The relationship between CRP concentration and HIV is unclear.2 The acute phase reaction includes a programmed increase in the liver’s synthesis of certain proteins (positive acute phase reactants) and a decrease in the synthesis of others (negative acute phase reactants) in response to acute infection and other stimuli.2 Symptomatic mild inflammatory disease or viral infection is commonly thought to increase CRP concentration from 10–40 mg/L, whereas concentrations of 40–200 mg/L are found in acute bacterial infection.21
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For a population with ongoing HIV infection, the level of CRP has been shown to be relatively low (median <4 mg/L) in various studies, indicating that HIV infection is not a highly inflammatory disease.19,22 In one study by Chaudhary et al, 85.7% of HIV-positive patients were negative for CRP (<6 mg/L), corroborating this fact.2 Higher CRP titers were observed as the HIV disease progressed from CDC group I (CD4 counts ≥500 cells/µL) to group III (CD4 counts <200 cells/µL).2 These results indicated increasing inflammation with disease progression and a role for CRP in HIV disease progression and a negative correlation of CRP levels with CD4 counts.2
This correlation was determined from baseline values and the association indicated long-term prognostic value for CRP levels and a potential role for CRP in monitoring the clinical course of HIV-infected individuals.2 The increased mortality rate in HIV-positive patients, who were also positive for CRP with high titres, point towards an association between baseline CRP levels and risk of mortality.2
A recent study by Lau et al, also showed a negative correlation between CRP and CD4 counts (r = -0.17, p < 0.001), and they concluded that HIV-infected individuals have a significant increase in CRP over time, and levels of CRP >2.3 mg/L are associated with a decreased time to the development of AIDS (relative time to AIDS, 0.36 y; p <0.001), compared with individuals with CRP levels of 1.2 mg/L or less, which remained significant after adjusting for CD4 lymphocyte counts and HIV-1 RNA levels.25
Another study from New York, found CRP to be a useful and inexpensive predictor of mortality in HIV-1-infected women.23 They observed that patients who had higher CRP values experienced much shorter survival time (p <0.001). C-reactive protein
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values of more than 4 mg/L were associated with a three- to fourfold increase in the relative hazard of death independent of age, CD4+ cell count, and HIV-1 RNA levels.23 Even when the analysis was restricted to patients with levels <4 mg/L, there was a significant log linear relationship between actual CRP value and the risk of mortality.23 A more recent study by Drain et al., has also corroborated the above findings, in which they showed that a high maternal CRP concentration was associated with a 2.26-fold (95% CI: 1.64, 3.12) greater risk of progression to stage 4 or death.24
A similar work was carried out in India, which was aimed at studying the profile of CRP in HIV-infected patients among South Indian population.19 Among the HIV-positive group, patients with CD4 count <350 cells/μL were found to have significantly higher CRP level than patients with CD4 >350 cells/μL (3.48 versus 2.14 mg/L, p=0.019) and Spearman's rank correlation showed a significant negative correlation of −0.427 (p<0.001).19 The median CRP concentration in the sera of HIV-infected patients was found to be significantly higher than HIV-negative controls.19
These results were also seen in a similar study of acute-phase protein kinetics in five HIV-positive patients and in the study from the Multicenter AIDS Cohort Study (MACS).18,25 The reason for fluctuation in CRP levels could be due to subclinical challenges to the immune system.19 Despite this observation among the HIV-positive patients, those with an absolute CD4+ cell count <350 cells/μL had higher CRP levels when compared to those with CD4+ cell count >350 cells/μL.19 This finding indicates that, although CRP is not usually considered a good inflammatory marker because of
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non-normal distribution of concentration, it is sensitive in the case of HIV infection independent of opportunistic infections.19
However, certain common infections such as malaria cause marked increase in CRP values that dropped to baseline levels when the illness subsides, with mean CRP of 94.5 mg/L on day 1 and 13.20 mg/L on day 7.85,86
The association between HIV, HBV and HCV co-infections has been described in Nigeria, as well as the effects of these viruses on the liver.87,88 In Miami, the changes in CRP levels in Hepatitis C (HCV) and HIV co-infection were evaluated in a cohort of 207 patients and final results suggested it to be a less sensitive marker than in HIV only patients.89 A recent study in Indonesia, 108 decompensated (ascitic) liver cirrhosis patients with hepatitis viral serological markers showing anti-HCV(+) in 45 patients, HBsAg(+) in 41 patients and cryptogenic in 22 patients, also revealed low correlation between ALT and CRP level which was statistically significant (r = +0.22; p= 0.02). A low negative correlation was also observed between serum albumin level and CRP (r = ─ 0.28; p = 0.003) .90
Although, CRP measurement lacks specificity, in Pneumocystis Jeroveci Pneumonia, elevations of CRP are associated with disease severity and poor outcome and might be used prognostically, together with other mortality risk factors.91 These findings will form the basis for future studies on the subject in our centre.
The usefulness of total lymphocyte count (TLC) in place of CD4 count in poor economies looks better than that of CRP, because it is cheaper and easier to perform even villages far apart and without electricity. But the total white cell count is lower in the
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Negroes and because of lower neutrophil count.92 This also compounded by fact that TLC was shown to be different in the Caucasians compared to the Negroes (higher in the Negroes) make its use as a marker of HIV disease progression less desirable.28-30,93,94
Hence, the search for other surrogate markers like CRP becomes prudent.
However, some draw backs to the use of CRP include inability to perform the test in villages far and without electricity and difficulty in getting the appropriate containers and timing of blood transfer from site to the laboratory.
The association found between CRP, CD4 count and increased mortality rate of HIV-infected patients is important from an economic and biological perspective.2 It may be especially useful when used in combination in underdeveloped countries, where there is pressing need for relatively inexpensive and easy-to-obtain markers of prognosis that can be used to determine when to initiate or change antiretroviral therapy.2 Hence, the useful-
ness of CRP should be explored in large studies if this inexpensive marker can
be used to initiate chemoprophylaxis in resource-limited settings.19 In Nigeria, ESR cut off of >65mm/hr was also shown to be useful in predicting low CD4+ cell count of <200 cells/µL, and is also cheap and easy to measure.95 But, generally CRP was found to be a better indicator of inflammation as discussed previously.4,34
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