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Reference Values of CD4 T Lymphocytes in Human Immunodeficiency Virus-Negative Adult Nigerians
Reference Values of CD4 T Lymphocytes in Human Immunodeficiency Virus-Negative Adult Nigerians
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1071-412X/05/$08.00 0 doi:10.1128/CDLI.12.4.525–530.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.
CD4 -cell counts, alongside other parameters, are of central try. As access to treatment increases, the need to determine local
importance in the monitoring of immune function. In Nigeria, reference values for CD4 -cell counts and factors that may affect
525
526 AINA ET AL. CLIN. DIAGN. LAB. IMMUNOL.
where discrepancies were found, manual verification and correction were per- RESULTS
formed. The data were analyzed with Stata 8 software (14). A two-sided P value of
#0.05 was considered significant. This analysis was restricted to HIV-seronegative individuals for
To assess bias from missing values, we compared the subjects for whom we did
whom CD4 -cell counts were available. A total of 762 pregnant
not have CD4 -cell counts with those for whom we had CD4 counts, with respect to
age and gender distributions, by using chi-square tests. We also conducted sensitivity women and 529 miners (297 men and 232 women) were recruited.
analyses on our final results to evaluate the impact of the exclusion of those subjects Of these, 22 male miners, 8 female miners and 79 pregnant
on our conclusions. Means and standard deviations of CD4 -cell count were women were HIV type 1 positive and were ex-cluded from our
computed by subgroup (male miners, female miners, and pregnant women). Group analysis. An additional 46 male and 54 female miners had missing
variances for continuous variables (age and CD4 -cell counts) were compared with
the variance ratio test and group means with two-sample t tests. For categorical
HIV test results and were also excluded from this analysis. CD4
variables, group proportions were compared with chi-square tests. The relationships -cell counts were not available for 135 men, 87 female miners,
between social, demographic, and behavioral characteristics and CD4 cell counts and 2 pregnant women, and they were also excluded from the
were examined by using linear regression and logistic regression models. In the analysis.
multiple linear regression analysis, CD4 -cell counts were used as a continuous
dependent variable and the independent variables included age, sex, marital status,
The subjects excluded on account of missing CD4 -cell counts
Education 0.01
c
1 yr 25 (26.6) 54 (60.7) 79 (43.9) 6 (0.9)
Primary (1–6 yrs) 35 (36.2) 31 (34.8) 65 (34.8) 185 (28.5)
Junior secondary (7–9 yrs) 11 (11.7) 2 (2.2) 13 (7.1) 112 (17.2)
Senior secondary (10–12 yrs) 18 (19.2) 1 (1.1) 19 (10.4) 204 (31.4)
for women in their first, second, and third trimesters were 790 at marriage by decades, parity (#4 versus 4), whether or not the
( 251), 763 ( 246), and 798 ( 264) cells per microliter, current pregnancy was the first, trimester of pregnancy, and
respectively. polygamous relationships (whether or not the husband had more
While none of the miners had a low CD4 -cell count ( 350 than one wife). Socioeconomic status was again evalu-ated with
cells/microliter), 25 (3.67%) of the pregnant women did. The two proxy variables: family car ownership and edu-cation. Effect
logistic regression analysis was therefore restricted to the 681 modifications among the covariates were also evaluated using
pregnant women for whom we had CD4 -cell counts. Based on interaction terms in the models. A number of different approaches
existing literature and the crude odds ratios obtained, po-tential were employed in covariate selection for our models. Forward,
predictor variables that were examined include alcohol use, backward, forward stepwise, and back-ward stepwise techniques
history of sexually transmitted infections in the previous 12 all gave the same result, with alcohol use and the indicator
months, history of genital discharge, marital status, male and variables for age by decades and mar-riage age by decades being
female circumcision (assessed separately by analysis stratified by the only risk factors significantly related to the odds of having a
gender), age by decades, religion (Christian or Muslim), age low CD4 -cell count (Table 2).
528 AINA ET AL. CLIN. DIAGN. LAB. IMMUNOL.
TABLE 2. Significant risk factors for low CD4 -cell counts in the CD8 , and total lymphocytes in pregnancy (2). There is evi-dence
pregnant womena that this effect of pregnancy on the CD4 -cell count may be
Subject parameter Crude parameter Adjusted parameterb modified by HIV infection, though. Van Benthem and his team
OR 95% CI OR 95% CI (22) did not find any significant differences in CD4 -cell counts in
HIV-infected pregnant women and nonpregnant controls. The
Alcohol taker
mean CD4 -cell count among pregnant women in our study was
No 1.00 1.00
Yes 3.72 1.20–11.49 5.15 1.48–17.97
771 cells/microliter, which is similar to findings in Indian women
Age (yrs) (4), who had a mean value of 764 cells/ microliter.
20 1.00 1.00 The documented relationship between gestational age and CD4
20–29 0.7 0.19–2.64 0.06 0.01–0.52 -cell levels in pregnant women varies in the literature. While
30–39 2.0 0.55–7.18 0.22 0.03–1.78
Marriage age (yrs)
Temmerman et al. (15) found no relationship between gestational
age and CD4 -cell counts in both HIV-positive and HIV-negative
women in Kenya, Tuomala et al. (18) found an increase in CD4
FIG. 1. Comparison of CD4 cell counts in the study population with published values from other populations (3, 7, 9, 11, 16, 17, 19, 20).
VOL. 12, 2005 REFERENCE VALUES OF CD4 T LYMPHOCYTES 529
By contrast, the Ethiopian study (10) reported significantly higher cessitate comparing the reference values presented here with those
CD4 -cell counts in women than in men, as did studies among from other regions of the country.
Indians (19) and Ugandans (17). It is not clear whether there are The main significance of this paper is in providing baseline
true variations across countries in the relationship between gender CD4 values for Nigeria. The fact that these baseline values are not
and CD4 -cell counts or these results are due to confounding identical to those from Western countries and even other African
factors. countries suggests that the current WHO guide-lines for ARV
The cutoff point of 350 cells per microliter was chosen be- therapy initiation in developing countries (23) may sometimes
cause of its implications for decision making in HIV clinical need to be adapted to country-specific CD4 - cell count reference
management. The current WHO guidelines for the initiation of values. In the absence of any established country-specific
antiretroviral therapy in adults and adolescents in resource-limited reference values for CD4 -cell counts, we rec-ommend these
settings is to treat patients infected with stage III or worse disease values for use by in-country clinicians.
and with a CD4 -cell count of less than 350 cells/microliter (23),
while in the United States, it is recom-mended that any patients ACKNOWLEDGMENTS
with CD4 -cell counts below 350 cells/microliter or viral loads The study research team for this AIDS Prevention Initiative in Nigeria
12. Menard, D., M. J. Mandeng, M. B. Tothy, E. K. Kelembho, G. Gresenguet, Vermund, S. Landesman, and D. Burns. 1997. Changes in total, CD4 and CD8
and A. Talarmin. 2003. Immunohematological reference ranges for adults from lymphocytes during pregnancy and 1 year post partum in human
Central African Republic. Clin. Diagn. Lab. Immunol. 10:443–445. immunodeficiency virus infected women. Obstet. Gynecol. 89:967–974.
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Prasertsilpa, A. Eksaengsri, and K. Kraisintu. 2003. Low-cost CD4 enumer- lymphocyte subsets in healthy Indian adults and the effects of sex, age, ethnicity
ation in HIV-infected patients in Thailand. Asian Pac. J. Allergy Immunol. and smoking. Cytometry 52B:32–36.
21:105–113. 20. Urassa, W. K., E. M. Mbena, A. B. Swai, H. Gaines, F. S. Mhalu, and G.
14. Statacorp. 2002. Stata statistical software, release 8. Statacorp, College Sta-tion, Biberfeld. 2003. Lymphocyte subset enumeration in HIV seronegative and HIV
Tex. seropositive adults in Dar es Salaam, Tanzania: determination of ref-erence
15. Temmerman, M., N. Nagelkerke, J. Bwayo, E. N. Chomba, J. Ndinya- values in males and females and comparison of two flow cytometric methods. J.
Achola, and P. Piot. 1995. HIV-1 and immunological changes during
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pregnancy: a comparison between HIV-1 seropositive and HIV-1 seronegative
21. U.S. Department of Health and Human Services. 2004. Guidelines for the use
women in Nairobi, Kenya. AIDS 9:1057–1060.
16. Tsegaye, A., T. Messele, T. Tilahun, E. Hailu, T. Sahlu, R. Doorly, A. L. of antiretroviral agents in HIV-1-infected adults and adolescents. De-partment of
Fontanet, and T. Rink de Wit. 1999. Immunohematological reference ranges Health and Human Services, Washington, D.C.
for adult Ethiopians. Clin. Diagn. Lab. Immunol. 6:410–414. 22. Van Benthem, B. H. B., P. Vernazza, R. A. Coutinho, and M. Prins. 2002.
17. Tugume, S. B., E. M. Piwowar, T. Lutalo, P. N. Mugyenyi, R. M. Grant, F. The impact of pregnancy and menopause on CD4 lymphocyte counts in HIV
W. Mangeni, K. Pattishall, and E. Katongole-Mbidde. 1995. Hematological infection in women and the Swiss HIV Cohort Study. AIDS 16:919–924.