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CD4 count as a surrogate for virologic failure. CD4 decline is recommended by WHO as a surrogate for VL to detect virologic failure. This has not proven to be successful for several reasons: 1) the CD4 measurement has substantial variation (30% for the 95% CI); 2) The CD4 count is generally measured only at 6 month intervals; 3) CD4 counts are often stable or they increase with a slow positive slope during viral failure according to data from large salvage trials (TORO, RESIST, POWER, BENCHMRK, TITAN, etc). Pharmacy records appear to be a better predictor of virologic failure in some settings (PLoS Med 2008;5:e109).
Total Lymphocyte Count (TLC): The TLC is sometimes used as a surrogate for CD4 count in resource-limited areas (JAMA 1993;269: 622; Am J Med Sci 1992;304:79). A TLC of <1200/mm³ combined with clinical symptoms is recommended as a surrogate for a CD4 count of <200 cells/mm³ as an indication for starting ART in the WHO guidelines (Scaling Up Antiretroviral Therapy in Resource Limited Settings, WHO, 2006). The addition of a hemoglobin ≤12 g/dL improves the sensitivity of the TLC for predicting a CD4 count <200/mm³ when the TLC is 1200-2000/mm³ (AIDS 2003;17: 1311). A report from Kenya concluded that the 1200/mm³ threshold underestimated advanced disease and they recommended a threshold of 1900/mm³as a better indicator of a CD4 count of 200/mm³ (E. Afr Med J 2007;84:466). Others have also found the correlation to be poor (JAIDS 2007;46:338; JAIDS Hum Retroviral 2007;19:238).
CD4 Repertoire: Progressive immunodeficiency in HIV infection is associated with both quantitative and qualitative changes in CD4 cells. The two major categories of CD4 cells are naïve cells and memory cells. In early life, all cells are naïve and express the isoform of CD45RA₊. Memory cells (CD45RA–) represent the component of the T-cell repertoire that has been activated by exposure to antigens. These are the CD4 cells with specificity for most opportunistic infections, such as P. jiroveci, cytomegalovirus (CMV), and Toxoplasma gondii. It is the depletion of these cells that accounts for the inability to respond to recall antigens, a defect noted relatively early in the course of HIV infection. Studies of HIV-infected patients show a preferential decline in naïve cells. With HAART, there is a threephase component to the CD4 rebound. The initial increase is due primarily to redistribution of CD4 cells from lymphatic sites. The second phase is characterized by an influx of CD4 memory cells with reduced T-cell activation and improved response to recall antigens. In the third phase there is an increase in naïve cells following at least 12 weeks of HAART (Nat Med 1997;5:533; Science 1997;277:112). By 6 months the CD4 repertoire is diverse. The competence of these cells is evidenced by favorable control of selected chronic infections such as cryptosporidiosis, microsporidiosis, and Molluscum contagiosum, the ability to discontinue maintenance therapy for disseminated MAC and CMV, and the ability to safely

Chapter 2: Laboratory Tests

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Chapter 1

Chapter 2

Chapter 3

Chapter 4

Chapter 5

Chapter 6

Chapter 7

Chapter 2: Laboratory Tests