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

By: Contributor(s): Publication details: 2011ISSN:
  • 00034819
Uniform titles:
  • Annals of internal medicine.
Online resources: Summary: <h3><span style="font-size: 8pt;">BACKGROUND <span style="font-weight: normal;">:</span> <span style="font-weight: normal;">Most clinical guidelines recommend that AIDS-free,<span class="apple-converted-space">&nbsp;</span><span class="highlight">HIV</span>-infected personswith CD4 cell counts below 0.350 × 10(9) cells/L initiate combined<span class="apple-converted-space">&nbsp;</span><span class="highlight">antiretroviral</span><span class="apple-converted-space">&nbsp;</span>therapy(cART), but </span><span style="font-weight: normal;">the optimalCD4 cell count at which cART should be initiated remains a matter of debate.</span></span></h3><h4><span style="font-size: 8pt;">OBJECTIVE <span style="font-weight: normal;">: </span><span style="font-weight: normal;">To identify the optimal CD4 cell count at which cART should be initiated.</span></span></h4><h4><span style="font-size: 8pt;">DESIGN <span style="font-weight:normal;&#xA;mso-bidi-font-weight:bold">: Prospective observational data from the</span><span class="apple-converted-space"><span style="font-weight: normal;">&nbsp;</span></span><span class="highlight"><span style="font-weight: normal;">HIV</span></span><span style="font-weight:normal;mso-bidi-font-weight:bold">-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.</span><span style="font-weight: normal;"></span></span></h4><h4><span style="font-size: 8pt;">SETTING<span style="font-weight:normal;&#xA;mso-bidi-font-weight:bold"> : </span><span class="highlight"><span style="font-weight: normal;">HIV</span></span><span class="apple-converted-space"><span style="font-weight: normal;">&nbsp;</span></span><span style="font-weight:normal;&#xA;mso-bidi-font-weight:bold">clinics in Europe and the Veterans HealthAdministration system in the United States.</span><span style="font-weight: normal;"></span></span></h4><h4><span style="font-size: 8pt;">PATIENTS<span style="font-weight:&#xA;normal;mso-bidi-font-weight:bold"> : 20, 971</span><span class="apple-converted-space"><span style="font-weight: normal;">&nbsp;</span></span><span class="highlight"><span style="font-weight: normal;">HIV</span></span><span style="font-weight:normal;mso-bidi-font-weight:bold">-infected, therapy-naivepersons with baseline CD4 cell counts at or above 0.500 × 10(9) cells/L and noprevious AIDS-defining illnesses, of whom </span><span style="font-weight: normal;">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.</span></span></h4><h4><span style="font-size: 8pt;">MEASUREMENT<span style="font-weight: normal;">S</span><span style="font-weight:normal;mso-bidi-font-weight:bold"> : Hazard ratios andsurvival proportions for all-cause mortality and a combined end point ofAIDS-defining illness or death.</span><span style="font-weight: normal;"></span></span></h4><h4><span style="font-size: 8pt;">RESULTS <span style="font-weight:&#xA;normal;mso-bidi-font-weight:bold">: 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 </span><span style="font-weight: normal;">combinedend point of AIDS-defining illness or death. Limitations: CD4 cell count at cARTinitiation was not randomized. Residual confounding may exist.</span></span></h4><h4><span style="font-size: 8pt;">CONCLUSION<span style="font-weight:&#xA;normal;mso-bidi-font-weight:bold"> : 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.</span></span><span style="font-size: 11pt; font-weight: normal;"></span></h4>
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&lt;h3&gt;&lt;span style="font-size: 8pt;"&gt;BACKGROUND &lt;span style="font-weight: normal;"&gt;:&lt;/span&gt; &lt;span style="font-weight: normal;"&gt;Most clinical guidelines recommend that AIDS-free,&lt;span class="apple-converted-space"&gt;&amp;nbsp;&lt;/span&gt;&lt;span class="highlight"&gt;HIV&lt;/span&gt;-infected personswith CD4 cell counts below 0.350 × 10(9) cells/L initiate combined&lt;span class="apple-converted-space"&gt;&amp;nbsp;&lt;/span&gt;&lt;span class="highlight"&gt;antiretroviral&lt;/span&gt;&lt;span class="apple-converted-space"&gt;&amp;nbsp;&lt;/span&gt;therapy(cART), but &lt;/span&gt;&lt;span style="font-weight: normal;"&gt;the optimalCD4 cell count at which cART should be initiated remains a matter of debate.&lt;/span&gt;&lt;/span&gt;&lt;/h3&gt;&lt;h4&gt;&lt;span style="font-size: 8pt;"&gt;OBJECTIVE &lt;span style="font-weight: normal;"&gt;: &lt;/span&gt;&lt;span style="font-weight: normal;"&gt;To identify the optimal CD4 cell count at which cART should be initiated.&lt;/span&gt;&lt;/span&gt;&lt;/h4&gt;&lt;h4&gt;&lt;span style="font-size: 8pt;"&gt;DESIGN &lt;span style="font-weight:normal;&amp;#xA;mso-bidi-font-weight:bold"&gt;: Prospective observational data from the&lt;/span&gt;&lt;span class="apple-converted-space"&gt;&lt;span style="font-weight: normal;"&gt;&amp;nbsp;&lt;/span&gt;&lt;/span&gt;&lt;span class="highlight"&gt;&lt;span style="font-weight: normal;"&gt;HIV&lt;/span&gt;&lt;/span&gt;&lt;span style="font-weight:normal;mso-bidi-font-weight:bold"&gt;-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.&lt;/span&gt;&lt;span style="font-weight: normal;"&gt;&lt;/span&gt;&lt;/span&gt;&lt;/h4&gt;&lt;h4&gt;&lt;span style="font-size: 8pt;"&gt;SETTING&lt;span style="font-weight:normal;&amp;#xA;mso-bidi-font-weight:bold"&gt; : &lt;/span&gt;&lt;span class="highlight"&gt;&lt;span style="font-weight: normal;"&gt;HIV&lt;/span&gt;&lt;/span&gt;&lt;span class="apple-converted-space"&gt;&lt;span style="font-weight: normal;"&gt;&amp;nbsp;&lt;/span&gt;&lt;/span&gt;&lt;span style="font-weight:normal;&amp;#xA;mso-bidi-font-weight:bold"&gt;clinics in Europe and the Veterans HealthAdministration system in the United States.&lt;/span&gt;&lt;span style="font-weight: normal;"&gt;&lt;/span&gt;&lt;/span&gt;&lt;/h4&gt;&lt;h4&gt;&lt;span style="font-size: 8pt;"&gt;PATIENTS&lt;span style="font-weight:&amp;#xA;normal;mso-bidi-font-weight:bold"&gt; : 20, 971&lt;/span&gt;&lt;span class="apple-converted-space"&gt;&lt;span style="font-weight: normal;"&gt;&amp;nbsp;&lt;/span&gt;&lt;/span&gt;&lt;span class="highlight"&gt;&lt;span style="font-weight: normal;"&gt;HIV&lt;/span&gt;&lt;/span&gt;&lt;span style="font-weight:normal;mso-bidi-font-weight:bold"&gt;-infected, therapy-naivepersons with baseline CD4 cell counts at or above 0.500 × 10(9) cells/L and noprevious AIDS-defining illnesses, of whom &lt;/span&gt;&lt;span style="font-weight: normal;"&gt;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.&lt;/span&gt;&lt;/span&gt;&lt;/h4&gt;&lt;h4&gt;&lt;span style="font-size: 8pt;"&gt;MEASUREMENT&lt;span style="font-weight: normal;"&gt;S&lt;/span&gt;&lt;span style="font-weight:normal;mso-bidi-font-weight:bold"&gt; : Hazard ratios andsurvival proportions for all-cause mortality and a combined end point ofAIDS-defining illness or death.&lt;/span&gt;&lt;span style="font-weight: normal;"&gt;&lt;/span&gt;&lt;/span&gt;&lt;/h4&gt;&lt;h4&gt;&lt;span style="font-size: 8pt;"&gt;RESULTS &lt;span style="font-weight:&amp;#xA;normal;mso-bidi-font-weight:bold"&gt;: 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 &lt;/span&gt;&lt;span style="font-weight: normal;"&gt;combinedend point of AIDS-defining illness or death. Limitations: CD4 cell count at cARTinitiation was not randomized. Residual confounding may exist.&lt;/span&gt;&lt;/span&gt;&lt;/h4&gt;&lt;h4&gt;&lt;span style="font-size: 8pt;"&gt;CONCLUSION&lt;span style="font-weight:&amp;#xA;normal;mso-bidi-font-weight:bold"&gt; : 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.&lt;/span&gt;&lt;/span&gt;&lt;span style="font-size: 11pt; font-weight: normal;"&gt;&lt;/span&gt;&lt;/h4&gt;

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