Impact of Early Initiation of Antiretroviral Therapy in Patients with Acute HIV Infection in Vienna, Austria

<div><p>Background</p><p>It is unclear whether antiretroviral therapy (ART) should be initiated during acute HIV infection. Most recent data provides evidence of benefits of early ART.</p><p>Methods</p><p>We retrospectively compared the clinical and immunological course of individuals with acute HIV infection, who received ART within 3 months (group A) or not (group B) after diagnosis.</p><p>Results</p><p>Among the 84 individuals with acute HIV infection, 57 (68%) received ART within 3 months (A) whereas 27 (32%) did not receive ART within 3 months (B), respectively. Clinical progression to CDC stadium B or C within 5 years after the diagnosis of HIV was less common in (A) when compared to (B) (P = 0.002). After twelve months, both the mean increase in CD4+ T cell count and the mean decrease in viral load was more pronounced in (A), when compared to (B) (225 vs. 87 cells/μl; P = 0.002 and -4.19 vs. -1.14 log10 copies/mL; P<0.001). Twenty-four months after diagnosis the mean increase from baseline of CD4+ T cells was still higher in group A compared to group B (251 vs. 67 cells/μl, P = 0.004).</p><p>Conclusions</p><p>Initiation of ART during acute HIV infection is associated with a lower probability of clinical progression to more advanced CDC stages and significant immunological benefits.</p></div

Study profile.

<p>Study profile for individuals with acute HIV infection according to treatment initiation and clinical progression during the follow up time. ART = antiretroviral therapy; CDC = Centers for Disease Control and Prevention; DLBCL = diffuse large cell B cell lymphoma; HIV = human immunodeficiency virus; ITP = idiopathic thrombytopenic purpura.</p

Baseline characteristics of the study population.

<p>Baseline characteristics of the study population.</p

Clinical progression.

<p>(a) Kaplan-Meier curve showing the time to progression to CDC B or C manifestations for group A (treatment initiation within 3 months after diagnosis) and group B (no treatment within 12 months). (b) Kaplan-Meier curve showing the time to progression to CDC B or C manifestations for group A (treatment initiation within 3 months after diagnosis) and B (no treatment within 12 months) censoring patients with a significant treatment interruption.</p

Characteristics of 8 cases with clinical progression to CDC B or C during follow-up.

<p>Characteristics of 8 cases with clinical progression to CDC B or C during follow-up.</p

Association of CMV-Specific T Cell-Mediated Immunity with CMV DNAemia and Development of CMV Disease in HIV-1–Infected Individuals

<div><p>Background</p><p>Among HIV-1–infected individuals, cytomegalovirus (CMV) reactivation and disease occur in the setting of advanced immunosuppression. The value of a standardized assessment of CMV-specific T-cell mediated immunity by the CMV QuantiFERON assay (CMV-QFT) has not yet been thoroughly investigated in HIV-1–infected subjects.</p><p>Methods</p><p>Prospective, longitudinal study in 153 HIV-1–infected subjects with a CD4⁺ T cell count < 350/μL who simultaneously underwent CMV-QFT, CMV serology testing and CMV-DNA quantification. Factors associated with CMV-QFT were evaluated. Clinical screening for CMV manifestations was then performed every 3 months.</p><p>Results</p><p>Among the 141 CMV IgG-seropositive individuals the CMV-QFT assay yielded reactive results in 84% (118/141), negative results in 15% (21/141) and indeterminate (negative mitogen IFN-gamma response) results in 1% (2/141) of subjects. The mean actual CD4⁺ T cell count was significantly higher in CMV-QFT reactive subjects, when compared to CMV-QFT non-reactive individuals (183 ± 102 vs. 126 ± 104 cells/μL, <i>P</i> = 0.015). A significantly lower proportion of CMV-QFT reactive vs. non-reactive patients displayed CMV DNAemia > 100 copies/mL (23% (27/118) vs. 48% (11/23), <i>P</i> = 0.02). Furthermore, a statistically significant inverse association between mitogen IFN-gamma response and CMV-DNAemia > 1000 copies/mL was observed (<i>P</i> < 0.001). During the observational period, 5 CMV end-organ manifestations were observed. In three of the CMV cases the CMV-QFT yielded indeterminate results.</p><p>Conclusions</p><p>While CMV-QFT reactivity indicates CMV-specific immunity, indeterminate results due to negative mitogen IFN-gamma response might reflect HIV-1-induced immunodeficiency. Thus, dependency upon CD4⁺ T cell count should be considered when interpreting CMV-QFT results.</p></div

Correlations between CD4⁺ and CD8⁺ T cell counts, as well as CMV-specific and mitogen IFN-gamma responses.

<p>CMV = cytomegalovirus</p><p>Correlations between CD4⁺ and CD8⁺ T cell counts, as well as CMV-specific and mitogen IFN-gamma responses.</p

Baseline charactersitics of the study population.

<p>AIDS = acquired immunodeficiency syndrome; ART = antiretroviral therapy; CDC = Center for Diseases Control and Prevention; CMV = cytomegalovirus; HIV-1 = human immunodeficiency virus type 1; IVDU = intravenous drug use; MSM = men who have sex with men</p><p>Baseline charactersitics of the study population.</p

Tukey’s schematic boxplot showing the association between CMV-specific and mitogen IFN-gamma response and both CD4⁺ (A, B) and CD8⁺ (C, D) T cell count.

<p>CD4⁺ T cell count tertiles: 1^st: < 115, 2^nd: 115–217, and 3^rd: > 217 cells/μL. CD8⁺ T cell count tertiles: 1^st: < 478, 2^nd: 478–903, and 3^rd: > 903 cells/μL.</p

Study profile for HIV-1 infected individuals who underwent CMV-QFT testing.

<p>CMV-QFT = Cytomegalovirus-QuantiFERON assay.</p