Cabotegravir and rilpivirine long acting injectables in a pregnant woman living with HIV.

This case report describes bimonthly LAI CAB/RPV prior to and throughout pregnancy. CAB concentration was comparable to non-pregnant individuals, RPV was 70-75% lower. No virologic failure orvertical transmission occurred. Despite placental transfer, no congenital malformations were noted. Bimonthly CAB/RPV LAI may not be suitable for pregnant women and monitoring of exposed infants is warranted.

Humoral response to SARS-CoV-2 vaccines in people living with HIV.

PURPOSE: To describe the humoral immune response to COVID-19 vaccines in people living with HIV and identify factors associated with the magnitude of anti-SARS-CoV-2 antibody concentrations. METHODS: Retrospective analysis of electronic patient files in a big single HIV center in Munich, Germany. Non-parametric methods were used for descriptive and comparative statistics. Generalized linear models were used to analyze associations of general and HIV-specific variables with anti-SARS-CoV-2 antibody concentrations after standard vaccination. RESULT: Overall, 665 people living with HIV were included into the analysis (median age: 53 [IQR: 43; 59]), 560 [84.2%] males). Median concentration of anti-SARS-CoV-2-antibodies was 1400 (IQR 664; 2130) BAU/mL. In 18 (2.7%) subjects, antibody concentrations below the threshold of 34 BAU/mL were found. Among PLWH with CD4 cell count < 200 cells/µL, median anti-SARS-CoV-2-Abs were 197 (IQR 44.6; 537.2) as compared to 1420 (IQR 687; 2216) for the group ≥ 200 cells/µL (p < 0.001). In a cumulative logit model, a vaccination scheme including an mRNA vaccine [OR: 4.64 (3.58; 6.02)], being female [OR: 2.14 (1.76; 2.61)], and having higher CD4 cells [OR per 100 cells/µL: 1.06 (1.04; 1.08)] were significantly associated with anti-SARS-CoV-2 antibody concentrations in higher quartiles, when adjusted for the time after vaccination. CONCLUSION: We found a robust antibody response in people living with HIV undergoing standard vaccination against SARS-CoV-2. mRNA-containing vaccination schemes, being female, and having a higher CD4 cell count was associated with a higher concentration of antibodies in people living with HIV in our study sample. Particularly in the subgroup with CD4 cell counts < 200 cells/µL, antibody response was poor.

Secondary Hyperparathyroidism in HIV-Infected Patients in Central Europe.

Secondary hyperparathyroidism (sHPT) might be a contributor to increased risk of osteoporosis in adult HIV patients but there is little data available on this issue in this particular population. The aim of the study was to investigate the prevalence of sHPT in an HIV-infected population with normal kidney function and to evaluate its risk factors in HIV patients. This cross-sectional study was carried out in a single HIV center in Germany using routine data from patients with normal kidney function attending the clinic between January 1st and December 31st, 2016. In total, 1263 patients were included [998 (79.0%) male, median age 48 (IQR 38-54) years]. In 214 patients (16.9%) elevated PTH levels with low or normal calcium levels were found. Multivariate logistic regression modeling showed significant associations with elevated PTH for African ethnicity [OR: 2.12 (95% CI: 1.42-3.16); p<0.001], low 25-hydroxyvitamin D levels [OR: 1.82 (95% CI: 1.32-2.51); p<0.001], low calcium levels [OR 1.69 (95% CI: 1.22-2.33); p=0.001], and use of tenofovir disoproxil fumarate [OR 2.33 (95% CI: 1.62-3.36); p<0.001]. Additional to common risk factors like vitamin D insufficiency and hypocalcemia, we found a significant association between the use of TDF and sHPT. Prospective data are needed to ascertain whether PTH-mediated bone loss is the underlying mechanism of TDF bone-toxicity. Additional screening of PTH even in HIV-infected patients with normal or low calcium levels may help to identify patients at increased risk of bone mineral density loss.

Tenofovir Disoproxil Fumarate Is Associated with a Set-Point Variation in the Calcium-Parathyroid Hormone-Vitamin D Axis: Results from a German Cohort.

BACKGROUND: Higher levels of parathyroid hormone have been associated with the use of tenofovir disoproxil fumarate (TDF) in people with and without HIV infection. Yet, alterations in calcium levels have never been elucidated in detail. OBJECTIVE: To compare the association of parathyroid hormone with serum calcium levels and other markers of calcium and bone metabolism in people living with HIV on TDF- and non-TDF-containing antiretroviral therapy. PATIENTS AND METHODS: A retrospective single center cohort study in Munich, Germany. Median and interquartile ranges and absolute and relative frequencies were used to describe continuous and categorical variables, respectively. The Mann-Whitney U test and chi2-test were used for comparisons. Multivariate median regression was performed in a stepwise backward approach. RESULTS: 1,002 patients were included (786 (78.4%) male; median age 48 (40-55) years). 564 patients (56.3%) had a TDF-containing ART regimen. PTH concentrations were 46.9 (33.0-64.7) pg/mL and 35.2 (26.4-55.4) pg/mL (P=0.001), 43.3 (30.8-59.8) pg/mL and 31.8 (22.3-49.6) pg/mL (P < 0.001), 46.1 (29.5-65.4) pg/mL and 33.4 (22.6-50.1) pg/mL (P < 0.001), and 37.8 (25.3-57.9) pg/mL and 33.8 (20.1-45.3) pg/mL (P=0.012) within the first, second, third, and fourth quartile of corrected calcium levels for patients with and without TDF-containing ART, respectively. In multivariate median regression, PTH concentration was significantly associated with Cacorr. (-32.2 (-49.8 to -14.8); P < 0.001), female sex (5.2 (1.2-9.2); P=0.010), 25(OH)D (-0.4 (-0.5 to -0.3); P < 0.001), and TDF-use (9.2 (6.0-12.5); P < 0.001). DISCUSSION: Higher levels of PTH seem to be needed to maintain normal calcium levels in PLWH on TDF-containing ART compared to non-TDF-containing ART. Optimal concentrations for 25-hydroxy vitamin D and calcium might therefore be different in people using TDF than expected from general populations but also people living with HIV with non-TDF-containing antiretroviral therapy. This might require different supplementation strategies but warrants further investigation.

Highly specific reasons for nonadherence to antiretroviral therapy: results from the German adherence study.

BACKGROUND: Reasons for and frequency of nonadherence to antiretroviral therapy (ART) may have changed due to pharmacological improvements. In addition, the importance of known non-pharmacologic reasons for nonadherence is unclear. METHODS: We performed a cross-sectional, noninterventional, multicenter study to identify current reasons for nonadherence. Patients were categorized by physicians into the following adherence groups: good, unstable, or poor adherence. Co-variables of interest included age, sex, time since HIV diagnosis, ART duration, current ART regimen, HIV transmission route, comorbidity, HIV-1 RNA viral load (VL), and CD4 cell count. Patients self-reported the number of missed doses and provided their specific reasons for nonadherent behavior. Statistical analyses were performed using Fisher's extended exact test, Kruskal-Wallis test, and logistic regression models. RESULTS: Our study assessed 215 participants with good (n=162), unstable (n=36), and poor adherence (n=17). Compared to patients with good adherence, patients with unstable and poor adherence reported more often to have missed at least one dose during the last week (good 11% vs unstable 47% vs poor 63%, p<0.001). Physicians' adherence assessment was concordant with patients' self-reports of missed doses during the last week (no vs one or more) in 81% cases. Similarly, we found a strong association of physicians' assessment with viral suppression. Logistic regression analysis showed that "reduced adherence" - defined as unstable or poor - was significantly associated with patients <30 years old, intravenous drug use, history of acquired immune deficiency syndrome (AIDS), and psychiatric disorders (p<0.05). Univariate analyses showed that specific reasons, such as questioning the efficacy/dosing of ART, HIV stigma, interactive toxicity beliefs regarding alcohol and/or party drugs, and dissatisfaction with regimen complexity, correlated with unstable or poor adherence (p<0.05). CONCLUSION: Identification of factors associated with poor adherence helps in identifying patients with a higher risk for nonadherence. Reasons for nonadherence should be directly addressed in every patient, because they are common and constitute possible adherence intervention points.

Dolutegravir monotherapy as treatment de-escalation in HIV-infected adults with virological control: DoluMono cohort results.

BACKGROUND: The potential toxicity of long-term antiretroviral therapy (ART) requires ongoing investigation of novel strategies for treatment of HIV-infected patients. Monotherapy with the integrase inhibitor (INSTI) dolutegravir (DTG) may offer a favourable safety profile. Additionally, DTG has a high barrier of resistance, crucial for successful maintenance of virological control. However, published data is sparse. METHODS: Retrospective, single-centre cohort study. We enrolled patients on suppressive ART who were switched to DTG monotherapy in routine clinical practice and fulfilled the following inclusion criteria: HIV RNA level <50 copies/ml for ≥6 months at time of switch (one blip <200 copies/ml with re-suppression accepted), no known INSTI resistance or prior INSTI failure, no replicative HBV infection and no history of AIDS. RESULTS: We identified 31 patients with 24-weeks of follow-up data. Previous ART included a non-nucleoside reverse transcriptase inhibitor, a boosted protease inhibitor or an INSTI in 32%, 6% and 61% of patients, respectively. At week 24, HIV RNA remained <50 copies/ml in all but two patients (94%). One patient chose to discontinue DTG monotherapy and another developed confirmed virological failure (HIV RNA 538 copies/ml) with new INSTI mutations (Q148H/G140S). Immune status and renal and metabolic function showed no statistically significant changes, apart from a significant decrease in gamma-glutamyl transferase. CONCLUSIONS: De-escalating to DTG monotherapy in selected patients might be a safe and feasible option. However, in one case evolution of INSTI resistance was observed. Further studies should assess particular risk factors for DTG monotherapy failure. In the meanwhile, caution is warranted.