Integrases of different retroviruses assemble as functional complexes with varying multimers of the protein. Retroviral integrases require a divalent metal cation to perform one-step transesterification catalysis. Tetrameric prototype foamy virus (PFV) intasomes assembled from purified integrase and viral DNA oligonucleotides were characterized for their activity in the presence of different cations. While most retroviral integrases are inactive in calcium, PFV intasomes appear to be uniquely capable of catalysis in calcium. The PFV intasomes also contrast with other retroviral integrases by displaying an inverse correlation of activity with increasing manganese beginning at relatively low concentrations. The intasomes were found to be significantly more active in the presence of chloride co-ions compared to acetate. While HIV-1 integrase appears to commit to a target DNA within 20 s, PFV intasomes do not commit to target DNA during their reaction lifetime. Together, these data highlight the unique biochemical activities of PFV integrase compared to other retroviral integrases.
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http://dx.doi.org/10.3390/biom11121910 | DOI Listing |
Lancet HIV
January 2025
Stichting HIV Monitoring, Amsterdam, Netherlands; Department of Infectious Diseases, Amsterdam Infection & Immunity Institute, Amsterdam University Medical Centre, University of Amsterdam, Amsterdam, Netherlands.
Background: Real-world data showing the long-term effectiveness of long-acting injectable cabotegravir and rilpivirine are scarce. We assessed the effectiveness of cabotegravir and rilpivirine in all individuals who switched to cabotegravir and rilpivirine in the Netherlands.
Methods: We used data from the ATHENA cohort, an ongoing observational nationwide HIV cohort in the Netherlands.
Viruses
December 2024
Global Health and Tropical Medicine, GHTM, Associate Laboratory in Translation and Innovation Towards Global Health, LA-REAL, Instituto de Higiene e Medicina Tropical, IHMT, Universidade NOVA de Lisboa, Rua da Junqueira 100, 1349-008 Lisboa, Portugal.
The high genetic variability of HIV-1 and the emergence of transmitted drug resistance (TDR) can impact treatment efficacy. In this study, we investigated the prevalent HIV-1 genotypes and drug-resistance-associated mutations in drug-naïve HIV-1 individuals in Cabo Verde. The study, conducted between 2018 and 2019, included drug-naïve HIV-1 individuals from the São Vicente, Boa Vista, Fogo, and Santiago islands.
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November 2024
Laboratory Branch, Division of HIV Prevention, National Center for HIV, Viral Hepatitis, STD and TB Prevention, Centers for Disease Control and Prevention, Atlanta, GA 30329, USA.
The HIV integrase inhibitor, dolutegravir (DTG), in the absence of eliciting integrase (int) resistance, has been reported to select mutations in the virus 3'-polypurine tract (3'-PPT) adjacent to the 3'-LTR U3. An analog of DTG, cabotegravir (CAB), has a high genetic barrier to drug resistance and is used in formulations for treatment and long-acting pre-exposure prophylaxis. We examined whether mutations observed for DTG would emerge in vitro with CAB.
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November 2024
Chantal BIYA International Reference Centre for Research on HIV/AIDS Prevention and Management, Yaoundé P.O. Box 3077, Cameroon.
Dual therapies (DT) combining integrase strand transfer inhibitors (INSTIs) with second-generation non-nucleoside reverse transcriptase inhibitors (2nd-Gen-NNRTIs) offer new possibilities for HIV treatment to improve adherence. However, drug resistance associated mutations (RAMs) to prior antiretrovirals may jeopardize the efficacy of DT. We herein describe the predicted efficacy of DT combining INSTIs + 2nd-Gen-NNRTI following treatment failure among Cameroonian patients.
View Article and Find Full Text PDFJ Int Assoc Provid AIDS Care
December 2024
Department of Internal Medicine, Kilimanjaro Christian Medical University College, Moshi, Tanzania.
Purpose: Chronic systemic inflammation from human immunodeficiency virus (HIV) may cause metabolic abnormalities in lipid metabolism. Additionally, the development of metabolic syndrome has been associated with specific anti-retroviral therapy, particularly dolutegravir. This study aimed to determine the prevalence and associated factors of metabolic syndrome among people living with HIV on dolutegravir-based anti-retroviral therapy.
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