Guidelines and practice of breastfeeding in women living with HIV-Results from the European INSURE survey.

INTRODUCTION: Antiretroviral therapy (ART) is integral to HIV prevention, including averting vertical transmission. The World Health Organization (WHO) recommends ART and breastfeeding for all women living with HIV for at least 12 months post-partum [1, 2]. Much of the data on HIV transmission through breastfeeding comes from low-resource settings, with a paucity of data on breastfeeding-related HIV transmission in women living with HIV in other settings. Women Against Viruses in Europe (WAVE), part of the European AIDS Clinical Society (EACS), aims to improve the standard of care for women living with HIV and sought to gain an understanding of breastfeeding guidelines and practice in women living with HIV across Europe. METHODS: A steering group convened by WAVE developed a survey to collate information on breastfeeding trends, practice, and guideline recommendations for women living with HIV in Europe and to establish interest in becoming involved in a collaborative breastfeeding network. The survey was disseminated to 31 countries in March 2022. RESULTS: In total, 25 eligible responses were received: 23/25 (92%) countries have HIV and pregnancy guidelines; 23/23 (100%) guidelines refer specifically to breastfeeding; 12/23 (52%) recommend against breastfeeding; 11/23 (48%) offer an option if certain criteria are met; 12/25 (48%) reported that the number of women living with HIV who breastfeed is increasing; 24/25 (96%) respondents were interested in joining a network on breastfeeding in women living with HIV. CONCLUSIONS: Recommendations vary, and nearly half of the guidelines recommend against breastfeeding. Many countries report an increase in breastfeeding. WAVE will establish a collaborative network to bridge data gaps, conduct research, and improve support for women living with HIV who choose to breastfeed.

[Consensus-Based Guidelines for Diagnosis, Prevention and Treatment of Tuberculosis in Children and Adolescents - A Guideline on Behalf of the German Society for Pediatric Infectious Diseases (DGPI)]. / S2k-Leitlinie zur Diagnostik, Prävention und Therapie der Tuberkulose im Kindes- und Jugendalter.

Recently, epidemiological data shows an increase of childhood tuberculosis in Germany. In addition to this, drug resistant tuberculosis becomes more frequent. Therefore, diagnosis, prevention and therapy in childhood and adolescence remain a challenge. Adult guidelines do not work for children, as there are age specific differences in manifestation, risk of progression and diagnostic as well as therapeutic pathways.The German Society for Pediatric Infectious Diseases (DGPI) has initiated a consensus-based (S2k) process and completed a paediatric guideline in order to improve and standardize care for children and adolescents with tuberculosis exposure, infection or disease.Updated dosage recommendations take age dependant pharmacokinetics in the treatment of drug sensitive but also drug resistant tuberculosis in account. In addition to this, there is a detailed chapter on perinatal exposure and disease as well as extrapulmonary manifestations.

[Postnatal therapy for congenital toxoplasmosis: a comparison of 2 different treatment approaches]. / Postnatale Therapie der konnatalen Toxoplasmose: Ein Vergleich zweier unterschiedlicher Vorgehensweisen.

Protocols recommended in the USA and Germany for the postnatal treatment of congenital toxoplasmosis are mainly based on the National Collaborative Chicago-based Congenital Toxoplasmosis Study that calls for daily administration of pyrimethamine in combination with sulfadiazine for several months, then 3 times a week. The recommended total duration of treatment is 12 months. This scheme necessitates frequent white blood cell counts that often result in the discontinuation of treatment because of severe neutropenia even with the concomitant administration of folinic acid. In contrast, the administration of pyrimethamine with sulfadoxine every 2 weeks for 2 years, as used by a referral centre in Toulouse, France, is associated with less toxicity. The efficacy may even be improved, as judged by the rate of new chorioretinal lesions. In the absence of larger randomised studies the Toulouse protocol appears to have several advantages when a decision has to be made to treat infants with congenital toxoplasmosis.

[Guideline for antiretroviral therapy of HIV-infected children and adolescents]. / Leitlinie der Pädiatrische Arbeitsgemeinschaft AIDS (PAAD) e.V. zur antiretroviralen Therapie bei HIV-infizierten Kindern und Jugendlichen (2011).

The HIV-infection in adults or children and adolescent differs substantially. Differences include the mode of infection, viral dynamics facing a developing immune system and the clinical course of the infection. In addition to the virological, immunological and epidemiological aspects the psychosocial situation is also very different. The above aspects and the decreased number of antiretroviral substances underline the need for specific guidelines for HIV-therapy in children and adolescents. The German Pediatric Working group AIDS (PAAD) has formulated this guideline in 2011 based on new study results, changes in international recommendations and newly available drugs.

Pharmacokinetic profile in late pregnancy and cord blood concentration of tipranavir and enfuvirtide.

The data on the use of tipranavir and enfuvirtide in pregnancy are very limited. We performed a pharmacokinetic profile in a pregnant woman with multidrug-resistant HIV-1 infection at 37 weeks gestation. Tipranavir levels were in the therapeutic range and the cord blood concentration at delivery was relatively high when compared with other protease inhibitors. No enfuvirtide was detected in the fetal compartment. Tipranavir and enfuvirtide were successfully used in pregnancy, but possible toxicities must be kept in mind.

Disease progression in HIV-1 infected children and adolescents--results of a German-Austrian cohort study.

OBJECTIVE: The Paediatric Working Group AIDS (PAAD) initiated a prospective cohort study in order to investigate disease progression in HIV- infected children and adolescents and the effect of antiretroviral treatment regimes. PATIENTS AND METHODS: Between 1998 and 2003, paediatric centres documented HIV-infected patients under clinical care using a questionnaire for basic data and annual follow up. Main outcome measures were: use of antiretroviral therapy, adverse events, disease progression and change of therapeutic regimes. RESULTS: 174 HIV- infected paediatric patients were followed up in 12 centres in Germany and Austria between 1998 and 2003. Initially 54 (31%) patients had no antiretroviral therapy, 35 (20%) received a two-drug regimen (ART) and 85 patients (49%) a highly active antiretroviral therapy (HAART>or=3 drugs). After an observation period of 5 years, 8 patients (4%) had no therapy, 17 (10%) were on ART and 134 patients on HAART (77%). The number of patients with salvage therapy (>or=4 drugs) increased from 5 (3%) to 15 patients (9%). 72 of 166 treated patients (43%) had no change of their drug regimes, 68 patients (41%) had one change and 26 patients (16%)>or=2 changes. Main reasons for changes were increased viral load (49%), immunologic deterioration (21%) and adverse events (14%). During the follow up period no patient died. According to the CDC classification, disease progression was seen in 48 of 174 patients (28%), of whom 20 had deteriorations of clinical categories (A, B, C) and 28 of immunologic categories. Using Kaplan-Meier curves, the mean time from study onset until change of clinical categories was 61 months for patients on HAART, 26 months for patients on ART and 14 months for patients without ART. CONCLUSION: In paediatric patients with HIV infection, disease progression has declined substantially by introduction of HAART. Superiority of HAART compared with ART was demonstrated. Non-adherence as well as other reasons for treatment failure have to be studied more carefully.

Increased rate of prematurity associated with antenatal antiretroviral therapy in a German/Austrian cohort of HIV-1-infected women.

OBJECTIVE: The aim of the study was to assess the risk of adverse pregnancy outcomes after antenatal antiretroviral therapy in a well-defined prospective cohort of nontransmitting HIV-infected women. METHODS: Prospective monitoring of 183 mother-child pairs from 13 centres in Germany and Austria, delivering between 1995 and 2001, was carried out. Following German-Austrian guidelines recommending an elective Caesarean section (CS) at 36 weeks, prematurity was defined as <36 weeks' gestation for these analyses. RESULTS: Of 183 mother-child pairs, 42% were exposed to antenatal monotherapy and 17% to dual therapy. Of the 75 women exposed to highly active antiretroviral therapy (HAART), 21 (28%) received protease inhibitor (PI)-based HAART and the remaining 54 received nonnucleoside reverse transcriptase inhibitor-based HAART. In multivariable analysis (176 pregnancies), PI-based HAART exposure during pregnancy was associated with an increased risk of premature delivery [adjusted odds ratio 3.40; 95% confidence interval (CI) 1.13-10.2; P=0.029, compared with monotherapy]. Congenital abnormalities affected 3.3% infants. Perinatally, 18.9% of children (34 of 179) had respiratory problems requiring interventions, which were associated with prematurity but not with type of treatment exposure. From adjusted regression analysis, the mean birth weight z-score for children exposed to HAART with PI (+0.46; 95% CI 0.01-0.92; P=0.047) or dual therapy (+0.43; 95% CI 0.03-0.82; P=0.034) was slightly but significantly higher than that for those exposed to monotherapy; head circumference was appropriate for gestational age and there were no significant differences between treatment groups. CONCLUSIONS: Use of antenatal PI-based HAART initiated before or during pregnancy was associated with a significantly increased risk of premature delivery at <36 weeks' gestation. The overall crude prematurity rate was 34% (63 of 183; 95% CI 28-42).

Lamivudine/abacavir maintains virological superiority over zidovudine/lamivudine and zidovudine/abacavir beyond 5 years in children.

OBJECTIVE: To describe the long-term efficacy over 5 years of regimens including combinations of abacavir, lamivudine and/or zidovudine in previously untreated children in the PENTA 5 trial. DESIGN: PENTA 5 was a 48-week randomised controlled trial comparing three dual nucleoside reverse transcriptase inhibitor (NRTI) combinations as part of first triple antiretroviral therapy (ART). METHODS: 128 ART-naïve children were randomised to zidovudine\lamivudine (n = 36), zidovudine\abacavir (45) or lamivudine\abacavir (47). Asymptomatic children (n = 55) were also randomised to nelfinavir or placebo; all other children received open-label nelfinavir. Analyses are intent-to-treat and adjusted for minor baseline imbalances and receipt of nelfinavir/placebo. RESULTS: Median follow-up was 5.8 years. By 5 years, 17 (47%), 28 (64%) and 18 (39%) children had changed their randomised NRTIs in the zidovudine\lamivudine, zidovudine\abacavir and lamivudine\abacavir groups respectively, but 18%, 50% and 50% of these changes were either early single drug substitutions for toxicity or switches with viral suppression (HIV-1 RNA < 400 copies/ml; e.g. to simplify regimen delivery). At 5 years, 55%/32% zidovudine\lamivudine, 50%/25% zidovudine\abacavir and 79%/63% lamivudine\abacavir had HIV-1 RNA < 400/< 50 copies/ml respectively (p = 0.03/p = 0.003). Mean increase in height-for-age 0.42, 0.68, 1.05 (p = 0.02); weight-for-age 0.03, 0.13, 0.75 (p = 0.02). Reverse transcriptase resistance mutations emerging on therapy differed between the groups: zidovudine\lamivudine (M41L, D67N, K70R, M184V, L210W, T215Y); zidovudine\abacavir (M41L, D67N, K70R, L210W, T215F/Y, K219Q); lamivudine\abacavir (K65R, L74V, Y115F, M184V). CONCLUSIONS: Five year data demonstrate that lamivudine\abacavir is more effective in terms of HIV-1 RNA suppression and growth changes, with lower rates of switching with detectable HIV-1 RNA than zidovudine\lamivudine or zidovudine\abacavir, and should be preferred as first-line NRTI backbone.

An effective and safe protocol involving zidovudine and caesarean section to reduce vertical transmission of HIV-1 infection.

OBJECTIVE: To investigate zidovudine prophylaxis with caesarean section to reduce mother-to-infant HIV transmission. INTERVENTIONS: Elective caesarean section before labour, usually at 36-38 weeks of gestation, plus a short oral course of zidovudine, normally starting at week 32, intravenous zidovudine before caesarean section and for 10 days for the neonate (the reduced Berlin regimen). RESULTS: Of 179 mother-infant pairs 104 received no antiretroviral prophylaxis or therapy (control group), 48 received the reduced Berlin prophylaxis regimen, 18 received combination therapy and nine received only part of the prophylaxis regimen. Of the antiretroviral group, 68 were delivered by elective caesarean section. The HIV transmission rate was zero in the antiretroviral group [95% confidence interval (CI) 0-4.7] and 12.6% (6.4-19.0) in the control group. The reduction in vertical transmission was 90% for the Berlin regimen, with an 80 and 70% reduction in risk associated with antiretroviral treatment and caesarean section, respectively. Maternal CD4 cell count but not viral load had some confounding effect on the reduction in risk attributed to caesarean section and the prophylactic regimen. Neonatal haematological abnormalities associated with antiretroviral intervention lasted for up to 7 weeks. Weight and length, although significantly lower at birth, were normal by 6-8 weeks. CONCLUSION: A much reduced three-arm regimen of zidovudine prophylaxis in combination with caesarean section before labour is highly effective in reducing the risk of vertical HIV transmission and is safe for the infant.

[Antiretroviral therapy in childhood]. / Antiretrovirale Therapie im Kindesalter.

The natural course of mostly perinatally acquired childhood HIV infection shows some special characteristics. Compared to adults the initial viral load is higher, persists for a longer period of time and without antiretroviral therapy up to 20% of infected children develop AIDS within the first year of life. It is therefore desirable to stop disease progression before an irreversible deterioration of the immune system has occurred by initiating early antiretroviral therapy. The choice of antiretroviral agents is difficult because data from adult studies cannot be directly applied to infants and data on antiretroviral therapy in pediatric patients are limited. The current national and international guidelines for antiretroviral therapy in perinatally acquired HIV infection are discussed.

A case of cow's milk allergy in the neonatal period--evidence for intrauterine sensitization?

Clinical manifestations of cow's milk allergy rarely occur in the first days after birth. We report on a newborn presenting with hemorrhagic meconium in the first hour of life followed by bloody diarrhea in the next few days. At day 14, an elevated total IgE, specific IgE to cow's milk and an eosinophilia in peripheral blood were found. Symptoms disappeared when the milk feed was changed to an extensively hydrolyzed casein-formula. Two challenges with cow's milk formula (on day 30 and at 7 months of age) were followed by recurrence of vomiting, watery diarrhea and failure to thrive. At the age of 17 months cow's milk was tolerated well. Although other pathogenetic mechanisms cannot completely be ruled out, there is strong evidence that cow's milk allergy--induced by intra-uterine sensitization--explains the symptoms in our patient. In conclusion, cow's milk allergy can occur even in the first days of life, and our clinical observation supports the concept of intra-uterine sensitization to allergens.