Document Detail


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.
MedLine Citation:
PMID:  23542637     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: Standard doses of herpes simplex virus (HSV) suppressive therapy reduce plasma HIV-1 RNA levels (0.25-0.53 log10 copies per milliliter) among HIV-1/HSV-2 coinfected persons. Postulated mechanisms for this effect include direct inhibition of HIV-1 by acyclovir or indirect reduction by decreasing HSV-associated inflammation. We hypothesized that high-dose valacyclovir would further reduce plasma HIV-1 RNA and that the effect would be mediated by greater suppression of HSV shedding.
METHODS: Thirty-four participants with HIV-1 and HSV-2 not on antiretroviral therapy were enrolled into a randomized, open-label crossover trial of valacyclovir 1000 mg twice daily or acyclovir 400 mg twice daily for 12 weeks, followed by a 2-week washout, and then the alternate treatment arm for 12 weeks. HSV DNA was measured from daily self-collected genital swabs for the initial 4 weeks of each arm, and HIV-1 RNA was quantified from weekly plasma samples.
RESULTS: Twenty-eight participants provided plasma samples and genital swabs on both acyclovir and valacyclovir. The genital HSV-2 shedding rate was the same on valacyclovir and acyclovir [7.8% vs. 8.2% of days; relative risk: 0.95; 95% confidence interval (CI): 0.66 to 1.37; P = 0.78]. Plasma HIV-1 RNA was 0.27 log10 copies per milliliter lower on valacyclovir compared with acyclovir (95% CI: -0.41 to -0.14 log10 copies per milliliter; P < 0.001); this was unchanged after adjustment for genital HSV-2 shedding.
CONCLUSIONS: High-dose valacyclovir reduces plasma HIV-1 RNA levels more than standard-dose acyclovir in HIV-1/HSV-2-seropositive persons not receiving antiretroviral therapy. The incremental reduction in plasma HIV-1 RNA achieved is not mediated by greater genital HSV-2 suppression.
Authors:
Tara Perti; Misty Saracino; Jared M Baeten; Christine Johnston; Kurt Diem; Negusse Ocbamichael; Meei-Li Huang; Stacy Selke; Amalia Magaret; Lawrence Corey; Anna Wald
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Publication Detail:
Type:  Clinical Trial; Journal Article; Randomized Controlled Trial; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of acquired immune deficiency syndromes (1999)     Volume:  63     ISSN:  1944-7884     ISO Abbreviation:  J. Acquir. Immune Defic. Syndr.     Publication Date:  2013 Jun 
Date Detail:
Created Date:  2013-05-13     Completed Date:  2013-07-08     Revised Date:  2013-08-09    
Medline Journal Info:
Nlm Unique ID:  100892005     Medline TA:  J Acquir Immune Defic Syndr     Country:  United States    
Other Details:
Languages:  eng     Pagination:  201-8     Citation Subset:  IM; X    
Affiliation:
Department of Medicine, University of Washington, Seattle, WA 98104, USA. tarap@u.washington.edu
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MeSH Terms
Descriptor/Qualifier:
Acyclovir / administration & dosage*,  analogs & derivatives*
Adult
Antiviral Agents / administration & dosage*,  therapeutic use
Coinfection
Cross-Over Studies
Cytomegalovirus / genetics
DNA, Viral / blood
Female
HIV Infections / complications*,  drug therapy,  virology*
HIV-1 / drug effects*,  genetics
Herpes Genitalis / complications*,  drug therapy
Herpesvirus 2, Human / drug effects,  genetics
Humans
Male
Middle Aged
Patient Compliance
RNA, Viral / blood
Valine / administration & dosage,  analogs & derivatives*
Viral Load
Virus Shedding / drug effects
Grant Support
ID/Acronym/Agency:
K24 AI071113/AI/NIAID NIH HHS; K24 AI071113/AI/NIAID NIH HHS; P01 AI030731/AI/NIAID NIH HHS; P01 AI30731/AI/NIAID NIH HHS; T32 AI007140/AI/NIAID NIH HHS; T32 AI07140/AI/NIAID NIH HHS
Chemical
Reg. No./Substance:
0/Antiviral Agents; 0/DNA, Viral; 0/RNA, Viral; 59277-89-3/Acyclovir; 7004-03-7/Valine; MZ1IW7Q79D/valacyclovir

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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