BACKGROUND:The combination of 2 broadly neutralizing antibodies (bNAbs), teropavimab and zinlirvimab, plus the capsid inhibitor lenacapavir, is a potential twice-yearly regimen for HIV-1 treatment. The level of bNAb susceptibility to maintain virologic suppression is unknown; therefore, we evaluated this combination in participants meeting stringent viral sensitivity criteria to only 1 of the 2 bNAbs. METHODS:This was a pilot study within a proof-of-concept phase 1b study. RESULTS:No serious treatment-emergent adverse events occurred and 8 of 10 participants remained virologically suppressed at week 26. CONCLUSIONS:More inclusive bNAb susceptibility criteria may be appropriate for future studies of this combination treatment. Clinical Trials Registration. NCT04811040.
Bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) is indicated for people with HIV who are virologically suppressed, including those with M184V/I. Data on B/F/TAF effectiveness during viremia with M184V/I are limited. This observational study retrospectively collected clinical/demographic data from adults with viremia and M184V/I receiving B/F/TAF or alternate antiretroviral therapy (ART). Virologic suppression at 3 and ≥ 6 months was evaluated. For participants with data, 5/5 (100%) and 7/8 (88%) on B/F/TAF and 4/6 (67%) and 7/10 (70%) on alternate ART achieved virologic suppression at 3 and ≥ 6 months, respectively. Virologic suppression was achieved in most people with HIV who were viremic with M184V/I on B/F/TAF, as with alternate ART.
Through 144 weeks in GEMINI-1/-2 and 48 weeks in STAT, dolutegravir/lamivudine demonstrated high rates of virologic efficacy and a good safety profile in individuals naive to antiretroviral therapy across baseline viral load categories, including in those with very high baseline viral load (≥500 000 copies/mL). Clinical Trials Registration. NCT02831673/NCT02831764; NCT03945981.
In order to secure cobalt for the clean energy transition, this paper evaluates a strategic U.S.-DRC partnership. It examines the geology of cobalt, the dynamics of production, and the concentration in relation to market risk periods. It calculates the effects of both industrial and artisanal mining on the environment and society. It models how resilient the supply chain would be in different policy situations. It looks at the investment framework, commercial agreements, and statutory laws that connect DRC development goals with U.S. demand. It contrasts models for accounting for community benefits, traceability technologies, and certification programs. It calculates the risks to human rights and greenhouse gas emissions that come with sourcing decisions. It is providing a model for a phased partnership. The first phase focuses on financing, mine formalization, purchasing transparency, and the ability to assist local governance. Phase two entails sharing technology transfer and reducing downstream processing. The method discusses supply security in terms of measurable social results. Trade data, satellite observations, research, and recent policy changes serve as the foundation for this paper. For investors, civil society, and policymakers, the paper offers useful policy tools. It provides a wide range of metrics to gauge growth and reduce supply shock vulnerability. The results are intended to direct the creation of policies that will guarantee essential raw materials without endangering ecosystems and communities.
Increased weight has been observed among treatment-naïve-and-experienced people living with HIV initiating bictegravir (BIC) and dolutegravir (DTG). Here, we report changes in weight and body mass index (BMI) following switch to a BIC versus DTG-based regimen (DBR) through 144 weeks. This observational study collected demographics, clinical characteristics, weight, and BMI from virologically suppressed adults switched to BIC/emtricitabine/tenofovir alafenamide (TAF), emtricitabine/TAF plus DTG, DTG/abacavir/lamivudine, DTG/rilpivirine (RPV), and DTG/lamivudine 2 years prior to switch through 144 weeks post-switch. Linear spline models were fit to estimate and compare the trajectories of weight and BMI changes observed pre-and-post-switch. Adjusted piecewise linear mixed-effects models were fit to examine factors associated with weight and BMI change pre-and-post-switch. At week 144, switching to BIC/emtricitabine/TAF versus a DBR were both associated with lower annualized weight gain post-switch (-0.88 kg/year vs -0.39 kg/year respectively, P = .15). DTG plus emtricitabine/TAF switches had the highest annualized weight gain (0.68 kg/year, 95% confidence interval: -0.32, 1.65) whereas, DTG/RPV switches had the lowest annualized weight gain (-2.22 kg/year, 95% confidence interval: -3.69, -0.62) post-switch. DTG/RPV and BIC/emtricitabine/TAF switches were the only groups with significantly lower annualized weight gain post-switch at week 144. Baseline BMI < 18.5 kg/m2 was associated with the highest annualized weight gain post-switch, whereas switching from protease inhibitors and self-report of dieting were associated with the lowest annualized weight gain post-switch. At week 144, switching to a BIC versus DBR were both associated with lower annualized weight gain post-switch among a large and diverse cohort of treatment-experienced people living with HIV.
