Absolute Lymphocyte Count Hiv India Health And Social Care Essay
CD4 counts have become a standard measure of immunodeficiency in adults infected with HIV in resource rich areas. However majority of HIV positive people now live in developing countries which are resource poor contributing to nearly 80% of the global share. World Health Organization (WHO) guidelines acknowledge that absolute lymphocyte count (ALC) may be used to make treatment decision in resource poor settings when CD4 count is not available. Whereas ALC is an inexpensive and useful marker for staging disease, the data evaluating the utility of ALC as inexpensive surrogate marker of CD4 cell count to guide therapeutic decisions is conflicting.
Aims: To evaluate absolute lymphocyte count (ALC) as a surrogate marker of the CD4 cell count in HIV infected persons being considered for ART or as a follow up.
Majority of HIV positive people now live in developing countries like in Sub-Saharan Africa and South East Asia contributing to nearly 80% of the global share . It is also true that this is also the region where there is resource limitation to address the problem like scarcity of CD4 estimation counters to initiate ART and followup. Access to ART is now growing . CD4 counts have become a standard measure of immunodeficiency in adults infected with HIV in resource rich areas where the burden of the pandemic is low . Mindful of this problem, the current guidelines from World Health Organization (WHO) acknowledge that total lymphocyte count (TLC) may be used to make treatment decision in resource poor settings when CD4 count is not available and patients are mildly symptomatic .
Absolute Lymphocyte Count (ALC) is an inexpensive and useful marker for staging disease, predicting progression to AIDS and death and monitoring response to ART. The rationale for the WHO's recommendation is that most studies concluded a decline in TLC was strongly correlated with a decline in CD4 count, though there were some discrepancies [5-10]. However the data evaluating the utility of ALC as inexpensive surrogate marker of CD4 cell count to guide therapeutic decisions is conflicting including a recent report which mentioned that ALC < 1200 cells/mm3 was not optimal for identifying patients requiring ART since it showed low sensitivity and specificity to predict CD4 count below 200 cells/mm3 [10,11].
This necessitates further study on the relationship between ALC and CD4. Therefore, the objective of this research was to assess the relationship between total lymphocyte count (ALC) and CD4 count in one of the resource poor countries, India.
Subjects and Methods:
The study was conducted at our hospital which is also a regional HIV/AIDS referral centre. Over 35 patients are seen each week including new and follow up cases. The hospital provides HIV care such as counselling, treatment of opportunistic infections, out patient as well as in patient care and all HIV related complications and lab tests (including CD4 lymphocyte count tests for all cases and outsourced viral load testing in select cases), all free of cost. The hospital also provides information to patients concerning the benefit of ART and access to drugs. Eligible patients with CD4 <350 cells/mm3 or WHO clinical stage 4 are started on ART which is also provided free of cost. The patient spectrum includes cases with HIV infection both with and without ART and also some who have advanced AIDS.
From May 2009 to Jun 2010,two hundred and forty one consecutive patients seen at our HIV/AIDS referral centre who had obtained Complete blood count (CBC) and CD4 measurements on the same blood sample, were eligible for the study. These study subjects were assessed for clinical illnesses on the same day as the lab test measurements. A standardized data collection form was completed for each patient. Patient data on enrollment included demographics, clinical and laboratory data.Complete past medical records of all patients were either in their possession or in our data bank, our centre being the regional referral centre for HIV/AIDS. All the patients were evaluated for current age, mode of detection of HIV (voluntary screening or high risk screening) and year of detection of HIV infection. All past medical records were perused. All patients were subjected to a detailed history and complete clinical examination for signs of HIV disease or other opportunistic infections. Two study physicians determined the WHO clinical stage10.
All patients underwent analysis for CD4+ T cell count at first detection, six monthly for first one and half years and yearly thereafter. A basic Hemogram, urine analysis, Liver function tests and serum creatinine was carried out. Screening for syphilis, hepatitis B and C was also done. Yearly Chest X ray and ultrasound of the abdomen was done. Computerised tomography (CT) scan of abdomen , head and chest was carried out in relevant cases. Baseline and thereafter two yearly Mantoux test was done. Baseline and thereafter two yearly Toxoplasma, Herpes Simplex virus 1 &2 and Cytomegalovirus antibody titres of IgG and IgM were also done. Serial weight records were also maintained. Any other relevant tests required for treatment of any specific cases were also undertaken. Laboratory data included CD4 measured by a FACS Counter and complete blood counts by manual method including hemoglobin (Hb) (Sahli’s method), white blood cell count (WBC) and Absolute lymphocyte count (ALC). All blood indices were done on the same sample for each patient. Quality Control is monitored by internal controls and external proficiency programs. Quality Assurance and Quality Improvement Programs are in place.The data set was de-identified and no addresses, unique identifiers or patient visit dates were included. The hospital ethics committee reviewed the study and cleared it for further processing.
The total number of cases with complete data on TLC and CD4 counts was 241. Mean value and standard deviations were calculated. Linear regression was carried out. Pearson correlation coefficient was also reported.
A total of 241 subjects were included in this study, all of which were males. The mean (standard deviation) age was 32.4 (8.3) years (ranging from 23–51 years), and the majority, 193 (80%) were below the age of 40 years. A little over one third of the study subjects had CD4 count less than 200 cells/mm3, and 75% had a count of less than 350 cells/mm3. The mean (standard deviation) of CD4 and ALC counts were 280.79 (168.896) cells/mm3 and 1950.28 (989.184) cells/mm3 for all subjects respectively.
The correlation coefficient r for logCD4 and logALC; and for square root CD4 and square root ALC are as in Figure 2. The linear regression coefficient (β) was ; that is for each 1% increase in TLC there was ncrease in CD4 count. The relationship between CD4 and ALC as per grouped data also does not follow any trend at either the upper or lower end of the CD4 range (Figure 3).
A study in 2004-05, in Europe and USA reported that absolute lymphocyte count was a strong predictor of short-term disease progression, being only marginally less predictive than CD4-cell percentage in the paediatric population. However Johnson et al (2009) concluded that low absolute lymphocyte count did not correlate with severe immunosuppression based on CD4 cell count in paediatric HIV infected population. According to the WHO's general principle to guide decision making about when to initiate ART in resource poor settings, a wider availability of CD4 testing is indispensable. However, the scarcity of this technology shouldn't be a cause to deter treatment while the patient's condition deteriorates if there is access to ALC and knowledge of clinical staging . Several studies revealed reasonably adequate sensitivity and specificity to consider ALC as a surrogate measure for CD4 [5-10].
Gupta and colleagues (2007), observed low sensitivity and specificity of ALC as an alternate marker to initiate ART. As it was reported by Jacobson and colleagues (2003), ALC may still be used in resource limited area with the understanding of its low sensitivity and specificity. Stebbing and colleagues also indicated that despite minimally less reliability of TLC as a surrogate for CD4, ALC is important tool in the absence of expensive equipment to measure CD4.
Our study observed no correlation between the CD4 counts and ALC counts at either lower counts of CD4 or the higher end.
Current WHO guidelines Dec 2009, in resource-limited settings clinical monitoring alone may be an option for the first 2 years of treatment. We agree with the present consensus that clinical monitoring alone may be better option than relying on ALC. It is time that we call curtains down on ALC as a surrogate marker of CD4 counts.
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