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Im vergangenen Jahr wurde die Leitlinie zur HIV-Postexpositionsprophylaxe uberarbeitet. Sie gibt konkrete Empfehlungen, was nach Verdacht auf eine HIV-Ubertragung zu tun ist und wann und wie antiretrovirale Medikamente verabreicht werden sollen.

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Interaktionen in der HIV-Therapie finden grostenteils an den Isoenzymen des Cytochromsystems in der Leber statt. Etwa die Halfte aller Medikamente wird uber das Isoenzym CYP 3A4 abgebaut. Proteasehemmer (PI) inhibieren das Isoenzym CYP 3A4, nicht nukleosidale reverse Transkriptase-Inhibitoren (NNRTI) induzieren das Enzym. Daraus ergeben sich vielseitige Interaktionen zwischen der Begleitmedikation und der antiretroviralen Therapie (ART). Die Arzneistoffe Mefloquin, Chinin und Lumefantrin zur Malariaprohylaxe und -behandlung werden uber CYP 3A4 metabolisiert. Ihr Abbau wird theoretisch von PI gehemmt beziehungsweise von NNRTI beschleunigt. Interaktionen fallen bei Mefloquin eher gering aus. Das Interaktionspotenzial von Chinin wird zurzeit evaluiert. Der Hersteller stuft Lumefantrin aufgrund fehlender Daten und theoretischer Uberlegungen zu erhohten Spiegeln unter PI als kontraindiziert ein. Fur Atovaquon wird diskutiert, ob die Dosis unter Lopinavir/ Ritonavir, Atazanavir/Ritonavir und Efavirenz ausreichend ist. Das Interaktionspotenzial der Antibiotika ist gering. Die meisten Antibiotika werden renal ausgeschieden. Antiretrovirale Substanzen, die hepatisch abgebaut werden, haben dagegen ein hohes Interaktionspotenzial. Interaktionen treten mit den Makrolidantibiotika auf: Clarithromycin ist mit Atazanavir aufgrund der QT-Prolongation kontraindiziert. Ansonsten sind fur Clarithromycin und Erythromycin Spiegelschwankungen unter einem PI und NNRTI zu beachten. Fur Clindamycin gibt es keine Daten. Azithromycin ist interaktionsarm.

Dt. Version erschienen u.d.T.: Diagnostik und Therapie Staphylococcus aureus bedingter Infektionen der Haut und Schleimhäute ([https://doi.org/10.1111/j.1610-0387.2011.07786_suppl.x](https://doi.org/10.1111/j.1610-0387.2011.07786_suppl.x))

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.To evaluate the efficacy of expert-advice-guided HAART switches in patients with triple-class failure.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.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.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.

Summary Hodgkin's disease (HD) is the most common non-acquired immunodeficiency syndrome (AIDS)-defining malignancy in human immunodeficiency virus (HIV)-infected patients. We analysed the outcome of patients with HIV-associated HD (HIV-HD) with respect to the use and efficacy of highly active antiretroviral therapy (HAART) and other prognostic factors. To evaluate the effects of several variables on overall survival (OS), Kaplan–Meier statistics and extended Cox regression analysis were performed. Response to HAART was used as a time-dependent variable and was defined as an increase of >0·1 × 109 CD4 cells/l and/or at least one viral load

Objective To evaluate the impact of immune recovery induced by highly active antiretroviral therapy (HAART) on the survival of AIDS patients with primary central nervous system lymphoma (PCNSL). Methods In a multicentric retrospective analysis, 29 HIV-infected patients with histologically confirmed PCNSL were identified. To evaluate median survival, Kaplan-Meier statistics were used. To explore the effects of different variables on survival, a Weibull accelerated failure time regression analysis was performed. Results Median age at manifestation of PCNSL was 39.1 years and median CD4 cell count was 11 x 10(6) cells/l. Seventy per cent of the patients had had a prior AIDS-defining illness. Cranial radiation (CR) was given to 12 out of 29 patients. Six patients were treated with HAART. Survival time of these patients and of the patients treated with CR alone differed significantly from those receiving neither CR nor HAART (median Kaplan-Meier survival estimate: 1093, 132, and 33 days, respectively). In the multivariate regression model, HAART and CR were identified as the only variables independently associated with prolonged survival. HAART versus no HAART and CR versus no CR increased the time to event by a factor of 6.1 (95% confidence interval, 2.4-16.0; P = 0.0002) and 3.1 (95% confidence interval, 1.5-6.3; P = 0.002), respectively. Four out of six patients on HAART showed a marked immune recovery and survived for more than 1.5 years, with two patients still alive. Conclusion Data from this cohort indicate that immune recovery induced by HAART leads to dramatic improvement in survival of patients with AIDS-associated PCNSL. These findings may have important implications for future treatment strategies.

1Hopital de la Pitie Salpetriere, Paris, France,2Hospital Germans Trias I Pujol, Barcelona, Spain,3Allgemeines Krankenhaus St Georg, Hamburg, Germany,4Universitatsspital, Zurich, Switzerland,5Auguste-Viktoria-Krankenhaus, Berlin, Germany,6Ospedale Civico, Lugano, Switzerland,7Hopital Jean Verdier, Bondy, France,8Glaxo Wellcome Inc, Research Triangle Park, North Carolina, USA, and9HIV and Opportunistic Infections Development Group, Glaxo Wellcome R&D, Greenford Road, Middlesex UB6 0HE, UK Objectives To evaluate antiretroviral efficacy of abacavir (ABC) in antiretroviral-experienced patients, by intensifying current antiretroviral therapy (CART) in patients with stable, detectable plasma HIV-1 RNA. Methods Thirty-two European centres recruited HIV-1 positive patients with ≤ 36 months of CART experience. Patients were randomized to receive either ABC (300 mg twice daily) plus CART (ABC + CART) or ABC placebo plus CART (CART). We assessed efficacy as measured by plasma HIV-1 RNA and CD4+ cell counts and safety at baseline, weeks 2, 4 and every 4 weeks thereafter until week 48. Protocol-defined criteria enabled patients to switch to open-label ABC from week 8 onwards. Results Ninety-two patients with a median plasma of 3.66 log10 HIV-1 RNA copies/mL and a median CD4+ cell count of 408 cells/μL were randomized to ABC + CART and 93 patients with a median plasma of 3.52 log10 HIV-1 RNA copies/mL and a median CD4+ cell count of 411 cells/μL were randomized to CART. From weeks 8–48, 11 (12%) patients in the ABC + CART group and 34 (37%) patients in the CART group switched to open-label ABC. At week 48, significantly more patients on ABC + CART (23/92, 25%) than on CART (5/93, 5%) had plasma ≤ 400 HIV-1 RNA copies/mL (P 5000 copies/mL (4/44, 9%). CD4+ cell counts increased by 102 cells/μL and 57 cells/μL at week 48 for the ABC + CART and CART groups, respectively (intent-to-treat, switch included). ABC addition had minimal impact on the CART safety profile. Conclusions ABC intensification, in CART-experienced patients with low viral loads and limited reverse transcriptase mutations, most of whom had previously been on double-therapy, resulted in a significant and durable plasma HIV-1 reduction and concomitant increase in CD4+ cell count. The presence of M184V at baseline had minimal impact on the efficacy of ABC.

Objective: To compare the antiviral activity of abacavir (ABC) with stable background therapy (SBG) and SBG alone in antiretroviral therapy-experienced subjects as demonstrated by the proportion of subjects with plasma HIV-1 RNA ≤ 400 copies/ml, plasma HIV-1 RNA and CD4 cell count profiles, and safety and tolerance of the two regimens over 16 weeks. Design: One-hundred and eighty-five HIV-1 infected adults, with CD4 cell counts ≥ 100 × 10 6 /l and plasma HIV-1 RNA of 400-50 000 copies/ml and who had received SBG therapy for at least 12 weeks, were randomized to receive ABC (300 mg twice daily) or placebo in a double blind, multi-centre study. Methods: Antiretroviral activity was assessed by measuring changes in plasma HIV-1 RNA levels and CD4 cell counts. Genotypic and phenotypic resistance was determined at baseline and week 16. Evaluation of safety and tolerance was based on clinical adverse events and laboratory analyses. Results: At week 16 significantly more subjects receiving ABC + SBG had plasma HIV-1 RNA ≤ 400 copies/ml (36/92, 39%) than subjects receiving SBG alone (7/93, 8%; P< 0.001). A similar response was observed in both the lamivudine naive and lamivudine-experienced subjects. The presence of the M184V mutation did not preclude an antiviral response to ABC; 73% of subjects with the M184V mutation alone experienced a ≥ 1.0 log 10 copies/ml reduction in plasma HIV-1 RNA or had a value of ≤ 400 copies/ml by week 16. Conclusions: ABC was generally well tolerated and exerted significant antiviral effect when added to combination antiretroviral therapy over 16 weeks.

Background: No data were available on the epidemiological and clinical characteristics of bacillary angiomatosis (BA) in Germany. Objective: To determine epidemiological and clinical data on HIV-associated BA. Methods: A chart review of all BA cases between 1990 and 1998 was performed in 23 German AIDS treatment units. Results: A total of 21 cases of BA was diagnosed. During this period, the participating HIV centers treated about 17,000 HIV-infected patients. As a result, a BA prevalence of 1.2 cases/1,000 patients can be assumed. 19 BA were localized in the skin; in 5 cases bones and in 4 cases the liver were involved. Out of 20 patients who received antibiotic therapy, 13 had complete remission. The median time of duration up to complete remission was 32 days (9–82). During the follow-up of the 20 patients, 7 relapses were observed. Conclusion: BA is a rare HIV-associated disease with a prevalence of 1,2 cases/1,000 patients in the presented study.

Background: Present combination antiretroviral therapy (cART) alone does not cure HIV infection and requires lifelong drug treatment. The potential role of HIV therapeutic vaccines as part of an HIV cure is under consideration. Our aim was to assess the efficacy, safety, and immunogenicity of Vacc-4x, a peptide-based HIV-1 therapeutic vaccine targeting conserved domains on p24Gag, in adults infected with HIV-1. Methods: Between July, 2008, and June, 2010, we did a multinational double-blind, randomised, phase 2 study comparing Vacc-4x with placebo. Participants were adults infected with HIV-1 who were aged 18-55 years and virologically suppressed on cART (viral load

We assessed the efficacy and safety of 10-d monotherapy with the orally administered CCR5 antagonist maraviroc in 63 HIV-1-positive individuals prescreened for the absence of CXCR4-using virus. Maximum reduction in viral load occurred at a median of 10-15 d, with a mean reduction of >or=1.6 log(10) copies/ml at all twice daily doses >or=100 mg. These results provide proof of concept that CCR5 antagonism is a viable antiretroviral therapeutic approach.

The human immunodeficiency virus type-1 (HIV-1) vaccine candidate F4/AS01 has previously been shown to induce potent and persistent polyfunctional CD4(+) T-cell responses in HIV-1-seronegative volunteers. This placebo-controlled study evaluated two doses of F4/AS01 1-month apart in antiretroviral treatment (ART)-experienced and ART-naïve HIV-1-infected subjects (1:1 randomisation in each cohort). Safety, HIV-1-specific CD4(+) and CD8(+) T-cell responses, absolute CD4(+) T-cell counts and HIV-1 viral load were monitored for 12 months post-vaccination. Reactogenicity was clinically acceptable and no vaccine-related serious adverse events were reported. The frequency of HIV-1-specific CD4(+) T-cells 2 weeks post-dose 2 was significantly higher in the vaccine group than in the placebo group in both cohorts (p0.05). Vaccine-induced HIV-1-specific CD4(+) T-cells exhibited a polyfunctional phenotype, expressing at least CD40L and IL-2. No increase in HIV-1-specific CD8(+) T-cells or change in CD8(+) T-cell activation marker expression profile was detected. Absolute CD4(+) T-cell counts were variable over time in both cohorts. Viral load remained suppressed in ART-experienced subjects. In ART-naïve subjects, a transient reduction in viral load from baseline was observed 2 weeks after the second F4/AS01 dose, which was concurrent with a higher frequency of HIV-1-specific CD4(+) T-cells expressing at least IL-2 in this cohort. In conclusion, F4/AS01 showed a clinically acceptable reactogenicity and safety profile, and induced polyfunctional HIV-1-specific CD4(+) T-cell responses in ART-experienced and ART-naïve subjects. These findings support further clinical investigation of F4/AS01 as a potential HIV-1 vaccine for therapeutic use in individuals with HIV-1 infection.

OBJECTIVE: To study syphilis in HIV infection focusing on immunocompromised patients with an atypical or aggressive clinical course of syphilis, inappropriate serological reactions or an unreliable response to therapy. STUDY DESIGN: A multicentre retrospective chart review using a standardised questionnaire for all patients with active syphilis. SETTINGS: Thirteen dermatological and medical centres throughout Germany, all members of the German AIDS Study Group (GASG). PATIENTS: Clinical data of 11,368 HIV infected patients have been analysed for cases of active syphilis requiring treatment. Asymptotic patients with reactive serological parameters indicating latent syphilis without a need for treatment were excluded. RESULTS: Active syphilis was reported in 151 of 11,368 HIV infected patients (1.33%, range per centre 0.3%-5.1%). Most of the 151 syphilis patients were male (93%) and belonged to the homosexual or bisexual exposure category for HIV infection (79%); another 6% were iv drug users. Among the 151 syphilis patients primary syphilis was diagnosed in 17.2%, maculopapular secondary syphilis in 29.1%, ulcerating secondary syphilis in 7.3%, neurosyphilis in 16.6% and latent seropositive syphilis without clinical symptoms but serological abnormalities indicating active syphilis in 25.2%. A history of prior treatments for syphilis was reported in 50%. At the time of syphilis diagnosis 26.5% of the patients were in CDC stage II, 33.8% in stage III and 24.5% in stage IV of HIV disease (CDC classification 1987). CD4 cell count was lowest in those with ulcerating secondary syphilis (mean 307, SD 140/microliters) and neurosyphilis (351, SD 235/ microliters). The highest CD4 count was found in patients with early primary and early secondary syphilis (444, SD 163/microliters and 470, SD 355/microliters). Inappropriate serological response to syphilis infection was found in 81 of 151 patients (54%). Remarkable findings were false negative VDRL titres (11 patients with non primary syphilis), false negative TPHA (1) or 19S-IgM-FTA-ABS-tests (16), and strongly reactive VDRL (> or = 512, 8) or TPHA titres (> or = 10 240, 47). Treatment failures were reported in at least 6 of 151 cases (4%). CONCLUSIONS: Atypical clinical and serological courses of syphilis were observed in HIV infected patients. Ulcerating secondary syphilis with general symptoms ("malignant syphilis") was 60 times more frequent than in historic syphilis series. Neurosyphilis was found in one sixth of those with active syphilis. Therefore lumbar puncture should be considered a routine in coinfections with HIV and syphilis. Treatment efficacy should be monitored carefully.

The degree of lipodermatosclerosis in chronic venous insufficiency was determined by high-resolution 20 MHz ultrasound. For comparison, skin biopsies were taken and examined by light microscopy. With increasingly extensive sclerosis, ultrasound showed increasing thickness of the dermis with a poorly defined border from the subcutaneous fat. In addition, an echolucent band appeared in the upper dermis, corresponding to regions of glomerular capillaries in histology. In our experience, high-resolution ultrasound examination allows rapid and objective quantification of lipodermatosclerosis.

We describe the first Mycobacterium haemophilum infection that occurred in a patient with human immunodeficiency virus in Germany and report 7 newly diagnosed cases of M. haemophilum infection. In the former case, a local M. haemophilum skin infection resolved as a result of successful antiretroviral therapy only; however, that clinical outcome may not be possible for more invasive forms of the disease.

Objectives Once-daily (qd) antiretroviral therapies improve convenience and adherence. If found to be effective, nevirapine extended release (NVP XR) will confer this benefit. The TRANxITION trial examined the efficacy and safety of switching virologically suppressed patients from NVP immediate release (NVP IR) 200 mg twice daily to NVP XR 400 mg qd. Methods An open-label, parallel-group, noninferiority, randomized (2:1 NVP XR:NVP IR) study was performed. Adult HIV-1-infected patients receiving NVP IR plus a fixed-dose nucleoside reverse transcriptase inhibitor (NRTI) combination of lamivudine (3TC)/abacavir (ABC), tenofovir (TDF)/emtricitabine (FTC) or 3TC/zidovudine (ZDV) with undetectable viral load (VL) were enrolled in the study. The primary endpoint was continued virological suppression with VL

Background Nevirapine (NVP) is a widely used non-nucleoside reverse transcriptase inhibitor. A once-daily extended-release (XR) formulation would potentially increase adherence and thus efficacy. Objective The aim of this study was to investigate the steady-state bioavailability of 2 once-daily tablet formulations of NVP XR (containing 25% or 20% hypromellose; NVP XR25 and NVP XR20, respectively) in 400- or 300-mg tablets compared with twice-daily immediate-release (IR) NVP 200-mg tablets. Methods This Phase Ib multinational, multicenter, open-label trial was conducted in patients aged 18 to 60 years, infected with HIV-1 (viral load, ≤50 copies/mL), and treated for ≥12 weeks with twice-daily NVP IR 200 mg. Patients were switched to NVP XR25 400 or 300 mg or NVP XR20 400 or 300 mg for 19 days. Plasma samples were collected over 24-hour periods at steady state. Primary end points were AUC 0–24,ss , C max,ss , and C min,ss , analyzed using an ANOVA statistical model on the logarithmic scale and 2-sided 90% CI. Sample size was determined assuming an intrasubject %CV of 20% for C max . Adverse events (AEs) and viral loads were monitored. Results Ninety-two patients were enrolled (NVP XR25 400 mg, 24 patients; NVP XR20 400 mg, 24; NVP XR25 300 mg, 21; NVP XR20 300 mg, 23). Compared with NVP IR, the AUC 0–24,ss values of the NVP XR formulations were lower (test/reference ratios: 79.5% [90% CI, 73.0–86.7; P = 0.544], 71.0% [90% CI, 63.3–79.7; P = 0.956], 90.3% [90% CI, 80.4–101.4; P = 0.044], and 83.7% [90% CI, 77.9–89.9; P = 0.148] with NVP XR25 400 mg, NVP XR20 400 mg, NVP XR25 300 mg, and NVP XR20 300 mg, respectively). The relative bioavailability of NVP XR25 was greater compared with that of NVP XR20. C max,ss values were lower with all NVP XR formulations compared with NVP IR. For C min,ss , NVP XR25 400 and 300 mg were not significantly different from NVP IR, with 90% CIs within the range of 80% to 125% ( P = 0.039 and P = 0.017, respectively). All AEs were mild or moderate, with no significant differences between treatment groups. No virologic failures (viral load, >50 copies/mL over 2 consecutive readings) were observed. Conclusions Extent of bioavailability was lower and t max,ss was delayed with all NVP XR formulations compared with NVP IR. The bioavailability of the NVP XR25 formulations was greater than that of the NVP XR20 formulations. C min,ss with NVP XR25 was similar to that with NVP IR. All of the NVP XR formulations were well tolerated. The 400-mg NVP XR25 formulation was selected for further development.

Background/Aim of the Study The study aimed to determine the cost impacts of antiretroviral drugs by analysing a long-term follow-up of direct costs for combined antiretroviral therapy, cART,-regimens in the nationwide long-term observational multi-centre German HIV ClinSurv Cohort. The second aim was to develop potential cost saving strategies by modelling different treatment scenarios. Methods Antiretroviral regimens (ART) from 10,190 HIV-infected patients from 11 participating ClinSurv study centres have been investigated since 1996. Biannual data cART,-initiation, cART-changes, surrogate markers, clinical events and the Centre of Disease Control- (CDC)-stage of HIV disease are reported. Treatment duration was calculated on a daily basis via the documented dates for the beginning and end of each antiretroviral drug treatment. Prices were calculated for each individual regimen based on actual office sales prices of the branded pharmaceuticals distributed by the license holder including German taxes. Results During the 13-year follow-up period, 21,387,427 treatment days were covered. Cumulative direct costs for antiretroviral drugs of €812,877,356 were determined according to an average of €42.08 per day (€7.52 to € 217.70). Since cART is widely used in Germany, the costs for an entire regimen increased by 13.5%. Regimens are more expensive in the advanced stages of HIV disease. The potential for cost savings was calculated using non-nucleotide-reverse-transcriptase-inhibitor, NNRTI, more frequently instead of ritonavir-boosted protease inhibitor, PI/r, in first line therapy. This calculation revealed cumulative savings of 10.9% to 19.8% of daily treatment costs (50% and 90% substitution of PI/r, respectively). Substituting certain branded drugs by generic drugs showed potential cost savings of between 1.6% and 31.8%. Conclusions Analysis of the data of this nationwide study reflects disease-specific health services research and will give insights into the cost impacts of antiretroviral therapy, and might allow a more rational allocation of resources within the German health care system.

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).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.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).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.

Objective In this paper, we describe the main objectives, the study design and the onset of the patient cohort of the German Competence Network for HIV/AIDS (KompNet). Furthermore, we depict sociodemographic and clinical baseline characteristics and an estimation of the coverage and representativity as to the composition of persons living with HIV/AIDS (PLWHA) in Germany. Methods The KompNet cohort is an open, retrospective and prospective, multicenter, disease-specific and nationwide cohort study that started gathering data in June 2004. Semi-annually, follow up visits of the patients are documented, covering clinical and sociodemographic data. At enrolment and three years afterwards, an EDTA-sample is taken; a serum-sample is taken at every follow up visit. Results As of 14.9.2008, a total of 15,541 patients were enrolled by 44 documenting sites. In September 2007, the cohort size was reduced to 10 outpatient clinics and fifteen private practitioners, covering a total of 9,410 patients. The documentation of these patients comprises 24,117 years of follow up-time since enrolment (mean: 2.6 years), 62,862 person years inclusive data documented retrospectively on course of HIV-infection and combined antiretroviral therapy (cART, mean: 6.7 years). 1,008 patients (10.7%) were lost to follow up and 175 (1.9%) died since enrolment. 84.9% of patients were men. Main risks of transmission were sex between men (MSM: 62.9%), heterosexual contacts (18.4%), intravenous drug use (IVDU: 7.0%) and origin from a high prevalence country (HPL: 5.2%). Mean age was 45 years. Conclusion The KompNet cohort covers about a quarter of all patients being under treatment in Germany. The composition of the cohort represents well the most important risks of transmission in Germany. The cohort contains a high proportion of patients being older than 49 years (28.1%). On basis of its comprehensive database and its biomaterials banks, the KompNet cohort serves as an important instrument to monitor and analyse the effects of combined antiretroviral therapy (cART) in Germany, interdigidating basis, clinical and psychosocial research in view to translational research.

Dt. Version erschienen u.d.T.: Streptokokkeninfektionen der Haut und Schleimhäute ([https://doi.org/10.1111/j.1610-0387.2007.06287_supp.x](https://doi.org/10.1111/j.1610-0387.2007.06287_supp.x))

The objective was to evaluate the feasibility and efficacy of a short-term, multi-agent and dose intensive regimen in AIDS patients with Burkitt or Burkitt-like lymphoma (BL/BLL) and to compare its efficacy with that of a conventional regimen. This was a retrospective, multi-center cohort study of all HIV-1-infected patients diagnosed with BL/BLL between 1990 - 2004. Patients were assigned to two different chemotherapy approaches. Group A received a protocol which was adapted from the German multi-center study group for adult acute lymphoblastic leukemia (GMALL). Group B received a conventional CHOP-based chemotherapy. Fifty-one patients were included in the analysis. In group A (n = 20), significantly more patients achieved complete remission (75% vs 40%, P = 0.02) than in group B (n = 31). One-year survival in group A was 65% compared to 44% in group B (P = 0.17). In a multi-variable Cox regression analysis, treatment according to the GMALL protocol was significantly associated with prolonged survival with a relative hazard rate of 0.13 (95% CI 0.03 - 0.63, P = 0.01). In conclusion, the short and intensive GMALL protocol for B-ALL/NHL is feasible in patients with AIDS-BL/BLL. Outcome may be improved compared to patients treated with CHOP-based regimens. In the era of HAART, more intensive chemotherapy regimens should be considered in patients with highly aggressive lymphomas.

Therapeutic drug monitoring (TDM) is gaining importance for improving the success of antiretroviral treatment in human immunodeficiency virus-infected patients. However, enfuvirtide (ENF) concentrations are not regularly determined. The objective of this work was to study the pharmacokinetics (PK) of ENF in patients treated in routine clinical settings, to develop a population PK model describing the concentration-time profile, and to establish PK reference values. A liquid chromatography-tandem mass spectrometry method was developed and applied to serum samples submitted for TDM. A two-compartment model with linear absorption and elimination was fitted to 329 concentrations from 131 patients. The PK model was used for simulations resulting in percentile curves for ENF levels for the full dosing interval. The model predicted that a median concentration of 1,968 ng/ml would be reached 12 h after administration of 90 mg of ENF, and 23% and 58% of patients are expected to have concentrations below 1,000 ng/ml and 2,200 ng/ml, respectively. Both values have been proposed as cutoffs for virological efficacy. The median maximum concentration of drug in serum (Cmax) of 3,943 ng/ml, predicted for 3 h after drug administration, is lower than the Cmax reported previously. We found an enormous interpatient variability at every time point, with concentration spectrums covering >1 log and 52% and 123% interindividual variabilities in the typical clearance and volume of distribution, respectively, in contrast to preexisting PK data. In summary, ENF levels are lower and more variable than expected. Many patients may achieve insufficient concentrations. Further covariate analysis in the population PK model might help to identify factors influencing the variability in ENF concentrations. Therapeutic drug monitoring (TDM) of protease inhibitors (PI) and nonnucleoside inhibitors of the reverse transcriptase (NNRTI) is slowly becoming established as an important tool for improving the success of antiretroviral treatment of human immunodeficiency virus (HIV)-infected patients. The ATHENA trial has shown that nelfinavir concentrations below a certain threshold are associated with high rates of virological failure (3, 4). Patients taking efavirenz also have lower chances of sustained viral suppressions when drug concentrations are below 1,000 ng/ml than when they are above this concentration (17). At the other end of the concentration spectrum, TDM may be beneficial for patients with excessive toxic drug effects. Concentration-controlled dose reductions in patients on ritonavir-boosted indinavir who suffer from renal toxicity may alleviate side effects without increasing the risk of therapeutic failure (3). With monitoring of drug levels, individual patients with extremely low or high concentrations can be identified, and a search for the underlying cause can be started, preventing precocious viral failure or unnecessary toxicity. The grow

This study was undertaken to analyze the differentiation profiles assessed by immunophenotyping in AIDS-related B-cell lymphoma (ARL) and their relation to the clinical course. Paraffin-embedded sections of 89 ARL cases during 1989 to 2004 were stained immunohistochemically with antibodies to CD3, CD10, CD20, CD38, CD138/Syndecan-1 (Syn-1), multiple myeloma-1/interferon regulatory factor-4 (MUM1/IRF4), B-cell lymphoma protein-2 (BCL-2), BCL-6, latent membrane protein-1 (LMP-1), and Ki-67. Expression of CD10 and CD20 were associated with better overall survival (OS; P = .009 and P = .04, respectively). Expression of CD20 was associated with longer disease-free survival (DFS; P = .03), whereas expression of CD138/Syn-1 was associated with shorter DFS (P = .03). OS and DFS were worse in patients with immunophenotypic profiles related to post-germinal center (GC) differentiation (BCL-6 and CD10 negative, MUM1/IRF4 and/or CD138/Syn-1 positive) when compared with GC differentiation (P = .01). When controlled for age-adjusted International Prognostic Index (IPI), prior AIDS-defining illness (ADI), and year of ARL diagnosis, a post-GC differentiation remained significantly associated with poor OS and DFS. Expression of CD10 was associated with a preserved immunocompetence, whereas CD20 was less frequent in patients developing ARL while on highly active antiretroviral therapy (P = .04). In summary, lack of CD20 or CD10 expression and a post-germinal center signature are associated with a worse prognosis in ARL.

Bacteria of the species Chlamydia trachomatis are divided into serovars that are associated with different disease manifestations. Serovars A-C cause trachoma, which occurs mainly in undeveloped countries. Serovars D-K are responsible for oculogenital infections, and serovars L1, L2, and L3 cause lymphogranuloma venereum (LGV). Infections of serovars A-K are usually confined to the mucosal epithelia of the eyes and the anogenital tract. In contrast, the L-serovars are more invasive and may induce genital ulcer or inguinal lymphadenopathy after passing the epithelial surface.1 While serovars D-K are distributed worldwide and represent the most frequent bacterial sexually transmitted disease in Europe and North America, LGV caused by the L-serovars is a very rare …

In the course of 2003, four men were diagnosed with lymphogranuloma venereum (LGV) at the Hamburg Institut für interdiziplinäre Infektiologie und Immunologie. All were men who have sex with men (MSM).

AIDS-related lymphoma (ARL) remains a frequent complication of HIV infection. We analyzed the outcome of patients with ARL with respect to the use and efficacy of highly active antiretroviral therapy (HAART) and to potential prognostic factors.This multicenter cohort study included patients with systemic ARL diagnosed between 1990-2001. We evaluated overall survival and the effects of several variables on overall survival using the Kaplan-Meier method and the extended Cox proportional hazards model. Response to HAART was used as a time-dependent variable and was defined as a CD4 cell count increase of/= 100 x 106 cells/l and/or at least one viral load500 copies/ml during the first 2 years following diagnosis of ARL.Among 203 patients with ARL, median overall survival was 9.0 months [95% confidence interval (CI), 7.6-12.4 months]. In the univariate analyses, age60 years, no previous AIDS, CD4 cell counts/= 200 x 106 cells/l, hemoglobin11 g/dl, Ann Arbor stages I-II and A, no extranodal lesion, response to HAART, and complete remission showed statistically significant association with prolonged overall survival. In the multivariate Cox model, the only factors independently associated with overall survival were response to HAART [relative hazard (RH), 0.32; 95% CI, 0.16-0.62], complete remission (RH, 0.24; 95% CI, 0.15-0.36), previous AIDS (RH, 1.92; 95%CI, 1.23-3.01) and extranodal involvement (RH, 2.85; 95% CI, 1.47-5.51).Efficacy of HAART was independently associated with prolonged survival in this large cohort of patients with ARL. Information on patient's response to HAART is crucial for the evaluation of future treatment strategies.

Introduction : Little is known about the well-being on long-term exposure to antiretroviral therapy. The ACTG Augmented Symptoms Distress Module (ASDM) is a validated tool which measures the presence of a total of 22 symptoms seen with HIV and quantifies the extent to which they cause distress to the patient. Methods : ELBE was a cross-sectional study that consecutively included adult HIV-infected patients presenting with viral suppression (

Objective: To assess HIV-1 isolate based resistance profiles from extensively pretreated patients and effects of a resistance guided switch of antiretroviral therapy. Methods: In a prospective study phenotypic and genotypic resistance analyses were performed on HIV infected individuals with failure of the current therapy and history of at least three antiretroviral regimens. Antiretroviral therapy was changed according to the results. Viral load and CD4 lymphocyte counts were measured at baseline, after 10 (SD 2), and 24 (2) weeks. Results: All patients (n=52) failed their actual regimen. Currently versus ever previously taking the specific drug, resistance associated mutations and phenotypic resistance to AZT and 3TC were found in over 80% of individuals; resistance to DDI and D4T was detected in less than 10% of cases. A resistance guided switch of therapy was followed by a median decrease of viral load of 0.5 log10 units after 24 weeks. Individuals resistant to two or more drugs compared with patients with resistance to less than two drugs of ongoing treatment, were switched to a regimen containing DDI, D4T, and a PI or NNRTI. After 10 (SD 2) weeks viral load decrease was pronounced in patients with resistance to at least two drugs in the previous regimen. Conclusions: Among different RTI, the profile of clinically relevant resistance indicates pronounced differences when looking at separate drugs. Regarding virological response, in the context of available drugs, resistance tested with currently used methods is of limited value in extensively pretreated patients and seems to have its value primarily in first or second switch of therapy.

To evaluate the impact of different antiretroviral therapies on the prognosis of AIDS patients affected by progressive multifocal leukoencephalopathy (PML).A retrospective analysis of all HIV-infected patients admitted to hospital between 1988 and 1996 found 29 patients (25 men) with histologically or PCR-confirmed PML. Their mean age was 39.3 years. The median CD4 cell count was 40 x 10(6)/l (mean, 106 x 10(6)/l). Six patients had CD4 cell counts200 x 10(6)/l. Fourteen patients never received or stopped antiretroviral therapy following diagnosis (group A), 10 patients were treated with nucleoside analogues alone (group B), and five patients started highly active antiretroviral therapy (HAART) including protease inhibitors (group C).The median survival following the onset of symptoms was 131 days, but differed significantly between the three groups: group A, 127 days; group B, 123 days; group C,500 days (P0.0002 for the difference between group C versus group A and B, stratified log-rank test). As of July 1997, four out of five patients on HAART were still alive 391, 500, 543, and 589 days after diagnosis of PML and have either experienced a resolution of the symptoms (three patients) or had progressed very slowly (one patient). A multivariate analysis using Cox regression found younger age at diagnosis to be the only other variable associated with improved survival (P0.02). CD4 cell count, gender, prior AIDS diagnosis, mode of HIV transmission, and therapy with foscarnet, cytarabine, or interferon-alpha did not affect survival in this cohort (P0.1).This study of a large cohort of patients with confirmed PML indicates that AIDS patients with PML may benefit significantly from HAART. All patients with PML should be offered optimal antiretroviral combination therapy.

Background: Kaposi’s sarcoma (KS) is the most frequent neoplasm in patients with AIDS, responsible for death in about 20–30% of the affected patients. Objective: To determine the frequency of opportunistic infections (OI) and change of CD4+ cell counts in patients with KS treated with chemotherapy compared to a group of matched-pair patients without chemotherapy. Methods: In a prospective study, the clinical courses of 35 HIV-infected patients with KS treated with chemotherapy were compared with 35 matched-pair patients without chemotherapy. Results: During the observation period of 6 months, 11 OI occurred in 10 patients of the chemotherapy group and 5 OI in 5 patients of the control group. With respect to the changes of CD4+ cell counts, no significant differences could be observed. Conclusion: The risk for OI in HIV-infected patients with KS is increased while receiving chemotherapy. This should be reflected upon when chemotherapy is taken into consideration.

Background: HIV infection is a risk factor for the development of Herpes zoster (HZ) and its complications. Prior to antiretroviral therapy (ART), HZ incidence in HIV-infected individuals ranged from 2.9-5.1/100 person-years. There is limited evidence for the impact of ART on HZ occurrence among HIV-infected adults. We analysed the incidence of, and risk factors for, HZ in a large cohort of German HIV-positive patients.Methods: The study population was taken from the German KompNet cohort, a nationwide multicenter HIV cohort study. The study population was defined by age (≥ 18 years), year of first positive HIV diagnosis, CD4 values ± 6 months from HIV diagnosis (t0), and month of HZ diagnosis. Incidences were estimated using a Poisson distribution, and uni- and multivariate Cox proportional Hazard ratio (HR) regression models were fitted to identify risk factors for developing an initial HZ episode. Independent variables were sex, age at HIV diagnosis, route of HIV transmission, ART status, CD4 count before HZ episode, immunosuppressive medication, and mode of data documentation (retrospective or prospective).Results: HZ incidence in the overall study population was 1.2/100 person-years. In a subset of patients for that we were able to examine risk factors the following was observed: We examined 3,757 individuals whose mean age at t0 was 38 years. Of those individuals, 96% were diagnosed with HIV in 1996 or later, with a mean observation time of 5.8 years. HZ episodes (n = 362) were recorded in 326 patients (8.7%), resulting in annual HZ incidences of 1.7/100 person-years overall, and 1.6/100 person-years for initial HZ cases. The main risk factors associated with an initial HZ episode were: not partaking in ART compared with an ART regimen containing a non-nucleoside reverse-transcriptase inhibitor (HR 0.530, p < 0.001) or a protease inhibitor (HR 0.624, p = 0.004); and lower CD4 count by 100 cells/μl (HR 0.918, p=0.001).Conclusions: HZ incidence was 4-11-fold higher than in non HIV-infected individuals, but in our study HZ incidences were lower than in previous studies relating to HIV-positive patients. We showed that ART is an important protective factor for HZ episodes. © 2013 Jansen et al.; licensee BioMed Central Ltd.

Background HIV infection is a risk factor for development of Herpes Zoster (HZ) and its complications. There is limited evidence on the impact of antiretroviral therapy (ART) on the occurrence of HZ among HIV-infected adults. Methods Study population was drawn from the KompNet HIV cohort. Inclusion criteria were: age ≥ 18 years, record of HIV diagnosis date (t0), record of CD4 count available ± 6 months from t0. Patients without month of HZ diagnoses were excluded. Study period was 1.1.1985–1.7.2010. Incidences of all HZ events were estimated assuming Poisson distribution, uni-/multivariate Cox proportional Hazard ratio (HR) regression models were fitted to identify risk factors for a first HZ event. Independent variables were: sex, age at HIV diagnosis, HIV transmission route, ART status, CD4-value before HZ episode, immunosuppressive medication, mode of data documentation (retrospective/prospective). Results Study population comprised 3,757 subjects (86% male, 66% MSM, 3% IVDU, 92% Caucasian), mean age at HIV diagnosis was 38 years, mean observation time was 5.8 years. 362 HZ events were recorded in 326 patients (8.6%), resulting in an HZ incidence of 16.7/1,000 PY overall and 16.1/1,000 PY for first HZ cases. Main risk factors associated with first HZ event were: no ART compared to an ART containing a non-nucleoside reverse-transcriptase inhibitor (NNRTI vs no ART; HR 0.530, p Conclusions According to former studies incidence of HZ in HIV-infected individuals was ∼5 times higher than in the general population. Our study showed ART as important protective associated factor for HZ events. Reasons may be earlier HIV-diagnosis, more recent picturing of ART, and low IVDU proportion in our study.

Wk 24 TRANxITION study data showed patients transitioned from immediate release nevirapine (NVP IR) twice daily (BID) to NVP extended release (NVP XR) once-daily (QD) demonstrated non-inferior efficacy to patients continuing on IR NVP BID. Similar safety was reported for NVP XR and NVP IR in the VERxVE study. Wk 48 efficacy/safety data from TRANxITION study are presented here. Supplement: Abstracts of the Tenth International Congress on Drug Therapy in HIV Infection http://www.biomedcentral.com/content/pdf/1758-2652-13-S4-info.pdf Conference: Tenth International Congress on Drug Therapy in HIV Infection 7-11 November 2010 Glasgow, UK (Published: 8 November 2010) doi:10.1186/1758-2652-13-S4-P45 Cite this article as: Arasteh et al.: 48-week efficacy and safety of transitioning virologically stable HIV-1 patients from nevirapine IR 200 mg BID to nevirapine XR 400 mg QD (TRANxITION). Journal of the International AIDS Society 2010 13(Suppl 4):P45. Full text: PubMed Central: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3113048/

Atazanavir (ATV)-based regimens have demonstrated efficacy and safety in both ARV-naive and -experienced patients. However, few reports have assessed effectiveness beyond 2 years. The aim of this study was to describe the long-term outcomes of ATV/r containing regimens in ARV-experienced patients in a clinical setting. Supplement: Abstracts of the Tenth International Congress on Drug Therapy in HIV Infection http://www.biomedcentral.com/content/pdf/1758-2652-13-S4-info.pdf Conference: Tenth International Congress on Drug Therapy in HIV Infection 7-11 November 2010 Glasgow, UK (Published: 8 November 2010) doi:10.1186/1758-2652-13-S4-P31 Cite this article as: Jansen et al.: Long-term efficacy and safety of atazanavir/ritonavir treatment in a real-life cohort of treatmentexperienced HIV patients. Journal of the International AIDS Society 2010 13 (Suppl 4):P31. Full text: PubMed Central: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3113033/