
The sickle cell trait-asymptomatic carriage is frequent in people originating from sub-Saharan Africa. Several host factors (including sickle cell anemia) have been previously reported to act upon the course of HIV disease. We studied the progression of infection in a cohort of African patients heterozygous for the sickle hemoglobin gene and harboring normal hemoglobin genes. No significant difference was evidenced between the two groups from this preliminary study.
Of the 33 million people infected with HIV, 22 million live in sub-Saharan Africa (SSA) . The HIV epidemic in western Europe is therefore now largely related to the flow of migrants from high-burden countries, mainly SSA. In France, patients originating from this area accounted for 27% of newly diagnosed HIV infection . A study of a small number of adults suggested that a significant proportion of HIV-1-seropositive patients with sickle cell anemia may be asymptomatic long-term nonprogressors. In these patients, the CD4+ T lymphocyte counts remained high and their viral burdens were remarkably lower than in nonsickle cell trait HIV-1-seropositive individuals. The data suggested that, in patients with both sickle cell anemia and HIV-1 infection, the retroviral disease may be positively affected by host factors of which absence of splenic function (due to recurrent episodes of microinfarction prior to HIV-1 infection) may be one . Nevertheless, heterozygous patients are much more frequent than homozygous sickle cell patients; approximately 8% of black Americans have heterozygous sickle cell trait-asymptomatic carriage, whereas only one in 600 is homozygous and has sickle cell disease. In certain areas of SSA, an estimated 40–60% of the population is heterozygous for sickle cell anemia, suggesting that 1–4% of babies born in this region have the disease . As, to our knowledge, it has never been studied previously, we decided to compare the progression of HIV infection in a cohort of patients originating from SSA, one group of which was heterozygous for the sickle hemoglobin gene and the other group with normal hemoglobin genes.
From 1 January to 31 December 2008, all HIV-1-seropositive patients originating from SSA attending our department were, after informed consent, prospectively tested for sickle cell disease, using hemoglobin analysis by HPLC (TOSOH, Tokyo, Japan). In addition, we compared the following parameters between heterozygous and nonsickle cell trait SSA born patients, demographic data (sex, age) and features concerning HIV infection (mean duration of follow-up, CD4+ T lymphocytes and HIV RNA at baseline and at the end of follow-up, number of lines of antiretroviral treatment during follow-up, and ratio of AIDS/non-AIDS patients).
The respective numbers and percentages of all adult HIV-1 patients (1256 patients) from the Internal Medicine Department of Lariboisière Hospital during the period of January–December 2008 were as follows, 714 (56.8%) native of SSA (269 men, 445 women), 471 (38%) whites [383 men, 88 women; native of Western Europe or French West Indies (393), North Africa (78)], 26 (2.1%) of South America, 24 (1.9%) of the Caribbean, and 19 (1.5%) of Asia. Of the 714 patients originating from SSA, 534 (76.5%) were tested. The 163 (23.5%) remaining patients were mostly lost to follow-up, and rarely refused the test. We first verified that the non-tested patients did not differ from our cohort by any of the studied parameters (age, duration of follow-up, CD4+ T lymphocytes, and HIV RNA at baseline and at the end of follow-up, number of lines of antiretroviral treatment during follow-up, repartition between AIDS/non-AIDS patients; data not shown).
We identified 93 patients heterozygous for the sickle hemoglobin gene (54 women, 39 men), accounting for 17.4% of the tested patients. They came from the Ivory Coast (27 cases), Cameroon (25 cases), Congo Republic (16 cases), Zaïre (nine cases), Ghana (two cases), Mali (two cases), Guinea Conakry (one case), Togo (one case), Central Africa (one case), Angola (one case), and other countries (eight cases), roughly reflecting the geographic distribution of HIV-1-infected, SSA born-patients attending our department. Mean age was 38.4 ± 7.2 years, with 21.5% of patients having clinical AIDS. Patients were treated successively by 2.1 ± 1.7 antiretroviral (ARV) regimens; baseline mean numbers of CD4+ T lymphocytes/μl and HIV RNA were 341 ± 216 and 5.4 ± 6.1, respectively. Present mean numbers of CD4+ T lymphocytes/μl and HIV RNA were 454 ± 340 and 4.2 ± 4.9 log10 copies/ml, respectively, reflecting the impact of ART, with a mean follow-up of 6.3 ± 4.0 years.
We also compared the demographic features (age, sex), clinical (duration of follow-up, percentage of AIDS patients), and biological data (CD4+ T lymphocytes counts and HIV RNA, both at baseline and present), as therapeutic aspects concerning HIV infection (number of ARV regimens), between the patients heterozygous for the sickle hemoglobin gene and those not carrying sickle cell trait among SSA born patients. As shown in Table 1, no statistically significant difference was evidenced between the two groups.
From this preliminary study, clinical outcome of HIV infection does not appear impacted by carrying sickle cell trait.
Author contributions, P.S. was responsible for data management, and writing of the article; E.M. was responsible for hemoglobin gene analysis; J-M.Z. and J.E. helped to write the article; G.S. and J-D.M. were responsible for statistical analysis; J-F.B. was responsible for study coordination.
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