HIV and Hepatitis.com Coverage of the
14th Annual Conference on Retroviruses
and Opportunistic Infections (14th CROI)
February 25 - 28, 2007, Los Angeles, CA

HIV Viral Load Predicts Disease Progression Better than CD4 Cell Count

By Liz Highleyman

Since the early years of the HIV/AIDS epidemic, clinicians have monitored patients’ CD4 cell counts as an indicator of immune systems decline and risk of disease progression. In the mid-1990s, they also began to routinely monitor HIV viral load, which is a direct measure of viral replication.Now, 2 studies presented at the recent 14th Conference on Retroviruses and Opportunistic Infections in Los Angeles have shown that viral load is a better predictor of HIV disease progression or death than CD4 count.

Study 1

In the first study, John Mellors, MD, and colleagues analyzed the predictive value of HIV RNA, CD4 cell count, and another measure known as CD38 relative fluorescence intensity (RFI) on CD8 T-cells, for time to CD4 cell decline, progression to AIDS, or AIDS-related death.

The study included more than 1600 HIV positive men enrolled in the Multicenter AIDS Cohort Study (MACS). CD4 cell count measurements and PCR tests for HIV RNA were performed for all participants; a subset was tested for CD38 RFI on CD8 T-cells. CD4 cell slope was estimated using data from 1985 through mid-1988.

Results
  • Overall, a single baseline HIV RNA measurement was the best predictor of disease progression, explaining 46.1% of the variability in time to AIDS.
  • Baseline CD4 cell count accounted for only 29.4% of the variability in time to AIDS.
  • The 2 markers combined explained 54.0% of the variability.
  • Among the subjects with available data, CD38 RFI explained 40.1% of the variability.
  • In these patients, HIV RNA and CD38 RFI combined explained 58.0% of the variability, and adding CD4 count had little effect.
  • HIV RNA level, CD4 count, and CD38 RFI explained very little of the variability in the rate of CD4 cell decline:
    • HIV RNA: 3.0%;
    • CD4 count: 7.1%;
    • CD38 RFI: 1.4%.
  • Medium-term CD4 cell decline -- which varied widely among individual patients -- was a poor predictor, accounting for only 2.9% of variability in time to AIDS

“A single HIV-1 RNA measurement was the best predictor of time to AIDS, explaining almost half of the variability in this clinically relevant outcome,” the investigators concluded. “High variance around CD4 regression lines likely accounts for the inability of any marker to explain CD4 cell decline. The predictive value of HIV-1 RNA for time to AIDS reaffirms the central role of viremia in AIDS pathogenesis and strongly supports the use of HIV-1 RNA for patient management.”

The results of this study conflict with those of a 1997 MACS study by Mellors and colleagues showing that initial baseline HIV viral load has a strong correlation with time to progression to AIDS. However, they confirm the results of a recent study by Benigno Rodriguez, MD, and colleagues showing that while high and low baseline HIV RNA loads predicted faster and slower short-term rates of CD4 cell decline overall, viral load was a poor predictor of the variability in CD4 decline among individual patients.

Univ of Pittsburgh, PA; Johns Hopkins Univ, Baltimore, MD; Northwestern Univ, Chicago, IL; and Univ of California, Los Angeles, CA.

Link to study abstract

 

Study 2

In a related study, Bryan Lau, MD, and colleagues investigated the relationship between HIV RNA levels and CD4 cell decline, as well as the predictive value of HIV RNA for clinical disease progression. They used a random-effects model to calculate CD4 count slope (changes over time) in 197 HIV seroconverters in the AIDS Link to Intravenous Experience (ALIVE) cohort with data available from 1988 to 1997, and determined the predictive value of the first HIV RNA measurement for subsequent CD4 slope prior to the development of AIDS.

In addition, they calculated short-term CD4 slopes (0.25, 0.5, 0.75, 1.0, 1.5, and 2 years) after an initial HIV RNA measurement between 1996 and 2005 for 392 patients in the Johns Hopkins HIV Clinical Cohort (JHHCC) who did not have clinical AIDS and were not receiving antiretroviral therapy. The predictive value of the first HIV RNA measurement and CD4 count were then determined for subsequent CD4 slopes.

Results  

  • The predictive value of a single HIV RNA measurement for CD4 decline over a median of about 3 years in the ALIVE cohort was minimal.
  • The predictive value of short-term CD4 slopes in the JHHCC cohort data was less than 0.05.
  • Initial CD4 cell count explained a large proportion (76%) of subsequent CD4 cell decline -- especially over a short period -- even after adjusting for HIV RNA levels. 
  • The predictive value of a single HIV RNA measurement for time to clinical AIDS or death in the ALIVE cohort was substantially higher (23%) than that of CD4 count.
  • After adjusting for CD4 counts, the predictive value of HIV RNA was reduced, but remained high.
  • A series of viral load tests over time was a much better predictor of disease progression (61%) than a single measurment.

“Our results confirm that HIV RNA has poor predictive value for CD4 slope alone, and that any explanation for rate of CD4 slope should account for initial CD4,” the researchers concluded. “However, our analysis showing high predictive value for clinical disease events even after adjusting for CD4 levels reinforces the importance of HIV RNA as an independent marker of HIV disease progression.”

Taken together, these studies suggest that HIV viral load is the best predictor of progression to AIDS or death over the long term, but that CD4 cell count can play a role in predicting short-term (i.e., 1-2 year) disease progression.

Johns Hopkins University, Baltimore, MD.

Link to study abstract

04/13/07

References

B Lau, S Gange, G Kirk, and others. Predictive Value of Plasma HIV RNA Levels for Rate of CD4 Decline and Clinical Disease Progression. 14th Conference on Retroviruses and Opportunistic Infections (CROI). Los Angeles, California. February 25-28, 2007. Abstract 140 (oral).

J Mellors, J Margolick, J Phair, and others. Comparison of Plasma HIV-1 RNA, CD4 Cell Count, and CD38 Expression on CD8 T Cells as Predictors of Progression to AIDS and CD4 Cell Decline among Untreated Participants in the Multicenter AIDS Cohort Study. 14th CROI. Abstract 139 (oral).

J Mellors, A Munoz, JV Giorgi, and others. Plasma viral load and CD4 lymphocytes as prognostic markers of HIV-1 infection. Annals of Internal Medicine 126(12): 946-954. June 15, 1997.

B Rodriguez, AK Sethi, VK Cheruvu, and others. Predictive value of plasma HIV RNA level on rate of CD4 T-cell decline in untreated HIV infection. JAMA 296 (12): 1498-1506. September 27, 2006.












































14th croi