Table 4Effect of Initiating Antiretroviral Therapy at Different CD4 Counts or Viral Load Thresholds on Progression to AIDS or Mortality

Author, year or study nameNumber of patientsDuration of followupComparison groups (CD4 count)MortalityProgression to AIDS or AIDS eventsMortality or progression to AIDS or AIDS events
Randomized Controlled Trials
Cohen et al, 2011109n=1,763 serodiscordant couples42 monthsDelayed treatment: Initiation after 2 consecutive measures of CD4 count ≤0.250 × 109 cells/mL or at onset of AIDS-related illness (n=877)

Early treatment: Immediate initiation of ART at CD4 count of 0.350-0.550 × 109 cells/mL (n=886)
Delayed treatment, 13/877 (2%) vs. early treatment, 10/886 (1%); HR, 1.3 (95% CI, 0.57 to 3.0)Extrapulmonary tuberculosis
Delayed treatment, 17/877 (2%) vs. early treatment, 3/886 (0.3%); RR, 5.7 (CI, 1.7 to 20)

Pulmonary tuberculosis
Delayed treatment, 15/877 (2%) vs. early treatment, 13/886 (2%); RR, 1.2 (CI, 0.56 to 2.4)
Delayed treatment, 65/877 (7%) vs. early treatment, 40/886 (5%); adjusted HR, 1.7 (CI, 1.1 to 2.5)
Severe et al, 2010130n=81621 monthsStandard treatment (n=408): Same intervention as early treatment group, started when CD4 count ≤0.200 × 109 cells/L

Early treatment (n=408): Started at CD4 count of 0.201–0.350 × 109 cells/L; lamivudine 150 mg + zidovudine 300 mg bid, efavirenz 600 mg qd
Standard treatment, 23/408 (6%) vs. early treatment, 6/408 (2%); unadjusted HR, 4 (95% CI, 1.6 to 9.8)Tuberculosis
Standard treatment, 36/408 (9%) vs. early treatment, 18/408 (4%); unadjusted HR, 2 (95% CI, 1.2 to 3.6)
Not reported
SMART Study Group, 2008131

Other publication:
SMART Study Group, 2006138
n=477 (249 ART-naive)18 monthsIntermittent ART/drug conservation group: CD4 count <0.250 × 109 cells/L or CD4 percentage <15% or symptomatic (n=131 ART-naive)

Continuous ART/viral suppression group: CD4 count >0.350 × 109 cells/L (n=118 ART-naive)
Not reportedDrug conservation vs. continuous ART (fatal and nonfatal AIDS events): 3/131 (2/100 person-years) vs. 1/118 (0.5/100 person-years); HR, 4.1; p=0.22Drug conservation vs. continuous ART: 4/131 (2.7/100 person-years) vs. 1/118 (0.5/100 person-years); HR, 5.3; p=0.13
Cohort Studies
HIV-CAUSAL Collaboration, 2011133

Other publication:
HIV-CAUSAL Collaboration, 2010134
12 cohorts
n=20,971 (restricted to patients with CD4 counts >0.500 × 109 cells/L at baseline)
Mean 1 year0.200 × 109 (n=8,066*)
0.250 × 109 (n=8,078)
0.300 × 109 (n=8,101)
0.350 × 109 (n=8,144)
0.400 × 109 (n=8,201)
0.450 × 109 (n=8,281)
0.500 × 109 (n=8,392)

*Patient-level data may cross CD4 thresholds
Initiation of ART at CD4 count of 0.500 × 109 cells/L (n=65/8392) vs.:
0.200 × 109 (n=99/8066): HR, 0.83 (CI, 0.68 to 1.03)
0.250 × 109 (n=95/8078): HR, 0.92 (CI, 0.78 to 1.09)
0.300 × 109 (n=97/8101): HR, 0.99 (CI, 0.84 to 1.18)
0.350 × 109 (n=94/8144): HR, 0.99 (CI, 0.82 to 1.19)
0.400 × 109 (n=89/8201): HR, 0.95 (CI, 0.79 to 1.16)
0.450 × 109 (n=81/8281): HR, 0.97 (CI, 0.88 to 1.09)

Initiation of ART at CD4 count of 0.350 × 109 cells/L (n=94/8144) vs.:
0.200 × 109 (n=99/8066): HR, 0.85 (CI, 0.68 to 1.05)
0.250 × 109 (n=95/8078): HR, 0.93 (CI, 0.75 to 1.16)
0.300 × 109 (n=97/8101): HR, 1.01 (CI, 0.79 to 1.28)
0.400 × 109 (n=89/8201): HR, 0.97 (CI, 0.85 to 1.10)
0.450 × 109 (n=81/8281): HR, 0.99 (CI, 0.79 to 1.22)
0.500 × 109 (n=65/8392): HR, 1.01 (CI, 0.74 to 1.41)
Not reportedInitiation of ART at CD4 count of 0.500 × 109 cells/L (n=158/8392) vs.:
0.200 × 109 (n=330/8066): HR, 0.53 (CI, 0.47 to 0.60)
0.250 × 109 (n=329/8078): HR, 0.60 (CI, 0.54 to 0.67)
0.300 × 109 (n=317/8101): HR, 0.68 (CI, 0.61 to 0.75)
0.350 × 109 (n=296/8144): HR, 0.72 (CI, 0.64 to 0.81)
0.400 × 109 (n=256/8201): HR, 0.78 (CI, 0.68 to 0.87)
0.450 × 109 (n=209/8281): HR, 0.88 (CI, 0.82 to 0.93)

Initiation of ART at CD4 count of 0.350 × 109 cells/L (n=296/8144) vs.:
0.200 × 109 (n=330/8066): HR, 0.73 (CI, 0.64 to 0.83)
0.250 × 109 (n=329/8078): HR, 0.83 (CI, 0.72 to 0.95)
0.300 × 109 (n=317/8101): HR, 0.93 (CI, 0.81 to 1.09)
0.400 × 109 (n=256/8201): HR, 1.06 (CI, 0.99 to 1.16)
0.450 × 109 (n=209/8281): HR, 1.20 (CI, 1.05 to 1.39)
0.500 × 109 (n=158/8392): HR, 1.39 (CI, 1.14 to 1.69)
HIV-CAUSAL Collaboration, 2010134

Other publication:
HIV-CAUSAL Collaboration, 2011133
12 cohorts
n=62,760
Mean 3 years<0.100 × 109 (n=5,319)
0.100 to <0.200 × 109 (n=6,521)
0.200 to <0.350 × 109 (n=14,886)
0.350 to <0.500 × 109 (n=15,360)
≥0.500 × 109 (n=20,674)
Initiation vs. no initiation of ART, by CD4 count:
<0.100 × 109: HR, 0.29 (CI, 0.22 to 0.37)
0.100 to <0.200 × 109: HR, 0.33 (CI, 0.25 to 0.44)
0.200 to <0.350 × 109: HR, 0.38 (CI, 0.28 to 0.52)
0.350 to <0.500 × 109: HR, 0.55 (CI, 0.41 to 0.74)
≥0.500 × 109: HR, 0.77 (CI, 0.58 to 1.01)
Not reportedNot reported
Kitahata et al, 200913522 cohorts
n=17,517
Mean 3 years0.351 to 0.500 × 109
Early therapy (n=2,084)
Deferred therapy (n=6,278)

>0.500 × 109
Early therapy (n=2,220)
Deferred therapy (n=6,936)
Initiation of ART at CD4 count 0.351 to 0.500 × 109 vs. ≤0.350 × 109: adjusted RR, 0.61 (CI, 0.46 to 0.83)

Initiation of ART at CD4 count >0.500 × 109 vs. ≤0.500 × 109: adjusted RR, 0.54 (CI, 0.35 to 0.83)
Not reportedNot reported
May et al, 2007136

Other publications:
Lanoy et al, 2009139
Moore et al, 2009140
12 cohorts
n=20,379
Mean 3 years<0.025 × 109 (n=2,034)
0.025 to 0.049 × 109 (n=1,295)
0.050 to 0.099 × 109 (n=2,059)
0.100 to 0.199 × 109 (n=3,782)
0.200 to 0.349 × 109 (n=5,550)
≥0.350 × 109 (n=5,659)
Initiation of ART at varying CD4 counts vs. <0.025 × 109 cells/L:
0.025 to 0.049 × 109: 111/1295 vs. 222/2034; HR, 0.82 (CI, 0.66 to 1.04)
0.050 to 0.099 × 109: 162/2059 vs. 222/2034; HR, 0.77 (CI, 0.63 to 0.95)
0.100 to 0.199 × 109: 202/3782 vs. 222/2034; HR, 0.67 (CI, 0.55 to 0.82)
0.200 to 0.349 × 109: 178/5550 vs. 222/2034; HR, 0.48 (CI, 0.39 to 0.60)
≥0.350 × 109: 130/5659 vs. 222/2034; HR, 0.34 (CI, 0.27 to 0.44)
Not reportedInitiation of ART at varying CD4 counts vs. <0.025 × 109 cells/L:
0.025 to 0.049 × 109: 277/1295 vs. 519/2034; HR, 0.85 (CI, 0.73 to 0.98)
0.050 to 0.099 × 109: 408/2059 vs. 519/2034; HR, 0.76 (CI, 0.66 to 0.87)
0.100 to 0.199 × 109: 445/3782 vs. 519/2034; HR, 0.49 (CI, 0.43 to 0.56)
0.200 to 0.349 × 109: 361/5550 vs. 519/2034; HR, 0.29 (CI, 0.25 to 0.33)
≥0.350 × 109: 298/5659 vs. 519/2034; HR, 0.23 (CI, 0.19 to 0.27)
When to Start Consortium, 200913718 cohorts
n=45,691 (24,444 received ART)
Mean 3 yearsCD4 count:
<0.051 × 109 (n=2,594)
0.051 to 0.150 × 109 (n=4,638)
0.151 to 0.250 × 109 (n=6,406)
0.251 to 0.350 × 109 (n=5,753)
0.351 to 0.400 × 109 (n=3,260)
0.451 to 0.500 × 109 (n=1,793)
Initiation of ART at varying CD4 counts vs. 0.351 to 0.400 × 109 cells/L:
0.451 to 550 × 109: HR, 0.93 (CI, 0.6 to 1.4)
0.251 to 0.350 × 109: HR, 0.83 (CI, 0.59 to 1.25)
0.151 to 0.250 × 109: HR, 0.67 (CI, 0.51 to 0.99)
Not reportedInitiation of ART at varying CD4 counts vs. 0.351 to 0.450 × 109 cells/L:
0.451 to 550 × 109: HR, 0.90 (CI, 0.76 to 1.29)
0.251 to 0.350 × 109: HR, 0.74 (CI, 0.59 to 0.95)
0.151 to 0.250 × 109: HR, 0.45 (CI, 0.37 to 0.53)
Writing Committee for the CASCADE Collaboration, 201113223 cohorts
n=9,455
Median 5 yearsUnique individuals (numbers overlap):
0 to 0.049 × 109 (n=183)
0.050 to 0.199 × 109 (n=1,521)
0.200 to 0.349 × 109 (n=4,459)
0.350 to 0.499 × 109 (n=5,527)
0.500 to 0.799 × 109 (n=5,162)
ART vs. no ART initiation during the index month, by CD4 count:
0 to 0.049 × 109: HR, 0.37 (CI, 0.14 to 0.95); RD, -18.2 (CI, -32 to -4.4)
0.050 to 0.199 × 109: HR, 0.55 (CI, 0.28 to 1.07); RD, -7.2 (CI, -10.1 to -4.4)
0.200 to 0.349 × 109 L: HR, 0.71 (CI, 0.44 to 1.15); RD, -1.4 (CI, -3.0 to 0.3)
0.350 to 0.499 × 109: HR, 0.51 (CI, 0.33 to 0.80); RD, -1.4 (CI, -2.2 to -0.6)
0.500 to 0.799 × 109: HR, 1.02 (CI, 0.49 to 2.12); RD, -0.4 (CI, -2 to 1.2)
Not reportedART vs. no ART initiation during index month, by CD4 count:
0 to 0.049 × 109: HR, 0.32 (CI, 0.17 to 0.59); RD, -30 (CI, -45.1 to -15)
0.050 to 0.199 × 109: HR, 0.48 (CI, 0.31 to 0.74); RD, -15 (CI, -19.7 to -10.3)
0.200 to 0.349 × 109: HR, 0.59 (CI, 0.43 to 0.81); RD, -4.8 (CI, -7 to -2.6)
0.350 to 0.499 × 109: HR, 0.75 (CI, 0.49 to 1.14); RD, -2.9 (CI, -5 to -0.9)
0.500 to 0.799 × 109: HR, 1.10 (CI, 0.67 to 1.79); RD, 0.3 (CI, -3.7 to 4.2)

ART = antiretroviral therapy; HR = hazard ratio; RD = risk difference; RR = relative risk.

From: 3, RESULTS

Cover of Screening for HIV: Systematic Review to Update the U.S. Preventive Services Task Force Recommendation
Screening for HIV: Systematic Review to Update the U.S. Preventive Services Task Force Recommendation [Internet].
Evidence Syntheses, No. 95.
Chou R, Selph S, Dana T, et al.

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