ABSTRACT
HIV infection reduces CD4+ T lymphocyte cell count (CCC) and this predisposes to opportunistic infections and associated malignancies. The study analyses the relationship between CD4+ and Absolute lymphocyte count (ALC) with a view to making ALC a surrogate for CCC. There were 20 control, 6 (30%) females and 14 (70%) males. Four hundred (400) adult Nigerians infected with HIV-1 participated in the study. Of these 187 (46.8%) and 213 (53.2%) were males and females respectively. They were assessed clinically and immunologically, and categorized into three clinical stages A, B, and C according to CDC criteria. Blood specimens were taken at enrollment for haematological parameters and CCC. Data was collated and analyzed. One hundred and eight (27%)of the study subjects were in stage A, 153 (38.5%) in stage B, and 139 (34.8%) in stage C. Two hundred and thirteen (53.3%) of the study subjects were in the HIV category while 187 (46.7%)in the AIDS category. The mean ALC of all the study subjects was 2.26-x 10
/l ± 1.86 while the mean CCC was 281.6-cells/µl ± 21.92. The mean ALC were 2.64-x 10
/l 2.87 for stage A, 2.32-x 10
/l ± 1.50 for stage B and 1.91-x 10
/l ± 0.96 for stage C. The mean CCC were 506 cells/l 260, 256 cells/l 128, 134 cells/l 80 for stages A, B, C respectively. The mean CCC for the HIV infected and AIDS category were 406 227-cells/l, 138 76.1
cells/l respectively. A statistically significantly low sensitivity of 48% and specificity 68% was obtained in overall study subjects. Coefficient of correlation between ALC and CCC was weak r- value 0.074, but was statistically not significant. However a strong association was obtained in the male gender. Absolute lymphocyte count is therefore a weak and an insensitive surrogate of CCC.
LIST OF TABLES S/N TABLES PAGE 1. 23 CDC listed AIDS defining illnesses………………………………….. 24 2. CDC Revised classification of HIV/AIDS-1993………………………… 26 3. WHO staging system for HIV-Laboratory Classification……………….. 29 4. Age and Sex Distribution of subjects……………………………………. 50 5. CDC Clinical/Immunological Stage Distribution of subjects. 51 6. Haematological Profile of the entire study subject 52 7. Haematological profile of subjects by CDC classification. 53 8. Pattern of Absolute lymphocyte count and CD4 cell count 54 9. Sensitivity and specificity of low Absolute lymphocyte count value as a predictor of Low CD4 cell count value of the general group.
10. Sensitivity and specificity of low Absolute lymphocyte count value as a predictor of low CD4 cell count value for stage A
11. Sensitivity and specificity of low Absolute lymphocyte count value as a predictor of low CD4 cell count value for stage B
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12. Sensitivity and specificity of low Absolute lymphocyte count value as a predictor of low CD4 cell count value for stage C
13. Sensitivity and specificity of low Absolute lymphocyte count value as a predictor of low CD4 cell count value for stage HIV group.
14. Sensitivity and specificity of low Absolute lymphocyte count value as a predictor of low CD4 cell count value for AIDS group.
15. Sensitivity and specificity of low Absolute lymphocyte count value as a predictor of low CD4 cell count value for male subjects.
16. Sensitivity and specificity of low Absolute lymphocyte count value as a predictor of low CD4 cell count value for female subjects.
LIST OF FIGURES S/N FIGURES PAGE 1. Schematic illustration of HIV-1 Virion………………………………….. 15 2. HIV Proviral genome……………………………… ……………………. 16 3. Multiple CD4 loss as a result of HIV infection………………………….. 17 4. Typical course of HIV infection………….……………………………… 18 5. Scattered diagram of PCV and ALC – General group…………………… 73 6. Scattered diagram of PCV and CCC – General group…………………… 74 7. Scattered diagram of Age and ALC – General group…………………… 75 8. Scattered diagram of Age and CCC – General group…………………… 76 9. Scattered diagram of ALC and CCC – General group………………….. 77 10. Scattered diagram of ALC and CCC – Stage A…………………… ……. 78 11. Scattered diagram of ALC and CCC – Stage B…………………………. 79 12. Scattered diagram of ALC and CCC – Stage C………………………… 80 13. Scattered diagram of ALC and CCC – AIDS group……………………. 81 14. Scattered diagram of ALC and CCC – HIV group…………………….. 82 15. Scattered diagram of ALC and CCC – Male…………………………… 83 16. Scattered diagram of ALC and CCC – Female………………………… 84
TABLE OF CONTENTS Title………………………………………………………….…………... ....i Dedication………………………………… …………………...………… …ii Declaration………………………………………………………..………. ..iii Certification………………………………………………………..……… .iv Acknowledgement……………………………………………..………….. ..v Abstract…………………………………………………….……..………. .vii List of Tables ……………………………………..……..……………..…viii List of Figures………………………………..………………………...…..ix
Introduction………………………………………………………..……… .1 Literature Review…………………………………………….……..…..….3 Aims and Objectives of the study…………………………….………...…38 Justification of the study……………………………………………...…...38 Materials and Methods…………………………… …………………….....39 Limitations of the study…………………………………………….…..…42 Results……………………………………………………………….…….
Discussions……………………………………………………………..….
Conclusion…………………………………………………………………
Recommendation…………………………………………………………..
References…………………………………………………………… ……
APPENDICES I. Consent form………………………………………………………..80 II. Collection of blood sample..………………..……………………….81 III. CD4 + T lymphocyte count……………………..…………………..82 IV. Precautions and sources of error..………………..………………….86 V. Immunocomb® II……………………………….…………………..90 VI. Genie II…………………………………………….………………..94 VII. Dynal ® Quant technique………………………….………………..98 VIII. Raw data of the study subjects…………….………..……………..109 IX. Raw data of the control……………………………………………120
CHAPTER ONE
INTRODUCTION
Acquired immunodeficiency syndrome (AIDS) is a spectrum of disease states characterized by progressive immunosuppression. This leads to the development of opportunistic infections (OIs), secondary neoplasm and neurological manifestation. 1, 2 It results from infection with the Human immunodeficiency virus (HIV). 1, 2
Fundamental in understanding AIDS related OIs, is the appreciation of the relationship between the level of the underlying immune dysfunction
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as measured by the CD4+ T lymphocyte cell count (CCC), and the incidence of AIDS defining OIs.
CD4+ T lymphocytes are a subset of thymocyte-derived lymphocytes. They are continuously expressed in the peripheral blood and lymphoid tissues.
CCC is presently considered as one of the best markers of HIV induced immune impairment. 5, 6 As the degree of immune deterioration correlates with the likelihood of development of OI. CCC may be used as a surveillance tool for the development of OIs. Opportunistic infections typically occur when the CCC drops to critical levels. Enumeration of CD4+ lymphocytes aids in the classification, chemoprophylaxis, monitoring of treatment and prognosis of HIV/AIDS. 1, 5, 7
At present there is no definitive cure for HIV/AIDS. The benefit of Highly Active Antiretroviral Therapy (HAART) lies in the timely and sustained suppression of viral replication, alongside the reversal of the progressive immune deficiency that is characteristic of HIV infection.
The reported benefits of antiretroviral therapy (ART) have encouraged its use in the clinical management of people living with HIV/AIDS (PLWHA) in several countries. 9, 10 Studies has shown that HAART has remarkably reduced HIV related morbidity and mortality. The availability and appropriate usage of HAART has improved the quality of life of PLWHA.
11, 12
In most laboratories, markers of disease progression useful in staging and initiation of infection prophylaxis such as CCC, p24 antigenaemia, viral
load (HIV RNA) serum neopterin, and 2 microglobulin are not measured. Logistic limitations hamper their routine measurement. 1, 5, 7
In Nigeria, the Federal Government, in January 2002, initiated a National Antiretroviral treatment programme as part of the expanded response to care for PLWHA.
In Nigeria, CCC count is prohibitively expensive or just not available; physicians are often left to make decisions regarding OIs prophylaxis without laboratory data on HIV stage. Several studies have shown ALC to correlate with CCC. 14 - 21 Therefore ALC being technologically simple, widely available and inexpensive may be used in place of CCC, if found to correlate significantly with CCC. These prompted the need for this study more so that this study has not been carried out in this region.
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