Preemptive Therapy Prevents Cytomegalovirus End-Organ Disease in Treatment-Naïve Patients with Advanced HIV-1 Infection in the HAART Era

<div><p>Background</p><p>The efficacy of preemptive therapy against cytomegalovirus (CMV) infection remains unknown in treatment-naïve patients with advanced HIV-1 infection in the HAART era.</p><p>Methods</p><p>The subjects of this single-center observation study were126 treatment-naïve HIV-1 infected patients with positive CMV viremia between January 1, 2000 and December 31, 2006. Inclusion criteria were age more than 17 years, CD4 count less than 100/μl, plasma CMV DNA positive, never having received antiretroviral therapy (ART) and no CMV end-organ disease (EOD) at first visit. The incidence of CMV-EOD was compared in patients with and without preemptive therapy against CMV-EOD. The effects of the CMV preemptive therapy were estimated in uni- and multivariate Cox hazards models.</p><p>Results</p><p>CMV-EOD was diagnosed in 30 of the 96 patients of the non-preemptive therapy group (31%, 230.3 per 1000 person-years), compared with 3 of the 30 patients of the preemptive therapy group (10%, 60.9 per 1000 person-years). Univariate (HR = 0.286; 95%CI, 0.087–0.939; p = 0.039) and multivariate (adjusted HR = 0.170; 95%CI, 0.049–0.602; p = 0.005) analyses confirmed that CMV-EOD is significantly prevented by CMV preemptive therapy. Multivariate analysis showed that plasma CMV DNA level correlated significantly with CMV-EOD (per log10/ml, adjusted HR = 1.941; 95%CI, 1.266–2.975; p = 0.002). Among the 30 patients on preemptive therapy, 7 (23.3%) developed grade 3–4 leukopenia. The mortality rate was not significantly different between the two groups (p = 0.193, Log-rank test).</p><p>Conclusions</p><p>The results indicate that preemptive therapy lowers the incidence of CMV-EOD by almost 25%. Preemptive therapy for treatment-naïve patients with CMV viremia is effective, although monitoring of potential treatment-related side effects is required.</p></div

Uni-and multi-variate analyses to estimate the risk of ATV/r use over other PIs-containing antiretroviral therapies for cholelithiasis.

<p>Model 2 was adjusted for age and body weight.</p><p>HR: hazard ratio, CI: confidential interval, ATV/r: ritonavir-boosted atazanavir, BMI: body mass index, eGFR: estimated glomerular filtration rate.</p

Clinical characteristics of patients who developed cholelithiasis.

<p>BMI: body mass index, PI: protease inhibitor, ATV/r: ritonavir-boosted atazanavir, LPV/r: lopinavir/ritonavir, ABC: abacavir, 3TC: lamivudine, ERCP: endoscopic retrograde cholangiopancreatography, PTGBD: percutaneous transhepatic gall bladder drainage.</p

Baseline demographics and laboratory data of patients who received ATV/r- and other-PIs-containing antiretroviral therapy (n = 1,242).

<p>*Arithmetic mean.</p><p>ATV/r: ritonavir-boosted atazanavir, PI: protease inhibitor, SD: standard deviation, BMI: body mass index, TDF: tenofovir, eGFR: estimated glomerular filtration rate.</p

Uni- and multi-variate analyses to estimate the associations of various factors with cytomegalovirus retinitis.

<p>Variables with p <0.05 in the univariate analysis were incorporated into the multivariate model. Anti-CMV treatment and history of AIDS were not added to the multivariate model because of multicollinearity with CMV diseases other than retinitis and CD4 count, respectively. History of AIDS was not added to the multivariate model because CMV retinitis is one of the AIDS-defining illnesses.</p><p>Uni- and multi-variate analyses to estimate the associations of various factors with cytomegalovirus retinitis.</p

Prevalence of ocular diseases according to CD4 cell count.

<p>Data are numbers (percentages).</p><p>CMV: cytomegalovirus</p><p>Prevalence of ocular diseases according to CD4 cell count.</p

Patient enrollment.

<p>*Both <i>M</i>. <i>avium</i> and <i>M</i>. <i>intracellulare</i> were detected in blood culture of one patient.</p

Baseline characteristics of the study patients at initiation of anti-mycobacterial treatment.

<p>Baseline characteristics of the study patients at initiation of anti-mycobacterial treatment.</p

Flow diagram of patient selection.

<p>ART, antiretroviral treatment; ATV, atazanavir; PIs, protease inhibitors; LPV/r, lopinavir/ritonavir; ATV/r, ritonavir-boosted atazanavir; FPV, fosamprenavir; FPV/r, ritonavir-boosted fosamprenavir; DRV/r, ritonavir-boosted darunavir.</p

Patient enrollment process.

<p>^¶Two patients had both HIV retinopathy and cataract, one had both cataract and diabetic retinopathy, and one had both HIV retinopathy and diabetic retinopathy. CMV: cytomegalovirus.</p