Background

• Appropriate time to start HAART is still debatable

• 1995: “Time to hit HIV, early and hard” Eradication thought to be possible• Early regimens had a lot of toxicity: CD4 200• Not 500, not 200, 350 than.

Study outline

• Study Design: cohort/observational

Patients stratified according to CD4 count at baseline. Two groups of interest CD4 350-500 and CD4 > 500. Early –therapy: HAART started within 6 months of CD4

count within prespecified range Deferred-therapy: HAART started after transition into lower

CD4 count range

Study outline• Setting: Patients from 60 sites managed by 22 research groups based

in Canada and US

• Participants: 17,517 asymptomatic patients with HIV infection who received care during the period of 1996-2005 and were therapy naïve.

• Data Collection: methods are not uniform. Some site collect prospectively, others retrospectively.

• Main Outcome: death from any cause

Results

Results

• Patients in deferred groups more likely to have HCV and hx of IVDU.

• Patients with CD4 > 500 that deferred Rx were less likely to have HIV RNA < 500 copies/ml 12 after initiation of Rx.

Results

• Adjustments also made for HCV status and Hx of IVDU• Analysis done with exclusion of data from each cohort

Results

Strengths

• Feasible study design/External validity• Death from all causes as end point• Sample size• Good vital systems: decrease in ascertainment

bias• Data available before intervention: decrease in

lead time bias• All strategies possible tested: interruption is bad• Sophisticated analytical methods

Weaknesses• Is intervention a marker for good outcome?• Differences in exposure to health care and follow-up not

addressed Health-seeking behavior (e.g., dif in viral suppresion) “Good Dr.” effect• ~45% did not change CD4 stratum and not analyzed= slow

progressors?• Cause of death known in only 16%• No KM curve.• Lack of central lab• Effects of resistance and long term toxicity not addressed (and

maybe not possible addressed)

Preliminary discussion points:

• Making decision on treatment based on observational data:

The HRT example• When decision to treat is marker for good

outcomes or a marker for bad outcomes• Can we or should we have a RCT for each and

every intervention?