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.

Treatment Intensification in HIV-Infected Patients Is Associated With Reduced Frequencies of Regulatory T Cells.

In untreated HIV infection, the efficacy of T cell responses decreases over the disease course, resulting in disease progression. The reasons for this development are not completely understood. However, immunosuppressive cells are supposedly crucially involved. Treatment strategies to avoid the induction of these cells preserve immune functions and are therefore the object of intense research efforts. In this study, we assessed the effect of treatment intensification [=5-drug antiretroviral therapy (ART)] on the development of suppressive cell subsets. The New Era (NE) study recruited patients with primary HIV infection (PHI) or chronically HIV-infected patients with conventional ART (CHI) and applied an intensified 5-drug regimen containing maraviroc and raltegravir for several years. We compared the frequencies of the immune suppressive cells, namely, the myeloid-derived suppressor cells (MDSCs), regulatory B cells (Bregs), and regulatory T cells (Tregs), of the treatment intensification patients to the control groups, especially to the patients with conventional 3-drug ART, and analyzed the Gag/Nef-specific CD8 T cell responses. There were no differences between PHI and CHI in the NE population (p > 0.11) for any of the studied cell types. Polymorphonuclear myeloid-derived suppressor cell (PMN-MDSC), monocytic myeloid-derived suppressor cell (M-MDSC), and the Breg frequencies were comparable to those of patients with a 3-drug ART. However, the Treg levels were significantly lower in the NE patients than those in 3ART-treated individuals and other control groups (p ≤ 0.0033). The Gag/Nef-specific CD8 T cell response was broader (p = 0.0134) with a higher magnitude (p = 0.026) in the NE population than that in the patients with conventional ART. However, we did not find a correlation between the frequency of the immune suppressive cells and the interferon-gamma+ CD8 T cell response. In the treatment intensification subjects, the frequencies of the immune suppressive cells were comparable or lower than those of the conventional ART-treated subjects, with surprisingly broad HIV-specific CD8 T cell responses, suggesting a preservation of immune function with the applied treatment regimen. Interestingly, these effects were seen in both treatment intensification subpopulations and were not attributed to the start of treatment in primary infection.

Effects of Prednisolone on Disease Progression in Antiretroviral-Untreated HIV Infection: A 2-Year Randomized, Double-Blind Placebo-Controlled Clinical Trial.

BACKGROUND: HIV-disease progression correlates with immune activation. Here we investigated whether corticosteroid treatment can attenuate HIV disease progression in antiretroviral-untreated patients. METHODS: Double-blind, placebo-controlled randomized clinical trial including 326 HIV-patients in a resource-limited setting in Tanzania (clinicaltrials.gov NCT01299948). Inclusion criteria were a CD4 count above 300 cells/µl, the absence of AIDS-defining symptoms and an ART-naïve therapy status. Study participants received 5 mg prednisolone per day or placebo for 2 years. Primary endpoint was time to progression to an AIDS-defining condition or to a CD4-count below 200 cells/µl. RESULTS: No significant change in progression towards the primary endpoint was observed in the intent-to-treat (ITT) analysis (19 cases with prednisolone versus 28 cases with placebo, p = 0.1407). In a per-protocol (PP)-analysis, 13 versus 24 study participants progressed to the primary study endpoint (p = 0.0741). Secondary endpoints: Prednisolone-treatment decreased immune activation (sCD14, suPAR, CD38/HLA-DR/CD8+) and increased CD4-counts (+77.42 ± 5.70 cells/µl compared to -37.42 ± 10.77 cells/µl under placebo, p < 0.0001). Treatment with prednisolone was associated with a 3.2-fold increase in HIV viral load (p < 0.0001). In a post-hoc analysis stratifying for sex, females treated with prednisolone progressed significantly slower to the primary study endpoint than females treated with placebo (ITT-analysis: 11 versus 21 cases, p = 0.0567; PP-analysis: 5 versus 18 cases, p = 0.0051): No changes in disease progression were observed in men. CONCLUSIONS: This study could not detect any significant effects of prednisolone on disease progression in antiretroviral-untreated HIV infection within the intent-to-treat population. However, significant effects were observed on CD4 counts, immune activation and HIV viral load. This study contributes to a better understanding of the role of immune activation in the pathogenesis of HIV infection. TRIAL REGISTRATION: ClinicalTrials.gov NCT01299948.

Dihydrocodeine/Agonists for alcohol dependents.

OBJECTIVE: Alcohol addiction too often remains insufficiently treated. It shows the same profile as severe chronic diseases, but no comparable, effective basic treatment has been established up to now. Especially patients with repeated relapses, despite all therapeutic approaches, and patients who are not able to attain an essential abstinence to alcohol, need a basic medication. It seems necessary to acknowledge that parts of them need any agonistic substance, for years, possibly lifelong. For >14 years, we have prescribed such substances with own addictive character for these patients. METHODS: We present a documented best possible practice, no designed study. Since 1997, we prescribed Dihydrocodeine (DHC) to 102 heavily alcohol addicted patients, later, also Buprenorphine, Clomethiazole (>6 weeks), Baclofen, and in one case Amphetamine, each on individual indication. This paper focuses on the data with DHC, especially. The Clomethiazole-data has been submitted to a German journal. The number of treatments with the other substances is still low. RESULTS: The 102 patients with the DHC treatment had 1367 medically assisted detoxifications and specialized therapies before! The 4 years-retention rate was 26.4%, including 2.8% successfully terminated treatments. In our 12-steps scale on clinical impression, we noticed a significant improvement from mean 3.7 to 8.4 after 2 years. The demand for medically assisted detoxifications in the 2 years remaining patients was reduced by 65.5%. Mean GGT improved from 206.6 U/l at baseline to 66.8 U/l after 2 years. Experiences with the other substances are similar but different in details. CONCLUSION: Similar to the Italian studies with GHB and Baclofen, we present a new approach, not only with new substances, but also with a new setting and much more trusting attitude. We observe a huge improvement, reaching an almost optimal, stable, long term status in around 1/4 of the patients already. Many further optimizations are possible.

HIV patients treated with low-dose prednisolone exhibit lower immune activation than untreated patients.

BACKGROUND: HIV-associated general immune activation is a strong predictor for HIV disease progression, suggesting that chronic immune activation may drive HIV pathogenesis. Consequently, immunomodulating agents may decelerate HIV disease progression. METHODS: In an observational study, we determined immune activation in HIV patients receiving low-dose (5 mg/day) prednisolone with or without highly-active antiretroviral therapy (HAART) compared to patients without prednisolone treatment. Lymphocyte activation was determined by flow cytometry detecting expression of CD38 on CD8(+) T cells. The monocyte activation markers sCD14 and LPS binding protein (LBP) as well as inflammation markers soluble urokinase plasminogen activated receptor (suPAR) and sCD40L were determined from plasma by ELISA. RESULTS: CD38-expression on CD8+ T lymphocytes was significantly lower in prednisolone-treated patients compared to untreated patients (median 55.40% [percentile range 48.76-67.70] versus 73.34% [65.21-78.92], p = 0.0011, Mann-Whitney test). Similarly, we detected lower levels of sCD14 (3.6 µg/ml [2.78-5.12] vs. 6.11 µg/ml [4.58-7.70]; p = 0.0048), LBP (2.18 ng/ml [1.59-2.87] vs. 3.45 ng/ml [1.84-5.03]; p = 0.0386), suPAR antigen (2.17 µg/ml [1.65-2.81] vs. 2.56 µg/ml [2.24-4.26]; p = 0.0351) and a trend towards lower levels of sCD40L (2.70 pg/ml [1.90-4.00] vs. 3.60 pg/ml [2.95-5.30]; p = 0.0782). Viral load in both groups was similar (0.8 × 105 ng/ml [0.2-42.4 × 105] vs. 1.1 × 105 [0.5-12.2 × 105]; p = 0.3806). No effects attributable to prednisolone were observed when patients receiving HAART in combination with prednisolone were compared to patients who received HAART alone. CONCLUSIONS: Patients treated with low-dose prednisolone display significantly lower general immune activation than untreated patients. Further longitudinal studies are required to assess whether treatment with low-dose prednisolone translates into differences in HIV disease progression.

Low dose prednisolone reduces CD4+ T cell loss in therapy-naive HIV-patients without antiretroviral therapy.

BACKGROUND: A favorable development of CD4+ T cells was noticed in therapy-naive HIV-patients without antiretroviral therapy (ART) taking 5 mg prednisolone daily. Based on these encouraging observations, prednisolone therapy in further HIV-patients without antiretroviral therapy was initiated. OBJECTIVE: To evaluate the effect of low dose prednisolone on therapy-naive HIV patients without antiretroviral therapy. METHODS: A retrospective analysis has been conducted comparing the development of CD4+ T cells, viral load and clinical outcome in all therapy-naive HIV-patients with (n = 65; CD4 > or =300/microl) or without (n = 136; CD4 > or =300/microl) prednisolone treatment for > or =6 months. RESULTS: After 3 years, therapy-naive patients on prednisolone therapy showed a CD4+ T cell increase of +50.1/microl whereas in the untreated group a decrease of -186.1/microl (p = 0.0021) was noted. After 12 months, nearly twice as much untreated patients experienced a first-time CD4+ T cell loss of >100/microl or initiation of HAART due to clinical development compared to prednisolone-treated patients (64.1% vs. 35.0%). CD4+ T cell increase was associated with viral load at baseline: Patients with lower viral loads at baseline (<30,000 copies/ml) showed a favorable development with statistically significant less drop-outs (defined as HAART-onset and/or prednisolone discontinuation for the prednisolone group) than patients with higher viral loads at baseline in the first 3 years in the prednisolone group. - CONCLUSION: Low dose prednisolone seems to be associated with a stabilization of CD4+ T cell count in therapy-naive HIV patients resulting in a pronounced prolongation of the potential time without HAART for many HIV patients.