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AIDS onset at high CD4+ cell levels is associated with high HIV load
K A Hennessey1, J V Giorgi, A H Kaplan
1Los Angeles Center of the Multicenter AIDS Cohort Study, Department of Epidemiology, UCLA School of Public Health, California, USA.
Insights
High HIV viral load and genital herpes predict AIDS development even with high CD4+ cell counts. This indicates elevated Human Immunodeficiency Virus (HIV) precedes CD4+ decline, influencing AIDS risk.
Area of Science:
- Immunology
- Virology
- Epidemiology
Background:
- Acquired Immunodeficiency Syndrome (AIDS) development is typically associated with low CD4+ T-cell counts.
- Factors influencing AIDS progression at higher CD4+ cell levels require further investigation.
Purpose of the Study:
- To identify predictors of AIDS development in Human Immunodeficiency Virus type 1 (HIV-1) infected individuals with CD4+ cell counts ≥300/mm³.
- To explore the relationship between viral load, specific infections, and clinical outcomes in this cohort.
Main Methods:
- A nested case-control study design was employed using data from the Multicenter AIDS Cohort Study (MACS).
- HIV-1-infected men who developed AIDS with CD4+ ≥300/mm³ (cases) were compared to similar men who remained AIDS-free for ≥2 years (controls).
- Plasma HIV-1 RNA levels, neopterin levels, and history of genital herpes were analyzed.
Main Results:
- Cases exhibited significantly higher mean plasma HIV-1 RNA levels (10^5.02 vs. 10^4.42, p<0.01) and neopterin levels (18.3 vs. 11.5 units/ml, p<0.05) compared to controls.
- A higher proportion of cases reported genital herpes in the year preceding diagnosis (21.9% vs. 4.4%, p<0.05).
- Elevated viral load preceded AIDS diagnosis in cases who developed AIDS within 6 months.
Conclusions:
- Higher plasma HIV-1 RNA levels and genital herpes infection are associated with AIDS development, even at relatively high CD4+ cell counts.
- Elevated HIV viral load appears to be a primary factor in AIDS risk, potentially preceding CD4+ T-cell count decline.
- These findings support the hypothesis that high viral replication is a critical determinant of AIDS progression.
Abstract:
To identify factors associated with development of AIDS at high CD4+ cell levels a nested case-control study using data from the Multicenter AIDS Cohort Study (MACS) was conducted. HIV-1-infected men who developed AIDS with > or =300/mm3 CD4+ cells (AIDS men) were compared to men who had > or =300/mm3 of CD4+ cells, but remained AIDS free for at least 2 years. The AIDS men had higher plasma HIV-1 RNA levels (mean 10(5.02) vs. 10(4.42), p<0.01) and neopterin levels (mean 18.3 vs. 11.5 units/ml, p<0.05) before the AIDS diagnosis than did the AIDS-free men. A significantly higher proportion of the AIDS men reported genital herpes within the year prior to their initial AIDS diagnosis than did the AIDS-free men (21.9 vs. 4.4%, p<0.05). The higher viral load at relatively high CD4+ cell levels in men who subsequently developed AIDS within 6 months supports the hypothesis that elevated levels of HIV precede CD4+ decline and are the major factor in determining risk of AIDS even at high levels of CD4+ cell levels.