PROCAARE: CLINICAL SCIENCE--MONITORING--HIV RNA

[Albert Shaw <ashaw@usa.healthnet.org>]

KEYWORDS: HIV RNA/ VIREMIA/ BRANCHED DNA/ PROGNOSIS
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Reference: Mellors, J.W., Rinaldo Jr., C.R., Gupta, P., White, R.M., 
Todd, J.A., Kingsley, L.A. (1996).  Prognosis in HIV-1 infection 
predicted by the quantity of virus in plasma.  Science 272: 1167-70.

This study examined over 200 HIV-1-infected homosexual or bisexual men in 
Pittsburgh, Pennsylvania enrolled as part of the Multicenter AIDS Cohort 
Study during 1984-85.  Plasma samples from 180 patients were subjected to 
a branched DNA amplification assay for HIV-1 RNA.  Patients were followed 
at 6 month intervals; median follow-up was 5.6 years for patients who 
developed AIDS and 10.6 years for those who did not (using 1987 CDC 
criteria).

There was a statistically significant (p<0.001) but weak (Spearman's r = 
-0.27) relation between plasma HIV-1 RNA and CD4 count.  However, HIV-1 
RNA was an excellent predictor of progression to AIDS: for example, 8% of 
subjects with less than 4530 RNA copies per ml plasma developed AIDS at 5 
years (median time to onset of AIDS in this group was greater than 10 
years) compared to 62% of subjects with over 36,270 copies per ml (median 
time to AIDS 3.5 years).  In addition, a strong correlation between HIV-1 
RNA at study entry and survival was observed; 5% of those with <4350 RNA 
copies per ml died within 5 years (median survival > 10 years), compared 
to 49% of subjects with > 36,270 copies per ml (median survival 5.1 
years).  CD4 counts at entry were a much poorer clinical predictor; only 
patients with CD4 counts below 321/mm3 were found to have a faster 
progression to AIDS or death.

Among patients with similar CD4 counts, the median time to death was 
correlated with differences in HIV-1 RNA.  For example, patients with CD4 
counts greater than 500/mm3 had differing survival depending upon whether 
the baseline HIV-1 RNA was less than the median value of 10,190 copies 
per ml (median survival 6.8 years; median CD4 count 781/mm3) or > 10,190 
copies per ml (survival could not be estimated as only 30% of these 
subjects died at 10 years of follow-up; median CD4 count 787/mm3).  A 
similar relation was reported for patients with CD4 counts below 500/mm3.

The mean of two consecutive HIV-1 RNA measurements (at study entry and 6 
months later) was found to provide improved information on disease 
progression and survival, while no such benefit was observed for 
consecutive CD4 count determinations.  Overall, a threefold increase in 
HIV-1 RNA was associated with a relative hazard of death of 1.55 
(p<0.001), compared with a hazard of 1.03 for each decrease of 100/mm3 in 
CD4 count (p>0.05) in Cox proportional hazard models using baseline 
measurements;  in a model using all available measurements, the hazard 
was 1.57 (p<0.001) for the threefold increase in RNA and 1.33 for a 
100/mm3 decrease in CD4 count (p<0.001).

This study, with its notably long period of follow-up, provides 
convincing evidence for the superiority of plasma HIV-1 RNA as a 
surrogate marker for disease progression and death.  Additional studies 
are needed to determine the optimal incorporation of HIV-1 RNA 
determination into the routine outpatient management of AIDS.