the cd4 count is a measure of immune status in hiv - infected individuals which measures the severity of immunosuppression more accurately than clinical staging of disease . it is therefore included in international ( who / unaids ) and national aids programme guidelines as a threshold marker to indicate the initiation of antiretroviral therapy ( art ) [ 1 , 2 ] . however , an accurate determination of cd4 cell count requires flow cytometry which is often unavailable in resource - limited settings for a variety of reasons . if cd4 testing is not available , who guidelines have previously recommended using clinical staging either alone or in combination with an absolute lymphocyte count for determining art eligibility . in fiji , a cd4 cell count is recommended to determine eligibility for initiating art but is often unavailable . an absolute lymphocyte count is therefore used as an alternative , with a count of 2300  cells/l being used to determine eligibility for art in an hiv - infected individual with clinical stage 1 or 2 . furthermore , fiji is now implementing the recent world health organization ( who ) guidelines which use a higher cd4 count ( 500 cells per mm ) than previously ( 350 cells per mm ) to determine eligibility . the implication of this change for the practice of using an absolute lymphocyte count as an alternative is not known . this study aimed to describe the cd4 counts and absolute lymphocyte counts in hiv - infected fijians prior to initiation of art , to determine the correlation between them in individual patients , and to evaluate the accuracy of a range of threshold values of absolute lymphocyte counts as an alternative to the recommended cd4 count threshold . this was a retrospective study which evaluated clinical records from all hiv - infected individuals in fiji up until 31 december 2012 . fiji is a low to middle income country with a population of 837,271 ( 2007 census ) . the ministry of health administers three major divisions and each division has a reproductive health clinic that provides care for all hiv - infected individuals in fiji . the first case of hiv infection was diagnosed in fiji in 1989 and art was introduced in 2004 . following the diagnosis of hiv infection , assessment for eligibility for art blood samples were taken at the reproductive health clinics and sent within 624 hours to the divisional hospital laboratory for full blood count , including total white blood cell and lymphocyte counts , and to the fiji centre for communicable disease control for cd4 cell count ( alere pima analyser ) . cd4 testing became available in fiji in 2010 but has been unavailable since early 2012 due to stock - out of laboratory reagents . at the time of initial clinical and laboratory assessment of the hiv - infected individuals included in the study , the guidelines in fiji recommended that art be initiated in hiv - infected individuals categorised as who clinical staging 3 or 4 and in those with a cd4 cell count of 350  cells / mm regardless of the clinical stage . when cd4 count was not available , the senior hiv clinician ( dab ) used an absolute lymphocyte count value of 2300  cells/l as a surrogate for a cd4 cell count of 350  cells / mm on the basis of studies from other settings . the national guidelines have recently been revised to be consistent with the new who guidelines that now recommend initiation of art in hiv - infected individuals that are categorized as who clinical stage 1 or 2 with a cd4 cell count of 500  cells / mm [ 3 , 5 ] . only those with complete data available for results of both absolute lymphocyte count and cd4 count for baseline and follow - up were included in the analysis . variables included age , gender , ethnicity , weight , the who clinical staging , and laboratory markers that included absolute lymphocyte count , haemoglobin , and cd4 cell count taken before and 3 months after initiation of art . data were collected and double - entered directly into an electronic data collection sheet ( epi data 3.1 ) . data were compared for discordance and corrections were made by verification with the patient folders to produce a finalized data set . positive predictive value , negative predictive value , and sensitivity and specificity of varying alc cut - offs were computed for cd4 counts 350  cells / mm and 500  cells / mm. the paired t - test was used to compare the differences in clinical markers in response to art . ethics approval for the study was obtained from the ethics advisory group of the international union against tuberculosis and lung disease , the fiji national health research committee , and national research ethics review committee . the data from 101 hiv - infected patients were available and were included in the study . the mean age of the patients was 34 years ( range : 18 to 61 years ) and 50% were males . prior to initiation of art , the median absolute lymphocyte count was 1429  cells/l ( range : 135 to 3825  cells/l ) and the median cd4 cell count was 157 cells / mm ( range : 6 to 722 cells / mm ) . the correlation between absolute lymphocyte count and cd4 cell count was weak ( r = 0.497 ) and this is illustrated in figure 1 . table 1 shows the frequency distribution and corresponding who clinical stage of patients using various cd4 cut - offs that have been applied in recommendations for the initiation of art . the majority of the patients had a cd4 count of 200 cells / mm at the time of initial assessment , and 86% had a cd4 count of 350 cells / mm which would indicate eligibility for art irrespective of clinical staging applying the guidelines in use at the time . of the 101 hiv - infected individuals , 88 ( 87% ) had an absolute lymphocyte count of < 2300  cells/l and 59 ( 58% ) were either clinical stage 1 or 2 and so required cd4 count data to determine eligibility for art . however , the majority of the 59 patients assessed as clinical stage 1 or 2 had cd4 counts of 350  cells / mm or of 500  cells / mm , 46 ( 78% ) and 55 ( 93% ) , respectively . of the 46 clinical stage 1 or 2 patients eligible to initiate art on the basis of a cd4 count of 350  cells / mm , 6 ( 13% ) had absolute lymphocyte counts of greater than 2300  cells/l and so would have been wrongly denied initiation of art if absolute lymphocyte count alone was used . on the other hand , all four ( 4% ) hiv - infected patients that had a cd4 count of > 500  cells / mm and were clinical stage 1 , and so ineligible for art , had an absolute lymphocyte count of less than 2300  cells/l . table 2 lists the calculated positive predictive values , negative predictive values , and sensitivities and specificities for a range of different absolute lymphocyte counts cut - offs that might be used as a surrogate for a cd4 cell count of 350  cells / mm. as expected , increasing the absolute lymphocyte count cut - off increased the sensitivity of the test for determining those with a cd4 count of 350  cells / mm , but with the cost of reduction in specificity . the sensitivity of the absolute lymphocyte count in use in fiji that has been used ( i.e. , < 2300  cells/l ) was 88.5% for a cd4 of 350  cells / mm in all patients , reflecting that the majority of patients had low numbers of both counts ( figure 1 ) . however , the specificity was only 13.5% as the majority ( 12 of 14 ) of patients with a cd4 of > 350  cells / mm had an absolute lymphocyte count level of < 2300  cells/l ( figure 1 ) . absolute lymphocyte counts for a cut - off of 500  cells / mm showed similar sensitivity to that found for a cd4 count of 350  cells / mm ( data not shown ) . an absolute lymphocyte count of 2300  cells/l had a sensitivity of 87.6% for a cd4 count of 500  cells / mm but a specificity of 0% because all four patients with a cd4 of > 500  cells / mm had an absolute lymphocyte count level of < 2300  cells/l . the response to art for weight and laboratory markers after 3 months of initiation is shown in table 3 . there was significant weight gain and increase in alc and cd4 counts after 3 months of art but no change in haemoglobin values . this study provides original data from fiji of clinical staging , cd4 counts , and absolute lymphocyte counts in hiv - infected individuals at the time of assessment for initiation of art . of the 101 individuals , 42% were indicated to receive art on the basis of clinical staging alone . of the remaining individuals of clinical stage 1 or 2 that required a cd4 count of 350  cells / mm to determine eligibility , as per recommendations at the time , the use of an absolute lymphocyte count of 2300  cells/l as a surrogate cut - off would have resulted in incorrect management in 10 ( 17% ) of 59 individuals : 6 eligible for art that would not receive art and an additional 4 not yet eligible for art that would have started art . with adoption of the recent recommendations of using a cd4 count cut - off of 500  cells / mm to determine eligibility , using an absolute lymphocyte count of 2300  cells/l as a surrogate cut - off would have resulted in all individuals receiving art including the 4 individuals with clinical stage 1 disease that had cd4 counts > 500  cells / mm. these findings are important and currently relevant for two main reasons . firstly , in line with who recommendations , the fiji national guidelines have recently increased the cd4 cell count to initiate art to 500  cells / mm from the previous 350  cells / mm [ 1 , 2 ] . this will increase the number of hiv - infected individuals that are eligible to receive art . we found that almost all ( 96% ) hiv - infected individuals had a cd4 count at the time of assessment that was 500  cells / mm. secondly , there is only one pima cd4 machine for cd4 testing in fiji and the cd4 test continues to be frequently unavailable due to the lack of laboratory reagents for testing . however , using an absolute lymphocyte count as a surrogate would have resulted in all individuals receiving art . due to the low absolute lymphocyte counts and cd4 counts in the majority of this population and a weak correlation between counts within individuals , it was difficult to determine an optimal cut - off that provides an acceptable balance between sensitivity and specificity . for example , if a low absolute lymphocyte count level with a high specificity was used , such as < 1500  cells/l , then nearly half of the hiv - infected individuals eligible for art by cd4 criteria would not receive treatment . an important limitation is the small number of hiv - infected individuals with complete data available for retrospective analysis . this study population of 101 individuals represented a convenience sample that was included on the basis of having complete test results available , when cd4 testing was only available for a limited time from 2010 . it is not certain therefore how representative this group might be for the wider population of hiv - infected individuals in fiji . further , clinical staging data were not collected prospectively and so it is difficult to validate accuracy of the clinical categorisation . it is also not possible to know the wider relevance of these findings to other populations . previous similar studies from a range of settings including early studies from the united states , england , and south africa [ 69 ] and more recent studies from low - resource settings such as india and nigeria [ 1013 ] have found variable results and have interpreted similar results differently . there are many factors that are likely to influence the results of absolute lymphocyte counts and cd4 counts in different populations apart from the effect of hiv infection , which include prevalence of other infections as well as other biological and genetic factors . these groups have different guidelines for art initiation which do not rely on cd4 counts   and previous studies have shown that alc would not be a substitute for cd4 count in these populations [ 14 , 15 ] . we did find that absolute lymphocyte count increased in response to 3 months of art as did cd4 count and weight . however , we did not determine whether alc could be a suitable alternative to cd4 to monitor response after 3 months of art or would provide additional benefit over clinical improvement and weight gain . in conclusion , the results of this study would not support the continued use of absolute lymphocyte count to determine art initiation in hiv - infected individuals in fiji . rather , when cd4 count is unavailable , the introduction of a recommendation to initiate all hiv - infected individuals on art should be considered .
introduction . 
 an absolute lymphocyte count is commonly used as an alternative to a cd4 count to determine initiation of antiretroviral therapy for hiv - infected individuals in fiji when a cd4 count is unavailable . 
 methods . 
 we conducted a retrospective analysis of laboratory results of hiv - infected individuals registered at all hiv clinics in fiji . 
 results . paired absolute lymphocyte and cd4 counts were available for 101 hiv - infected individuals , and 96% had a cd4 count of 500  cells / mm3 . 
 correlation between the counts in individuals was poor ( spearman rank correlation r = 0.5 ) . 
 no absolute lymphocyte count could be determined in this population as a suitable surrogate for a cd4 count of either 350  cells / mm3  or 500  cells / mm3 . 
 the currently used absolute lymphocyte count of 2300  cells/l had a positive predictive value of 87% but a negative predictive value of only 17% for a cd4 of 350 cells / mm3 and if used as a surrogate for a cd4 of 500  cells / mm3 it would result in all hiv - infected individuals receiving art including those not yet eligible . 
 weight , cd4 count , and absolute lymphocyte count increased significantly at 3 months following art initiation . 
 conclusions . 
 our findings do not support the use of absolute lymphocyte count to determine antiretroviral therapy initiation in fiji .