Publications by authors named "Rima Acosta"
Article Synopsis
- - SARS-CoV-2 has evolved to evade current monoclonal antibodies (mAbs), emphasizing the need for more resilient treatments that can neutralize various viral strains.
- - A new human mAb called VIR-7229 has shown the ability to effectively neutralize multiple variants of SARS-CoV-2 and other related viruses, due to its unique targeting of a critical viral region known as the receptor-binding motif (RBM).
- - VIR-7229 demonstrates a high resistance to the emergence of virus escape mutants, making it a promising candidate for future therapies against evolving coronaviruses.
Currently circulating SARS-CoV-2 variants have acquired convergent mutations at hot spots in the receptor-binding domain (RBD) of the spike protein. The effects of these mutations on viral infection and transmission and the efficacy of vaccines and therapies remains poorly understood. Here we demonstrate that recently emerged BQ.
View Article and Find Full Text PDFBackground: Bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) is a single-tablet regimen recommended for HIV-1 treatment. The safety and efficacy of B/F/TAF as initial therapy was established in two Phase 3 studies: 1489 (vs dolutegravir [DTG]/abacavir/lamivudine) and 1490 (vs DTG + F/TAF). After 144 weeks of randomized follow-up, an open-label extension evaluated B/F/TAF to 240 weeks.
View Article and Find Full Text PDFBackground: We investigated whether deep sequencing of archived HIV DNA of antiretroviral-naive persons with acute/early HIV infection could identify transmitted drug resistance mutations (DRM), per the IAS drug resistance algorithm, which are not detected by routine bulk (consensus) sequencing.
Methods: Deep sequencing of HIV DNA from peripheral blood mononuclear cells and consensus sequencing from concurrent blood plasma (BP) was performed from antiretroviral (ART)-naive adults with recent infection. We compared the prevalence of low-frequency (2%-20%) and high-frequency (>20%) nonnucleoside reverse transcriptase inhibitor (NNRTI), nucleoside reverse transcriptase inhibitor (NRTI), and protease inhibitor (PI) DRM.
Currently circulating SARS-CoV-2 variants acquired convergent mutations at receptor-binding domain (RBD) hot spots. Their impact on viral infection, transmission, and efficacy of vaccines and therapeutics remains poorly understood. Here, we demonstrate that recently emerged BQ.
View Article and Find Full Text PDFObjective: We investigated the prevalence of preexisting M184V/I and associated risk factors among clinical trial participants with suppressed HIV and evaluated the impact of M184V/I on virologic response after switching to bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF).
Design: Participant data were pooled from six clinical trials investigating the safety and efficacy of switching to B/F/TAF in virologically suppressed people with HIV.
Methods: Preexisting drug resistance was assessed by historical genotypes and/or baseline proviral DNA genotyping.
The integrase strand transfer inhibitor (INSTI)-based regimens bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF), dolutegravir (DTG)+FTC/TAF, DTG/lamivudine (3TC), and DTG/rilpivirine (RPV) are all approved for treatment of HIV-infected patients, with various limitations. Here, time to viral breakthrough (VB) and resistance barrier using simulated human drug exposures at either full or suboptimal treatment adherence to each regimen were compared. At drug concentrations corresponding to full adherence and 1 missed dose ( and -1), no VB occurred with any regimen.
View Article and Find Full Text PDFArticle Synopsis
- Preexisting drug resistance to HIV treatments can limit effectiveness, but the combination therapy of bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) has shown safety and effectiveness in some patients, even those with specific drug resistance mutations.
- A study involving 1907 individuals revealed that only 20 participants (1%) had primary resistance to integrase strand transfer inhibitors (INSTI-R), mostly maintaining their viral load suppression over 48 weeks of B/F/TAF treatment without significant issues.
- Overall, this small group of participants successfully managed their HIV with B/F/TAF, suggesting that this treatment could work for others with similar drug resistance if validated in future research.
Article Synopsis
- Two Phase 3 studies showed bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) is as effective as other HIV treatments, with no resistance emerging over 144 weeks.
- Analysis of resistance after 3 years revealed very low rates of pre-existing drug resistance among participants, which did not impact treatment outcomes.
- Overall, treatment with B/F/TAF and other regimens led to high and sustained rates of HIV-1 viral suppression, even in individuals with some baseline resistance.
Simulating HIV Breakthrough and Resistance Development During Variable Adherence to Antiretroviral Treatment.
J Acquir Immune Defic Syndr
March 2021
Article Synopsis
- Lifelong HIV-1 suppression is challenged by poor adherence to medication and the development of drug resistance; regimens that allow for missed doses could help patients.
- In vitro experiments were conducted to observe viral breakthrough (VB) and resistance when simulating different adherence levels to two antiretroviral therapies: BIC+FTC+TAF and DTG+3TC.
- Results indicated that BIC+FTC+TAF retained effectiveness even with missed doses, while DTG+3TC became less effective with more missed doses, leading to higher chances of resistance development.
Background: Study 4030 was a phase 3, randomized, double-blinded study of 565 HIV-1 RNA-suppressed participants switching to bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) or dolutegravir (DTG)+F/TAF. Nucleoside reverse transcriptase inhibitor (NRTI), non-NRTI, and protease inhibitor resistance (-R) was allowed, but integrase strand transfer inhibitor-R was excluded. Here, we describe the detailed resistance analysis.
View Article and Find Full Text PDFBackground: Bictegravir (B)/emtricitabine (F)/tenofovir alafenamide (TAF) is guideline-recommended treatment for human immunodeficiency virus type 1 (HIV-1). We evaluated whether people receiving dolutegravir (DTG) plus F/TAF or F/TDF (tenofovir disoproxil fumarate) with viral suppression can switch to B/F/TAF without compromising safety or efficacy, regardless of preexisting nucleoside reverse transcriptase inhibitor (NRTI) resistance.
Methods: In this multicenter, randomized, double-blinded, active-controlled, noninferiority trial, we enrolled adults who were virologically suppressed for ≥6 months before screening (with documented/suspected NRTI resistance) or ≥3 months before screening (with no documented/suspected NRTI resistance) on DTG plus either F/TDF or F/TAF.
Article Synopsis
- In a study analyzing the effectiveness and safety of two HIV treatment regimens over 144 weeks, a combination of bictegravir, emtricitabine, and tenofovir alafenamide was found to be as effective as a dolutegravir-based regimen for treatment-naive patients.
- *The studies included 1,274 participants who were randomly assigned to receive either the bictegravir regimen or various dolutegravir regimens, with the primary endpoint showing non-inferiority at week 48.
- *By week 144, the efficacy results showed that a high percentage of participants in both treatment groups maintained low plasma HIV-1 RNA levels, indicating continued effectiveness of the bictegravir regimen.*
Article Synopsis
- Bictegravir combined with emtricitabine/tenofovir alafenamide (B/F/TAF) is an effective and well-tolerated HIV treatment, showing no resistance in treatment-naive and suppressed patients for 48 weeks.* -
- In a phase 3 trial, 472 women with suppressed HIV were randomly assigned to either switch to B/F/TAF or continue their current regimen, with results demonstrating that switching was as effective as staying on the original treatment.* -
- The study highlights B/F/TAF as a safe option for women living with HIV, providing essential insights into the efficacy and tolerability of antiretroviral therapy specifically for this group.*
Article Synopsis
- The study compares the long-term efficacy, safety, and tolerability of a single-tablet HIV treatment (bictegravir, emtricitabine, and tenofovir alafenamide) against a dual regimen (dolutegravir with emtricitabine and tenofovir alafenamide) over 96 weeks.
- Conducted as a randomized, double-blind trial across 126 centers in 10 countries, the study involved treatment-naive adults with HIV-1 and followed a strict inclusion criteria, ensuring participants had specific health parameters.
- Results showed that both treatment groups yielded similar rates of achieving undetectable HIV levels, demonstrating the new single-tablet regimen's effectiveness over the monitored timeframe.
Article Synopsis
- * It was a phase 3, randomized, double-blind trial conducted at 122 centers in nine countries with 631 HIV treatment-naive adults participating.
- * Results indicated that both treatments were effective, with a focus on assessing the proportion of participants achieving an undetectable HIV viral load after 96 weeks, contributing valuable long-term data for future HIV treatment options.
In clinical studies GS-US-380-1489 (study 1489) and GS-US-380-1490 (study 1490), bictegravir-emtricitabine-tenofovir alafenamide (B-F-TAF), dolutegravir-abacavir-lamivudine (DTG-ABC-3TC), and dolutegravir plus emtricitabine-tenofovir alafenamide (DTG+F-TAF) treatment achieved high rates of virologic suppression in HIV-1 treatment-naive participants through week 48. Preexisting primary drug resistance was present at levels of 1.3% integrase strand transfer inhibitor resistance (INSTI-R), 2.
View Article and Find Full Text PDF