ArticleCell host & microbe2008
Acyclovir is activated into a HIV-1 reverse transcriptase inhibitor in herpesvirus-infected human tissues.
Article in Cell host & microbe, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
76 citing papers in PubMed, 1 synthesis or guideline pooled it, 115 citations in OpenAlex.
- Herpes simplex virus type 2 and HIV disease progression: a systematic review of observational studies.BMC infectious diseases · 2013Pooled it
- Effect of valaciclovir on CD4 count decline in untreated HIV: an international randomized controlled trial.The Journal of antimicrobial chemotherapy · 2019Trial
- Valacyclovir Decreases Plasma HIV-1 RNA in HSV-2 Seronegative Individuals: A Randomized Placebo-Controlled Crossover Trial.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2015Trial
- High-dose valacyclovir decreases plasma HIV-1 RNA more than standard-dose acyclovir in persons coinfected with HIV-1 and HSV-2: a randomized crossover trial.Journal of acquired immune deficiency syndromes (1999) · 2013Trial
- Short communication: T cell activation in HIV-1/herpes simplex virus-2-coinfected Kenyan women receiving valacyclovir.AIDS research and human retroviruses · 2013Trial
- Partner characteristics predicting HIV-1 set point in sexually acquired HIV-1 among African seroconverters.AIDS research and human retroviruses · 2013Trial
- Effect of daily aciclovir on HIV disease progression in individuals in Rakai, Uganda, co-infected with HIV-1 and herpes simplex virus type 2: a randomised, double-blind placebo-controlled trial.The Lancet. Infectious diseases · 2012Trial
- High-dose valacyclovir HSV-2 suppression results in greater reduction in plasma HIV-1 levels compared with standard dose acyclovir among HIV-1/HSV-2 coinfected persons: a randomized, crossover trial.The Journal of infectious diseases · 2011Trial
- Valganciclovir reduces T cell activation in HIV-infected individuals with incomplete CD4+ T cell recovery on antiretroviral therapy.The Journal of infectious diseases · 2011Trial
- Trial
- Long-term impact of acyclovir suppressive therapy on genital and plasma HIV RNA in Tanzanian women: a randomized controlled trial.The Journal of infectious diseases · 2010Trial
- Daily acyclovir for HIV-1 disease progression in people dually infected with HIV-1 and herpes simplex virus type 2: a randomised placebo-controlled trial.Lancet (London, England) · 2010Trial
- Acyclovir and transmission of HIV-1 from persons infected with HIV-1 and HSV-2.The New England journal of medicine · 2010Trial
- An SRR1 domain-containing protein is required for efficient Orsay virus replication inJournal of virology · 2025Article
- Glyoxal Caging of Nucleoside Antivirals toward Self-Activating, Extended-Release Prodrugs.Journal of the American Chemical Society · 2024Article
- Recent Advances in the Synthesis of Acyclic Nucleosides and Their Therapeutic Applications.Topics in current chemistry (Cham) · 2024Review
- Activation-neutral gene editing of tonsillar CD4 T cells for functional studies in human ex vivo tonsil cultures.Cell reports methods · 2024Article
- Infection of the Ex Vivo Tonsil Model by HTLV-1 Envelope-Pseudotyped Viruses.Pathogens (Basel, Switzerland) · 2023Article
- Article
- Reduced and highly diverse peripheral HIV-1 reservoir in virally suppressed patients infected with non-B HIV-1 strains in Uganda.Retrovirology · 2022Article
16 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
17 authors at 8 institutions in 4 countries.
Funding
Abstract
For most viruses, there is a need for antimicrobials that target unique viral molecular properties. Acyclovir (ACV) is one such drug. It is activated into a human herpesvirus (HHV) DNA polymerase inhibitor exclusively by HHV kinases and, thus, does not suppress other viruses. Here, we show that ACV suppresses HIV-1 in HHV-coinfected human tissues, but not in HHV-free tissue or cell cultures. However, addition of HHV-6-infected cells renders these cultures sensitive to anti-HIV ACV activity. We hypothesized that such HIV suppression requires ACV phosphorylation by HHV kinases. Indeed, an ACV monophosphorylated prodrug bypasses the HHV requirement for HIV suppression. Furthermore, phosphorylated ACV directly inhibits HIV-1 reverse transcriptase (RT), terminating DNA chain elongation, and can trap RT at the termination site. These data suggest that ACV anti-HIV-1 activity may contribute to the response of HIV/HHV-coinfected patients to ACV treatment and could guide strategies for the development of new HIV-1 RT inhibitors.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.