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Biphasic rate of CD4+ cell count decline during progression to AIDS correlates with HIV-1 phenotype
P T Schellekens1, M Tersmette, M T Roos
1Central Laboratory of The Netherlands Red Cross Blood Transfusion Service, Amsterdam.
Insights
In HIV-1-infected men, CD4+ lymphocyte decline accelerates significantly about 18 months before AIDS diagnosis. This rapid decline correlates with a more virulent, fast-replicating HIV-1 phenotype.
Area of Science:
- Immunology
- Virology
- Epidemiology
Background:
- Human Immunodeficiency Virus type 1 (HIV-1) infection leads to a progressive decline in CD4+ lymphocytes, a hallmark of disease progression.
- Understanding the kinetics of CD4+ cell loss is crucial for predicting disease progression and therapeutic timing.
Purpose of the Study:
- To investigate the rate of CD4+ lymphocyte decline in asymptomatic HIV-1-infected homosexual men.
- To correlate the kinetics of CD4+ cell decline with HIV-1 biological phenotype and progression to Acquired Immunodeficiency Syndrome (AIDS).
Main Methods:
- A cohort of 187 initially asymptomatic homosexual men infected with HIV-1 were monitored every 3 months for 5 years.
- CD4+ lymphocyte counts were enumerated, and progression to AIDS (excluding Kaposi's sarcoma) was recorded.
- The rate of CD4+ cell decline was analyzed in relation to HIV-1 biological phenotype in 43 participants.
Main Results:
- CD4+ lymphocyte counts showed a slow, continuous decline in asymptomatic HIV-1-infected individuals.
- A biphasic decline was observed in men who progressed to AIDS, with a significant threefold to fivefold acceleration starting approximately 18 months before diagnosis.
- Rapid CD4+ cell decline was associated with syncytium-inducing, fast-replicating HIV-1 isolates, while non-syncytium-inducing isolates predominated during slower decline phases.
Conclusions:
- A significant increase in the rate of CD4+ lymphocyte loss occurs around 18 months prior to AIDS diagnosis.
- This accelerated decline may be linked to the emergence of a more virulent HIV-1 phenotype, characterized by fast replication and syncytium induction.
Objective:
To determine the kinetics of decline of CD4+ lymphocytes in HIV-1-infected asymptomatic homosexual men.
Methods:
CD4+ lymphocytes were enumerated in a cohort of 187 HIV-1-infected initially asymptomatic homosexual men seen at 3-month intervals over 5 years. During follow-up, 45 men progressed to AIDS (excluding cases presenting with Kaposi's sarcoma). Correlation between rate of CD4+ cell decline and presence of a particular HIV-1 biological phenotype was analysed in 43 participants.
Results:
CD4+ cell counts declined slowly and continuously in HIV-1-seropositive men who remained asymptomatic during follow-up. A biphasic CD4+ cell count decline was observed in the group who developed AIDS: the decline was slow and steady (5.6 x 10(6)/l per month, similar to that observed in the asymptomatic group) until 18 months before AIDS diagnosis, but became three to five times faster thereafter. Rapid CD4+ cell decline was significantly related to syncytium-inducing, fast-replicating HIV-1 isolates; during the period of slow and steady CD4+ cell count decline, non-syncytium-inducing isolates were predominant.
Conclusions:
At an average of 18 months preceding AIDS diagnosis, a three to fivefold increase in the rate of loss of CD4+ lymphocytes occurs, and may be related to the appearance of a more virulent HIV-1 phenotype.