title: Use of acyclovir for suppression of human immunodeficiency virus infection is not associated with genotypic evidence of herpes simplex virus type 2 resistance to acyclovir: analysis of specimens from three phase III trials.
abstract: Herpes simplex virus type 2 (HSV-2) is the most common cause of genital ulcer disease and is a cofactor for HIV-1 acquisition and transmission. We analyzed specimens from three separate phase III trials of acyclovir (ACV) for prevention of HIV-1 acquisition and transmission to determine if failure of ACV to interrupt HIV acquisition and transmission was associated with genotypic ACV resistance. Acyclovir (400 mg twice daily) or placebo was provided to HSV-2-infected persons at risk of HIV-1 infection in the Mwanza and HPTN 039 trials and to persons dually infected with HSV-2 and HIV-1 who had an HIV-negative partner in the Partners in Prevention study. We extracted HSV DNA from genital ulcer swabs or cervicovaginal lavage fluids from 68 samples obtained from 64 participants randomized to ACV and sequenced the HSV-2 UL23 gene encoding thymidine kinase. The UL23 sequences were compared with published and unpublished data. Variants were observed in 38/1,128 (3.4%) nucleotide positions in the UL23 open reading frame, with 58% of these encoding amino acid changes. No deletions, insertions, or mutations known to be associated with resistance were detected. Thirty-one of the variants (81.5%) are newly reported, 15 of which code for amino acid changes. Overall, UL23 is highly polymorphic compared to other loci in HSV-2, but no drug resistance mutations were detected that could explain the failure to reduce HIV incidence or to prevent HIV-1 transmission in these studies.
authors: London School of Hygiene and Tropical Medicine, London, United Kingdom.
authors: Deborah
authors: D
authors: Watson-Jones
authors: Anna
authors: A
authors: Wald
authors: Connie
authors: C
authors: Celum
authors: Jairam
authors: J
authors: Lingappa
authors: Helen A
authors: HA
authors: Weiss
authors: John
authors: J
authors: Changalucha
authors: Kathy
authors: K
authors: Baisley
authors: Clare
authors: C
authors: Tanton
authors: Richard J
authors: RJ
authors: Hayes
authors: Joshua O
authors: JO
authors: Marshak
authors: Rula Green
authors: RG
authors: Gladden
authors: David M
authors: DM
authors: Koelle
mesh_terms: D000212:Acyclovir / Q000008:administration & dosage* / Q000494:pharmacology; D000293:Adolescent; D000328:Adult; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods*; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000494:pharmacology; D004279:DNA, Viral; D024882:Drug Resistance, Viral; D005260:Female; D005836:Genitalia, Female / Q000821:virology; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000302:isolation & purification; D006558:Herpes Genitalis / Q000150:complications / Q000188:drug therapy* / Q000821:virology; D018258:Herpesvirus 2, Human / Q000187:drug effects* / Q000302:isolation & purification; D006801:Humans; D008969:Molecular Sequence Data; D010919:Placebos / Q000008:administration & dosage; D017422:Sequence Analysis, DNA; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D004279:DNA, Viral; D010919:Placebos; D000212:Acyclovir