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

The <i>IL28B</i> SNP, rs12979860, is associated with HCV treatment response in a cohort of HCV/HIV-1 co-infected patients.

<p>Patients that completed therapy were genotyped for the <i>IL28B</i> SNP (rs12979860) using a Taqman allele discrimination assay. Genotype frequencies were compared between patients who achieved SVR following treatment (n = 101) and those who did not achieve SVR (n = 48). Differences in frequency distribution between groups were tested for significance by a trend test.</p>1<p>Genotype for a subset of these patients, n = 72, has previously been described (Reference 16)</p

The presence of both <i>KIR2DS3</i> and <i>IL28B-T</i> alleles synergise to increase the odds of HCV treatment failure.

<p>ORs for <i>KIR2DS3</i> alone, <i>IL28B-T</i> carriers (CT or TT) alone, and <i>KIR2DS3</i> with <i>IL28B-T</i> compared with neither risk factor present were calculated from multinominal logisitic regression. The contribution of individual and combined risk factors to the ORs is graphically represented in the bar chart. Positive OR indicates an association with increased odds of treatment failure. ^aOdds ratio (95% confidence interval). * adjusted OR including HCV genotype and HAART as co-variates.</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

<i>KIR2DS3</i> gene frequency is increased in co-infected patients that fail to achieve SVR.

<p><i>KIR2DS3</i> was genotyped in our cohort by PCR-SSP. The carrier frequency of <i>KIR2DS3</i> in 149 HCV/HIV-1 co-infected treated with peg-IFN and ribavirin was compared in 101 patients who achieved SVR following treatment and 48 patients who did not achieve SVR. Differences in frequency populations were tested for significance by χ² test. Odds ratio with 95% confidence intervals is shown.</p

Baseline characteristics of the study population.

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

Main clinical characteristics of the population included in on-treatment analysis.

<p>Patients who completed a course of pegylated-IFN and Ribavirin therapy were included in the SVR analysis. SVR, sustained virological response; VL, viral load; Rx, treatment; ALT, alanine aminotransferase; AST, aspartate aminotransferase; HAART, highly active antiretroviral therapy; NS, not significant.</p

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

The <i>IL28B</i> SNP, rs12979860, is associated with RVR in a cohort of HCV/HIV-1 co-infected patients.

<p>Patients were genotyped for the <i>IL28B</i>-associated SNP, rs12979860. Frequencies of the various genotypes were compared between patients that achieved an RVR (n = 61) and those that did not achieve RVR (n = 88) after 4 weeks of treatment. A χ² trend test was used to compare the data.</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