Monitoring HIV infection
Counting CD4 lymphocyte numbers (the “CD4 count”) is an important part of monitoring HIV infection. A progressive downward trend in CD4 cells reflects disease progression and decreased life expectancy, even in the absence of symptoms.
Epidemiological studies have firmly correlated distinct ranges of CD4 cell counts with risk of particular opportunist infections. Recent data show that monitoring either the absolute CD4 lymphocyte count or the ratio of CD4 to CD8 cells, the 4:8 ratio, are both equally good at monitoring progression in HIV infection. β2 microglobulin and neopterin are molecules shed from activated lymphocytes; serum levels increase with progressive HIV infection and can be a useful adjunct to CD4 counts in monitoring.CD4 lymphocyte numbers have a diurnal variation and delays in the sample reaching the immunological laboratory (for example, when a sample is held overnight) also cause profound changes. Because CD4 lymphocyte counting is a lengthy process, most consistent results are obtained when samples are taken at a set time in the morning and sent straight to the lab. In case of unavoidable hold ups, samples should not be refrigerated.
Box 3.1 Positive and negative effects of immune responses
Antibody
Beneficial effects
• Neutralising antibody (demonstrated in vitro only) might
prevent primary infection and destroy some infectious particles
• Evidence for beneficial effect of passive transfer of antibody in man requires confirmation
Harmful effects
• Antibody may also help the virus to enter cells with Fc receptors
• Immune complexes may cause tissue damage, anemia and neutropenia
Cellular immune responses
Beneficial effects
• A strong CD8 response is correlated with primary resistance in some individuals and with long-term survival
• Cytotoxic T-cells may delay the progress of disease by killing infected cells.
• They produce CD8 T-cell anti-viral factor (CAF) which inhibits viral replication and may be important in slowing disease progression
Har mful effects
• They may kill uninfected cells which take up shed gp120
• Abnormal cytokine secretion may cause immunopathology (perhaps including encephalopathy)
Table 3.2 Protective mechanisms of CD8 T-cells
| Cytotoxic | Non-cytotoxic | |
| Property or | Death of infected | Inhibition of viral |
| mechanism | cells | replication |
| Antigen specificity | Specific for e pitopes of viral proteins | Non-specific |
| Cell contact needed? | Yes | No |
| Mechanism or CAF | Perforin or fas/fas L | CC chemokines |
| Induction by vaccination? | Yes | Not known |
Box 3.2 Causes of CD4 lymphopenia
• HIV infection: seroconversion illness and during disease progression
• Acute viral infections*
• Tuberculosis*
• Sarcoidosis*
• Corticosteroid therapy
• Purine metabolism defects; ADA and PNP deficiency
• SLE
• Reduce CD4 counts when not associated with HIV and can further reduce levels in HIV infection. ADA, Adenosine deaminase; PNP, Putine nucleoside phosphorylase
CD4 counts should never be used as a substitute for an HIV test because low peripheral blood counts are seen in other conditions. The classic examples are sarcoidosis and tuberculosis (without HIV). Used inappropriately in these settings, a CD4 lymphocyte count may incorrectly suggest a diagnosis of HIV infection. CD4 counts may be low during seroconversion illness but usually recover initially during the asymptomatic phase. Hence there is a need to carry out several baseline CD4 counts if subsequent monitoring is to be useful.