Timing of cART initiation after a first AIDS‐defining event (ADE): temporal changes in clinical attitudes in a large cohort of HIV‐infected patients
Authors: Cingolani A , Cozzi‐Lepri A , Ammassari A , Mussini C , Magnani G , Caramello P , Angarano G , Bonfanti P , De Luca A , Mura M , Girardi E , Antinori A , d'Arminio Monforte A 
Published: November 2012

Criteria of cART initiation after a first ADE have been modified over time based on evidence suggesting that treatment should be initiated earlier. The impact of these changes on clinical practice is unknown. Objective of this analysis was to evaluate temporal changes of time of starting cART after a first diagnosis of ADE in ART‐naïve patients (pts).

Methods

All HIV+ enrolled in ICONA Foundation Study who presented with a diagnosis of ADE while cART‐naïve regardless of CD4 cell count were included. Pts were grouped according to have ADE for which additional medications that may have interactions with cART are required (Tb, atypical mycobacteriosis, non‐Hodgkin lymphoma) [group A], ADE treatable only by cART (PML, isosporidiasis/cryptosporidiasis, KS, wasting syndrome) [group B] and ADE treatable with specific drugs (PCP, toxoplasmic encephalitis, CMV disease, esoph candidiasis, bacterial pneumonia, cervical cancer, cryptococcosis) [group C]. Standard survival analysis by KM was used to estimate the cumulative percentage of pts starting cART, overall and after stratification for calendar period of diagnosis (1996–2000, 2001–2008, 2009–2011) and type of ADE (groups A, B, C). Multivariable Cox regression was used to investigate association between calendar year of ADE and time to cART initiation after controlling for demographics.

Summary of results

A total of 715 pts with a first ADE were observed over 1996‐2011 (group A, n=187; B, n=123; C, n=405). 519 (73%) male, median age 38 (IQR:33–45), median CD4+64 (23–187)/mm3 and HIV/RNA 5.25 (4.57–5.70) log10 cps/mL, with no differences by calendar period. By 30 days from ADE, 23% (95% CI: 19–27) of those diagnosed in 1996–2000 have started cART vs. 32% (95% CI: 25–39) in 2001–2008 and 36% (28–44) after 2009 (log‐rank p=0.001). After stratifying by CD4 at ADE, 45% of pts with CD4<50/mm3, 30% of those with 51–200/mm3 and 16% of those>201/mm3 had started cART by 30 days (p<0.0001). Restricting the analysis to pts diagnosed after 2009, the percentages of cART initiation were 9% for group A, 52% for group B and 39% for group C (p=0.05). The table shows the relative hazards of starting cART from fitting a multivariable Cox regression model.

Conclusions

In our ‘real‐life’ setting, time from AIDS diagnosis to cART was significantly shorter in pts diagnosed in more recent years, although for most ADE cART initiation was less prompt than expected, even in pts with severe immunodeficiency.

Calendar Period
Crude RH (95% CI)
p‐value
Adjusted RH (95% CI)
p‐value

1996–1999
1.00

1.00

2000–2008
1.19 (0.95, 1.50)
0.132
1.18 (0.88, 1.57)
0.272

2009+
1.51 (1.16, 1.96)
0.002
1.36 (0.89, 2.08)
0.151

Type of ADE
Crude RH (95%)
p‐value
Adjusted RH (95% CI)
p‐value

A
1.00

1.00

B
2.59 (1.90, 3.53)
<.001
2.24 (1.44, 3.48)
<.001

C
2.09 (1.65, 2.67)
<.001
1.14 (0.99, 2.00)
0.058