Clinical Prognostic Value of RNA Viral Load and CD4 Cell Counts during Untreated HIV-1 Infection—A Quantitative Review
Figure 5
Schematic natural history model of HIV-1 replication driving rates of CD4 decline and clinical progression.
A. Survival varies among individuals according to the level of viral replication – which is indicated by RNA after reach of the setpoint in the first months after seroconversion: patients with highest RNA (red lines) have shortest survival; patients with lowest RNA (green lines) have longest survival. Rates of CD4 decline varies according to (1) RNA setpoint; and (2) pre-infection CD4, which varies independently without influencing prognosis upon infection. Individuals with high CD4 before infection have faster subsequent CD4 decline (bold lines) than individuals with low pre-infection CD4 (dashed lines) – for a given RNA and duration of survival. This natural history model has earlier been proposed based on data of cohorts of homosexual men in New York city and Washington DC [89]. B. Refinement of natural history model to incorporate prognostic determinants not (or not entirely) operating through RNA and CD4; these increase the within-population variability in survival (x-axis range). ‘Age’ here could symbolically be taken to also stand for other factors independently associated with prognosis: e.g. good immune constitution at baseline or low exposure to pathogens causing opportunistic infections, instead of young age.