Switching to Doravirine in cART-Experienced Patients: An Effective and Highly Tolerated Option With Substantial Cost Savings.

BACKGROUND: Doravirine is a non-nucleoside reverse transcriptase inhibitor with demonstrated efficacy as a third agent in treatment-naive and treatment-experienced people living with HIV (PLWH) in registration studies. However, limited real-world data are available. METHODS: By searching electronic health care records, PLWH using doravirine-based regimens were selected with at least 1 year of follow-up after their first prescription. All stable PLWH who were switched to a doravirine-based regimen were included in the analysis. The primary outcome was the durability of a doravirine-based regimen 1 year after prescription. Reasons for stopping were also collected. Secondary outcomes for PLWH continuing a doravirine-based regimen after 1 year were routine laboratory assessment, body mass index, and differences in medication costs compared with their previous cART. RESULTS: A total of 687 patients (92% men) were included from September 2019 to August 2022: 97.7% switched to doravirine/tenofovir/lamivudine (DOR/TDF/3TC). After 1 year, 94/687 (13.6%) PLWH stopped this therapy. The main reason for discontinuation was patient-reported adverse events in 70/687 (10.2%). Medical reasons for discontinuation included increased alanine tranaminase levels in 6/687 (0.9%), decreased estimated glomerular filtration rate in 3/687 (0.4%), and precautions after diagnosis of osteoporosis in 2/687 (0.3%) patients. Virologic failure occurred in 4/687 cases (0.6%), and 1 case demonstrated resistance mutations. The secondary outcomes demonstrated a statistically significant increase in alanine tranaminase levels and decrease in LDL-c levels. The switch to a doravirine-based regimen in the Netherlands reduced medication costs by 27%. CONCLUSIONS: This study demonstrated that switching to a doravirine-based regimen, mostly DOR/TDF/3TC, was highly effective and generally well tolerated, with substantial cost savings.

Does a proactive procedure lead to a higher uptake of predictive testing in families with a pathogenic BRCA1/BRCA2 variant? A family cancer clinic evaluation.

The uptake of genetic counseling and predictive genetic testing by family members at risk for hereditary tumor syndromes is generally below 50%. To address this issue, a new guideline was introduced in the Netherlands in 2019 that aims to improve the sharing of information within families. In addition to cascade screening supported by follow-up telephone calls with the proband, municipal records were accessed to allow the geneticist to contact at-risk family members directly. We evaluated this procedure in 32 families with a (likely) pathogenic germline BRCA1/BRCA2 variant diagnosed at our hospital between May 1, 2020, and July 31, 2021, comparing current uptake with outcomes achieved for 33 families diagnosed in 2014. Fifteen months after diagnostic testing of the proband, the uptake was 43% (120/277), comparable to the 44% (87/200) registered previously. Among a subgroup of women at 50% risk aged 25-75 years, 71% (47/66) were tested, comparable to an earlier uptake of 69% (59/86). Of the 34 at-risk relatives we contacted directly, 17 (50%) underwent predictive testing. In conclusion, we found no evidence that the new procedure leads to a substantially increased uptake. Future research should be primarily aimed at understanding intrafamilial communication barriers.

The uptake of predictive DNA testing in 40 families with a pathogenic BRCA1/BRCA2 variant. An evaluation of the proband-mediated procedure.

When hereditary breast and ovarian cancer (HBOC) due to a BRCA1/BRCA2 germline pathogenic variant is diagnosed, the proband will be asked to inform other at-risk family members. In the Netherlands, a guideline was introduced in 2012 which provided detailed recommendations regarding this proband-mediated procedure. We now evaluated the uptake of predictive BRCA1/BRCA2 testing in 40 consecutive HBOC families diagnosed in our centre in 2014. We performed a retrospective observational study of all 40 families in which a pathogenic BRCA1/BRCA2 germline variant was identified during 2014. We scored the uptake of predictive and confirmatory testing by the end of 2018 and explored factors associated with the level of uptake. Two families were excluded. In the remaining 38 families, among 239 family members ≥18 years at 50% risk of being a mutation carrier or at 25% risk if the family member at 50% risk was deceased, 102 (43%) were tested. Among 108 females 25-75 years of age at 50% risk, 59 (55%) underwent predictive or confirmatory testing, and among 43 males at 50% risk with daughters ≥18 years, 22 (51%) were tested. Factors which complicated cascade screening included family members living abroad, probands not wanting to share information and limited pedigree information. In conclusion, the standard proband-mediated procedure of informing relatives seems to be far from optimal. We suggest a tailored approach for each family, including the option of a direct approach to at-risk family members by the geneticist. In addition, we suggest detailed monitoring and follow-up of families.