Background: Recent data from 13 cohorts in Europe and North America (the ART Cohort Collaboration) showed that in patients (pts) starting HAART CD4 count at baseline is the dominant prognostic factor. Initial response to therapy, reflected in CD4 count and HIV-1 RNA measured some months (mos) after initiation, may also be useful in predicting disease progression and identifying high risk patients (pts).

Methods: Eligible pts had repeat CD4 count and HIV-1 RNA measured 3–9 mos after starting therapy (called 6-mo measurements hereafter). We examined associations of prognostic factors with 1) AIDS-free survival, and 2) survival using Weibull models, with delayed entry at the later of a) 6 mos after starting HAART, and b) date of the repeat measurement.

Results: Of 9,323 treatment-naïve pts (13,408 years follow-up), 152 died and 374 developed AIDS or died. Lower 6-mo CD4 and higher 6-mo HIV-1 RNA were strongly associated with decreased AIDS-free survival and survival. Baseline CD4 and RNA were not associated with progression after controlling for 6-mo levels (See table). Age > 50, transmission via injection drug use and CDC stage C events before or 0–6 mos after starting therapy were associated with decreased AIDS-free survival and survival.

Hazard ratios (95% CI) for the association of CD4 count (cells/mL) and HIV-1 RNA (copies/mL) with progression to AIDS or death from 6 mos after starting HAART

	Baseline CD4*	6-month CD4*
< 25	1	1
25–49	1.25 (0.86,1.83)	0.48 (0.27,0.83)
50–99	1.11 (0.77,1.61)	0.50 (0.32,0.78)
100–199	1.39 (0.95,2.03)	0.30 (0.19,0.48)
200–349	1.00 (0.62,1.60)	0.17 (0.10,0.28)
³ 350	0.78 (0.45,1.34)	0.14 (0.07,0.24)

*Controlling for the other CD4 measurement, and baseline and 6-month RNA

	Baseline RNA*	6-month RNA*
³ 100 000	1	1
10,000–99,999	0.81 (0.63,1.04)	0.65 (0.45,0.94)
500–9,999	1.00 (0.69,1.45)	0.41 (0.27,0.62)
< 500	1.06 (0.63,1.78)	0.32 (0.23,0.43)

*Controlling for the other RNA measurement, and baseline and 6-month CD4

Conclusions: CD4 count and HIV-1 RNA measured around 6 mos after starting therapy are strongly associated with subsequent AIDS-free survival and survival. However baseline levels and, equivalently, change from baseline to 6 mos, are of little or no relevance once 6-mo levels are taken into account. Prognostic models, based on these data, have been developed and should be of use to pts and their clinicians.