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.

[Specific concepts of care for pregnant women with drug addiction or HIV infection]. / Spezifische Betreuungskonzepte für schwangere Frauen mit Sucht- bzw. HIV-Konflikten.

In the last 10 years about 130 women with a drug addiction and more than 100 HIV-positive pregnant women were treated at the 1. University Hospital of Obstetrics and Gynaecology in Munich. Besides a specialized medical treatment both groups required intensive psychosocial care. HIV-infected people are still isolated and suffer from the social stigmata. Their essential needs for sexuality and children of their own are often ignored or even condemned because of irrational fears about HIV, which continue despite rapid medical improvements. The life-expectancy for example has increased since the inauguration of protease inhibitors. Vertical transmission of HIV is below 2% through medical treatment in pregnancy, elective cesarean section and renunciation of breastfeeding. Drug addicted pregnant women are given the opportunity to change their life in order to care for their children appropriately. The basis for this is a substitution with levomethadone and elimination of the use of other drugs. The addicted women often can reduce the dosage of levomethadone during the course of their pregnancy and sometimes can cease totally. Normally they are highly motivated and thus can ease the withdrawal symptoms of their newborns following delivery. By establishing a reliable social net during pregnancy mothers learn to recognize the demands of their children after birth and thus emotional and cognitive deficits can be prevented.

Detection of cervical antibodies to human papillomavirus type 16 (HPV-16) capsid antigens in relation to detection of HPV-16 DNA and cervical lesions.

A more sensitive luminescence immunoassay (LIA) for human papillomavirus type 16 (HPV-16) was developed and used to measure HPV-16 antibodies in cervical samples from 292 college-aged women who were examined at 4-month intervals. Of the 609 collected samples, IgG, IgA, and secretory piece-associated antibodies to HPV-16 were detected in 12%, 6%, and 8%, respectively, of samples tested. Cervical IgG antibodies were most strongly associated with HPV-16 DNA detected within the previous 12 months (odds ratio, 3.3; 95% confidence interval, 1.4-7.8). Secretory IgA (cervical IgA- and secretory piece-positive) was most strongly associated with detection of a squamous intraepithelial lesions 4-8 months earlier (odds ratio, 6.4; 95% confidence interval, 1.9-21.8). As with serum HPV-16 antibodies, there appears to be a several-month delay between cervical HPV infection and detection of cervical antibodies.

Complications after caesarean section in HIV-1-infected women not taking antiretroviral treatment.

HIV-1-infected women have a considerably increased risk of postoperative morbidity after caesarean sections. We showed that this risk was independent of current antiretroviral therapy.

Genital human papillomavirus infection in women who have sex with women.

Genital infection with human papillomavirus (HPV), as determined by polymerase chain reaction detection of HPV DNA and prevalence of HPV-6 and -16 serum antibodies, was investigated in 149 women who were sexually active with women. By use of HPV L1 consensus primers and hybridization to types 6/11, 16, 18, 31/33/35/39, and 45 and a generic probe, HPV DNA was detected in 30% of subjects; of these, 20% had type 31/33/35/39, 18% had type 16, and 2% had type 6/11. Of 21 subjects reporting no prior sex with men, HPV DNA was detected in 19% and squamous intraepithelial lesions in 14%. By capture ELISA with HPV-6 and -16 L1 capsids, 47% of subjects were seropositive for HPV-16 and 62% for HPV-6. Current smoking was associated with detectable HPV DNA. Genital HPV infection and squamous intraepithelial lesions are common among women who are sexually active with women and occur among those who have not had sex with men.

HLA-A2-restricted peripheral blood cytolytic T lymphocyte response to HPV type 16 proteins E6 and E7 from patients with neoplastic cervical lesions.

The DNA from human papillomavirus (HPV) can be detected in 90% of cervical carcinomas. To address whether patients infected with HPV can mount efficient T cell responses to this pathogen we examined the cytotoxic T lymphocyte (CTL) response of peripheral blood mononuclear cells (PBMC) from patients with abnormal genital epithelial cells. PBMC from 11 HLA-A2+ patients were stimulated with CaSki, a cervical carcinoma cell line that is HPV 16+ and HLA-A2+. The CTL were screened for reactivity to the cervical carcinoma cell line C33A (HPV-, HLA-A2+) transfected with the HPV 16 E6 or E7 genes or the plasmid without insert. The CTL of 1 patient showed particularly strong CaSki and HPV E6 or E7 protein-specific cytotoxicity in a HLA-A2+-restricted fashion. In contrast, these CTL lysed neither a vector-only transfectant, the natural killer cell (NK) target, K562 nor the lymphokine-activated killer cell (LAK) target, Daudi. HLA-A2 restriction was demonstrated by the lack of recognition of a HLA-A2- CaSki cell line developed in our laboratory. The CTL line was cloned and 99 clones were harvested and screened; 51 clones lysed CaSki, of which 17 did not lyse the A2- CaSki. Of these HLA-A2- restricted clones, 8 did not lyse C33A transfectants, 6 lysed all C33A transfectants, 3 lysed C33A-E7 only and none lysed C33A-E6 only. These data imply that, within the bulk CTL line, HLA-A2-restricted recognition of antigens was restricted to CaSki antigens, antigens common to cervical carcinoma (CaSki plus C33A), or HPV-16-E7-derived antigen on the clonal level. The E7-restricted clones were negative for recognition of known HLA-A2-binding peptides from E7.

Efficacy trial of topically administered interferon gamma-1 beta gel in comparison to laser treatment in cervical intraepithelial neoplasia.

OBJECTIVE: Dose dependent response of cervical intraepithelial neoplasia (CIN) to topically administered interferon (IFN) gamma was assessed and compared with conventional laser therapy. PATIENT AND METHODS: 33 women were included in a randomized phase II trial which was double blinded for IFN dosages. Twenty-four patients received IFN gamma-1 beta gel and a control group of nine patients was treated with laser surgery. 18 patients had smears suggesting CIN II and 15 patients had smears suggesting CIN III. The response was assessed 6 months after starting of IFN gamma-1 beta treatment or having laser surgery. RESULTS: Topical IFN gamma-1 beta treatment gave a cure rate of 42% independent of IFN dosage as compared to an 89% cure rate with laser therapy (P = 0.02). Patients with CIN II responded better compared with patients with CIN III. Current smokers showed a significantly lower cure rate whereas use of oral contraceptives (OC) did not influence response. High viral load with high risk types of human papillomaviruses (HPV) was associated with a better response.