hiv / aids continues to exact an enormous toll throughout the world , in both human and economic terms , posing a serious impediment to the growth and economic stability of many developing countries . infection with hiv-1 produces a prolonged , gradually progressive disease which leads to opportunistic infections and eventually death . the likelihood and timing of development of clinical aids following seroconversion , for any particular individual , are not readily predictable ; the use of nonclinical markers has become critically important to patient management . the various phases of hiv infection , including the early asymptomatic phase , are associated with quantifiable laboratory findings . laboratory surrogate markers of hiv infection , are by definition , measurable traits that correlate with the development of clinical aids [ 2 , 3 ] . the cost of antiretroviral therapy has dramatically reduced and this has led to the increased use of antiretroviral therapy ( art ) in developing countries . in view of that , inexpensive laboratory tests are also needed to monitor disease progression and treatment response in hiv infected individuals , living in resource - limited environments most heavily impacted by the epidemic . currently the standard methods used to monitor hiv infection are clinical assessment , flow cytometry based cd4 t lymphocyte count ( cd4 counts ) measurement , and molecular assays to quantify plasma viral load ( pvl ) . though clinical assessment remains the most feasible approach , it lacks sensitivity in determining disease stage , progression , and therapy response ; therefore , it is to be used in conjunction with laboratory measures . cd4 counts measurement and pvl quantification require expensive equipment and considerable skill , so few laboratories in resource limited countries can offer these tests free of cost . therefore , alternative laboratory parameters are being investigated in the hope that these would reduce the economic burden of hiv / aids in the developing countries . hiv triggers polyclonal b cell activation , increased t cell turnover , production of proinflammatory cytokines , and increased number of activated t cells . the levels of most cytokines in serum or plasma are not measurable in the normal state and are often not measurable in hiv infection . an alternative to measuring the excess cytokines in the circulation is the measurement of specific cytokine actions , for example , the induction of soluble products ( surrogate markers for cytokines ) in plasma or serum . the principal surrogate markers are neopterin , tnf receptor ii ( tnf - rii ) , cd23 , c - reactive protein , and soluble interleukin 2 receptor ( sil-2r ) , respectively . the hiv community is now faced with myriad concerns : which measures serve as the best proxies for initiation of art , monitoring hiv disease progression , and monitoring the effect of art and to what extent they accurately reflect patient status , the ethics of providing a particular standard of care in one area of the world but providing an alternative or substandard of care in another . in view of the above , this study was undertaken to evaluate the potential role of immune activation markers including neopterin and sil-2r levels in monitoring hiv disease among patients attending our art clinic . one hundred newly diagnosed hiv seropositive subjects were enrolled for the study after obtaining an informed consent and proper counseling . all study subjects were categorized into three study groups : cd4 counts < 200  cells/l ( group a , 33 subjects ) , 200500  cells/l ( group b , 34 subjects ) , and > 500  cells/l ( group c , 33 subjects ) . the levels of serum neopterin were measured using the commercially available enzyme immunoassay ( b.r.a.h.m.s ) . the levels of soluble interleukin 2 receptor ( sil-2r ) were measured by the commercially available enzyme immunoassay ( immunotech ) . plasma viral load ( pvl ) was estimated using amplicor hiv-1 monitor test , version 1.5 ( roche diagnostics ) , by the standard procedure . group a cases were initiated on art including 2 nucleoside reverse transcriptase inhibitors ( nrtis ) plus 1 nonnucleoside reverse transcriptase inhibitors ( nnrti ) as per national aids control organisation recommendations . these cases were followed up after six months for evaluation of response to art by measuring the cd4 counts , levels of sil2r , serum neopterin , and pvl . groups b and c cases were followed up after a period of six months to monitor disease progression by measuring the cd4 counts , levels of sil2r , and serum neopterin . forty - two age and sex matched hiv negative healthy controls were also included for comparing cd4 counts , levels of sil2r , and serum neopterin with hiv positive individuals . to detect whether there was a significant difference in the levels of individual markers between baselines and followup wilcoxon signed rank test was applied . to analyze the correlation between different markers at baseline and at followup the diagnostic performance of different immunological tests was evaluated using receiver operating characteristic ( roc ) curve analysis . the predominant age group in males and females was 2630 years . the majority ( 75% ) of the study subjects enrolled were from urban areas . thirty - one percent males and forty - two percent females were illiterate ( table 1 ) . the values of cd4 counts were significantly higher ( p < 0.5 ) in the healthy control group as compared to hiv positive study subjects ( 805  cells/l versus 279  cells/l ) at baseline . the values of neopterin ( 6.3  nmol / l versus 25.5  nmol / l ) and sil-2r ( 4.4  pm versus 63.0  pm ) were significantly lower ( p < 0.5 ) in the healthy control group as compared to the hiv seropositive study subjects ( table 1 ) . out of the 100 subjects recruited in our study only 68 subjects reported for followup . nine subjects expired and 23 were lost to followup . among group a subjects , adherence rate was > 95% . six ( 18.2% ) subjects died within six months and 5 ( 15.2% ) were defaulters . twenty two ( 66.6% ) subjects reported for followup . among group b subjects , one subject ( 2.9% ) died within six months and 3 subjects ( 8.8% ) were defaulters . thirty ( 88.2% ) subjects reported for followup . among group c subjects , two subjects ( 6.1% ) died within six months and 15 subjects ( 45.4% ) were defaulters . a , there was a statistically significant rise in the median cd4 counts after art although two cases showed immunological failure as per naco guidelines . there was statistically significant decrease in median neopterin levels and median level of sil-2r after followup . at baseline , pvl ranged from 2636 to > 750,000  copies / ml with a median pvl at the baseline of 165,000  copies / ml . at followup 90% of study subjects had undetectable level of viremia ( viral load of < 400  copies / ml ) , while 2 cases showed 407 & 1100  copies / ml of hiv-1 rna . among group b , there was a fall in the level of cd4 counts at followup which was statistically insignificant but a statistically significant increase in median level of neopterin and median level of sil-2r at followup was observed . among group c , a statistically significant fall in the cd4 counts was observed at followup along with the statistically significant increase in median level of neopterin and median level of sil-2r at followup ( table 2 ) . among group a , cd4 count had a negative correlation with neopterin and sil-2r at baseline and followup both but it was statistically insignificant . pvl had a positive correlation with serum neopterin ( correlation coefficient : 0.375 , p value : 0.103 ) and sil-2r ( correlation coefficient : 0.517 , p value ; 0.020 ) at baseline . among group b , cd4 count had a negative correlation with serum neopterin and sil-2r at baseline and followup both and it was found to be statistically significant only for neopterin at followup . among group c , cd4 count had a negative correlation with neopterin and sil-2r at baseline and followup both , but it was statistically insignificant ( table 3 ) . median levels of serum neopterin ( 38.6  nmol / l versus 19.5  nmol / l , p value < 0.5 ) and sil-2r ( 96.1  pm versus 46.6  pm , p value < 0.5 ) were significantly higher in subjects with cd4 counts < 200  cells/l as compared to subjects with cd4 counts > 200  cells/l . in our study , roc curve analysis suggests s. neopterin levels of > 25.1  nmol / l and sil-2r levels of > 47.1  pm as cut off value for cd4 count of < 200 cells/l ( table 4 ) . all group a subjects in our study showed good clinical improvement after six months of art and no subject showed clinical failure . there was a statistically significant rise ( 111  cells/l to 216  cells/l ) in the cd4 counts among subjects on art , indicating a good immunological response which is supported by another indian study , in which the median cd4 cell count after 3 months of art rose to 304  cells / mm , and at 6 months the median was 328  cells / mm . for groups b and c subjects , the median cd4 counts at baseline were 305  cells/l & 580  cells/l , while at followup the median count was 274  cells/l & 487  cells/l , respectively . in a study conducted by mehendale et al . on indian seroconverters , between the two periods of 91360 days after seroconversion and 361720 days after seroconversion , the annual decline in cd4 cell count was 120  cells / year among patients who were not on art . a study from france demonstrated that the difference between baseline cd4 t - cell count and count after 3 years was 240/mm in the untreated group of hiv-1 infected patients with cd4 t - cell count above 500/mm . among group a subjects , art significantly decreased the levels of s. neopterin ( 38.6  nmol / l to 11.2 our results correlate with a study conducted by amirayan - chevillard et al . which showed that art significantly decreased the circulating levels of neopterin by about 30% ( 15.6  1.5  ng / ml for treated versus 22.3  3.7  ng / ml for nave patients ) . for groups b and c subjects , the median level of neopterin at baseline was 22.9 nmol / l and 16.2  nmol / l , respectively , which significantly increased to 37 nmol / l and 27.6  nmol / l at followup , respectively . in a study by mildvan et al . in 2005 it was shown that elevated baseline values for neopterin were associated with greater subsequent risk of clinical disease progression . in a head - to - head comparison that was adjusted for cd4 counts and hiv-1 rna levels , elevated values for neopterin were the strongest predictors of increased risk of clinical disease progression 6 months later . in another study by mellors et al . , it was seen that plasma viral load was the single best predictor of progression to aids and death , followed by cd4 lymphocyte count and serum neopterin levels . among group a , the median level of sil-2r significantly decreased ( p value < 0.5 ) from 96.1  pm to 45.5  pm after six months of art . our findings were in contrast to the findings of bonnet et al . , who in their study established that sil-2r levels did not decrease significantly throughout the follow - up period in 46 therapy nave patients ( difference of 0.32  iu / ml , p value : 0.44 between baseline and a followup after 12 months of art ) . there was a significant rise in the level of sil-2r for groups b & c subjects from 60.9  pm & 35.1  pm at baseline to 77.8  pm & 53.1  pm at followup . schulte and meurer in their study measured sil-2r levels in 88 patients with hiv infection . mean sil-2r values increased with the progression of the disease and were most pronounced in patients with aids . they established that sil-2r is a valuable parameter in monitoring the course of the hiv infection . in our study , among group a , 90% of study subjects at followup had undetectable level of viremia ( pvl of < 400  copies / ml ) which is supported by another study in which 95% of these patients had pvl less than 400  copies / ml after 6 months of art . pvl had a positive correlation with neopterin and sil-2r at baseline but this correlation was significant for only sil-2r (  = 0.517 , p value < 0.05 ) . in one earlier study no correlation was found between evolutions of hiv rna and sil-2r from baseline to six months after art ( p > 0.05 ) , but a significant positive correlation was noted between evolution of sil-2r and hiv rna ( r = 0.36 , p < 0.05 ) from baseline to month 12 . median levels of serum neopterin & sil-2r were found to be significantly higher in subjects with cd4 counts < 200  cells/l as compared to subjects with cd4 counts > 200  cells/l ( p value < 0.05 ) . in our study , roc curve analysis suggests s. neopterin levels of > 25.1  nmol / l ( sensitivity 90.9% , specificity 67.4% ) and sil-2r levels of > 47.1  pm ( sensitivity 95.5% , specificity 60.9% ) as cutoff values for cd4 count of < 200  cells/l . this observation suggests that these markers can be utilized for initiation of antiretroviral therapy in hiv infected individuals . however , their cutoff values need to be calculated from further larger studies . levels of these markers also showed significant decreases in response to art at followup . however , larger studies are required to derive the levels of these markers that suggest an appropriate treatment response . in patients with cd4 counts > 200  cells/l , these markers are helpful in predicting disease progression ; however , large scale studies are required to establish the utility of these markers in predicting the disease progression .
a prospective study was carried out to evaluate the efficacy of serum neopterin and soluble il-2 receptor ( sil-2r ) concentrations in comparison to cd4 count to study the progression of hiv disease and monitor response to art in hiv cases . 
 one hundred newly diagnosed hiv seropositive subjects were recruited . 
 cd4 counts were determined by facs system . 
 serum neopterin and sil-2r levels were measured using enzyme immunoassay . in our study , 
 levels of neopterin and sil-2r were significantly higher in subjects with cd4 < 200 cells/l ( with s. neopterin levels of > 25.1  nmol / l and sil-2r levels of > 47.1  pm as cutoff values for cd4 < 200 cells/l ) compared to those in subjects with cd4 > 200 cells/l at baseline which indicate that these markers can be utilized for initiation of art in hiv cases . 
 the levels of these markers decreased significantly after initiation of art . in patients with cd4 
 > 200 cells/l , these markers are helpful in predicting disease progression .