Of 2011 patients with at least two provider visits, 1034 met inclusion criteria. 430 were excluded because their first pre-HAART CD4<750 was under 200, 42 had no pre-HAART CD4<750, 232 had a prior AIDS-defining event, 240 had been on prior non-HAART antiretroviral therapy, and 33 had both a prior AIDS-defining event and prior antiretroviral therapy.
Of the 1034 included patients, 73% were male, 42% African-American, and 8% had injection drug use as probable infection route. At study entry, the median age was 35 years (interquartile range (IQR) = 28 – 42), and the median CD4 was 403 (301 – 528). The median follow-up was 35 months (14 – 65), and the median number of visits per year was 6.4 (4.5 – 9.5). Sixty percent started HAART during follow-up; among those initiating HAART, the median time to initiation was 4.1 months (1.7 – 17.3). The median CD4 prior to HAART initiation was 342 (264 – 462). Male sex, high CD4, and low HIV-1 RNA were associated with lower odds of starting HAART.
During follow-up, 93 patients died (9%), 82 experienced at least one AIDS event (8%) (25 of these patients later died), and 20 had a non-AIDS event (2%) (7 of these patients later died). contains the number of patients who had an event within 6, 12, 24, and 36 months of study entry. also includes the number of persons without an outcome at 6, 12, 24, and 36 months due to loss to follow-up, end-of-study censoring, or artificial censoring because their data were incompatible with all treatment rules. Male sex, younger age, and lower CD4% were generally associated with more loss to follow-up.
Number of patients who died, had an AIDS-defining event (ADE), a non-AIDS defining event (NADE), or were censored according to follow-up period.
Optimal CD4 to initiate HAART
demonstrates estimation of the optimal CD4 to initiate HAART in order to maximize health 12 months after study entry, based on utility 1 () and utility 2 (). We estimated that health 12 months after study entry was maximized by following the rules “start HAART within 3 months of first CD4 measurement below 554” (95% CI = 459–750) and 354 (288 – 386) for utilities 1 and 2, respectively. Notice that the confidence intervals correspond to rules in where the best-fitting curves were similar to their maximum levels. Note also that most patients were asymptomatic after 12 months. Therefore, most utility 2 scores were between 0.9 and 0.95 (), and a relatively small number of deaths had a large influence on estimates.
Figure 2 Estimating the optimal CD4 level to initiate HAART in order to maximize health 12 months after study entry. A. The distribution of regimen rules compatible with patients’ CD4/HAART histories. The rules are “start HAART within 3 months (more ...)
Similar analyses were performed for both utilities at k = 6, 12, 24, and 36 months. Estimates and 95% confidence intervals for the optimal CD4 level to start HAART for both utilities and at all time points are given in . Results were dependent on the choice of utility and the follow-up period.
Estimates (squares and circles) and 95% confidence intervals (vertical lines) of the optimal CD4 count at which to initiate HAART in order to maximize both utilities 6, 12, 24, and 36 months after study entry.
To maximize health as defined by utility 1 at k months, the optimal rule was to “start HAART within 3 months of first CD4 measurement below” 495 (95% CI=468–522), 554 (459 – 750), 489 (427 – 750), and 509 (460 – 750) for k = 6, 12, 24, and 36 months, respectively. The confidence intervals widened for increasing k because fewer people were followed for the longer periods of time. In contrast, to maximize utility 2 (quality-of-life) at k months, the optimal rule for starting HAART was to “start within 3 months of first CD4 measurement below” 337 (201 – 442), 354 (288 – 386), 358 (294 – 750), and 475 (287 – 750) for k = 6, 12, 24, and 36 months, respectively.
Secondary analyses considering alternative utilities and regimen rules are reported in the eAppendix
). Briefly, analyses that did not include non-AIDS events in the utility were similar to those presented above (eg, optimal rule estimated as “start HAART within 3 months of CD4 measured below 563” instead of 554 for CD4-based utility at k
= 12 months). Analyses that assigned worse health metrics to individuals who had changed regimens favored starting HAART at somewhat lower CD4 counts (eg, 414 for CD4-based utility at k
=12 months). Analyses that included only candidate rules in the range x
= 201–500 were generally a little lower than primary estimates (eg, 449 for CD4-based utility at k
= 12 months). Analyses comparing the candidate rules x
= 201–500 but restricted to those with at least one pre-HAART CD4≥500 generally favored starting HAART at slightly lower CD4 levels (eg, 404 for CD4 -based utility at k
= 12 months). We also performed secondary analyses to estimate the optimal rule for starting a modern, efavirenz-based regimen, artificially censoring subjects who started other regimens. Our estimated CD4 thresholds for starting efavirenz-based HAART were slightly lower (eg, 509 for CD4-based utility at k
= 12 months). The results of other secondary analyses using utilities based on survival, ADE-free survival, and AIDS/non-AIDS-events-free survival were quite variable, presumably due to small numbers of events.