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A 52 year old patient was admitted to the hospital for further clarification of a cystic structure in the region of the spleen hilus noticed in the upper abdominal sonogram. The investigations revealed a spontaneous splenorenal shunt in hepatic cirrhosis.

Forty-one HIV-positive homosexual men (mean age 39.8 [23-72] years) with malignant lymphomas were examined with the object of exploring the clinical and pathological spectrum of HIV-associated lymphomas in Central Europe, and their therapeutic aspects. There were 33 patients with non-Hodgkin lymphoma of high malignancy and four with non-Hodgkin lymphoma of low malignancy; four further patients suffered from Hodgkin's disease. 27 patients died during the period of observation. The mean survival period after diagnosis was 5.5 months. It depended on the stage reached by the lymphoma at the time of diagnosis: 11.8 months in stage I, 10.6 months in stage II, 7 months in stage III, 3.3 months in stage IV and 1.3 months in patients with primary involvement of the central nervous system by the lymphoma. Eight out of nine patients with highly malignant non-Hodgkin lymphoma in stage I or II attained complete and lasting remissions after chemotherapy or irradiation. However, only minimal prolongation of life was achieved in the 16 patients with lymphomas in stages III or IV. The response rate among all patients treated (complete and partial remissions) was 75%; 45% achieved complete remission. Hodgkin's disease responded well to standard therapy, but the disease rapidly recurred in every case.

A 45-year-old man with AIDS was treated for a recurrence of cerebral toxoplasmosis with sulphadiazine, 4 g, and pyrimethamine, 75 mg, daily. Owing to a lack of appetite and dysphagia he drank rather little water during the first week of treatment. On the 13th day after starting the drugs he had bilateral renal colics and renal failure was diagnosed (serum creatinine 3.8 mg/dl). Ultrasound examination demonstrated multiple stones with bilateral urinary retention. After parenteral fluid replacement, alkalization of the urine with sodium-potassium-hydrogen citrate and N-butylcopolamine a stone, consisting of sulphadiazine and acetylsulphadiazine, was passed after two days. Three days later the creatinine concentration was within normal limits, and in further two days the ultrasound picture was normal. It is pointed out that diarrhoea, fever or dysphagia often prevent sufficient fluid intake in AIDS patients. Satisfactory oral fluid intake and alkalization of urine is thus of great importance for avoiding complications during sulphadiazine treatment.

Antibodies against HTLV-III, neopterin levels in blood and urine, TH/TS ratio and hepatitis marker were determined in 34 clinically symptom-free persons known to be intravenous drug abusers. 15 persons were positive in the ELISA and Western-blot tests. There was a strong reaction to protein p24 compared with that to protein p41. In 12 of 14 persons who were antibody-positive the neopterin level in morning urine was elevated; an abnormal TH/TS ratio was present in nine of 13 persons. In future, determination of neopterin and of antibodies against certain proteins of HTLV-III may make it possible to provide a simple way of prognosticating on the course of an HTLV-III infection.

Topics highlighted at the XVI International AIDS Conference in Toronto included HIV/AIDS vaccine research, entry inhibitors, integrase inhibitors, new NNRTIs and PIs, single-agent therapies, pre-exposure prophylaxis and microbicides. Beside the large scientific part, policy and funding were of great concern. Within this article we are trying to focus on topics with direct clinical relevance. This includes new epidemiological and resistance data, results from current studies investigating established and novel antiretroviral drugs and drug classes as well as new findings in therapy management and strategies.

Objectives Approximately 10% of HIV-infected patients fail to respond properly to highly active antiretroviral therapy (HAART). Among other factors, genetic variants of chemokine receptors have been shown to modify the course and outcome of HIV infection. Our objective was to investigate whether a failure of virological response is associated with polymorphisms of the chemokine receptors or cofactors. Methods A total of 256 HIV-infected patients receiving HAART and 221 healthy controls were analysed for the chemokine receptor 5 (CCR5)-Δ32-bp, stromal derived factor 1 (SDF1)-3′A and chemokine receptor 2 (CCR2)-64I polymorphisms. Treatment failure was defined as failure to lower the viral load below 50 HIV-1 RNA copies/mL within the first year of treatment despite good adherence. Genomic DNA was extracted from peripheral blood lymphocytes (PBL) and amplified by polymerase chain reaction (PCR). Results Successful treatment was associated with heterozygosity for the CCR5-Δ32-bp variant found in 24 of 184 responders (13%) vs. one of 72 nonresponders (1.4%; P=0.004). Eighty-four of 184 responders (45.7%) vs. 25 of 72 nonresponders (34.7%) were heterozygous for the SDF1-3′A allele (P=0.073). The CCR2-64I polymorphism was rare in both groups: 4.9% in responders vs. 1.4% in nonresponders (P=0.175). The odds ratio for successful treatment was 4.7 for individuals who tested positive for at least one variant allele of the three polymorphisms. Comparison of genotype frequencies between HIV-infected and healthy individuals showed highly significant differences (P

Seit Einfuhrung der antiretroviralen Medikamente, insbesondere der Proteaseinhibitoren, hat die Mortalitat und Morbiditat der HIV-Infektion signifikant abgenommen. Eine haufige Nebenwirkung dieser Therapie ist das Lipodystrophiesyndrom, ein vielfaltiger, aber charakteristischer Symptomenkomplex, der durch korperliche und metabolische Veranderungen gekennzeichnet ist. Dieses Syndrom besteht aus einer charakteristischen Fettverteilungsstorung mit einer Zunahme des intraabdominalen Fetts, der Bildung eines “Stiernackens” und zugleich einem Schwund des subkutanen Fetts an den Extremitaten und im Gesicht. Dazu konnen eine Hyperlipidamie und eine Insulinresistenz kommen. Die Pathogenese des Lipodystrophiesyndroms ist nicht geklart.

A 39-year-old female patient with familiar neurofibromatosis developed a sarcoma in the hollow of the knee that appeared clinically and sonographically as a Baker cyst. Following an operation to remove the tumour and subsequent local radiation treatment multiple metastases appeared distant to the primary tumour from which the patient died. On the observation of a Baker cyst in a patient with neurofibromatosis the possibility of malignant degeneration must be kept in mind and an operation carried out immediately.

Derzeit gilt methodisch nicht nur die Messung der Anzahl von CD4-Zellen sondern auch der quantitative Nachweis retroviraler RNA als Aktivitatsindikator einer HIV-Infektion. Dabei kommt dem RNA-Nachweis eher noch grosere diagnostische Bedeutung zu. Bei symptomatischen Patienten ist die Indikation zur antiretroviralen Dreierkombination, heute Goldstandard der Therapie, unabhagnig von CD4-Zellzahl und HIV-RNA gegeben. Bei asymptomatischen Patienten richtet sich die Indikation zum Therapiebeginn nach der HIV-RNA im Plasma. Therapieindikationen sind: >5000–10000 RNA-Kopien/ml, CD4-Zahl unter 350/μl oder CD4-Zahl

In dieser Kasuistik wird die Krankengeschichte eines 35jahrigen Patienten vorgestellt, der in unserer Klinik mit den Symptomen eines nephrotischen Syndroms aufgenommen worden war. Differentialdiagnostisch fuhrten der histologische Befund einer fokalen Glomerulosklerose und der serologische Nachweis einer HIV-Infektion zu der Diagnose einer HIV-assoziierten Nephropathie. An diese Erkrankung sollte, wenngleich in der kaukasischen Bevolkerung bisher sehr selten beschrieben, bei nephrotischem Syndrom und gleichzeitigen Risikofaktoren fur eine HIV-Infektion gedacht werden. Therapeutisch konnte durch die Gabe von Steroiden bei dem beschriebenen Patienten eine vorubergehende deutliche Besserung des Krankheitsbildes erreicht werden; allerdings mus einschrankend gesagt werden, das die Behandlung mit Steroiden bei HIV-infizierten Patienten kontrovers diskutiert wird. Die Moglichkeit der Kombinationstherapie mit neu entwickelten Proteaseinhibitoren sollte als Behandlungsstrategie auf jeden Fall in Betracht gezogen werden, auch wenn bisher in der Therapie der HIV-assoziierten Nephropathie keine publizierten Verlaufsbeobachtungen unter dieser Behandlung vorliegen.

Chemokine receptors are essential for human immunodeficiency virus (HIV) cell entry. CXCR4 and CCR5 are the two most relevant receptors and by inhibition of each of them a delayed onset of disease could be achieved. As both receptors are used at different stages of disease due to the domination of different HIV strains, a dual blockage of CXCR4 and CCR5 could be highly valuable for inhibiting viral transmission and replication.

The results of serological tests for Toxoplasma gondii IgG in 31 HIV-infected patients with toxoplasmic encephalitis (TE) and 49 HIV-infected patients seropositive for Toxoplasma gondii but without TE were compared. All patient had a CD4+ lymphocyte count150/microliters. Of the TE patients, 22 (71%) were designated as having relatively high IgG levels on the basis of the following Toxoplasma IgG titre combination: Sabin-Feldman testor = 1:256, indirect hemagglutination testor =1:1024, direct agglutination testor = 1:14,580. Only 3 patients without TE had relatively high IgG titres. Relatively high IgG titres indicated TE with a positive predictive value of 88% in HIV-infected patients with CD4+ cell counts150/microliters, and could be observed in most patients several months prior to the first clinical and radiological signs of TE.

Monocytes/macrophages play a critical role in the pathogenesis of HIV infection, both as targets for virus replication and as sources of production of multifunctional cytokines. Endothelins, peptides with potent vasoconstricting activities originally isolated from endothelial cells, are also produced and secreted by macrophages in a manner similar to that of other cytokines. In an attempt to explore the potential role of endothelins in HIV-infection, we investigated the effect of the HIV-1 envelope glycoprotein, glycoprotein 120, on monocytic endothelin-1 production. This glycoprotein has been identified as a potent stimulator of monokines such as TNF-alpha and IL-6, which have been implicated as potential mediators of HIV-encephalopathy. We found that glycoprotein 120, similar to LPS, stimulates the secretion of endothelin-1, as well as TNF-alpha, from macrophages in a concentration-dependent manner. Using reverse transcriptase polymerase chain reaction, we found that circulating monocytes in HIV-infected individuals show a distinct expression of the endothelin-1 gene that is not detectable in healthy controls, indicating chronic activation of this gene in HIV-infection. In addition, cerebral macrophages in patients with HIV-encephalopathy were strongly positive for endothelin. Thus, monocytic endothelins appear to be stimulated during HIV infection. Their potent vasoactive properties render them potential candidates for mediating alterations in the cerebral perfusion pattern associated with the AIDS dementia complex.

Still's disease was diagnosed in a 40-year-old patient as a cause of psycho-organic syndrome with complete disorientation and stupor, sensory and motor aphasia. There were no signs of a tumour, cerebrovascular accident, bacterial or viral infection. The patient recovered quickly from the cerebral disturbances under treatment with corticosteroids. Similar symptoms in adult patients with Still's disease are seldom found in the literature.

During an oral glucose tolerance test (oGTT) and an isoglycaemic intravenous glucose infusion, blood glucose and the responses of insulin and glucose-dependent insulinotropic polypeptide (GIP) were measured in six healthy volunteers. On a subsequent occasion a constant infusion of human synthetic GIP (2 pmol kg-1 min-1 for 30 min and 0.5 pmol kg-1 min-1 for another 30 min was given to each subject, again with a simultaneous infusion of glucose to maintain isoglycaemia to the oGTT. During the oGTT, plasma GIP concentrations rose from 92pM18 pmol 1-1 to 257 pM42 pmol 1-1 60 min after ingestion of glucose (meanpMSEM). When glucose was administered intravenously plasma GIP levels did not rise significantly over basal. The infusion of hGIP mimicked the physiological plasma GIP response after oral glucose during the first 60 min of the study. Plasma insulin concentrations were significantly lower between 45 and 60 min than during the oGTT (438 pM 67 vs. 200pM48 pmol l-1p

Nucleoside analogues such as Didanosine and Stavudine are known to cause metabolic and body habitus changes during antiretroviral therapy. The most frequently observed are lactic acidosis, hypercholesterinaemia, hypertriglyceridaemia and lipodystrophy.Over one year we monitored a cohort of 43 patients who switched from either Stavudine, Didanosine or the combination of both to Tenofovir. A group of 11 patients was kept on their original regimen and acted as control group. Blood samples were taken every 3 months from baseline, anthropometric measurements were performed at baseline, after 6 and 12 months.During observation the levels of lactic acid and cholesterol decreased significantly in the switch group while virologic and immunologic efficacy remained stable. Serum creatinine levels rose significantly in patients switched to Tenofovir, but remained within physiological limits. The mean skin fold thickness increased significantly by 1.8 mm in the switch group after 6 months (por =0.001 - p = 0.032).These results implicate an improvement of lipid profiles, serum lactate and lipodystrophy in HIV-positive patients after switch to Tenofovir. As a moderate increase in serum creatinine levels was observed, the renal function of patients on a Tenofovir-based regimen should be monitored closely.

Highly active antiretroviral therapy (HAART) has markedly decreased HIV-associated mortality. It consists of a combination of three antiretroviral drugs from four different classes: nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, protease inhibitors and inhibitors of virus-cell fusion. Increasing resistance against antiretroviral drugs calls for the development of new compounds and drug classes. The growing understanding of molecular mechanisms in HIV-replication led to the identification of further steps which might serve as novel antiretroviral targets. Uninfected cells could be protected from HIV by inhibiting extracellular binding mechanisms. Improvement of existing antiretroviral drugs and further development of novel therapeutic targets will enrich antiretroviral treatment.

ehr als 60 Prozent der AIDS-Falle in der Bundesrepublik werden in den Stadffigb vg*4a ten Berlin, Munchen, Hamburg, Koln, Dusseldorf und Frankfurt betreut. Doch breiten sich HIV und AIDS auch auserhalb von Grosstadten aus. Funfzehn Prozent der von uns behandelten AIDSPatienten wohnen nicht in Munchen, sondern in kleineren Stadten in ganz Bayern. Es besteht kein Zweifel daran, das heute bei jedem niedergelassenen Arzt und in jedem Krankenhaus Patienten mit HIV-Infektionen erscheinen konnen. Es ist daher sinnvoll und notwendig, sich mit den einer HIV-Infektion folgenden Krankheitsbildern vertraut zu machen. Die gewohnte Vorstellung, die Zugehorigkeit zu einer sogenannten Risikogruppe sei das wichtigste Indiz fur eine HIV-Infektion, verliert zunehmend an Bedeutung (Abbildung 1). Der Anteil der heterosexuell akquirierten Infektionen nimmt zu. Da dies besonders fur die noch nicht an AIDS erkrankten Patienten gilt, ist auf erste Symptome und Indikatoren einer HIV-Infektion zu achten. Durch die heute verfugbaren praventiven Behandlungsmoglichkeiten liegt ein rechtzeitiger Nachweis im Interesse des Patienten, da die Lebenserwartung der Erkrankten von dem fruhzeitigen Erkennen opportunistischer Infektionen abhangig ist. Erste klinische Symptome einer HIV-Infektion sind bei etwa 10 bis 20 Prozent der Patienten als akute HIV-Krankheit wenige Wochen nach der Infektion zu beobachten. Die Beschwerden entsprechen denen einer akuten Virusinfektion mit Fieber, Gliederschmerzen, feinflekkigem Exanthem, eventuell Lymphknotenschwellung, Durchfallen, starken Kopfschmerzen. Im DifferentialDie HIV-Infektion ist heute auch in Deutschland so verbreitet, das sich in jeder Praxis und Klinik HIV-Patienten vorstellen konnen. Die Beschaftigung mit den resultierenden Krankheitsbildern gehort daher zu den Fortbildungspflichten. Grose Aufmerksamkeit ist vor allem den „Markerkrankheiten" zu schenken, die fruh auf eine solche Infektion hinweisen. Je fruher die Diagnose einer opportunistischen Infektion gestellt und eine adaquate Therapie eingeleitet werden, desto besser ist die Prognose. Fortschritte werden auch in der prophylaktischen Behandlung der Komplikationen des Immundefektes erzielt. In der antiviralen Therapie ist AZT (Zidovudine) inzwischen etabliert, die Berichte uber seine Effekte in der Fruhtherapie bei asymptomatischen Patienten zwar vielversprechend, aber noch nicht definitiv zu beurteilen.

Recently, the 15th International AIDS Conference took place in Bangkok, Thailand. This conference used to be an almost exclusively science-oriented conference reporting on new developments in diagnostic tools, drug discovery, and other medical advances, making it a "must attend" event for most scientists. In the year 2000, this congress was hosted by South Africa in Durban, for the first time in a developing country - focusing on the particular needs of poor countries and also stressing that scientific approaches are not the only relevant and important aspects of this global epidemic. While many scientist (including this author) perceived the changing emphasis of the meeting with regret ("only science will solve this problem"), the immediate view on the epidemic in areas with poor resources has proven beyond doubt that HIV is far more than just a viral infection. With the latest conference taking place in Bangkok, several particular aspects were demonstrated: after Africa, Asia is the largest hot spot in the worldwide spread of HIV with the highest increase in infections. Also, this country can serve as an admirable example of political will and successful battle to constrain the epidemic despite a serious lack of resources.

A-M Bauer, T Sternfeld, S Horster, M Schunk, F-D Goebel and JR BognerDepartment of Infectious Diseases, Medizinische Poliklinik, University Hospital of Munich, Munich, GermanyObjectivesIt is unknown whether high levels of lactate result from enhanced production or decreaseddegradation. We therefore investigated differences in the kinetics of plasma lactic acid inHIV-infected patients receiving or not receiving highly active antiretroviral therapy (HAART)and in uninfected controls after submaximal ergometric exercise.MethodsTen healthy controls, 11 HIV-infected therapy-nai¨ve patients, 15 HIV-infected patients on HAARTwith normal baseline lactate levels, and nine HIV-infected patients on HAART with elevated baselinelactate levels >2 mmol/L performed 10 min of ergometric exercise, with a heart rate of 200 beats/minminus age. Lactate levels were measured at baseline, at the end of exercise and 15, 30, 45, 60 and120 min thereafter.ResultsMean baseline lactate levels were 1.4, 1.5, 1.5 and 2.8 mmol/L in the controls, the therapy-nai¨vepatients, the patients on HAART with normal lactate levels and the patients on HAART with elevatedlactate levels, respectively. Maximum lactate levels after exercise were similar in all groups (9.7, 9.4,9.0 and 10.1 mmol/L, respectively). Significant differences were found in the slope of lactate declinebetween controls and untreated individuals (P50.038) and between patients on HAART withnormal baseline lactate and patients on HAART with elevated baseline lactate (P50.028).ConclusionsDifferences in lactate metabolism do exist between healthy controls and HIV-infected therapy-nai¨veindividuals. Thus, HIV infection in itself may influence lactate levels. Elevated baseline lactate levelsare associated with a delayed decline of lactate after exercise. These results could be explained byimpaired lactate clearance. Lactate production upon exercise does not seem to be affected bybaseline lactate levels.Keywords: hyperlactataemia, lactate metabolism under exercise, lactic acidosis, mitochondrialtoxicityReceived: 24 November 2003, accepted 23 March 2004

Highly active antiretroviral therapy has resulted in remarkable reduction of morbidity and mortality of HIV infection. With increasing duration of therapy metabolic alterations such as hyperlipidemia, diabetes mellitus type 2 and lipodystrophy are encountered which considerably reduced quality of life for the patients. These adverse events are most likely due to protease inhibitors and nucleoside analogues with synergistic effects. The pathogenesis is related to metabolic alterations of the adipocytes with cellular insulin resistance and enhanced apoptosis of these cells caused by adipocytic cytokines such as adiponectin, leptin, TNF-alpha and interleukin 2. Switch of therapy regimens with elimination of the most suspicious substances and certain protease inhibitors can lead to improvement of deranged metabolism. Also symptomatic therapy is possible to cope with hyperlipidemia and diabetes, although no effective treatment is available to reverse already existing lipodystrophy. Our knowledge about the pathogenesis of these alterations might lead to new concepts and causal therapy in the future.

Treatment failure after preceding protease inhibitors (PI) is often due to resistance mutations. Our objective was to evaluate amprenavir (APV) in pre-treated patients and to correlate it with pre-existing mutations. - Fourty five patients were entered in an open label prospective study (6/99-12/2000). Pre-treatment was 6.2 years +/- 2.4 (2-11.3) and included a mean of 4.13 nucleosides (RTIs) and 2.73 PIs. Genotypic resistance testing was performed prior to the switch. APV dose was 1200 mg/d in combination with ritonavir (RTV) boosting (2 x 100mg) and 2 x 1200 mg/d in 6 patients without RTV. Co-medication was selected based on treatment history and results of genotypic testing. - The median duration of treatment at analysis was 34 weeks. Plasma viral load (VL) average at baseline was 4.6 log subset 10 +/- 08. After 24 weeks the mean VL reduction was 1.4 log subset 10 +/- 1.2 3.86-0.40s). A VL reduction of1.5 log subset 10 was found in 16/45 patients (36%), 21/45 (47%) patients achieved a VL400 cp/ml, and 12/45 (27%) a VL50 cp/ml. CD4 cells increased from a mean baseline of 208/microl +/- 185 to 318/microl +/- 253. Fourty percent (18/45) of patients had a CD4 gain of more than 100 cells/microl. Genotypic resistance determination showed PI mutations in 87% of patients tested. The average number of mutated codons was 4.54. Three of 4 patients with I84V mutation did not achieve an undetectable VL. - Our findings demonstrate that APV and APV/RTV plus two additional antiretrovirals has a good virological and immunological success rate in pre-treated patients. Presence of more than two APV resistance mutations was associated with treatment failure.

In addition to readily controllable short-term side effects, highly active antiretroviral therapy (HAART) also has long-term side effects: lipodystrophy syndrome, hyperlipoproteinemia, insulin resistance, elevated glucose tolerance sometimes leading to diabetes mellitus and lactic acidosis. The pathogenesis remains uncertain although various hypotheses have been advanced. A number of approaches for the treatment of lipodystrophy are available, the effects of which, however, have not been confirmed by study results. Hyperlipoproteinemia probably means an increased cardiovascular risk, but a final pronouncement on this is not yet possible. Fibrates and statins are currently applied for treatment, but interactions with HAART medicaments have to be considered. HAART-induced diabetes mellitus presents clinically as type 2 diabetes, and is treated accordingly.

Objective: To identify risk factors for the development of lipodystrophy in HIV infected patients on highly active antiretroviral therapy. Methods: A survey among patients with HIV infection using an anonymous questionnaire was conducted in 10 European countries between December 1998 and December 1999. Nine hundred and four people receiving antiretrovirals, were included in the analyses. Results: 368 (41%) people reported an increase in abdominal girth since commencing current antiretroviral treatment. Breast enlargement was reported by 106 people (12%). Lipoatrophy signs were reported by approximately one-third of the people: 291 (32%) complained about decrease in facial fat and 300 (33%) reported decrease in buttock fat. One hundred and thirty-one (15%) people reported both lipoatrophy signs and an increase in abdominal girth (mixed lipodystrophy syndrome). In multivariate analysis, the development of the mixed lipodystrophy syndrome was associated with a longer use of indinavir (OR=1.03, 95% CI: 1.00–1.06), ritonavir (OR=1.06, 1.02–1.09) and stavudine (OR=1.05, 1.02–1.08) and also with age, a longer duration of HIV seropositivity and an advanced stage of HIV infection. Conclusions: This study suggests that multiple factors are associated with the occurrence of lipodystrophy, including the prolonged use of protease inhibitors.

Lipodystrophy resp. lipoatrophy and metabolic disorders under antiretroviral therapy are mainly imputed to protease inhibitors. Nucleoside-analogues are suspected to cause lactatea-cidosis as well. The treatment does not pursue standardized concepts. The lipodystrophic alterations which are not endangering the patient but are often cumbersome for him, can be met by PI-saving therapy in a few cases. Against hyperlipidemia cholesterol-synthesis inhibitors are currently debated. Diabetes-therapy follows the conventional concepts. In case of lactate-acidosis antiretroviral therapy must be discontinued temporarily.