Phase 3 clinical studies showed non-inferiority of long-acting intramuscular cabotegravir and rilpivirine dosed every 4 weeks to oral antiretroviral therapy. Important phase 2 results of every 8 ...weeks dosing, and supportive modelling, underpin further evaluation of every 8 weeks dosing in this trial, which has the potential to offer greater convenience. Our objective was to compare the week 48 antiviral efficacy of cabotegravir plus rilpivirine long-acting dosed every 8 weeks with that of every 4 weeks dosing.
ATLAS-2M is an ongoing, randomised, multicentre (13 countries; Australia, Argentina, Canada, France, Germany, Italy, Mexico, Russia, South Africa, South Korea, Spain, Sweden, and the USA), open-label, phase 3b, non-inferiority study of cabotegravir plus rilpivirine long-acting maintenance therapy administered intramuscularly every 8 weeks (cabotegravir 600 mg plus rilpivirine 900 mg) or every 4 weeks (cabotegravir 400 mg plus rilpivirine 600 mg) to treatment-experienced adults living with HIV-1. Eligible newly recruited individuals must have received an uninterrupted first or second oral standard-of-care regimen for at least 6 months without virological failure and be aged 18 years or older. Eligible participants from the ATLAS trial, from both the oral standard-of-care and long-acting groups, must have completed the 52-week comparative phase with an ATLAS-2M screening plasma HIV-1 RNA less than 50 copies per mL. Participants were randomly assigned 1:1 to receive cabotegravir plus rilpivirine long-acting every 8 weeks or every 4 weeks. The randomisation schedule was generated by means of the GlaxoSmithKline validated randomisation software RANDALL NG. The primary endpoint at week 48 was HIV-1 RNA ≥50 copies per mL (Snapshot, intention-to-treat exposed), with a non-inferiority margin of 4%. The trial is registered at ClinicalTrials.gov, NCT03299049 and is ongoing.
Screening occurred between Oct 27, 2017, and May 31, 2018. Of 1149 individuals screened, 1045 participants were randomised to the every 8 weeks (n=522) or every 4 weeks (n=523) groups; 37% (n=391) transitioned from every 4 weeks cabotegravir plus rilpivirine long-acting in ATLAS. Median participant age was 42 years (IQR 34–50); 27% (n=280) female at birth; 73% (n=763) white race. Cabotegravir plus rilpivirine long-acting every 8 weeks was non-inferior to dosing every 4 weeks (HIV-1 RNA ≥50 copies per mL; 2% vs 1%) with an adjusted treatment difference of 0·8 (95% CI −0·6–2·2). There were eight (2%, every 8 weeks group) and two (<1%, every 4 weeks group) confirmed virological failures (two sequential measures ≥200 copies per mL). For the every 8 weeks group, five (63%) of eight had archived non-nucleoside reverse transcriptase inhibitor resistance-associated mutations to rilpivirine at baseline. The safety profile was similar between dosing groups, with 844 (81%) of 1045 participants having adverse events (excluding injection site reactions); no treatment-related deaths occurred.
The efficacy and safety profiles of dosing every 8 weeks and dosing every 4 weeks were similar. These results support the use of cabotegravir plus rilpivirine long-acting administered every 2 months as a therapeutic option for people living with HIV-1.
ViiV Healthcare and Janssen.
Relevance. The development of the HIV epidemic in different parts of the word is accompanied by the dynamics of its manifestations, including a change in the role in epidemics of various routes of ...transmission, “risky groups” and shifts in the gender structure of morbidity. The study of the epidemic process in dynamics, including the gender indicators of the epidemic, is important for forecasting the epidemic and modernizing prevention strategies. The aim of the study is to assess the gender characteristics of the manifestations of the epidemic process of HIV infection in the Republic of Tatarstan. Materials and methods. A retrospective analysis of the incidence of HIV-infection among women and men in the Republic of Tatarstan (Russia) for the period of 1996–2018 was carried out. We used information from database of AIDS-centre of Tatarstan Republic. Incidence of HIV in association with age, ways of transmission, social status was calculated for men and women separately. We analyzed the role of main transmission routes in different age groups over the entire period of the epidemic (1987–2018). The data is processed in Microsoft Office Excel 2010. Results. Incidence rate of HIV per year in men is higher then in women from 1999 (p < 0,05). In the structure of the adult population's incidence of HIV infection, the proportion of women increased by 2.4 times: from 14.8 ± 0.7% in 2001 to 35.6 ± 1.3% in 2018 (p < 0.001). During the entire follow - up period of 1996-2018, the most common route of getting infection for men was intravenous (68%); most of women (73,3%) got HIV via sexual rout including women, living in areas with the highest prevalence of drug addiction. The proportion of sexual route of HIV-transmission increased from 5.6 ± 0.5% in 2001 to 52.3 ± 1.7% in 2018 for men, and from 23.7 ± 2.2% in 2001 to 84.6 ± 1.7% in 2018 for women (p < 0.001). Dynamic of HIV-epidemic is presented by involvement of older age groups. With age, the proportion of people who were infected via sexual rout increases in both women and men groups. Conclusion. The dynamics of the epidemiological manifestations of HIV infection in the Republic of Tatarstan for the period 1996–2018 has many similarities among women and men: they have unidirectional changes, and the incidence rates decreases for people under 30 years. The incidence rates for men are higher than those for women, however, the development of the epidemic is accompanied by an increase in the proportion of women, for whom, unlike men, regardless of the age and prevalence of drug addiction in the territory the live, the sexual route of infection is predominant.
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