Risk of progression and the value of surrogate markers

One of the hardest problems confronting the physician dealing with an asymptomatic patient with HIV infection is predicting how soon that patient will progress to symptomatic disease or AIDS. This issue is important, firstly in terms of counselling and secondly, to decide which patients may benefit from antiretroviral treatment or prophylaxis to prevent opportunistic infections.

Variables associated with rapid disease progression include a symptomatic PHI, older age at diagnosis and receiving a large inoculum of virus, for example via a contaminated transfusion from a donor with a high viral load. The effect of prophylaxis against opportunistic infections (for example cotrimoxazole for pneumocystis and toxoplasmosis) has been to delay the onset of AIDS and to change the pattern of disease represented by the first AIDS-defining illness. Antiretroviral treatment has independently been shown to increase survival before and after AIDS. Some infected individuals do not progress for many years and work is in progress to determine whether this is due to their genetic makeup, amount of viral inoculum, characteristics of the infective virus or their immune system.

Many laboratory indices have been used as prognostic indicators, both to evaluate disease progression and treatment efficacy. The most widely used are the CD4 absolute lymphocyte count or percentage and the viral load. At least two CD4 measurements should be obtained before initiating prophylaxis for opportunistic infections or antiretroviral therapy, as the CD4 count is subject to diurnal and seasonal variation and reduced by intercurrent infection. A fall in CD4 cells is associated with disease progression, particularly if the rate of decline is rapid. Likewise, at least two viral loads, from the same laboratory using the same assay, should be obtained to avoid interassay variation. Some HIV clades are more difficult to monitor with certain assays and the laboratory should be informed of the country of origin of the patient.

Patients who may need close monitoring include individuals whose CD4 count falls below 350 cells/mm3, those with a rapidly declining CD4 count, those with a rising viral load and patients who are symptomatic as they may all be candidates for antiretroviral therapy. Patients who present with persistent constitutional symptoms, mouth or skin problems should be considered for antiretroviral therapy irrespective of CD4 count and viral load. These issues are discussed further in the chapters on treatment of infections and antiretroviral agents.

Figure 4.9 Vesicles of varicella zoster
Figure 4.10 Cervical intraepithelial neoplasia

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