REVIEW OF LOW CD4 COUNT AND IMPLICATIONS IN HIV
Since the mid 1990’s, highly active retroviral therapy (HAART) has significantly and radically modified AIDS prognosis by suppressing viral replication and consequently allowing immune restoration1,2. Central to this innovative therapeutic approach to national guidelines in most resource-rich settings and part of the WHO 2013 consolidated guidelines is the monitoring of viral load (VL). However, in low- and middle- income countries with limited resources and restricted access to more costly second and third-line drugs, the utility of viral load monitoring is under heated debate3. In resource-constrained settings CD4+ T-lymphocyte counts have ...view middle of the document...
30% of these patients had CD4 counts less than 300 which by current standards would qualify them for commencing HAART if they were HIV positive, and 41% had CD4 counts less than 400. They concluded the T-cell depression they observed was unpredictable and did not correlate with severity of illness, predicted mortality rate, or survival rate.
A decreased CD4/CD8 ratio as well as impaired CD4 function in HIV-negative hemophiliacs was reported by Antonaci et al. Concluding impairment of immune function in hemophiliacs was regardless of HIV infection10. A similar conclusion was also reached by Madhok et al.11 from a study which showed that clotting factor concentrate impairs the cell mediated response to a new antigen in the absence of infection with HIV.
In a cohort study of HIV-positive TB patients and HIV-negative TB patients12 Beck et al. found that CD4 counts were significantly lowered in HIV-negative patients with an average of 748, compared to 1043 in healthy controls while also observing significantly lowered CD4/CD8 ratios. Another study concerning the diurnal variation of CD4 counts compared the variation in HIV-positive and HIV-negative people and found significant variance in both. They found greater variation in HIV- negative people13, but that both groups followed a pattern that coincides with known daily fluctuations of cortisol which also causes low CD4 and total T-lymphocyte counts14.
A number of studies have looked at immunosuppression resulting from malnutrition. One such study from India where malnutrition is extremely common found that reduced CD4 counts were a natural physiological effect of malnutrition15 leading to a variety of immune system dysfunctions which allow infectious diseases to thrive. The effects of stress on the immune system have also been looked at by a growing number of studies16,17,18. Some of these studies have looked at people under chronic stress such as people suffering from depression, recently divorced or separated, primary caregivers of demented family members. Stress causes a state of immunodeficiency characterized by a reduction of the number of T-lymphocytes, with special targeting of CD4, helper T-cells. The ratio of CD4/CD8 has also been reported to reduce with a relative increase in CD8, suppressor/cytotoxic T-cells.
It is remarkable that a wide spectrum of conditions is associated with significantly depressed CD4 counts and reduced CD4/CD8 ratios. The fact that HIV negative people with many of these conditions suffer reduced counts raises the need for caution and a careful appraisal of the use of CD4 counts to make diagnostic and treatment decisions. There is also the distinct possibility that the conditions responsible for depressed immune response due to reduced CD4 counts can further aggravate the depreciation of immune competence in HIV-positive individuals.