Surrogate markers for disease progression in treated HIV infection.

Abstract

OBJECTIVE:

To characterize the relationships among highly active antiretroviral therapy (HAART), HIV-1 RNA levels, immune system markers, and clinical outcome in a cohort of HIV-1-infected homosexual men.

PATIENTS:

A total of 123 men enrolled in the Amsterdam cohort study of HIV-1 infection and AIDS with a documented seroconversion for HIV-1 antibodies and known date of seroconversion were included in this study.

METHODS:

CD4 + /CD8 + T-cell counts and HIV-1 RNA levels in plasma were measured approximately every 6 months. Dates of starting and stopping antiretroviral therapy were also recorded. The relationship between HIV-1 RNA in plasma, CD4 + /CD8 + T-cell counts and HAART and their influence on clinical outcome were examined using a graphical chain modeling approach. Generalized estimating equations were used to examine correlations among the three disease markers. Hazards models with time-dependent covariates were used to examine the influence of HAART and the disease markers on progression to AIDS.

RESULTS:

HAART was significantly associated with reduced disease progression (relative hazard [RH] of AIDS, 0.20;, 95% confidence interval [CI], 0.05-0.85). The most recent HIV-1 RNA measurement and CD4 + T-cell count are independently associated with disease progression (adjusted RH for HIV-1 RNA 1.8 per log 10 increase; 95% CI, 1.2-2.6, p =.002; adjusted RH for CD4 + 0.48 per 100 x 10(6)/L increase; 95% CI, 0.40-0.58; p <.001). Depending on these measurements, HAART was no longer significantly associated with AIDS (adjusted RH, 0.81; 95% CI, 0.18-3.6; p =.78).

CONCLUSIONS:

HIV-1 RNA levels in plasma and CD4 + T-cell counts are currently considered as effective surrogate markers for the effect of HAART on disease progression in this cohort.

• Authors: A C Ghani, F de Wolf, N M Ferguson, C A Donnelly, R Coutinho, F Miedema, J Goudsmit, R M Anderson
• Journal: Journal of acquired immune deficiency syndromes (1999) (J Acquir Immune Defic Syndr) Vol. 28 Issue 3 Pg. 226-31 (Nov 01 2001) ISSN: 1525-4135 [Print] United States
• PMID: 11694828 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers
• RNA, Viral

Topics

• Antiretroviral Therapy, Highly Active
• Biomarkers (blood)
• CD4 Lymphocyte Count
• CD4-CD8 Ratio
• Cohort Studies
• Disease Progression
• HIV Infections (blood, drug therapy, immunology, pathology)
• Humans
• Male
• Prognosis
• RNA, Viral (blood)
• Viral Load