Effectiveness of Dolutegravir in People on Rifampin-Based Tuberculosis Treatment

Background: Tenofovir-lamivudine-dolutegravir (TLD) is the WHO-preferred first-line regimen for people with HIV, but drug-drug interactions between dolutegravir (DTG) and rifampin (RIF) require an additional 50mg DTG (TLD+50) in people receiving tuberculosis (TB)/HIV co-treatment. RIF is a key drug in TB treatment, but is a potent inducer of metabolizing enzymes and efflux transporters, which can markedly lower drug concentrations. There are limited data on the effectiveness of TLD+50 in people with TB/HIV from program settings. Method(s): We conducted a prospective, observational study at 12 sites in 6 countries (Haiti, Kenya, Malawi, South Africa, Uganda, Zimbabwe). Participants received concomitant TLD+50 and RIF-based TB treatment provided as standard of care by HIV and TB treatment programs. Primary outcome was HIV-1 RNA <1000 copies/mL (cpm) at end of TB treatment. New DTG resistance mutations were defined as those present at end of TB treatment but not present at start. Result(s): From 11/2019-6/2021, we enrolled 91 participants with TB/HIV, including 75 ART-naive participants (82%) starting TLD+50 after a median of 15 days on TB treatment, 10 ART-naive participants (11%) starting TLD+50 and RIF together, 5 (5%) starting TB treatment and changing to TLD+50 after a median of 3.3y on TLD, and 1 (1%) starting RIF and TLD+50 after changing from EFV/3TC/TDF. Median age was 37y (IQR 32-43), 35% were female, 100% cis-gender, median CD4 count was 120 cells/mm3 (IQR 50-295), 87% had HIV-1 RNA >1000 copies/mL. Two participants died during TB treatment (week 4 disseminated TB, week 12 suspected COVID-19), 1 interrupted TLD+50 due to jaundice;and 1 discontinued TB treatment due to drug-induced liver injury. Among 89 surviving participants, 6 were lost to follow-up and a further 10 had no HIV-1 RNA result due to missed or remote visits. Primary virologic outcome was therefore assessed in 73 (80%), of whom 69 (95%, Wald 95% CI 89-100%) had HIV-1 RNA <=1000 cpm;68 (93%) had HIV-1 RNA <200 cpm. No sex specific differences in viral suppression were observed. No DTG resistance mutations were detected among 4 participants with HIV-1 RNA >1000 cpm. Conclusion(s): Concomitant RIF-containing TB treatment and TLD+50 was welltolerated and achieved excellent viral suppression in a cohort of predominantly ART-naive people with TB/HIV. These multi-country data from program settings support feasibility and effectiveness of current treatment approaches for TB/ HIV co-infection.

Rates of Antipsychotic Drug Prescribing Among People Living With Dementia During the COVID-19 Pandemic.

Importance: Concerns have been raised that the use of antipsychotic medication for people living with dementia might have increased during the COVID-19 pandemic. Objective: To examine multinational trends in antipsychotic drug prescribing for people living with dementia before and during the COVID-19 pandemic. Design, Setting, and Participants: This multinational network cohort study used electronic health records and claims data from 8 databases in 6 countries (France, Germany, Italy, South Korea, the UK, and the US) for individuals aged 65 years or older between January 1, 2016, and November 30, 2021. Two databases each were included for South Korea and the US. Exposures: The introduction of population-wide COVID-19 restrictions from April 2020 to the latest available date of each database. Main Outcomes and Measures: The main outcomes were yearly and monthly incidence of dementia diagnosis and prevalence of people living with dementia who were prescribed antipsychotic drugs in each database. Interrupted time series analyses were used to quantify changes in prescribing rates before and after the introduction of population-wide COVID-19 restrictions. Results: A total of 857 238 people with dementia aged 65 years or older (58.0% female) were identified in 2016. Reductions in the incidence of dementia were observed in 7 databases in the early phase of the pandemic (April, May, and June 2020), with the most pronounced reduction observed in 1 of the 2 US databases (rate ratio [RR], 0.30; 95% CI, 0.27-0.32); reductions were also observed in the total number of people with dementia prescribed antipsychotic drugs in France, Italy, South Korea, the UK, and the US. Rates of antipsychotic drug prescribing for people with dementia increased in 6 databases representing all countries. Compared with the corresponding month in 2019, the most pronounced increase in 2020 was observed in May in South Korea (Kangwon National University database) (RR, 2.11; 95% CI, 1.47-3.02) and June in the UK (RR, 1.96; 95% CI, 1.24-3.09). The rates of antipsychotic drug prescribing in these 6 databases remained high in 2021. Interrupted time series analyses revealed immediate increases in the prescribing rate in Italy (RR, 1.31; 95% CI, 1.08-1.58) and in the US Medicare database (RR, 1.43; 95% CI, 1.20-1.71) after the introduction of COVID-19 restrictions. Conclusions and Relevance: This cohort study found converging evidence that the rate of antipsychotic drug prescribing to people with dementia increased in the initial months of the COVID-19 pandemic in the 6 countries studied and did not decrease to prepandemic levels after the acute phase of the pandemic had ended. These findings suggest that the pandemic disrupted the care of people living with dementia and that the development of intervention strategies is needed to ensure the quality of care.

EFFICACY of TENOFOVIR-LAMIVUDINE-DOLUTEGRAVIR for INITIAL and FIRST-LINE SWITCH ART

Background: Single-tablet tenofovir disoproxil fumarate/lamivudine/dolutegravir (TLD) has been rapidly adopted as 1st-line ART for patients initiating treatment and switching from virally-suppressive NNRTI-based 1st regimens in PEPFAR programs. There are limited data, however, on effectiveness and emergence of resistance to TLD in programmatic settings where plasma HIV-1 RNA and drug resistance testing are not used widely. Methods: A prospective observational study is being performed at 13 ACTG sites in six countries (Haiti, Kenya, Malawi, South Africa, Uganda, Zimbabwe) coincident with TLD rollout to assess efficacy and emergence of HIV drug resistance following TLD for 1st, 2nd or 3rd-line ART. This report focuses on the 2 Groups that completed enrollment and 6 months of follow-up: Group 1b (Gp1b) participants on NNRTI-based ART for at least 6 months with HIV-1 RNA ≤1000 cps/mL before switch to TLD;and Group 4 (Gp4) ART-naïve participants initiating 1st-line TLD. The primary objective was to estimate the proportions of participants on TLD with HIV-1 RNA ≤1000 cps/mL and with new DTG resistance mutations at 6 months. Results:\From 10/2019-10/2020, we enrolled 600 participants who started TLD: 421 in Gp1b (median age 41years;80% female) and 179 in Gp4 (median age 35years;42% female). In Gp1b, median time on ART was 6.6y (IQR 3.3-10.3);88% were taking EFV with 3TC+TDF or FTC+TDF. In Gp4, median baseline HIV-1 RNA was 4.4 log10 cps/mL (IQR 3.5-5.1). Six participants in Gp1b (1.4%) and 6 in Gp4 (3.4%) discontinued TLD by 6 months, due to withdrawal or loss to follow-up (6 participants), adverse events considered related to TLD (4), and death (2;both Gp4;1 from TB, 1 unknown cause). Among participants followed on TLD to 6 months, 90% in Gp1b (373/415) and 86% in Gp4 (149/173) had a 6-month HIV-1 RNA result (missing values mainly due to COVID-related virtual visits). HIV-1 RNA ≤1000, <200 and <50 cps/mL was achieved in 99%, 98.4%, and 96% of participants in Gp1b and in 90%, 87.2%, and in 84.6% of Gp4, respectively (Table). A new mutation possibly selected by DTG was observed in 1 participant in Gp1b (T97AT) and none in Gp4. Conclusion: TLD was well tolerated and achieved excellent viral suppression in ART-naïve participants and in participants who switched from virally-suppressive 1st-line ART. An emerging InSTI mutation of uncertain significance was seen in only one participant. These data support early tolerability and efficacy of TLD transition in the public sector.

Impact of the COVID-19 pandemic on use of anti-dementia medications in 34 European and North American countries.

INTRODUCTION: The impact of the COVID-19 pandemic on the global use of anti-dementia medication is unknown. We aimed to determine the changes of anti-dementia medication use in Europe (EU) and North America (NA) during the pandemic. METHODS: This is a cross-sectional study using sales data of anti-dementia medications in 2019 and 2020 from 34 EU and NA countries. The monthly uses of anti-dementia medications from January through June in 2020 were compared to the corresponding months in 2019 for each country. RESULTS: In the pre-pandemic period of January to March 2020, 70 out of 102 (3 months x 34 countries) measurements (68.6%) of monthly sales volume showed an increase. In contrast, 76.5% and 85.3% countries showed reduced sales in April and May 2020, respectively. DISCUSSION: These findings indicate changes in use of anti-dementia medications during the pandemic. The delivery of pharmaceutical care for dementia patients may be heavily disrupted in certain countries.