To determine the therapeutic effect of sulfur amino acid supplementation in HIV infection we randomized 40 patients with antiretroviral therapy (ART; study 1) and 29 patients without ART (study 2) to treatment for 7 months with N-acetyl-cysteine or placebo at an individually adjusted dose according to a defined scheme. The main outcome measures were the change in immunological parameters including natural killer (NK) cell and T cell functions and the viral load. Both studies showed consistently that N-acetyl-cysteine causes a marked increase in immunological functions and plasma albumin concentrations. The effect of N-acetyl-cysteine on the viral load, in contrast, was not consistent and may warrant further studies. Our findings suggest that the impairment of immunological functions in HIV+ patients results at least partly from cysteine deficiency. Because immune reconstitution is a widely accepted aim of HIV treatment, N-acetyl-cysteine treatment may be recommended for patients with and without ART. Our previous report on the massive loss of sulfur in HIV-infected subjects and the present demonstration of the immunoreconstituting effect of cysteine supplementation indicate that the HIV-induced cysteine depletion is a novel mechanism by which a virus destroys the immune defense of the host and escapes immune elimination.

Skeletal muscle tissue from SIV-infected macaques was previously found to contain abnormally high sulfate and low glutathione levels indicative of an excessive cysteine catabolism. We now confirm the peripheral tissue as a site of massive cysteine catabolism in HIV infection and have determined the urinary loss of sulfur per time unit. The comparison of the sulfate concentrations of the arterial and venous blood from the lower extremities of 16 symptomatic HIV+ patients and 18 HIV- control subjects (study 1) revealed (1) that the peripheral tissue of HIV+ patients with or without highly active antiretroviral therapy (HAART) releases large amounts of sulfate and (2) that plasma sulfate, thioredoxin, and interleukin-6 levels are elevated in these patients. A complementary investigation of 64 asymptomatic HIV+ patients and 65 HIV- subjects (study 2) revealed increased plasma sulfate levels in the asymptomatic patients. The analysis of the daily urinary excretion of sulfate and urea of another group of 19 HIV+ patients and 22 healthy HIV- subjects (study 3) confirmed (1) that HIV+ patients experience a massive loss of sulfur and (2) that this loss is not ameliorated by HAART. The sulfur loss of asymptomatic patients was equivalent to a mean loss of about 10 g of cysteine per day. If extrapolated, this would correspond to an alarming negative balance of approximately 2 kg of cysteine per year under the assumption that the normal sulfate excretion equivalent to approximately 3 g of cysteine per day is balanced by a standard Western diet. The abnormally high sulfate/urea ratio suggests that this process drains largely the glutathione pool.

To determine the therapeutic effect of sulfur amino acid supplementation in HIV infection we randomized 40 patients with antiretroviral therapy (ART; study 1) and 29 patients without ART (study 2) to treatment for 7 months with N-acetyl-cysteine or placebo at an individually adjusted dose according to a defined scheme. The main outcome measures were the change in immunological parameters including natural killer (NK) cell and T cell functions and the viral load. Both studies showed consistently that N-acetyl-cysteine causes a marked increase in immunological functions and plasma albumin concentrations. The effect of N-acetyl-cysteine on the viral load, in contrast, was not consistent and may warrant further studies. Our findings suggest that the impairment of immunological functions in HIV+ patients results at least partly from cysteine deficiency. Because immune reconstitution is a widely accepted aim of HIV treatment, N-acetyl-cysteine treatment may be recommended for patients with and without ART. Our previous report on the massive loss of sulfur in HIV-infected subjects and the present demonstration of the immunoreconstituting effect of cysteine supplementation indicate that the HIV-induced cysteine depletion is a novel mechanism by which a virus destroys the immune defense of the host and escapes immune elimination.

German-Austrian recommendations for HIV1-therapy in pregnancy - Update 2008 Bernd Buchholz (University Medical Centre Mannheim, Pediatric Clinic), Matthias Beichert (Mannheim, Gynecology and Obstetrics Practice), Ulrich Marcus (Robert Koch Institute, Berlin), Thomas Grubert, Andrea Gingelmaier (Gynecology Clinic of the Ludwig Maximilians University of Munich), Dr. med. Annette Haberl (HIV-Department, J. W. Goethe-University Hospital, Frankfurt), Dr. med. Brigitte Schmied (Otto-Wagner Spital, Wien). In Germany during the last years about 200-250 HIV1-infected pregnant women delivered a baby each year, a number that is currently increasing. To determine the HIV-status early in pregnancy voluntary HIV-testing of all pregnant women is recommended in Germany and Austria as part of prenatal care. In those cases, where HIV1-infection was known during pregnancy, since 1995 the rate of vertical transmission of HIV1 was reduced to 1-2%. This low transmission rate has been achieved by the combination of anti-retroviral therapy of pregnant women, caesarean section scheduled before onset of labour, anti-retroviral post exposition prophylaxis in the newborn and refraining from breast-feeding by the HIV1-infected mother. To keep pace with new results in research, approval of new anti-retroviral drugs and changes in the general treatment recommendations for HIV1-infected adults, in 1998, 2001, 2003 and 2005 an interdisciplinary consensus meeting was held. Gynaecologists, infectious disease specialists, paediatricians, pharmacologists, virologists and members of the German AIDS Hilfe (NGO) were participating in this conference to update the prevention strategies. A fifth update became necessary in 2008. The updating process was started in January 2008 and was terminated in September 2008. The guidelines provide new recommendations on the indication and the starting point for HIV-therapy in pregnancies without complications, drugs and drug combinations to be used preferably in these pregnancies and updated information on adverse effects of anti-retroviral drugs. Also the procedures for different scenarios and risk constellations in pregnancy have been specified again. With these current guidelines in Germany and Austria the low rate of vertical HIV1-transmission should be further maintained.

Fragestellung: Ziel der Untersuchung war, durch die Analyse der Schwangerschaftsverläufe HIV-infizierter Frauen und deren kindlichem Outcome an 10 deutschen gynäkologisch-geburtshilflichen HIV-Schwerpunktzentren die aufgetretenen Komplikationen und die resultierende Rate der vertikalen Transmission zu eruieren. Patientinnen und Methodik: Es wurden insgesamt 599 Schwangerschaften HIV-infizierter Mütter aus den Jahren 1999 -2003 aus 10 Einrichtungen der Schwerpunktversorgung in die Untersuchung aufgenommen. Folgende Parameter wurden hierbei erfasst: Infektionsmodus und -zeitpunkt der Mutter, Entbindungsmodus und Gestationsalter bei Geburt, CD4-Zellzahl bei Feststellung der Schwangerschaft sowie peripartal, Viruslast im Verlauf, ART (antiretrovirale Therapie) zuvor, ART in der Schwangerschaft, Schwangerschaftskomplikationen sowie kindlicher Infektionsstatus und allgemeiner kindlicher Gesundheitszustand. Ergebnisse: In 55 % der Fälle wurden eine oder mehrere Schwangerschaftskomplikationen dokumentiert, am häufigsten vorzeitige Wehentätigkeit (21,4%) und vorzeitiger Blasensprung (4,7 %). 595/599 Schwangerschaften endeten mit einer Lebendgeburt; davon wurden 98,3 % per Sectio caesarea entbunden. 20,3% der Schwangeren erlitten eine Frühgeburt. Fast 50 % der Frauen benötigten eine hochaktive antiretrovirale Mehrfachtherapie (HAART). Die kindliche Infektionsrate betrug 1,68 % (10 Kinder). Schlussfolgerung: Die Ergebnisse zeigen, dass eine in Abstract Objective: The study was performed to evaluate the course of pregnancies of HIV-infected women and their fetal outcome at 10 German reference gynecology/obstetrics departments to provide an overview of occurring complications and the rate of mother-to-child transmission (MTCT). Material and Methods: 599 pregnancies of HIV-infected mothers in the years 1999 -2003 at 10 German reference gynecology/obstetrics departments were recruited for evaluation. Data collected were: mode and time of infection and time of first diagnosis, mode and week of delivery, CD4 count and viral load at diagnosis of pregnancy and at delivery, antiretroviral therapy before and during pregnancy, pregnancy complications, fetal infection and general health status. Results: 595/599 pregnancies resulted in a live birth delivered in 98.3 % by cesarean section. In 55 % of the pregnancies one or more complications were documented. The most common were premature contractions (21.4 %) and premature rupture of the membranes (4.7 %). 20.3 % of the pregnant women delivered prematurely. Almost 50% of the women needed a highly active antiretroviral combination therapy (HAART). The vertical transmission rate was found to be 1.68 % (10 children). Conclusions:The study shows that the rate of mother-to-child transmission (MTCT) finally resulting after therapy according to the German-Austrian recommendations for HIV therapy in pregnancy is very low (under 2 %). Nevertheless, in order to achieve Originalarbeit 1058