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Purpose: Hitherto, studies on highly active antiretroviral therapy (HAART) initiation have shown partly inconsistent results. Our study investigated the clinical course and course of immune status after HAART initiation at CD4-cell-count/μl of treated patients between 250 and 349 (group 1), compared to 350-449 (group 2), on the basis of the cohort of the Competence Network for HIV/AIDS (KompNet cohort)., Methods: Patients had to be HAART-naïve. Medication had to start at the earliest in 1996, being at least triple combination therapy. The primary endpoints of death, first AIDS-defining illness and first drop of CD4-cell-count/μl below 200 were evaluated as censored event times between the initiation of HAART (t (0)) and the date of the first event/date of last observation. Probabilities of event-free intervals since t (0) were calculated by Kaplan-Meier estimation, compared by logrank tests. The results were adjusted for confounders using Cox regression. Additionally, incidences were estimated., Results: A total of 822 patients met the inclusion criteria (group 1: 526, group 2: 296), covering 4,133 patient years (py) overall. In group 1, 0.64 death cases/100 py were found, with the corresponding vale being 0.17 in group 2. In group 1, 1.38 AIDS-defining events/100 py occurred, whereas it was 0.78 in group 2. In group 1, 2.64 events of first drop of CD4-cell-count/μl below 200 occurred per 100 py, compared to 0.77 in group 2. Kaplan-Meier estimations showed borderline significant differences regarding death (p = 0.063), no differences regarding first AIDS-defining illness (p = 0.148) and distinct differences regarding the first drop of CD4-cell-count/μl below 200 (p = 0.0004)., Conclusions: The results gave a strong hint for a therapy initiation at higher CD4-cell-count/μl regarding the outcome of death in treated patients. A distinct benefit was shown regarding the first decline of CD4-cell-count/μl below 200.

Background: Clinical studies suggest expert recommendations as a possibility to optimize highly active antiretroviral therapy (HAART) in patients with multi-drug resistant virus strains. An online system (RADATA) has been developed to provide expert advice for the drug therapy of HIV-infected patients., Objective: To evaluate the efficacy of expert-advice-guided HAART switches in patients with triple-class failure., Methods: Virological and immunological outcome of patients having undergone at least three prior ART regimens, including nucleoside inhibitor (NRTI), nonnucleoside reverse transcriptase inhibitor (NNRTI), and protease inhibitor (PI) use, were analyzed. Changes in HIV-RNA and CD4-cell count were evaluated every 3 months., Results: 183 patients with a median baseline viral load of 3.90 log copies/ml (1.88-6.54 log) and a CD4-cell count of 298 c/ll (5-910 c/ll) were eligible for analysis. The patients had a median of seven prior ART regimens and a treatment duration of 83 months. A median of three (range 0-8) NRTI-, two (0-7) thymidine-associated (TA), one (0-4) NNRTI-, and three (0-13) PI-associated resistance mutations were present at baseline. Despite available resistance analyses and expert recommendations, 66% (n = 119) of the patients started a new ART regimen without any active drugs according to the resistance analysis. The HIV-RNA declined by a median of 0.61 log and 0.92 log after 12 and 24 months, respectively, while the CD4-cell count rose by a median of +9 c/microl and +25 c/microl during this period. No significant differences related to number of prior regimens or number of active substances used could be found., Conclusion: Despite extensive pre-treatment and multiple resistances against prescribed HAART, our patients demonstrated a decline in viral load and a stable CD4-cell count over the observation period. We conclude that the activity of antiretroviral regimens is not exclusively explained by the current algorithms used for estimating antiretroviral drug activity.

Objective: To describe the clinical course and risk factors of death in highly active antiretroviral therapy (HAART)-treated patients with progressive multifocal leukencephalopathy (PML); to evaluate the efficacy of cidofovir in addition to HAART., Methods: Retrospective multicenter cohort study of PML in HIV-1-infected patients. Diagnosis of PML was confirmed by histology or by positive polymerase chain reaction for JC virus (JCV) in cerebrospinal fluid (CSF) or was made by typical radiologic and clinical findings., Results: Thirty-five cases of PML were identified. The diagnosis was made by histology (9 cases), detection of JCV in CSF (17 cases), and by radiologic findings (9 cases). Upon manifestation of PML, 15/35 patients had never received HAART, and 11/35 were on HAART for >6 months (median 1126 days). In 9/35 cases, clinical manifestation of PML occurred within 6 months after initiation of HAART. All patients received HAART after PML diagnosis. After a median follow-up of 553 days (range 28-2694 days), the median survival time was not reached. In 12 patients who were treated concomitantly with cidofovir, cumulative survival was significantly shorter than in patients without cidofovir (P = 0.03). Patients in whom PML was diagnosed while on HAART demonstrated a trend toward a shorter survival than HAART-naive patients (P = 0.15)., Conclusions: PML continues to occur in HIV-1-infected patients even when they are treated with HAART. Patients developing PML on HAART had a trend toward a shorter median survival compared with treatment-naive patients, and cidofovir therapy was not associated with improved survival in this cohort.

Background: HIV-infected patients fail viral load suppression, because resistance against antiretroviral drugs arises or for other reasons. HIV-resistance analyses can aid to achieve effective HAART regimen. Furthermore, clinical benefits from genotyping in study settings are significantly higher for treating physicians, who can include external advice from HIV-experts into HAART switch., Objective: To develop a compiling internet presence to provide expert advice for HAART switch in general practice of HIV-infected individuals after therapy failure. -, Design: A multifactorial (genotyping, drug monitoring, adherence, expert advice) interdisciplinary internet service (www.radata.de) with an associated server hosted database., Patients and Methods: HIV-infected patients after failure to HAART are eligible for registration to the Radata project. Genotyping is performed according to protocols specific for each participating institution. Therapeutic drug monitoring (NNRTIs, PIs) follows setting for drug level detection by mass spectrometry. An adherence self-report is completed by every patient. Clinical documentation is provided by the treating Primary Care Physician. Clinical expert advice for implementation into HAART switch in daily clinical practice for treating physicians is provided by HIV-experts according to data obtained. Clinical and laboratory follow-up visits are scheduled firstly 4 weeks after HAART switch and three monthly afterwards, over a period of one year., Results: Technical resources and a compiling internet presence for generation of resistance analysis based expert advice were developed. Initially, 7 HIV-treatment centres, 7 laboratories and 17 HIV advisors contribute to Radata database project. 15 patients were enrolled during test period. 30 expert advices were generated during the test phase. Expert advice was provided in 6 weeks median for implementation into HAART switch. 13 out of 15 expert advices were implemented into HAART switch by treating Primary Care Physicians., Conclusions: Radata is a novel database concept with features to generate expert advice for implementation into HAART switch of HIV-infected subjects. A test period has shown, that the concept is technically approved to fit all requirements with regard to data collection, evaluation and to generate expert advice for therapy switch in daily clinical practice.

Objective: To explore the significance of HHV-8 viremia in HIV-positive individuals for the risk of developing Kaposi's sarcoma (KS) in the era of highly active antiretroviral therapy., Methods: 237 HIV-positive patients were included in this prospective evaluation and followed over an average duration of 34 months. HHV-8 DNA in peripheral blood mononuclear cells (PBMCs) and CD4-lymphocytes were determined. In addition AIDS-defining conditions and antiretroviral therapy were documented of all participating subjects., Results: HHV-8 DNA was detectable in PBMCs of 12.6% out of all individuals. 53.3% of these patients initially complained about KS, although 9.2% of patients without HHV-8 DNA in PBMCs were found on KS as well. Furthermore, four patients in total were observed with newly developed KS during follow up visits. None of these patients were noted with detectable HHV-8 DNA at their initial evaluation., Conclusions: Prevalence of HHV-8 DNA in PBMCs of subjects in this investigation was quite similar to former investigations. However, new diagnosed KS occurred less frequently than demonstrated in previous studies. All of those observed patients with new KS manifestations were negative for HHV-8 DNA in PBMCs at study entry. This observation differs from earlier studies which have postulated the detection of HHV-8 DNA in PBMCs as a predictive value for development of KS. Due to results as presented, a single HHV-8 DNA test in blood has no predictive value in support of predictability of KS development. With respect toto costs and to a less complicated performance antibody assays should be preferred.