When to initiate combined antiretroviral therapy to reduce the mortality of HIV-infected individuals

By:

Cain, L.E

Contributor(s): Publication details: 2011ISSN:

00034819

Uniform titles:

Annals of internal medicine.

Online resources:

Click here to access online

Summary: <h3>BACKGROUND : Most clinical guidelines recommend that AIDS-free, HIV-infected personswith CD4 cell counts below 0.350 × 10(9) cells/L initiate combined antiretroviral therapy(cART), but the optimalCD4 cell count at which cART should be initiated remains a matter of debate.</h3><h4>OBJECTIVE : To identify the optimal CD4 cell count at which cART should be initiated.</h4><h4>DESIGN : Prospective observational data from the HIV-CAUSAL Collaboration anddynamic marginal structural models were used to compare cART initiationstrategies for CD4 thresholds between 0.200 and 0.500 × 10(9) cells/L.</h4><h4>SETTING : HIV clinics in Europe and the Veterans HealthAdministration system in the United States.</h4><h4>PATIENTS : 20, 971 HIV-infected, therapy-naivepersons with baseline CD4 cell counts at or above 0.500 × 10(9) cells/L and noprevious AIDS-defining illnesses, of whom 8392 had a CD4cell count that decreased into the range of 0.200 to 0.499 × 10(9) cells/L andwere included in the analysis.</h4><h4>MEASUREMENTS : Hazard ratios andsurvival proportions for all-cause mortality and a combined end point ofAIDS-defining illness or death.</h4><h4>RESULTS : Compared with initiating cART at the CD4cell count threshold of 0.500 × 10(9) cells/L, the mortality hazard ratio was1.01 (95% CI, 0.84 to 1.22) for the 0.350 threshold and 1.20 (CI, 0.97 to 1.48)for the 0.200 threshold. The corresponding hazard ratios were 1.38 (CI, 1.23 to1.56) and 1.90 (CI, 1.67 to 2.15), respectively, for the combinedend point of AIDS-defining illness or death. Limitations: CD4 cell count at cARTinitiation was not randomized. Residual confounding may exist.</h4><h4>CONCLUSION : Initiation of cART at a threshold CD4count of 0.500 × 10(9) cells/L increases AIDS-free survival. However, mortalitydid not vary substantially with the use of CD4 thresholds between 0.300 and0.500 × 10(9) cells/L.</h4>

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<h3>BACKGROUND : Most clinical guidelines recommend that AIDS-free,&nbsp;HIV-infected personswith CD4 cell counts below 0.350 × 10(9) cells/L initiate combined&nbsp;antiretroviral&nbsp;therapy(cART), but the optimalCD4 cell count at which cART should be initiated remains a matter of debate.</h3><h4>OBJECTIVE : To identify the optimal CD4 cell count at which cART should be initiated.</h4><h4>DESIGN : Prospective observational data from the&nbsp;HIV-CAUSAL Collaboration anddynamic marginal structural models were used to compare cART initiationstrategies for CD4 thresholds between 0.200 and 0.500 × 10(9) cells/L.</h4><h4>SETTING : HIV&nbsp;clinics in Europe and the Veterans HealthAdministration system in the United States.</h4><h4>PATIENTS : 20, 971&nbsp;HIV-infected, therapy-naivepersons with baseline CD4 cell counts at or above 0.500 × 10(9) cells/L and noprevious AIDS-defining illnesses, of whom 8392 had a CD4cell count that decreased into the range of 0.200 to 0.499 × 10(9) cells/L andwere included in the analysis.</h4><h4>MEASUREMENTS : Hazard ratios andsurvival proportions for all-cause mortality and a combined end point ofAIDS-defining illness or death.</h4><h4>RESULTS : Compared with initiating cART at the CD4cell count threshold of 0.500 × 10(9) cells/L, the mortality hazard ratio was1.01 (95% CI, 0.84 to 1.22) for the 0.350 threshold and 1.20 (CI, 0.97 to 1.48)for the 0.200 threshold. The corresponding hazard ratios were 1.38 (CI, 1.23 to1.56) and 1.90 (CI, 1.67 to 2.15), respectively, for the combinedend point of AIDS-defining illness or death. Limitations: CD4 cell count at cARTinitiation was not randomized. Residual confounding may exist.</h4><h4>CONCLUSION : Initiation of cART at a threshold CD4count of 0.500 × 10(9) cells/L increases AIDS-free survival. However, mortalitydid not vary substantially with the use of CD4 thresholds between 0.300 and0.500 × 10(9) cells/L.</h4>

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