Not Recommended, But Done: Breastfeeding with HIV in Germany.

Breastfeeding (BF) in mothers living with HIV (MLWH) is still discussed controversially in resource-rich settings. In Germany, where formula feeding is recommended for MLWH single BF cases have been reported, but no systematic data collection and analysis are available so far. This study, titled HELENE, aims to fill this data gap. A questionnaire covering the course of BF was distributed by a graduate student visiting each study site. Information was collected from patient files and by personal communication with the health care provider. Primary study objectives were the duration of BF and the maternal antiretroviral treatment (ART). Fifteen treatment centers across Germany contributed a total of 42 BF cases, observed from May 2009 to July 2020. There was an increasing number of BF cases over time. The median duration of BF was 20 weeks varying from single BF of colostrum to 104 weeks. All BF women except one elite controller received ART: 39% non-nucleoside reverse transcriptase inhibitor-, 37% INSTI-, 29% protease inhibitor-based regimens; one woman was on maraviroc. Thirty-nine percent of the ART regimens included drugs that were not recommended by the German-Austrian pregnancy guidelines. Our findings highlight the diversity of BF cases in Germany in terms of duration, maternal ART, and monitoring. Since the number of BF cases is increasing, guidelines are obliged to implement more detailed recommendations on BF, the monitoring of BF mothers, and the follow-up of the infants. There is an urgent need for prospective national and European data collections to further improve HIV prevention of mother-to-child transmission (PMTCT) in the setting of BF.

Genetic CD21 deficiency is associated with hypogammaglobulinemia.

BACKGROUND: Complement receptor 2 (CR2/CD21) is part of the B-cell coreceptor and expressed by mature B cells and follicular dendritic cells. CD21 is a receptor for C3d-opsonized immune complexes and enhances antigen-specific B-cell responses. OBJECTIVE: Genetic inactivation of the murine CR2 locus results in impaired humoral immune responses. Here we report the first case of a genetic CD21 deficiency in human subjects. METHODS: CD21 protein expression was analyzed by means of flow cytometry and Western blotting. CD21 transcripts were quantified by using real-time PCR. The CD21 gene was sequenced. Wild-type and mutant CD21 cDNA expression was studied after transfection of 293T cells. Binding of EBV-gp350 or C3d-containing immune complexes and induction of calcium flux in CD21-deficient B cells were analyzed by means of flow cytometry. Antibody responses to protein and polysaccharide vaccines were measured. RESULTS: A 28-year-old man presented with recurrent infections, reduced class-switched memory B cells, and hypogammaglobulinemia. CD21 receptor expression was undetectable. Binding of C3d-containing immune complexes and EBV-gp350 to B cells was severely reduced. Sequence analysis revealed a compound heterozygous deleterious mutation in the CD21 gene. Functional studies with anti-immunoglobulin- and C3d-containing immune complexes showed a complete loss of costimulatory activity of C3d in enhancing suboptimal B-cell receptor stimulation. Vaccination responses to protein antigens were normal, but the response to pneumococcal polysaccharide vaccination was moderately impaired. CONCLUSIONS: Genetic CD21 deficiency adds to the molecular defects observed in human subjects with hypogammaglobulinemia.

Switching to atazanavir improves metabolic disorders in antiretroviral-experienced patients with severe hyperlipidemia.

OBJECTIVE: To describe the efficacy and change in lipid profile in patients with severe hyperlipidemia after switch to an atazanavir-containing highly active antiretroviral therapy regimen. DESIGN AND METHODS: Open-field, 24-week, prospective observational cohort study including 33 HIV-infected, antiretroviral-experienced patients with hyperlipidemia. Changes in lipid profiles were evaluated by analyses of triglycerides, total cholesterol, high- and low-density lipoprotein (HDL and LDL) cholesterol, and efficacy by HIV RNA and CD4 cell changes, both from baseline to week 24. RESULTS: A rapid and significant decrease of 46% (5.81 +/- 4 mmol/L vs. 3.16 +/- 2.6 mmol/L, P = 0.002) in triglyceride levels was shown. Similarly, a sustained improvement of 18% was observed in total cholesterol levels during the first 24 weeks after switching to atazanavir (6.45 +/- 1.9 mmol/L vs. 5.3 +/- 1.3 mmol/L, P = 0.001). After 24 weeks of treatment there was a significant decrease of 22% in non-HDL cholesterol (5.76 +/- 1.9 mmol/L at baseline vs. 4.5 +/- 1.3 mmol/L at 24 weeks; P = 0.003). HDL and LDL cholesterol profiles did not change significantly as did the viral load or CD4 cell count. CONCLUSIONS: Switching to atazanavir results in a significant improvement in HIV therapy-induced hyperlipidemia. A switch to atazanavir is proposed as a valuable option to improve atherogenic lipid profiles while maintaining virologic control.