German-Austrian recommendations for HIV-therapy in pregnancy and in HIV-exposed newborn - update 2005.

In Germany during the last years about 200-250 HIV 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 HIV infection was known during pregnancy, since 1995 the rate of vertical transmission of HIV 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 HIV infected mother. To keep pace with new results in research, approval of new anti-retroviral drugs and changes in the general treatment recommendations for HIV infected adults, in 1998, 2001 and 2003 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 third update became necessary in 2005. The updating process was started in January 2005 and was terminated in September 2005. The guidelines provide new recommendations on the indication and the starting point for 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 HIV-transmission should be further maintained.

Reproductive assistance to HIV-discordant couples--the German approach.

An estimated 35 000 Germans are infected with HIV, and 75% of these are of childbearing age. Couples with one infected partner are faced with the risk of infection of the healthy partner. By using assisted reproduction techniques (ART) and virus-free sperm it is possible to fulfil the desire for children while minimising the risk of acquisition of infection. Therefore since 1991 in Germany ART is offered to couples of HIV-positive males and seronegative females. However, established programmes in different centres were temporarily suspended due to serious doubts about the reliability and safety of the sperm preparation technique (density gradient centrifugation and swim-up). -. Since 1997 processed sperm samples are routinely tested for HIV by highly sensitive detection methods and cryopreserved. Only if the test is negative are the processed spermatozoa used for homologous insemination, in-vitro fertilization or intracytoplasmatic sperm injection. This procedure removes most medical as well as legal considerations. At present 3 reproductive units in Germany offer reproductive assistance to HIV-discordant couples, and a further 9 institutions plan to establish that procedure. From 1991 to 1999, 54 women were treated by ART. 30 pregnancies occurred and 24 children were born. So far no maternal or infant infection was observed after treatment.

Improvement of immune functions in HIV infection by sulfur supplementation: two randomized trials.

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.

Massive loss of sulfur in HIV infection.

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.

[Prenatal care of a HIV-1-positive pregnancy and birth]. / Die Betreuung der HIV-1-positiven Schwangerschaft und Geburt.

Mother-to-child (vertical) transmission of the human immunodeficiency virus type-1 (HIV-1) is now the main route of infection in HIV-positive children. Without any medical measures and avoiding breastfeeding the rate of vertical HIV-1-transmission is 15-20% in Europe. The rate of vertical HIV-transmission in the German centers is today approximately 2%. This low risk is the result of interdisciplinary prenatal care, antiretroviral therapy according to the individual risk profile as well as cesarean section before onset of labor, and antiretroviral treatment of neonates in the centers.

[Incidence of congenital infections]. / Untersuchung zur Häufigkeit konnataler Infektionen.

The discussions on the pros and cons of obstetric screening for connatal infections have been going on for years. We, therefore, conducted a prevalence study of the most common connatal infections. HIV infection, rubella and syphilis were not subjects of this study. We analysed the relevance of these infections in 512 pregnant women and their newborn infants at the moment of delivery. Further serological tests were run three months post partum, if necessary even for a longer period. Cytomegaly IgG antibodies were found in 46% of the examined women, IgM antibodies in 1.3%. Women under the age of twenty and women of low social standing showed the highest rate of prevalence of infection with CMV. The prevalence of IgG antibodies against parvovirus B 19 was 29%. In 10 mothers, positive IgM titers were found at the time of delivery. In all these women, pregnancies had been uneventful. However, 9 mothers exhibited a significantly raised abortion rate within the last 20 months before delivery. 7 of 512 women turned out to be HBs antigen carriers, 3 women and their babies were anti-HCV positive. The prevalence of toxoplasmosis IgG antibodies was 36%, of IgM antibodies 5.3%. By further investigation (Toxo ISAGA, Toxo IgA) we were able to detect one child with connatal toxoplasmosis. We conclude, that screening for parvovirus B 19 and hepatitis C is required only, if there are contact or clinical hints that the patients might have acquired either one of these infections. But we postulate, that a routine screening programme for hepatitis B and toxoplasmosis should be carried out in all pregnant women.(ABSTRACT TRUNCATED AT 250 WORDS)